G.W.H. Stamp • N.A.

Wright

Advanced
Histopathology
Foreword by Colin L. Berry

Springer-Verlag
London Berlin Heidelberg New York
Paris Tokyo Hong Kong
G.W.H.Stamp, MBChB, MRCPath
Clinical Research Fellow, Imperial Cancer Research Fund, Royal College of
Surgeons, 35-43 lincoln's Inn Fields, London WC2A 3PN, UK and Honorary
Consultant in Histopathology, Hammersmith Hospital, Du Cane Road,
London W12 OHS, UK
N.A.Wright, MA, DSc, MD, PhD, FRCPath
Professor and Director, Department of Histopathology, Royal Postgraduate Medical
School, Hammersmith Hospital, Du Cane Road, London W12 OHS, UK and Associate
Director and Head of Histopathology Unit, Imperial Cancer Research Fund, Royal
College of Surgeons, 35-43 Lincoln's Inn Fields, London WC2A 3PN, UK

With contributions from:

Dr T. Clarke, MA, MBBChir, MRCPath, Senior Registrar in Histopathology,
Royal Devon and Exeter Hospital, Exeter, Devon EX2 SAD, UK
Dr F. Barker, MA, MBBS, MRCPath, Senior Registrar in Histopathology and
Dr M.B. Prentice, BMedSci, MBBS, FRCPathAust, Registrar in Histopathology
Hammersmith Hospital, Du Cane Road, London W12 OHS, UK

ISBN-13:978-3-540-19589-4 e-ISBN-13:978-l-4471-1753-7
DOl: 10.1007/978-1-4471-1753-7

British Library Cataloguing in Publication Data

Stamp, G.W.H. (Gordon W.H.), 1955-
Advanced histopathology.
1. Medicine. Histopathology
I. Tide ll. Wright, N.A. (Nicholas Alcwyn), 1943- 611'.018
ISBN-13:978-3-540-19589-4

Library of Congress Cataloging-in-Publication Data

Stamp, G. W. H. (Gordon W. H.). 1955-
Advanced histopathology/ G.W.H. Stamp and N.A. WrighL
p. cm.
ISBN-13:978-3-540-19589-4 (U.S. alk. paper)
1. Histology, Pathological-Examinations, questions, etc. 2. Histology,
Pathological-Oudines, syllabi, etc. I. Wright, N. A. (Nick A.), 1943- ll. Tide.
RB43.S73 1989
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Foreword

It is easy to be confident that an appropriate body of advice is

available to candidates about the content of an examination
once you have passed it. Prospectively, the Primary and Final
Examinations of the Royal College of Pathologists will appear
to most to involve the assimilation of what seems at the time an
inexhaustible volume of data, and the recent change in the
College examination system has not diminished this concern
for the majority of candidates. The guidelines for training for
the new Part I examination state that this is the "major hurdle
of the MRCPath" and it is clear that it will determine whether
candidates are suitable for training which will permit them to
practise independently as consultants after Part II.
These general aims and objectives do not answer questions
such as "How much do I need to know about
glomerulonephritis?" or "Where do I stop with the
lymphomas?" This text attempts to resolve the difficulty of
knowing what standard to aim at, using College questions as
its starting point. It concentrates on the essential basis of any
single answer; many candidates for the new three-year
examination will know more about individual topics than is
stated here. However, it is the breadth of information required
which is a feature of College examinations and this text should
help with this problem.
There are a number of important additional points. You will
not pass if you do not do an adequate post-mortem or present
it clearly, if you do not know something about special
techniques, if you have ignored cytology, or if you suppose
surgical pathology can be learned by picture matching. Many
slides are put into practical examinations to see how you think
about problems - it is not necessary to know all the answers
but you do have to behave sensibly when confronted with
something difficult.
The Government White Paper on the National Health Service
should have convinced you that it is important to know about
management issues and to be able to evaluate your own
work pattern critically (and financially). If you pass the
vi Foreword

examination(s) you can be confident that this phase of your

training has been satisfactorily completed and that you have
demonstrated a high standard of proficiency - an important
achievement.

London Colin L.Berry, PhD, FRCPath

October 1989 Professor of Morbid Anatomy
The London Hospital Medical College
Preface

We assume you have bought, or are thinking of buying, this

book because you are faced, horribile dictu, with the
Histopathology examinations of the Royal College of
Pathologists, or some related ordeal.
If you have not taken the examination before, then, apart
from advice from your seniors (who may not have taken the
examination personally, being Grandfathers, or even worse,
achieved their MRCPath status through research) and myth-
ology prevalent among your peers, you will not know what to
expect. If you have taken the examination, then you have
obviously been failed, albeit by biased and intransigent
examiners. Take comfort: help is on the way.
Following an initial discussion between Nick Wright and
Colin Berry, it was decided to attempt a vade-mecum for
prospective examination candidates. Gordon Stamp prepared
the initial and final drafts, enlisting the substantial help of Fred
Barker, Tom Clarke and Mark Prentice; Colin Berry's
continuing guidance has been invaluable and without Susan
Chandler, who deciphered our holographic offering, this book
would not have been possible.
Keep this book beside you during your revision effort, take
careful heed of the advice given, and behave in the examination
in the manner suggested, and if you don't pass this time, then
there is obviously something wrong with the examination
system, and you should join the serried ranks of those who
clamour for examination reform (again).
Unless you positively enjoy examinations, then you will
certainly not be looking forward to the event. We hope that this
book will to some extent allay your fears, give you encourage-
ment, and help minimise your negative feelings.
We would like to take this opportunity of wishing you luck
(an important ingredient in these examinations) and stay off
the B-blockers.

London, Gordon Stamp

September 1989 Nick Wr~ght
Contents

Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Preparation for the Examination ...................... 2
Pathology Textbooks and Journals .................... 3
Application for the Final Examination. . .. . . . ..... . . .. . 8

The Written Examination. . .. . . . . . . • .. • .. . . . . • • • • • . .. 9

General Preparation..... . . . .. . . . . .. . . . . .. . . . . ... . . . . 9
Essay Format. . .. . . . . .. . . . .... .. ...... . ..... . .. . . .... 10
Essay Plans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

MRCPath Essay Questions (1969-1989) ••.•..•••.••.•• 17

Sections
1. General Pathology........ .. . . . . .. . . . . .... . ... . . . . . 17
2. Neoplasia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
3. Lyrnphoreticular System. . . . . . . . . . . . . . . . . . . . . . . . . . . 75
4. Alimentary Tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
5. Cardiovascular and Respiratory Systems ............ 113
6. Endocrine System. . .. . . . . .. . ............ . . . .. . . ... 147
7. Renal Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
8. Central Nervous System...... . . .. . . . . .......... . .. 179
9. Osteoarticular Pathology....... ... .... ........ . . . .. 193
10. Reproductive System . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 207
11. Dermatopathology................................ 217
12. Miscellaneous. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 223
13. Short Notes Questions . . . . . . . . . . . . . . . . . . . . . . . . . . .. 243

The Written Examination: Practical Aspects. . . . . . . . . . • 249

The Practical Examination •••.•••••.......•••..•.•••• 251

Introduction ........................................ 251
Presentation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 252
x Contents

The Necropsy: Preparation to

Examination Standard ........................... 252
The Necropsy: Procedures............................ 254
Removal of Organs . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 256
Systematic Dissection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 259
Presentation of the Post Mortem ........... . . . . . . . . . . . 274
Writing the Report .......................... '......... 275
Special Techniques .................................. 281
Paediatric and Neonatal Necropsies. . . . . . . . . . . . . . . . . .. 284

Surgical Pathology Slides. . . . • . • . • • • • • • • • • • • . . . . . . • • • 287

Recommended Approach to Examination of Sections. . . . 287
Assessment of the Clinical Information . . . . . . . . . . . . . . .. 287
Naked Eye Examination. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 288
Writing the Report. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 289
Types of Cases Used in the Examinations.............. 289
Preparation for the Surgical Histopathology. . . . . . . . . . .. 291
Material Sources and their Utilisation for
Surgical Pathology Revision. . . . . . . . . . . . . . . . . . . . . . 293
Current Literature ........ " . ....... ..... . . . .. . . . .... 296
Routine Surgical Reporting . . . . . . . . . . . . . . . . . . . . . . . . . .. 296
Specialised Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 297

Cytology ................•...............••......... 299

General Principles in Examination Preparation . . . . . . . .. 299
Approach to Cytology Specimens . . . . . . . . . . . . . . . .. 300
Screening Technique. . .. . . . . .. . . . . .. . . . . . . . . . . ... 301
Cytological Reports. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 301
Standards in Cytology . . . . . . . . . . . . . . . . . . . . . . . . . .. 302
Common Cytological Specimens in Examinations....... 304
Gynaecological. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
Non-gynaecological. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 305

Surgical Dissection and Macroscopic Examination. • . .. 307

Preparation for Surgical Dissection. . . . . . . . . . . . . . . . . . .. 307
Special Stains ....................................... 308

Necropsy Histology.... .. . ... . . .. ... . . . .. . . . . ..... .. 310

Mounted Museum Specimens ('Pots').................. 311
Case Discussion or Clinico Pathological Correlations. . .. 312
Electron Micrographs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 313

Cl)'ostat Sections................... ............... .. 317

Contents xi

The Viva Voce Examination................. . .. .•. •.. 325

Introduction..................................... . .. 325
The Examination Itself . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 325
Notification of Results ............................... 327
Envoi............................................... 328

Appendix 1
Reference List of Major Texts......................... 329
Additional Reading/Reference List. . . . . . . . . . . . . . . . . . .. 330

Appendix 2
Teaching Courses in Histopathology and Morbid
Anatomy........................................... 331

Appendix 3
Professional Societies and Associations . . . . . . . . . . . . . . .. 335

Regulations Regarding the Examinations for

Membership (Medically qualified candidates) . . . . . . . . . . 336

Regulations Regarding the Examinations for Membership

(Candidates without a medical qualification) . . . . . . . . . .. 338
Introduction
The final part of the examination for membership of the Royal College of
Pathologists was introduced in 1962 in order to provide a professional quali-
fication which would establish whether a candidate was capable of undertaking
the duties and responsibilities of a consultant. As such, the examination was
intended to be set at a relatively greater degree of difficulty than other profession-
al examinations for membership of the other medical colleges, which are taken
relatively early in training, assessing suitability for training. The Primary examin-
ation was designed to fulfill this role, success in which enabled candidates to
pursue more advanced training in registrar and senior registrar posts.
Naturally, over the years the examination has been refined and expanded with
the advances in histopathology and morbid anatomy, in common with most
medical and scientific disciplines, and it is true to say that a higher standard is
expected than say ten or fifteen years ago, especially with the emergence of a
more science-based approach to pathology which has greatly increased our
understanding of the pathogenesis of disease.
Unfortunately, little advice is available to prospective candidates and the onus
on preparation for the examination has remained largely up to the individual
concerned. This is to a large extent a consequence of the broad scope of skills and
knowledge expected of a modern pathologist, so that revision courses along the
lines of those offered for MRCP or PRCS examinations are impractical because
of the difficulties in organising the complex material required. It could, however,
be argued that the examination is intended to assess the results of five or more
years of training to a satisfactory level of competence in all respects, which could
not possibly be achieved during a 'crammer' course. Instead, individual courses
in aspects of histopathology, morbid anatomy or specialised disciplines such as
paediatric pathology are available, but they are not a compulsory requirement of
training, and attendance is selective, based on the trainee's perception of need,
measured against financial considerations and utilising a finite amount of study
leave.
As many candidates are not made aware of the format of the Final examination
during their junior appointments (especially if based overseas) it is not surprising
that many do not have an organised general training covering all important
aspects, which allows the practice and perfection of certain of the skills required.
This cannot be left until the last minute as part of the revision programme. For
instance, those who have tried to remove a spinal cord for the first time or made a
serious attempt to understand the classification of lymphomas in the few weeks
heading up to the examination will know the folly of leaving preparation too late.
Therefore it seemed obvious that an explanatory overview of both the examin-
ation and preparation requirements, aimed at potential candidates, would be of
value, to enable the optimal planning of a training programme. As such we do not
intend to provide anything approaching a comprehensive account of disease
states, but instead suggest some approaches to the problems encountered during
the examination, with guidance to more detailed sources of information where
appropriate. Considerable emphasis is placed on the ability to provide clinically
useful information in a succinct, relevant fashion, the hallmark of a competent
histopathologist in routine hospital service and teaching commitments, as well as
in the examination.
A relatively informal style is used, since this is not designed to be a
conventional textbook of pathology. This may provoke some criticism from the
more intellectual reader, especially as it could be argued that the obvious is being
2 Advanced Histopathology

stated in some sections. However, while these views may appear superfluous
when the examination is some way off, it often happens that the finer pOints of
self-discipline and perception are the first faculties to be lost in a stress situation.
The more capable readers may want to exercise their critical ability by taking issue
with some of the ideas and views expressed, which is often of greater benefit.
This book is divided into sections to cover all aspects of the examination,
including both the written papers and various parts of the practical sessions.
Within this framework there is an attempt to cover most of the problems
commonly encountered by trainee pathologists and examination candidates, and
those areas which are identified by examiners as serious deficiencies. It is hoped
that the advice given will enable a candidate to direct revision in a coordinated,
logical fashion, avoiding unnecessary repetition or over-emphasis, and moreover
enable the principles outlined to be applied to sound histopathological practice.

Preparation for the Examination

The Final examination is essentially an exercise to try to establish whether a
candidate has achieved a satisfactory level of competence during his training,
which will enable him to function as a consultant. As such, there is need to display
a broad base of knowledge, and the ability to apply it in a practical manner.
Nevertheless it is important to realise that the examination is very much a 'game
situation' with limited relevance to the way histopathology is actually done. Like
all games, it has its rules, SUbtleties, refinements, and indeed fools; it is necessary
to win, as, besides ignominy, the price of losing is expensive, if nothing else. This
book might be regarded as a guide to 'winning' within the rules, but only just
within the rules. The main problem, for many candidates, is that few indeed know
the rules.
A further concern is that most histopathology training in this country is carried
out by accident, so to speak. Trainees wait in departments, and are taught on, and
learn about, those cases which happen to come their way. Consequently, whatever
the deficiencies of such a process, the choice of training positions becomes critical.
In order to achieve the required standard, it it essential to try to choose registrar
and senior registrar posts which will cover most aspects of pathology, or will give
access to some specialised areas (e.g. paediatric pathology, neuropathology, renal
pathology) which may otherwise not be covered. There is a tendency for some
trainees to stay at one particular institution and apply for more senior positions
within it, with the more able pathologists encouraged to go for research positions.
While this may be suitable for some trainees, some might be pressed to do research
for not entirely altruistic reasons by their superiors and others may find that they
will have serious deficiencies in their experience by the time the Final examination
comes. In general it can be recommended that candidates have worked in at least
two university departments or Regional Health Authorities by the time the
examination comes around, which should enable a broader degree of experience
to be obtained, because it is the usual practice to link district general hospital
posts with a university department, certainly at senior registrar level, and with
many registrar posts.
If this is not possible, it may be possible to attend specialist units by personal
arrangement with the pathologists concerned, to gain some practical experience.
This is often the case with university lecturers, who may remain in post for up to
six years, with restricted provisions for rotation to other units or departments. If
further experience is required, it is most important to. plan this early on, and not
leave it until six months or so before the examination when the dreadful day is
Introduction 3

looming. The need to revise several areas means that full attention to the subject
would be impossible, and such trainees often end up being a nuisance rather than
an asset to a particular unit, especially if some of their colleagues have the same
idea.
The choice of training posts is a highly individual business, but make sure that
the more junior positions will give a good grounding in general pathology,
perhaps with some specialist applications as a bonus. It is a mistake to specialise
in a particular discipline (e.g. neuropathology or paediatric pathology) until some
time after successfully taking the Primary examination, and even when this
decision is made it is important to ensure that adequate access to the general
aspects of routine work is included. In general, most departmental heads
recognise this and make allowances, but it is largely up to the individual concern-
ed to assess their own progress and particular requirements, and not become too
obsessed with the specialty pathology at the expense of the general ability which
is so important in the examination.
Another important component of training is to attend various courses both
within and outside the region. Most university hospitals within a particular
Regional Health Authority conduct training courses for both the Primary and
Final examinations, and it is essential to attend these if at all possible. It will also
enable the establishment of valuable contacts with colleagues, against whom
trainees are able to gauge their own progress. Other general and specialist courses
are available on a national basis and again, there is probably an optimal time to
attend these. It is often advisable to consider going well in advance of taking the
examination so any areas of ignorance can be corrected and practised. Most
trainees learn about the value of these courses by personal recommendations of
contemporaries or more senior colleagues, but it is important to look for the
advertisements in the British Medical Journal, major pathology journals, the Royal
College of Pathologists' Bulletin or symposia organised by Pathological Societies
to see if there are any which fulfil particular requirements, or which may be newly
organised. In addition, remember that most of the more useful courses are
frequently oversubscribed, and therefore early application is essential. Many
candidates ignore this every year and are disappointed. A detailed list of courses,
with a brief summary of their content and organisation is provided in Appendix 2.
It is naturally very difficult to provide anything more than general recommend-
ations in respect of training posts, and a trainee's own assessments and those of
predecessors should act as a guide to senior colleagues and department heads
who are responsible for ensuring that a reasonable level of comprehensive
experience can be acquired. It is recommended that each trainee critically reviews
their position every six months, taking steps to improve on 'grey' areas on a
gradual basis, without having to cram everything in just before the examination.
This requires more self-discipline than might be imagined at first!

Pathology Textbooks and Journals

During the period of training, candidates will have access to a wide range of
books and journals, and it is sometimes very difficult to assess which are more or
less essential as a basis for revision, and which are more detailed and require
selective reading, or perhaps are less relevant to the examination. It is difficult to
make specific recommendations on every Pathology textbook or journal available,
as each individual's requirements and preferences will be different (e.g. a
university lecturer versus a registrar in a district general hospital), but the lists of
textbooks cited in Appendix 1 (and of Journals in Appendix 3), may provide a
4 Advanced Histopathology

basis upon which each candidate could start to evaluate his or her own needs.
Most trainees would be familiar with all of these by the time of the examination,
but many are specialised and are better read at leisure than for revision purposes
for reasons already stated. The following section inevitably contains a degree of
bias according to personal experience with these texts, and must therefore be
evaluated with a degree of circumspection by the reader.
Some of the larger textbooks which cover aspects of general and systematic
pathology are invaluable, providing a very good basis for further reading, and
having an adequate amount of information for undergraduate or some post-
graduate pathology teaching, and even contain enough material for answering
many essay questions. Used as a standard referral, it is possible to add in
information from other more specialised sources to provide sufficiently compre-
hensive accounts of most entities. One way to assimilate this information is to
work on cases encountered during routine surgical pathology or necropsies,
always reading up on these subjects at the time, which retains the interest due to
the clinical relevance.
Among these texts, Muir's Textbook of Pathology (ed. J.R. Anderson, 1985) is
rather basic, although admirably comprehensive and very readable. Quickly
scanning through the pages can enable a swift identification of those areas with
which a candidate may not be fully conversant, and can revise accordingly. It
might be reasonable to say that a Final examination candidate should have a
standard of knowledge of any subject to the level of this text as a minimum
requirement.
Pathologic Basis of Disease (eds. Robbins, Cotran & Kumar, 1989) has established
itself as a superbly concise account of general and systematic pathology, which
contains sufficiently detailed material for most undergraduate and basic post-
graduate teaching requirements, and to answer many questions in the written
section of the Final examination; this is reflected in the number of times this work
is cited in the references in this book. It is important not to become over-reliant on
such texts however, because although comprehensive, they are not geared
towards the working surgical pathologist, and thus require supplementation.
Systemic Pathology (ed. W. St. C. Symmers, 3rd edition Vols. 1-6 1978) is still a
useful source of reference, but is now rather dated. However, it fulfilled the
requirement of a textbook which was equally applicable to necropsy pathology or
surgical histopathology. The fourth edition is now being published as several
volumes, emerging at the rate of about two per year, and considerably more
detailed as a consequence. Only three volumes are available to date, but these will
eventually form a substantial basis for all Departmental libraries, and may be
essential reading for the dedicated pathologist.
There are innumerable works on surgical histopathology, but Ackerman's
Surgical Pathology (ed. J. Rosai, 1989) is a superb example and widely regarded as
a standard 'bench' book in most Pathology departments, if not for personal
ownership. Some of the examination questions could be comprehensively answer-
ed by information derived from this text, especially from some of the less
frequently consulted chapters (such as the mediastinum). However, it should be
noted that many areas (such as renal, pulmonary and CNS biopsy pathology) are
not covered to any degree, and it would be necessary to recognise this is the case
before deciding on the choice of other books for training and revision.
The Armed Forces Institute of Pathology 'fascicles' are too detailed for revision
purposes (except for selective review of certain volumes where information is
comprehensive, e.g. tropical and extraordinary pathology, tumours of the salivary
glands etc.) or conversely where specialised pathological texts are often more
detailed than necessary for the required standard (e.g. tumours of the central
Introduction 5

nervous system). These fascicles are invaluable for reference purposes in a

Departmental library, especially when working on current problems rather than
examination revision, and are sufficiently inexpensive when ordered direct from
the Institute's publishers for most pathologists to seriously consider adding them
to their personal collections.
With regard to necropsy pathology, there are a few textbooks which deal with
the technical details of the procedure but one concise, well-illustrated book which
also covers aspects of post mortem room facilities, safety, forensic and specialised
techniques is Post Mortem Procedures (Gresham & Turner, 1979). It is surprising
that there are so few works on this subject. Books covering macroscopic pathology
are of some use in this respect, but are often limited for the more advanced
pathologist as they, of necessity, can only illustrate the typical example, whereas
most problems arise from the complex cases with atypical features.
More specialised textbooks are a greater problem for the trainee, for it is
difficult to know to what level of detail and complexity to delve into any partic-
ular system or subspecialty, and there is a bewildering variety of texts now
available on any particular subject, from equally eminent authors. It is of little
value to document all of the available choices, but the references cited at the end
of some of the sections have been consulted during the preparation of this book.
The titles in Appendix 1 are recommended as a minimum available for consult-
ation in a Departmental or personal collection, although it is acknowledged that
others equally deserving of consideration have not been cited. The choice of
specialist books should ideally be made after consultation with a respected senior
colleague with experience in that field, or amongst contemporaries. It is often best
to consult the book in a hospital library before purchasing it, however. It is
recommended that at least one text on each major system should be available for
consultation during training and revision.
Having obtained such a text, try to use it as a practical book relating to routine
practice as far as possible. Relatively few of these books are conducive to light
reading, and reading through 100-200 pages in a session will result in very little
retention of information unless the reader is fortunate enough to have a
'photographic' memory. Even if this could be the case, it is a different matter to
know how to apply this knowledge.
An essential set of books for all examination candidates are the Recent Advances
in Histopathology (Appendix 1), and it is most important to obtain the most recent
edition as soon as it is published. Not only do they contain a wealth of up-to-date
information on a variety of topical subjects, generally in a very readable form, but
more importantly the written examination questions are frequently related to the
contents of the recent editions. The more recent volumes are a valuable source of
information on various trends and entities in surgical pathology, and such
examples often appear in the practical examination. Volumes 10 onwards should
be acquired (and sections of Volume 9 consulted if possible), and it should be
noted that they are as useful for day-to-day work as for examination revision.
One of the other main ways which will help to accumulate information and
understand it, is to have a teaching commitment. A great deal of factual
information can be learned by preparing undergraduate lectures or post mortem
presentations, and it is recommended that all candidates grasp these opportun-
ities. It is far easier for lecturers, who have to teach on a regular basis, but even
registrars and senior registrars should have ample chances to teach in most
rotating posts, certainly in university departments. Even in a district general
hospital, there are often medical students, junior colleagues or surgeons who
would appreciate pathology tuition. Although there is a tendency to try to avoid
such teaching, regarding it as an imposition or even a chore, it should be
6 Advanced Histopathology

remembered that the benefits will become obvious later when communicating
with clinical colleagues, and in the examination situation where a fluent and
relevant discourse on various subjects is required.
In addition to textbooks, it is advisable that you keep up with current advances
described in the major pathology journals. There are many journals to choose
from, and some are certainly very specialised and more suited to the specialist. As
a start, it is recommended that the general reviews in Histopathology, Journal of
Pathology, Human Pathology and the American Journal of Surgical Pathology are
consulted on a regular basis. Reading the major original articles takes up relative-
ly little time provided some time is left aside for this every month. This has to be
a regular commitment, otherwise a large backlog will accumulate and defeat the
object of the exercise. Providing it is possible to adhere to this plan, a surprisingly
large spread of knowledge can be accumulated after only a few months.
Editorials often provide a very useful overview of the more important articles,
and are well worth reading because they are more concise and place the articles in
a broader context.
The articles in Histopathology and the American Journal of Surgical Pathology have
a very heavy emphasis on diagnostic surgical pathology, and are a rich source of
information on newly described entities and application of modern techniques to
diagnosis. The Journal of Clinical Pathology contains a broad spread of articles
concerning the other major pathological diSciplines as well as histopathology, so
that selection is necessary. This is a useful reference for technical methods which
are of practical use in surgical pathology. The Journal of Pathology concentrates
more on experimental pathology and the theoretical basis of disease, but contains
very useful review articles and editorials, as well as papers on more general
aspects of pathology. Human Pathology carries papers of general histopathological
interest which are relevant to all levels of experience, and some of the largest
series of particular entities may be found in this journal, with abundant
illustration. Archives of Pathology and Laboratory Medicine contain articles and
reviews in a similar vein, but are usually somewhat more concentrated.
In general, it is difficult to select and assimilate the information from more
detailed journals such as Laboratory Investigation, specialist cancer journals,
American Journal of Pathology or Virchows Archivs to name but a few, because these
assume a high standard of knowledge on the part of the reader, and often fail to
provide the background perspective which is necessary for the less experienced
pathologist. Attempting to read the relatively technical articles in these Journals
may well be counter-productive, squandering energies which could be directed
into absorbing more basic and general aspects which are often included in the
recommended journals.
It may prove impossible to read all of the original articles in the Journals
selected, but a useful compromise may be to read the abstract thoroughly, combin-
ed with an examination of the illustrations, which are the focal point of many
pathological articles. (The review articles are designed to be read in full however.)
A swift 'scan' of the discussions may reveal some background information which
is also of value. It is probably true that the message of any such article could be
summarised in one or two sentences in the vast majority of cases.
Another very useful device for general reference, and for revision purposes
when a specific article or subject is required, is to photocopy the subject indexes in
the major journals, (which are found in the December issues) and keep these in a
separate file. Copies of the previous five years should be sufficient. It is important
not to be too ambitious, restricting the choice to the major journals previously
recommended, otherwise the amount of information becomes too unwieldy and
defeats the purpose.
Introduction 7

Rather than mechanically wading through a number of articles in anyone

session, a useful 'aide memoire' is to make short notes or paragraph summaries of
the more important current advances in pathology. The more relevant articles
may also be identified after informal discussion with colleagues, or in the context
of a journal review 'club' organised on a Departmental or Regional basis.
Membership of the Association of Clinical Pathologists and of the Pathological
Society of Great Britain and Ireland entail automatic subscription to the Journal
of Clinical Pathology and the Journal of Pathology respectively. Histopathology is
sent to members of the International Academy of Pathologists. Application
details can be obtained from the sources in Appendix 3. As well as other
benefits, membership of these organisation entails access to other very useful
publications, especially the ACP who have completed a series of broad-sheets
on a various topical subjects, the Model Training Programme (currently under
review) and the Education supplement. These can be supplied on request. All
of these organisations arrange symposia and international meetings which
are frequently highly relevant to trainees, details of which are sent automatically
to members.
Associate membership of the Royal College of Pathologists brings with it
the College Bulletin, which oftea contains very useful review articles and views
on current problems. The College also issues handbooks on various subjects
which may not be adequately covered elsewhere, such as health Service
laboratory management and safety. Such issues may assume a much higher
profile in future examinations, and should not be overlooked in preparation
or training.
Health and safety considerations in pathology have come to receive much
greater emphasis in recent years, culminating in the publication of the Howie
Report (HMSO 1982). This is mandatory reading for all trainee pathologists, and is
surprisingly concise. Examination questions have been set directly relating to this
Report, and it contains advice on conduct during post mortem examinations and
in the laboratory, which candidates will be expected to know in detail and carry
into practice, for the protection of others as much as themselves. It is most
important to be aware of any future recommendation on laboratory safety and
management which may be published or implemented.
It is very difficult to keep up with many of the advances or sources of
information when working alone, and candidates are urged to join a group of
contemporaries working for the examination in order to share information on
symposia, meetings and courses, and to set up 'slide clubs' and 'journal clubs'.
Regular meetings (usually once a month) to present and review cases and articles
are invaluable. Although it requires some effort to organise such meetings,
especially for trainees working at district hospitals within a Region, the benefits to
be gained far outweigh any minor inconveniences.
The preceding ideas are not intended to be comprehensive guidelines for the
ideal training post or examination preparation, but it is often difficult to identify
those areas which may be under-represented or over-emphasised within any
particular appointment. The ACP Model Training Programme contains more
detailed and considered opinion on these aspects. The interchange of ideas among
colleagues at a similar level of training is however of far more value in terms of
self-advancement than the information which can be gleaned from any book. It is
also suggested that every chance to teach others in pathology is taken, both in
formal lectures and in informal tutorials or necropsy demonstration, for this is
where the most valuable preparation is done. Finally, avoid reading books or
journals as a chore - this is a certain way to become disillusioned and disheartened
with the task in hand!
8 Advanced Histopathology

Application for the Final Examination

For trainees who have entered histopathology before December 1988, the Final
examination is held in Spring and Autumn each year, and the dates are advertised
in advance in the Bulletin of the Royal College of Pathologists which is distributed to
Associate Members. There are strict closing dates for formal applications which
are usually mid-February for the Spring of that year, and mid-May for the
Autumn (the longer interval required because of the intervening academic
vacation period).
Trainee pathologists are eligible to sit the written part of the Final examination
after obtaining the Primary MRCPath and completing at least three years full-time
in recognised posts, (and candidates must always ensure that these posts are
suitable by checking with the College before appointments if the situation is
unclear). Different arrangements apply to those working in part-time posts, and
candidates working overseas should write to the College for advice.
Application forms may be obtained from the Examinations Secretary at the
College. The present fee payable for both parts of the examination is £150. A
member of the College must act as a sponsor (preferably the head of department)
and be able to certify that the applicant is capable of cutting and staining a frozen
section, and has completed three months formal experience in cytopathology.
Candidates who wish to withdraw their application after the closing date may
forfeit a proportion of the fee.
As from January 1989, new regulations are applied. There will be no Primary
examinations; the main examination will be taken after three years full-time
experience in histopathology, and will be of the same format as the current Final
examination, and at the same standard. However, candidates will only be
expected to perform at a level commensurate with their experience, whatever that
might mean. There follow two further years of higher professional training, and to
acquire the magic letters of MRCPath, a further 'exit' component is required: this
can be (i) the presentation of a successful MD /PhD in an appropriate subject, (ii)
the passing of a practical examination slanted towards one of the specialties, such
as dermatopathology or gynaecological pathology, or (iii) a practical examination
in what might be called general histopathology.
We suspect that all candidates, with an eye on consultant selection committees,
will choose the last option. Some few able individuals will take (i) and (iii), or (ii)
and (iii), and the odd academic or monomaniac will elect to do (i) or (ii) only. The
merits of this new system are unknown and debatable; this examination-ridden
training period is certainly not what the proponents of freeform envisaged. One
thing is certain, histopathology trainees will have to get used to taking
examinations, like it or lump it. Whether you regard examinations as a necessary
or unnecessary evil there is no doubt that the MRCPath examination will loom
large on the horizons of trainees for generations to come. In essence therefore, this
book is suitable for both groups of trainees.
 9

The Written Examination

General Preparation

The preceding chapter dealt with much of the general preparation for achieving a
satisfactory standard in histopathology. The written examination is intended to
ascertain whether a candidate has achieved a certain degree of broad theoretical
knowledge, and in recent years there has been an increasing tendency to set
questions which are related to mechanisms of disease and their clinical relevance,
or to the practical application of scientific observations. The papers now tend to
strike a balance between diagnostic and 'academic' pathology (see e.g. April 1988,
Oct 1985). The first paper is devoted to principles of pathology to ensure that the
candidate has a clear understanding of the pathogenesis of disease. Questions
may be included on principles of techniques used in histopathology but details of
technical methods are not expected. The second paper is devoted to clinical
aspects of histopathology. Questions should cover a wide range of the conditions
seen in consultant histopathological practice including autopsies and cyto-
pathology. A question on the organisation or management of a histopathology
laboratory is appropriate for this part of the examination. We recommend that all
candidates review some of the papers early on in training, in order to cover many
of the areas in question, and obtain some idea of the standards required. As the
examination approaches, it is important to establish that this knowledge can be
converted into a reasonable written answer, which like all skills is a result of both
planning and practice.
The earlier this is started, the more proficient a candidate will become, but few
have the inclination to begin much before a year in advance of the examination,
and the majority will start in earnest around five to six months beforehand. It is
naturally very difficult to assess how much time is required to prepare, as some
candidates will have achieved much more than others during the course of their
training, and learning abilities vary enormously. However, at this stage an
individual should at least have a rough idea of their learning capacity and how
much time will need to be devoted.
Comparisons with colleagues' progress can often prove to be disheartening,
because they often appear to be achieving that much more. However, it is
surprising how distorted their recollection of the amount of revision work
completed can be! Each candidate must decide how much work they can
reasonably be expected to achieve within the timetable they have set themselves
and work steadily, while remembering that few achieve all that was originally
intended.
Assuming the decision has been made to apply for the written examination, the
general aspects should be considered first. Even for revision, good writing instru-
ments and paper are essential, and the work should be conducted in a relatively
peaceful environment. An assessment of the general writing style should be made
at this stage, since this is the time to try to correct bad or illegible handwriting,
and improve the layout of the work. Always check that spelling is correct, and
that correct grammar is being used. These factors are important, because a badly
handwritten, poorly laid out answer will always be looked on less favourably
than a well presented one, even if the content is identical, and some examiners
will even ignore illegible sections of an answer. Colleagues or secretaries should
be asked to comment on whether improvements can be made on this score. If so,
it follows that such alterations will require to be consistently put into effect.
10 Advanced Histopathology

A distinctive and neat layout could be introduced when taking lecture notes, or
writing up post mortem or surgical pathology reports. Other details such as
underlining, side headings, neatly crossing out mistakes, etc. can be practised. If a
writing style looks 'professional' it will inevitably create a better impression.

Essay Format

Most of this book is concerned with the approach to the written answers, both to
illustrate technique and to provide revision exercises. Past papers can be obtained
from the Examinations secretariat at the Royal College of Pathologists, for which a
small charge is made. Whether or not the ability of medical graduates to express
themselves clearly in written prose has been eroded by years of inspired guess-
work imposed by the computer-besotted, literacy-debasing protagonists of the
MCQ the experience of most examiners in the written part of the Final
Examination is that candidates do not know how to approach the planning and
execution of an essay. Please, therefore, do not skip this section; it is as important
as any. Assuming that a candidate has established a reasonable essay writing
style, the recommended approach is to construct essay 'plans', using side
headings and key words to represent contents of a sentence or paragraph. The
alternative is to write out essays in full, but this is generally a tedious and time-
consuming business. An essay plan can be constructed within a shorter period of
time using appropriate articles or texts, and will enable an assessment of balance
and emphasis in an essay.
It is vital that the ability to translate a plan into an essay style is acquired, and
should be a matter of regular practice, starting with a plan, then writing the essay,
within a reasonable time limit. At first this may taken in excess of an hour, but you
should aim to complete both within 45 minutes, the time allowed in the exam-
ination itself. (The plan may be written on the answer papers, as long as it is
indicated quite clearly that it is only an outline, which is left as such or neatly
crossed through.)
The outline has another benefit, in that few examiners will resist reading it.
They will see the general organisation and grasp the answer swiftly, and note that
the candidate has (hopefully) included all the major points. In the event that an
answer cannot be completed, the examiner might take into account the general
direction of the answer, and what was intended as the remainder.
One major advantage is that all the planning is concentrated into one 5-7
minute session at the beginning, rather than as a more diffuse, sustained effort
which often leads to inconsistency and inaccuracy. It is less tiring to construct
paragraphs of a suitable length to fit the overall framework, without having to
continually recall complex detail while writing. This avoids problems with
'freestyle' essays which very often result in distorted answers, with over-detailed
description at the beginning, and gradual deterioration towards the latter half as
time begins to run out.
In addition, facts are often recalled out of 'sequence' or in an illogical fashion.
These can be more easily slotted into an essay plan, but it is very difficult to adopt
prose-style answers to take account of these variations. It is important to attempt
to estimate how much time might be required for each section and adhere to it.
The plan should also be laid out neatly, with enough gaps to add in information
which comes to mind during the course of writing the answer.
Some candidates do not have the confidence to spend five minutes or so
preparing an outline, believing it to be time better spent on the actual answer.
The Written Examination 11

Ultimately, this is a matter for personal preference but, certainly for revision
purposes, plans save much effort in writing and allow concentration on the
important principles and key words necessary, and so we have used this
construction in our approach in this book.
Papers back to 1969 have been examined and the questions have been arbitrar-
ily grouped into broad categories such as cardiovascular system and lung, central
nervous system, alimentary system, etc. We have obviously emphasised the more
recent questions, and where the subject has appeared more than once, an outline
which could provide the basis for an essay is usually suggested. In general, plans
have been considered for about a quarter of the total number of questions. For the
remainder there are paragraph summaries suggesting possible approaches to the
answer, including observations on the wording of the question which may affect
the emphasis on particular aspects of a subject. The suggested outlines are not
attempting to provide compehensive answers, and issue might be taken with
some points, but in general it is believed these should lead to an adequate pass
mark if properly expanded.

Essay Plans
The examples generally occupy 1 to 1.5 pages, and are usually based on one or
two reference articles. Wherever possible attempts have been made to identify
any questions apparently related to recently published material just prior to the
examination of that year (e.g. Chapters in Recent Advances in Pathology, Journal
review articles or subjects of 'topical' interest at that time). These outlines are
probably longer than the reader as an individual would construct in practice (and
some would certainly take more than 5 minutes to write out), but there has been a
deliberate attempt to avoid using too many abbreviations in order to make them
more readable. In practice each person would devise their own abbreviation style,
although it should not be too incomprehensible, remembering that it is for the
examiner's benefit as much as their own.
A notation style of format has been used for the sections following the
introduction, subdividing the answer into sections which are generally labelled 1),
2) 3) etc. with subsections a) b) c), and even smaller subheadings i) ii) iii). In this
way the information has been laid out to put the appropriate degree of weighting
on the answers, concentrating on the more important entities at the beginning,
and gradually introducing less common or perhaps less relevant ones.
If the side headings are underlined, it usually indicates a paragraph or more of
writing is required. Adjacent to this, some key words have been inserted, which
need to be expanded to anything from a sentence to a whole paragraph. The bare
minimum of factual information has been introduced, but if it is not clear exactly
how to expand a particular section it is an indication to read up about the subject
from the reference or other sources. Enough space has been left in order to
introduce other ideas as the reader feels appropriate or when more recent
information comes to hand.
Naturally, the pathological aspects figure predominantly in most of the
answers, but in many of the questions, subheadings such as Gross Pathology,
Microscopic Features, Immunohistochemical Findings, etc. have been left without
further key words. This is because, in some situations, the reader would be
expected to know how to provide the necessary expansion for these sections or
the necessary information would usually be found in the reference.
The overall result is intended to be a skeleton plan, addressing most of the
ground intended by the question. A distinctive layout to the plan makes it easier
12 Advanced Histopathology

to recall the content of certain parts of this structure while continuing to write the
essay, avoiding the need to continually keep referring back to it. Theoretically you
only require to look up small subsections whose presence you recall by the
'pattern' created by the plan, but have forgotten the content. This may become
clearer once it has been practised a few times.
The introductory paragraphs should include an indication of the clinical
background to some diseases, including the age range, rare incidence, frequency
of disease in the population, distinction from other diseases, clinical relevance of
the pathological diagnosis and importance for patient management, etc. In more
theoretical questions the exact meaning of terms used should be explained and the
relevant aetiological factors and pathogenetic mechanisms should be outlined as
appropriate.
In general, the introductory paragraph should include
a) an appraisal of the scope of the question
b) definition of the terms used in the question
c) an explanation of the background to the problem
d) an indication of the general direction(s) of the answer if only a selection of
the possible aspects are to be discussed.

The only 'hard' facts which need to be included at this stage are statistical (e.g.
epidemiological and clinical data). The introduction has not been expanded in
many of the plans because in an examination situation the subjects in section a)
and c) require a descriptive approach, and d) is merely a brief overview of the
following plan. The introduction is an essential part of a structured answer and,
being the first section the examiners will read, a demonstration of a grasp of the
essential aspects of the question will undoubtedly influence their attitude to the
remainder.
You will find that there is generally too much information to be included in the
answer to have time for a concluding paragraph, but on occasion this may be
appropriate. It is probably of much less importance than the introductory
paragraph, merely because the examiner will have already formed an opinion
about the essay by this stage.
The majority of the questions have not been formulated as Elssay plans, but
there is an explanatory paragraph illustrating various points whi~h may relate to
the wording of the question, or assessments of the general directi()n of the answer
and possible areas of misunderstanding, and suggestions as to tHe content of the
essay. They are not intended to be comprehensive, and it is suggested that the
questions are used for practice essay plans and essay writing, as well as reading
up on the suggested references and any other source the reader is aware of, which
has not been cited.
It would be reasonable to ask why one should cover in detail previous essay
questions, rather than cover areas on which questions have not been asked. The
answer is of course that there are only a limited number of subjects in pathology
about which sufficient detailed knowledge could be expected for a candidate to
write for 40 minutes or so. It is also worthwhile noting that 20 questions per
annum need to be set, which means that subjects can be covered more than once,
and often are. However, although it is unusual for identical questions to be set,
subtle alterations in the wording of the questions may mean radical alterations in
the answer. Nevertheless, diligent study of previous papers, coupled with an
elementary knowledge of probability, enabled one of the contributors to have
prepared more or less specimen answers to no less than six out of the eight
The Wrttten Examination 13

required questions in the two papers. There is no reason why you should not do at
least as well.
In addition to repeated questions, most aspects of pathology would be covered
by using these plans and paragraphs as revision exercises for the written
examination. The knowledge gained will not only help in routine work, but there
are other sections of the examination where it may prove useful, including the
viva voce examination. Logical, structured answers to questions guided by a
recalled plan are more impressive than ill thought-out answers. These sorts of
frameworks are a basis for all parts of the examination, and can be adapted to
each circumstance.
However, it is inadvisable to try to memorise the plans and adhere rigidly to
them for the reasons outlined in the preceding paragraphs, in that an alteration in
a wording of a question may alter the content of the answer. The examination
should be approached with the intention to construct an entirely new plan for
each question, perhaps using sections or subsections previously revised, but with
the introduction of new ideas relevant to the question. This is easier than it
sounds, but practice is essential!
The emphasis has been placed on the more recent questions, and it should be
appreciated that some older questions are outdated, and do not lend themselves
to an adequate answer in the light of current knowledge (e.g. on lymphomas). It
would be a useful exercise to try to 'update' such questions, or construct a
question which may be set on this or a closely related subject, but this has not
been attempted in this book.
Regarding the practical aspects of writing the actual answer, while it is
suggested that the divisions outlined in the plan are followed in general, this may
be difficult to introduce in some circumstances. Strictly speaking, an essay should
not include side and subheadings, etc. but it is justifiable in this situation to make
some division and organisation in most cases in order to break up what would
otherwise be long tracts of writing. If nothing else, it stops the tendency for
overlong and repetitious discussion, which provides few marks for a lot of effort.
Experience indicates that examiners vary considerably in their appreciation of
headings and subheadings. Remember, because of the vicissitudes of time and
commitments, examiners are usually marking against the clock, and there is
nothing more daunting in this situation than to be confronted by page after page
of handwriting, unredeemed by space, heading or indeed paragraph.
Diagrams and illustrations may be very useful as part of an answer and should
be included if at all possible. It is a good idea to make a file of drawings and
diagrams on a variety of subjects. If these are relevant to the question, ensure that
they can be reproduced quickly, accurately and above all neatly. Scruffy,
'thumbnail' sketches on the other hand definitely detract from an answer. So, if a
diagram is to be attempted, it should occupy at least half a page and be drawn
boldly. A descriptive title is necessary but more important subjects in each system
need to be practised in advance of the examination.
It would be a mistake to try to construct a novel diagram or illustration during
the course of the answer in the actual examination, as it would be unlikely to be a
success at the first attempt, and the time involved in considering it would far
outweigh any benefit.
There is also a temptation to include them where they are not strictly relevant
in certain circumstances, but this should be resisted. Diagrams are most useful
where they avoid the necessity for long tracts of explanatory text, and must relate
to the most central aspects of the question.
14 Advanced Histopathology

A few suggested examples for diagrams include the following:

1) Gastrointestinal tract
a) Architecture of various polyps
b) Duke's classification of carcinoma of the rectum
c) Portal circulation and effects of portal hypertension
d) Early gastric cancer - microscopic patterns

2) Cardiovascular system
a) Types of dissecting aneurysms
b) Myocardial infarction - anatomical and topographic distribution
c) Patterns of emphysema
d) Atherosclerosis - general microscopic architecture

3) Genitourinary system
a) Dysplasia and intraepithelial neoplasia - grading patterns
b) Sites of urinary obstruction

4) Lymphoreticular system
a) Architecture of lymph node and spleen (and involvements by disease)
b) Morphology of lymphoid cells - normal and neoplastic
c) Morphology of granulomas

5) Central nervous system

a) Location of intracranial haemorrhage - gross anatomical patterns
b) Structure of the eye and location of pathology
c) Cerebral arterial circulation

6) Musculoskeletal system
a) Sites and effects of osteosarcoma
b) Normal bone and metabolic bone disease - microscopic architecture

7) Skin
a) Classification of melanoma - types and invasive patterns
b) Cutaneous lymphoid proliferation
c) Bullous disease of the skin - location of bullae

Other ideas may come to mind during revision. It would be a useful exercise to
compile a list of about ten diagrams for each category. One way of doing this is to
consider providing one potential diagram for each essay plan attempted during
revision.
Up to three references are provided with each outline plan or explanatory
paragraph in the following sections, and where possible they are related to the
question around the time it was set, if the appropriate article is identified.
Generally speaking, they are taken from the most popular and easily available
texts for both general and diagnostic work, together with the review articles and
journals outlined previously and under Appendix 1. Single articles in journals or
other texts are referenced in full. Every candidate should be able to add to the list
as articles are encountered during training or revision.
All of the written examination questions back to 1969 have been included in
the following sections, dividing them in a systematic basis into the following
groups. It is acknowledged that there will be overlap between some of the groups.
The Written Examination 15

1) General Pathology
2) Neoplasia
3) Lymphoreticular System
4) Alimentary Tract
5) Cardiovascular and Respiratory Systems
6) Endocrine System
7) Renal Pathology
8) Central Nervous System
9) Osteoarticular Pathology
10) Reproductive System
11) Dermatopathology
12) Miscellaneous
13) Short notes questions

About one in four of the answers are in the form of outline plans, and the
remainder are as explanatory paragraphs. The questions are set out in reverse
order chronologically, but some questions are grouped with others on a similar
theme from previous years. Where a topic has recurred there is usually an essay
plan on the question having the broadest scope, and the differences in emphasis
and approach in the other variants are compared by short explanatory
paragraphs.
One disadvantage to grouping the questions in this way is that it does not give
much insight into the 'balance' of individual examinations, hence the recommend-
ation that the actual papers are reviewed to retain some idea of this.
By the time the examination is near, a candidate should feel able to mentally
construct a reasonable outline to most of the questions when perusing the papers.
Having said this, it is important not to feel demoralised if the perfect approach to
the answer is not immediately apparent, as is common with most people; ideas
come to mind during actual formulation of the plan and to a lesser extent during
the essay writing itself. What is important is the ability to get started and have
some idea of the direction. Those whose approach is to look at a question and
announce they can answer it with little difficulty almost always turn out to have a
very superficial grasp of the subject. It is important not to take any notice of such
colleagues, as they may unnecessarily reduce one's level of confidence. One final
word of advice: answer the question! There are few things more irritating for
examiners than candidates who regard even the most clearly formulated question
as an excuse to un selectively regurgitate the sum total of their knowledge of that
subject.
MRCPATH ESSAY QUESTIONS
1969-1989

1. General Pathology
18 Advanced Histopathology

Give an account of amyloidosis

Introduction

General features of amyloidosis

Gross appearances

a) localised, systemic
b) iodine staining

Microscopic appearances

a) conventional - cellular distribution

b) special stains - Congo Red, dichroism, thioflavine T, metachromatic dyes
c) ultrastructure
d) X-ray diffraction - beta pleated sheet

Associated protein

a) amyloid-P

Classification of amyloid

a) AL (immunological associated)
b) AA (reactive systemic)
c) AA (hereditary - FMF)
AF (neuropathic)
d) AE (localised-endocrine)
AS (localised-cardiac)
AS (localised-cerebral)

Distribution
AL - heart, nerves, tongue, skin, kidney
AA - liver, spleen, kidney

Distinction

KMn04 preincubation abolishes Congo Red binding to AA

Associations

a) myeloma/occult immune dyscrasia

b) serum - M band
c) urine - Bence-Jones protein/light chains
1. General Pathology 19

a) chronic disorders (e.g. osteomyelitis, RA)

b) neoplasms (e.g. renal adenocarcinoma)

Heredofam ilia I

a) rare
b) fever and recurrent serositis

Localised

a) nodular (lung, larynx, skin, etc.)

b) endocrine tumours (?conversion of hormone secretion)
c) cardiac (senile)
d) cerebral (Alzheimer's plaques)

Pathogenesis

a) light chains
b) unknown 'amyloidogenic' factors
c) immunohistochemical evidence

a) serum AA (acute phase reactant)

b) ?defective breakdown
c) reduced degrading activity in FMF & RA

Com pi i cati ons

1) Cardiac
2) Renal
3) CIT

(October 1981, Paper 1, Question 4)

References

1) Cohen, A.S., Connors, L.H. The pathogenesis and biochemistry of

amyloidosis. ]. Pathol. (1987) 151: 1-10.
2) Hind, C.R.K., Pepys, M.B. Amyloidosis. Hospital Update (1984) 10(7-9):
593-597;637-648; 737-747.
20 Advanced Histopathology

Discuss the aetiology of amyloid

The wording of this question makes it difficult to know exactly what is required as
the distinction between aetiology and pathogenesis is necessarily rather blurred in
this subject. The sections on aetiology (pathogenesis) given in the previous
answer, including classification and a description of the nature of amyloid could
be expanded, avoiding pathological appearances and consequences since this is
clearly not required. This illustrates a need for an essay plan, since it would be
very easy to drift off the central theme. (October 1984, Paper 1, Question 1)

What is known of the fine structure and chemical composition of

amyloidl Comment on the distribution of this substance in
primary, secondary and senile amyloidosis
(November 1976, Paper 1, Question 4)

Discuss the nature and pathogenesis of the various types of

amyloidosis
These questions could be answered in a very similar way to the essay outline.
(April 1975, Paper 2, Question 1)

What are mast cellsl Describe how you would demonstrate them
in histological sections. In what disease processes are they
involvedl (November 1974, Paper 1, Question 1)

Discuss the role of the mast cell in health and disease

Questions which are clearly designed to assess the breadth of knowledge of a

candidate, and their ability to integrate material gleaned from a variety of sources
into a potentially interesting account. It is probably of value to compile an essay
plan on this subject for general revision purposes if nothing else, and the series of
articles given in references 2 and 3 are eminently readable. The essay should cover
normal morphology, function and demonstration of mast cells, and the pathology
would either cover the role in various sites in the body (as in the given references)
or under involvement in various pathogenetic mechanisms and pathology, e.g.
Type I hypersensitivity reactions, angiogenesis, neoplasia, etc.
(October 1981, Paper 1, Question 2)
1. General Pathology 21

References

1) Taussig, M.J. Hypersensitivity. In: Processes in Pathology and Microbiology.

2nd edition. p153-157. Blackwell Scientific Publications, Oxford (1984).
2) Mitchell, E.B. The mast cell: structure and function. Hospital Update (1984) 9:
1367-1378.
3) Holgate, S.T., Kay, A.B. Mast cells and the lung. Hospital Update (1984) 10:
151-162.

Give an account of the role of the macrophage in tuberculosis

and neoplasia
In spite of having been the subject of investigation for many years, the functions
of the macro phages and their regulation are only partly understood. This
incompleteness of knowledge is reflected in the difficulty of composing an answer
to this question. The first part is the easier as it requires a description of the well-
known morphology of tuberculous inflammation, and the first reference provides
some information about the mononuclear phagocyte system, about ultrastructure
and speculation upon the function of the macrophage in granulomatous
inflammation. The pathologist searching the general texts for an account of
macrophages in neoplasia will be disappointed. The immune response is a very
complicated subject, in which the macrophage plays a role in antigen presentation
to T cells, antibody production by B cells, and phagocytosis.
(November 1977, Paper 2, Question 2)

References

1) Robbins, S.L., Cotran, R.S., Kumar, V. The mononuclear phagocyte system,

and immune response and immunosurveillance. In: Pathologic Basis of
Disease, 4th edition. p61-63j 374-376j 296-298. W.B. Saunders, Philadelphia
(1989).
2) Taussig, M.J. The immune response and neoplasia. In: Processes in Pathology
and Microbiology, 2nd edition. pl14-117; 745-749. Blackwell Scientific
Publications, Oxford (1984).

Discuss the role of products synthesised by the macrophage in

disease
Introduction

Nomenclature
Distribution and role in mononuclear phagocyte system
General functions 1) Phagocytosis and bacterial killing
2) Immune response
3) Wound healing and chronic inflammation
4) Neoplasia
22 Advanced Histopathology

Products synthesised in each group

1) PhaBocytosis and bacterial killinB

a) C3b and Fc receptors - engulfment after opsonisation

b) lysozyme - glucosidase affecting cells walls
c) other lysozymal hydrolases
d) 02 dependent mechanism for killing? ~02 or OH
2) Immune response
a) MHC + processed Ag presentation to T lymphocytes
Role of HLA DR
Relation to antibody production
b) IL-1 - T4 lymphocyte stimulation
3) Wound healinB and chronic inflammation
a) neutrophil chemotactic factor
b) arachidonic acid metabolites - vasodilatation
- vascular permeability
c) haemostasis - coagulation activated by tissue thromboplastin
d) enzyme release - fibrinolysis (plasminogen activator)
- collagenase
- elastase
e) IL-1
i) release of PgE in hypothalamus? resets thermoregulatory centre (i.e.
fever)
ii) f muscle catabolism
iii) f haemopoiesis
iv) collagenase production by fibroblasts
v) fibrogenesis
f) TNF
i) endotoxic shock
ii) angiogenesis

4) Neoplasia
a) non-specific cytotoxicity
? lysosyme enzymes following activation
? complement or proteases
b) TNF - cytotoxic to cells in vitro
y interferon sensitises cells to killing
(October 1988, Paper 1, Question 2)
References
1) Auger, M.J. Mononuclear phagocytes. Br. Med. J. (1989) 298: 546-548
2) Robbins, S.L., Cotran, R.S., Kumar V. Inflammation and repair. In: Pathologic
Basis of Disease, 4th edition. p39-86. W.B. Saunders, Philadelphia (1989).
3) Taussig, M.J. Inflammation and the immune response. In: Processes in
Pathology and Microbiology, 2nd edition. p23; 114-117; 147-148; 745-749.
Blackwell Scientific Publications, Oxford (1984).
1. General Pathology 23

Discuss the role of the eosinophil in disease

Introduction

Origin and lineage

Morphology
Histochemical staining
General disease associations - 'allergic' disease,
parasitic disease, neoplasia, unknown

Normal function

Surface 'BG and Fc receptors

Granule content
a) basic proteins (EBP)
b) PAF
c) leukotrienes
d) phospholipase D
e) arylsulphatase B
f) histaminase
g) eosinophil cationic protein (ECP)

Pathological states
'AllerBic'

a) asthma and mucosal inflammation

i) mast cell - IgE binding
ii) eosinophil chemo-attraction (ECF-A)
iii) granules
- leukotrienes
- bronchoconstriction
- vascular permeability
iv) anti-inflammatory
b) eosinophilic gastroenteritis
c) drug reaction - idiosyncrasy
d) hypereosinophilic syndrome
e) endocardial fibrosis
i) peripheral eosinophils - degranulated
- dysmorphic
ii) action of EBP
iii) thrombosis - PAF
24 Advanced Histopathology

Parasitic disease
a) IgG binds to parasite
b) eosinophil binding (Fc receptors)
c) EBP and ECP released
d) IgE production (mast cell binding)
e) ECP-A released
f) also IgE-mediated parasite binding
g) Fc receptors on eosinophils

Neop/asia

1) Primary
a) eosinophilic leukaemia
2) Reactive
a) Hodgkin's disease
i) IgE fixation
ii) chemoattractants
iii) ? interleukin 5
b) squamous ca lung
i) uterine cervix
ii) ? mechanism
iii) chemoattractants (good prognostic indicator)
c) metastatic carcinoma
i) blood eosinophilia
d) epithelioid haemangio-endothelioma
e) unknown
i) e.g. histiocytosis X
ii) T cell lymphoma
iii) ? IL5

Idiopathic skin diseases

1) Eosinophilic cellulitis
a) flame figures
2) Eosinophilic spongiosis
a) pemphigus prodrome
3) Eosinophilic fasciitis
(October 1984, Paper 2, Question 1)

References

1) Spry, C.J.F. New properties and roles for eosinophils in disease. J. Royal Soc.
Med. (1985) 78: 844-848.
2) Lowe, D., Jopizzo J., Hutt, M.S.R. Tumour-associated eosinophilia: a review. J.
Clin. Pathol. (1981) 34: 1343-1348.
3) Taussig, M.J. Inflammation and immune response. In: Processes in Pathology
and Microbiology, 2nd edition. p 145-146; 153-156. Blackwell Scientific
Publications, Oxford (1984).
1. General Pathology 25

Write an essay on the clinical manifestations and

histopathological changes in graft versus host disease
At present this subject has received surprisingly scant attention in the major
textbooks, and comprehensive reviews are hard to find. The organs predomin-
antly affected are skin, gut and liver, and latterly respiratory tract changes are
described, and both acute and chronic types of the disease could be described for
each of these sit~s. This is one subject where, at present, a candidate who is up to
date with the literature or has attended symposia on the subject would have a
distinct advantage. (April 1987, Paper 2, Question 2

Reference

1) Snover, D.C. Acute and chronic graft versus host disease. Human Pathol.
(1984) 15: 202-205.

Discuss the morphological features and pathogenesis of sickle cell

disease
This question does not require discussion of the aetiology of this disease, which is
known (but which could be mentioned in the introduction). The pathogenesis of
the disease should ideally be considered first, as the morphological changes are a
consequence. The biochemical abnormalities and the effects of oxygen tension,
presence of other haemoglobins, MCHC or pH all require consideration, and how
the rheological effects in the cells are produced. The morphological features
include the effects of anaemia on various organisms, and consequences of
erythrohyperplasia of bone marrow and other sites. The consequences of chronic
sickling are due to capillary stasis, thrombosis and infarction affecting bone, liver,
lung, brain, spleen and kidney, with the more florid effects in acute cases. Other
considerations include the general association of chronic diseases such as growth
retardation and susceptibility to infection. (April 1973, Paper 2, Question 3)

Reference

1) Robbins, S.L., Cotran, R.S., Kumar, V. Sickle cell disease and the kidney.
In: Pathologic Basis of Disease, 4th edition. p666-670; 1070. W.B. Saunders,
Philadelphia (1989).

Discuss the role of Iysosomes in pathological processes

Lysosomes contain a variety of toxic degradative enzymes which normally are
contained safely within the lysosomal membrane and are released into a phagolys-
osome under physiological conditions. Asbestos, silica and copper ions cause
disruption of macrophage lysosomal membranes with subsequent cell damage
and fibrosis following repair. Histiocyte lysosomes can also act as 'dustbins' when
macromolecules (sphingolipids, for example) accumulate due to lack of specific
lysosomal enzymes, so a description of the major types of 'storage disorders'
26 Advanced Histopathology

could comprise a major part of the answer. Other aspects could include a
consideration of deficient lysosomal function as found in chronic granulomatous
disease of childhood where there is a lack of myeloperoxidase killing in
neutrophils.
(April 1970, Paper 1, Question 4)

Reference

1) Allison, A.C. Lysosomes in pathology. In: Recent Advances in Histopathology

10. N. Woolf, P.P. Anthony (eds.). Churchill Livingstone, Edinburgh (1978).

Discuss the effects of ionising radiation on human tissue

(October 1986, Paper 1, Question 2)

Discuss the effect of ionising radiation on cells and tissues

Introduction

Definition of ionising radiation

Radiation measurement - grays/rads
Types of ionising radiation
Energy transfer
Linear

Extent of radiation injury

a) type
b) dose
c) sensitivity
d) genetic susceptibility

Effects of injury
1) Acute

a) single large dose

i) 10 000 rad - death < 2 hours
ii) 2-5000 rad - death 2-5 days (GIT damage)
iii) 300-1000 rad - death 10-14 days (haemopoietic failure)
b) multiple smaller doses
i) 50-300 rad - haemopoietic suppression
GI crypt cell damage
1. General Pathology 27

2) Chronic
a) lung
i) 3-6 months post dose, vascular changes and fibrosis
b) kidney
i) tubular damage
c) colon
i) ? vascular damage with muscular fibrosis and strictures
d) lymphoedema
i) lymphatic fibrosis
e) skin
i) atrophy, elastosis, appendage loss and telangiectasia, 'radiation'
fibroblasts
f) bone
i) necrosis
g) eye
i) cataract formation
h) gonads
i) atrophy of germ cells

Carcinogenesis

1) Leukaemia
a) post therapeutic and atomic bomb survivors

2) Thyroid carcinoma
a) head and neck irradiation

3) Osteosarcoma
a) 'dial' painters - radiation

4) Bronchial carcinoma
a) uranium miners
(November 1969, Paper 1, Question 1)

Reference

1) Robbins, S.L., Cotran, R.S., Kumar, V. Neoplasia and environmental

pathology. In: Pathologic Basis of Disease, 4th edition. p273-275; 504-511.
W.B. Saunders, Philadelphia (1989).

Describe the pathological effects of radiation

While ionising radiation should again comprise the major part of this essay,
consideration should also be given to other forms of radiation, especially
ultraviolet radiation and to a lesser extent infrared radiation.
(April 1984, Paper 1, Question 4)
28 Advanced Histopathology

Describe the late complications of radiotherapy in different

organs
This question requires greater attention to the chronic effects of radiation detailed
previously, with greater description of the microscopic features and vascular
changes, together with tumours produced, although the mechanisms producing
tumours are not required.
(April 1971, Paper 2, Question 5)

Discuss the spectrum of pathology and pathogenesis of diseases

associated with alpha-1-antitrypsin deficiency
Introducti on
Nature of alpha-I-antitrypsin
Genetic features - autosomal co-dominant inheritance
- multiple alleles at each locus
- significance of M & Z alleles
- Z gene frequency (4%) and homozygote PiZZ
frequency (0.03-0.006)

Disease associations and pathology

1) Acute cholestatic hepatitis in infancy
2) Cirrhosis in adolescence
3) Hepatocellular carcinoma
4) Pulmonary emphysema

Pathogenesis
1) Emphysema
a) effect of smoking
i) heterozygotes
ii) homozygotes
iii) antielastase activity
iv) neutrophil activity (e.g. smoking) in basal lobes
v) distribution of alveolar walls - panacinar emphysema

2) Liver disease
a) heterozygote
i) liver cell globules - non secreted alAT
ii) ? association with chronic liver disease homozygote
b) i) normal
ii) infantile intrahepatic cholestasis - unknown pathogenesis
iii) cirrhosis - ? deficient antiprotease activity
iv) hepatocellular carcinoma ? related to cirrhosis
(October 1982, Paper I, Question 5)
1. General Pathology 29

References

1) Garver, R.I. et al. Alpha-1-antitrypsin deficiency and emphysema caused by

homozygous inheritance of non-expressing alpha-1-antitrypsin genes. New
Engl. J. Med. (1986) 314: 762-766.
2) Scheuer, P.J. Causation of liver disease: recent developments. In: Recent
Advances in Histopathology 10. N. Woolf, P.P. Anthony (eds.). p179-192.
Churchill Livingstone, Edinburgh (1978).

Discuss the pathology and pathogenesis of iron overload states

Introduction
1) Definitions
a) haemochromatosis
b) haemosiderosis

2) Normal Fe metabolism
a) absorption
b) transport
i) enterocyte
ii) plasma
iii) hepatocyte
c) storage
i) ferritin
ii) haemosiderin

3) Histochemical identification

Primary Fe overload

a) excessive
b) HLA A3, B14linkage
c) gene frequency (5%) and prevalence (0.3%)
d) chromosome 6p

1) TBI
a) up to 80 g (n 5 g)

2) Sites
a) parenchymal organs
b) skin
c) joints
30 Advanced Histopathology

3) Clinical features
a) cirrhosis
b) diabetes
c) skin pigmentation
d) cardiomyopathy

4) Pathology
a) liver
i) cirrhosis
ii) hepatocellular carcinoma
b) pancreas
i) exocrine
ii) endocrine
c) myocardium
d) pituitary
i) trophic atrophy, e.g. testis
e) skin
i) melanin pigmentation
ii) Fe deposits
f) joints
i) pyrophosphate arthropathy

Pathogenesis

1) Experimental evidence
a) superoxides and free radicals - peroxidation of lysosomal lipid
membranes
b) ferric ions - hepatic and pancreatic fibrogenesis

Secondary Fe overload
a) no genetic association
b) clinical features similar or less marked
c) TB1 normal

Pathogenesis

1) Excessive Fe intake
a) transfusion in chronic dyserythropoiesis
b) alcoholism
c) diet (e.g. Bantu beer)
(October 1980, Paper 2, Question 4)

Reference

1) Powell, L.W., Bassett, M.L., Halliday, J.W. Haemochromatosis: 1980 update.

Gastroenterology (1980) 78: 374-381.
1. General Pathology 31

Write an essay on hydatid disease

(October 1978, Paper 1, Question 4)

Describe in detail the structure of a hydatid cyst and give an

account of the life cycle of the parasite responsible for it
Introduction

Echinococcus granulosus and E. multilocularis

Epidemiology

Life cycle

1) Primary host
a) canines

2) Intermediate host
a) herbivores

3) Accidental host
a) man
i) ingestion of ova
ii) duodenal hatching
iii) larvae invade bowel wall
iv) cyst formation after 5-10 years

4) Sites of parasitic cysts

a) liver
b) lungs, bone, brain and others

5) Cyst structure
a) macroscopic
i) E. granulosus
ii) E. multilocularis
b) microscopic
i) host inflammatory reaction
ii) fibrous capsule
iii) outer non-nucleated layer
iv) inner germinative layer
v) human +/- brood capsules
vi) calcification and atrophy
32 Advanced Histopathology

Complications

1) Rupture and anaphylaxis

2) Pressure effects
3) Secondary bacterial infection
4) Membranous glomerulonephritis
5) Cholecystitis
6) Pathological fracture
7) Embolism
8) E. multilocularis - invasion and metastasis
(November 1974, Paper 1, Question 3)

Reference

1) Robbins, S.L., Cotran, R.S., Kumar, V. Fungal, protozoal and helminthic

diseases and sarcoidosis. In: Pathologic Basis of Disease, 4th edition.
p421; 422. W.B. Saunders, Philadelphia (1989).

Describe the life cycle of the parasite responsible for hydatid

disease, and the histological features of the cysts. How does this
disease differ from cysticercosis?
As well as outlining hydatid disease as for the previous essay, the differences in
the life cycle of the pork tapeworm together with its pathological appearances,
including distribution and complications of the cysts, should be outlined. This
will probably comprise a quarter to a third of the total essay time, and the hydatid
section should be abbreviated accordingly.
(October 1979, Paper 2, Question 2)

Describe the pathological changes that may be produced by

infection with Toxoplasma gondii
(November 1971, Paper 2, Question 3)

Give an account of the pathology of toxoplasmosis. Which

subjects are particularly susceptible to this infection? How is it
transmitted?

Introd ucti on

T. gondii - parasitic protozoon

Epidemiology
Prevalence (antibody studies)
Morphological features a) tachyzoite
b) bradyzoites/cysts
1. General Pathology 33

Life cycle
Primary host: cats
Intermediate host: rodents and birds (ingestion of faecal oocysts)
Accidental host: human (ingestion of faecal oocysts)

Clinical features
1) Adult
a) mononucleosis syndrome (cf EBV, CMV)
i) cervical lymphadenopathy
ii) lymphocytosis
iii) fever

2) Concenital
a) transplacental infection
i) death
ii) microcephaly
iii) choroidoretinitis
iv) hydrocephalus

3) Infantile
a) pneumonia
b) myocarditis

4) Reactivation
a) encephalitis (immunosuppression)
b) choroidoretinitis

Pathological features
1) Lymphadenopathy
a) follicular hyperplasia with sinus histiocytosis
b) epithelioid granulomas

2) CNS
a) microglial nodules with tachyzoites
b) necrosis, thrombosis
c) hydrocephalus
d) cysts

3) Myocardium
a) inflammatory reaction to parasites

4) Retina
a) granulomatous inflammation
(April 1982, Paper 1, Question 1)
34 Advanced Histopathology

References

1) Robbins, S.L., Cotran, R.S., Kumar, V. Fungal, protozoal and helminthic

diseases and sarcoidosis. In: Pathologic Basis of Disease, 4th edition.
p410; 411. W.B. Saunders, Philadelphia (1989).
2) Anon. Toxoplasmosis. Br Med J (1981) 282: 249-250.

Outline the clinico-pathological features of leprosy in terms of

immune response to Mycobacterium leprae

Introduction

Epidemiology
Transmission
General clinical features

Cutaneous leprosy

1) Tuberculoid IT

Clinical features

Pathology
a) Granulomata
b) Perineural disease
c) Wade-Fite-Bacilli +/- or -
d) Lepromin test and immunohistochemistry
e) T4 cells predominate

2) Lepromatous leprosy (LL)

Clinical features

a) poor immunological response

Pathology

a) Grenz zone
b) Lepra cells, no granulomas
c) Wade-Fite-Bacilli +ve
d) Lepromin test -ve
e) Immunohistochemistry - T8 cells (few)

Systemic spread
1. General Pathology 35

Variants

1) Borderline BB
Others BL, BT
2) Indeterminate (early)
Perineural lymphocytes +ve
3) Erythema nodosum leprosum
Immune complex disease following treatment of LL
Leucocytoclastic vasculitis
Glomerulonephritis
4) Histoid leprosy
Post treatment
Dermatofibroma-like lesion - Wade Fite +ve
(April 1985, Paper 1, Question 3)
References

1) Hutt, M.S.R., Spencer, H. Tropical diseases in Britain. In: Recent Advances in

Histopathology 10. N. Woolf, P.P. Anthony (eds.). p303-324. Churchill
Livingstone, Edinburgh (1978).
2) Lucas, S.B. Histopathology of leprosy and tuberculosis - an overview. Br.
Med. Bull. (1988) 44: 584-599.

Discuss the immunopathological basis of the lesions found in

leprosy

To answer this question the lesions which may be seen in leprosy need to be
identified. This may be confusing as leprosy is classified by both clinical
appearances and by the histopathological changes present in a biopsy. It is best in
this answer to use a pathological classification, thus the lesions occurring in
leprosy may be classified as follows - Indeterminate leprosy, Tuberculoid leprosy,
Borderline leprosy, Lepromatous leprosy and Reaetionalleprosy.

The specific cellular composition of the infiltrates, as demonstrated by immuno-

histological analysis, can be described for each, and as well as cell mediated
responses, the humoral factors and hypersensitivity reactions in reactionalleprosy
should also be considered. (April 1988, Paper 1, Question 2)

Discuss the pathology of human T cell Iymphotrophic virus III

(HTLV III/LA V) infection

Introduction

Nature of virus
Routes of infection
Cellular receptor (CD4)
Life cycle - T4 lymphocyte - permissive and lytic
Monocyte/macrophage - permissive
36 Advanced Histopathology

Pathological effects

1) Reticuloendothelial system

a) immunosuppression and decreased T4lymphocytes

b) polyclonal B cell stimulation (? envelope derived gp120 glycoprotein)
c) autoimmune haemolytic anaemia
d) NHL high grade extranodal
e) lymph node
i) hyperplastic
ii) diffuse hyperplasia
iii) lymphocyte depletion

2) eNS

a) toxoplasmosis
b) cryptococcal meningitis
c) subacute encephalitis
d) ? multiple sclerosis
e) PMLE (JC virus)
f) CMV encephalitis and retinitis
g) CNS lymphoma

3) Respiratory system

a) pneumocystis pneumonia
b) mycobacterium tuberculosis (and atypical mycobacteria)
c) pneumococcal pneumonia
d) alveolar proteinosis
e) lymphoid interstitial pneumonia

4) Alimentary tract

Mouth and oesophagus

a) candidiasis
b) herpes simplex
c) CMV

Intestine

a) cryptosporidiosis
b) isopora belli
c) herpes simplex
d) CMV
e) Atypical mycobacteria
,. General Pathology 37

Anal

a) herpes simplex
b) genital warts

Neoplasms

a) Kaposi's sarcoma
b) NHL

5) Skin
a) seborrhoeic dermatitis
b) molluscum contagiosum
c) Kaposi's sarcoma
(April 1986, Paper 2, Question 3)

References

1) Ho, D.O. et al. Pathogenesis of infection with human immunodeficiency virus.

New Engl. J. Med. (1987) 317: 278-286.
2) Millard, P.R., Chapel, H.M. Immunodeficiency states including AIDS. In:
Recent Advances in Histopathology 13. P.P. Anthony, R.N.M. MacSween
(eds.) p129-158. Churchill Livingstone, Edinburgh (1987).

Discuss the pathological lesions which may develop in the

gastrointestinal tract in a patient with AIDS

Introduction

Definition of AIDS
Clinical features of gut disease
Frequence and epidemiology

Infections

1) Protozoal
a) cryptosporidiosis
i) sites - (SI + / - LJ)
ii) microscopic
b) entamoeba histolytica
i) site (LI + / - liver)
ii) microscopic
c) strongyloidiasis
i) sites(SI)
ii) microscopic
38 Advanced Histopathology

2) Fungal
a) candida
i) sites (mouth, oesophagus)
ii) macroscopic
iii) microscopic
b) aspergillus
i) disseminated disease

3) Bacterial
a) mycobacterium avium
i) site (51, stomach)
ii) intracellular - microscopic
b) spirochaetosis
i) site (LI)
c) others

4) Viral

a) CMV
i) site (whole GIT)
ii) microscopic
b) HSVI
i) sites (mouth, oesophagus, rectum)
c) HPV
i) sites (mouth, anus)
d) HBV
i) sites (liver)

Tumours

7) Kaposi's sarcoma
a) sites
b) macroscopic
c) microscopic
d) behaviour

2) Lymphoma
a) NHL primary and secondary involvement
(April 1988, Paper 2, Question 5)

References

1) Millard, P.R., Chapel, H.M. Immunodeficiency states including AIDS. In:

Recent Advances in Histopathology 13. P.P. Anthony, R.N.M. MacSween
(eds.) p129-158. Churchill Livingstone, Edinburgh (1987).
2) Rotterdam, H., Sommers, S.c. Alimentary tract biopsy lesions in the acquired
immune deficiency syndrome. Pathology (1985) 17: 181-192.
1. General Pathology 39

Describe the macroscopic and microscopic appearances of the

lesions of primary gout and discuss their pathogenesis

Notice the wording in this question, whereby only primary gout should be
considered in terms of pathogenesis. An outline knowledge of purine metabolism
would clearly be essential to answer this question adequately, but there are a large
number of pathological changes which can occur in this condition, which should
provide more than enough for an essay length answer given due consideration.
(April 1978, Paper I, Question 3)

Reference

1) Robbins, S.L., Cotran, R.S., Kumar, V. Gout and gouty arthritis. In: Pathologic
Basis of Disease, 4th edition. p1355-1360. W.B. Saunders, Philadelphia (1989).

Write an essay on arteritis

(April 1983, Paper I, Question 5)

Write an essay on arteritis

Perhaps a question set to catch out those who believe they are never repeated! It
is, fortunately, a relatively straightforward answer that is required, but it is
important to try to show some flair by subdividing the primary arteritides into
granulomatous and non-granulomatous and large, medium or small vessels, and
then highlight the major diagnostic and pathogenetic differences between each
condition, rather than list each condition and describe them in a 'repetitive'
fashion. Vasculitic processes secondary to infection or other cause should also be
included.
(October 1984, Paper I, Question 5)

References

1) Mitchinson, M.J. The vasculitis syndromes. In: Recent Advances in

Histopathology 12. P.P. Anthony, R.N.M. MacSween (eds.) p223-240.
Churchill Livingstone, Edinburgh (1984).
2) McCluskey, R.T. et al. Vasculitis in primary vasculitides, granulomatoses and
connective tissue diseases. Human Pathol. (1983) 14: 305-315.

Tabulate the causes of abnormal pigmentation. Outline the

procedure you would adopt to identify an abnormal pigment seen
in a histological section of liver (details of method are not
required but the principles of the techniques should be indicated)

This question should appeal to any diagnostic histopathologist, and although the
table requires some thought, given that all pigments throughout the body should
40 Advanced Histopathology

be considered, the remainder of the question is really a 'bench mark' for the
examination - if candidates cannot answer this adequately without revision, they
would probably not have the standard of experience required.
(November 1976, Paper 1, Question 1)

Reference

1) Bancroft, J.D., Cook, H.C. Manual of Histological Techniques. Churchill

Livingstone, Edinburgh (1984).

Discuss the role of the HLA system in the pathogenesis of disease

This is a complex issue and one which is quite difficult to answer given the wide
range of diseases with which the HLA associations are thought to playa part. It is
probably best to discuss the theoretical functions of the HLA molecules, and
discuss how these may be deranged or contributory in general terms, rather than
taking specific diseases and attempting to explain the individual possible
mechanisms. (April 1984, Paper 1, Question 2)

Reference
1) Dick, H.M., Powis, S.H. HLA and disease: possible mechanisms. In: Recent
Advances in Histopathology 13. P.P. Anthony, R.N.M. MacSween (eds.)
Churchill Livingstone, Edinburgh (1987).

Give an account of genetically determined immunodeficiencies

This is a particularly difficult question to answer for those who do not have a
particular interest in this field, as the area is complex. It would be better to group
the diseases according to the specific immune defect rather than the mode of
inMritance. A preliminary diagram illustrating the particular level of the defect
would be of value to avoid unnecessary repetition. The pathological changes of
the primary condition should be defined in each case, along with the sequelae of
the immunodeficiency. (November 1977, Paper 2, Question 1)

References
1) Paradinas, F. Primary and secondary immune disorders. In: Lymph Node
Biopsy Interpretation, A.G. Stansfeld (ed.). p159-163. Churchill Livingstone,
Edinburgh (1985).
2) Berry, C.L. Spleen, lymph nodes and immunoreactive tissues. In: Paediatric
Pathology, p565-606. Springer-Verlag, Berlin (1989).
1. General Pathology 41

Discuss the visible abnormalities of human karyotype and their

relation to disease

The introduction to this essay should include methods of karyotyping and an

explanation of the terms used in cytogenetic disorders such as trisomy, mono-
somy, mosaicism, translocation, inversion, deletion, etc. This question excludes
genetic disorders e.g. sickle cell disease or multifactorial inherited disorders such
as congenital heart disease. One or more examples from each group should be
included with discussion of their major associated conditions (e.g. trisomies with
associated congenital heart disease, leukaemia and Alzheimer's disease), together
with descriptions of the sex chromosome disorders and their possible
consequences (e.g. malignancy developing in cryptorchid testes) to ensure a
comprehensive assessment. (April 1981, Paper 1, Question 2)

Reference

1) Robbins, S.L., Cotran, R.S., Kumar, V. Genetic disorders. In: Pathologic Basis
of Disease, 4th edition. p121-136. W.B. Saunders, Philadelphia (1989).

Discuss the causation of congenital malformation

(April 1970, Paper 1, Question 3)

Discuss the aetiology of congenital malformation

This question requires a systematic approach to the answer, dividing the known
aetiological factors into groups such as chromosomal, infections, toxins and drugs
and their effects at various stages in embryogenesis and foetal development.
Speculation on the so-called multifactorial causes would be appropriate.
(April 1971, Paper 1, Question 4)

References

1) Robbins, S.L., Cotran, R.S., Kumar, V. Diseases of infancy and childhood-

congenital malformations. In: Pathologic Basis of Disease, 4th edition.
p519-523. W.B. Saunders, Philadelphia (1989).
2) Berry, c.L. Congenital Malformations. In: Paediatric Pathology, p41-61.
Springer-Verlag, Berlin (1989).

Discuss the pathology of chronic alcoholism

Introduction

Definition
Incidence
Acute alcoholism - clinical features
Chronic alcoholism - clinical features
- associated deficiencies
42 Advanced Histopathology

1) Liver
a) Steatosis
i) pathogenesis
ii) morphology
b) Alcoholic hepatitis
i) morphology
c) Alcoholic cirrhosis
i) morphology

2) Pancreas
a) Chronic pancreatitis
i) incidence
ii) morphology

3) Gastrointestinal tract
a) Mouth
i) carcinoma
b) Oesophagus
i) Mallory-Weiss syndrome
ii) carcinoma
c) Stomach
i) gastritis
ii) peptic ulceration

4) Heart
a) Cardiomyopathy
i) macroscopic
ii) microscopic
iii) ultrastructure

5) Nervous system

a) Neuritis and SACD

i) pathogenesis
ii) microscopic
b) Cerebellar atrophy
c) Wernicke's encephalopathy
i) microscopic features
d) Trauma
i) e.g. subdural haematoma
e) Korsakoff's psychosis
i) chronic lesions
ii) neuronal degeneration (chromatolysis and lipofuscin accumulation)
(April 1978, Paper 1, Question 2)
1. General Pathology 43

Reference
1) Robbins, S.L., Cotran, R.S., Kumar, V. Environmental pathology - ethyl
alcohol. In: Pathologic Basis of Disease, 4th edition. p490-492. W.B. Saunders,
Philadelphia (1989).

Discuss the pathological effects of prolonged alcohol in organs

other than the liver
This question only allows a brief resum~ of all the possible effects, since these are
so widespread, but the more significant in clinical terms should be emphasised. In
the alimentary system, acute and chronic pancreatitis, gastric and oesophageal
inflammation and Mallory-Weiss syndrome are important, but although liver
pathology is specifically excluded, the effects of portal hypertension such as
varices, ascites and splenomegaly should be included. Central nervous system
effects are important and varied, including indirectly associated conditions such
as subdural haematomas. Other organs affected include the heart
(cardiomyopathy), endocrine system, haemopoietic system, respiratory system
(tuberculosis and aspiratic pneumonia) among others. Thus this essay requires
considerable organisation with the use of a plan, and some element of selection.
(April 1988, Paper 2, Question 3)

Reference
1) Edmondson, H.A. Pathology of alcoholism. Am. J. Clin. Pathol. (1980) 74:
725-742.

Describe the lesions of sarcoidosis and discuss the aetiology of

this condition
The lesion of sarcoidosis should be described firstly in general terms of the
granulomas, with their characteristic features (e.g. asteroid and Schaumann
bodies, fibrosis) and their evolution, and then consider the effects on various
organs in order of clinical importance and frequency (e.g. lungs, lymph node, eyes
etc.). It is always difficult to answer questions such as this where the aetiology is
unknown, but there is opportunity to discuss the immunological abnormalities
and proposed aetiologies with the arguments against them.
(November 1970, Paper I, Question 4)

References

1) Robbins, S.L., Cotran, R.S. & Kumar, V. Fungal, protozoal and helminthic
diseases and sarcoidosis. In: Pathologic Basis of Disease, 4th edition.
p427-429. W.B. Saunders, Philadelphia (1989).
2) Anon The immune response in sarcoidosis. Lancet (1987) ii: 195-196.
44 Advanced Histopathology

Describe the reaction of tissues to minerals containing silica

This question requires some knowledge of mineralogy as well as pathology, and
as well as acute, subacute and chronic silicosis, there are materials such as glass
and, more importantly, asbestos to consider. The pathological reactions associated
with the latter would constitute an essay on their own.
(November 1971, Paper 2, Question 4)

References

1) Gibbs, A.R. Industrial lung disease. In: Recent Advances in Histopathology

13. P.P. Anthony, R.N.M. MacSween (eds.) p109-129. Churchill Livingstone,
Edinburgh (1987).
2) Dunnill, M.S. Industrial lung disease. In: Pulmonary Pathology. p399-438.
Churchill Livingstone, Edinburgh (1982).

Give an account of the pathological changes which may be found

in systemic sclerosis (generalised scleroderma)
This would constitute a straightforward essay which is easily divided up into the
general aspects of the disease, and how it affects different organ systems. Ensure
that in an answer such as this you would start with the most frequent organs
involved (e.g. skin, gut) and those which have the most serious clinical
consequences (kidney), before considering those with relatively minor or
infrequent involvement. Consideration of the pathogenesis and aetiology of the
disease is not needed in questions worded like this, but some insight into these
aspects would almost certainly be required in future questions on this subject.
(April 1972, Paper 1, Question 5)

References

1) Jayson, M.I.V. Systemic sclerosis: a collagen or microvascular disease? Br.

Med. J. (1984) 288: 1855-1857.
2) Robbins, S.L., Cotran, R.S. & Kumar, V. Diseases of immunity. In: Pathologic
Basis of Disease, 4th edition. p204-209. W.B. Saunders, Philadelphia (1989).

Describe and discuss the histological changes produced by

pathogenic fungi

Introduction

Fungal types
Pathogenicity (immunodeficiency)
Range of tumour responses
1. General Pathology 45

Deep mycoses
1) Candidiasis
a) fungal morphology and staining
b) tissue response
i) mucocutaneous - acute & chronic inflammation
- abscesses
- granuloma
ii) systemic - microabscesses
- endocarditis
2) Mucormycosis
a) fungal morphology and staining
b) tissue response
i) rhinocerebral - osteomyelitis
- vascular invasion
ii) pulmonary
iii) gastrointestinal

3) AsperBillosis
a) fungal morphology and staining
b) tissue response
i) allergic - asthma
- alveolitis
- bronchopulmonary
- aspergillus
ii) colonising - aspergilloma
iii) invasive

4) Cwtococcosis
a) fungal morphology and staining
b) tissue response
i) meningeal - granulomatous
- immunosuppression
ii) pulmonary - early
- late
5) Coccidioidomycosis
a) fungal morphology and staining
b) tissue response
i) primary pulmonary - suppurative
- granulomatous
ii) progressive - suppurative/granulomatous
6) Histoplasmosis
a) fungal morphology and staining
b) tissue response
i) latent
ii) primary
iii) disseminated
46 Advanced Histopathology

7) Chromomycosis
a) fungal morphology and staining
b) tissue response
i) dermal inflammation
ii) epidermal hyperplasia

Superficial mycoses
1) Candida
a) tissue responses
i) suppurative (thrush)
ii) chronic

2) Tinea
a) tissue responses
i) chronic inflammatory response

(This question could equally well be answered by taking the various tissue
responses e.g. suppurative, granulomatous, etc. and enumerating the causative
organisms.) (October 1985, Paper 1, Question 4)

References
1) Robbins, S.L., Cotran, R.S., & Kumar, V. Fungal, protozoal and helminthic
diseases aqd sarcoidosis. In: Pathologic Basis of Disease. 4th edition.
p385-396. "f.B. Saunders, Philadelphia (1989).
2) Anthony, P.P. A guide to the histological identification of fungi in tissues. J.
Clin. Patholl (1973) 26: 828-831.

Describe the pathology of neurofibromatosis

In such a question, the best approach would be to split up the various aspects into
side headings with brief descriptions, very closely following the essay plan style.
There should really be a concentration on the most frequent findings such as the
neurofibromas, cafe au lait spots and Lisch nodules, followed by a description of
the abnormalities in the skeleton and other organs, and finally the most clinically
significant complications such as malignant transformation of neurofibromas and
other neoplasms. (April 1976, Paper 2, Question 1)

References

1) Robbins, S.L., Cotran, R.S. & Kumar, V. Genetic disorders. In: Pathologic Basis
of Disease, 4th edition. p139; 140. W.B. Saunders, Philadelphia (1989).
2. Neoplasia
48 Advanced Histopathology

Outline the criteria necessary to establish a viral

aetiology for tumours and discuss these in respect of human
carcinogenesis

Introduction
Evidence for viral aetioloBY
a) animal studies - contagious examples rare
b) human - HPV only proven example

Criteria for establishing viral aetioloBY

Koch's postulates a) always associated with disease
b) isolated and grown in pure culture
c) late pure culture produces diseases in susceptible animal
d) organism isolated from latter
Problems in application to human tumour viruses

Human tumour viruses

a) skin tumours
i) experimental studies
ii) isolation of virus
iii) localisation of viral DNA
iv) in situ hybridisation
b) cervical carcinoma
i) epidemiology
ii) cytological features
iii) immunochemical and DNA analytical studies

2) Herpes viruses
a) EB virus
i) Burkitt's lymphoma
- epidemiology
- cell culture isolation of viruses
- hybridisation studies
- in vitro lymphoid cell transformation
ii) nasopharyngeal carcinoma
- epidemiology
- isolation of virus
- hybridisation studies
iii) immunosuppression and lymphoma
- evidence
b) Herpes simplex type 2
i) cervical carcinoma
- epidemiology
- hybridisation studies
- virus isolation studies
2. Neoplasia 49

3) Hepatitis B virus (HBV)

i) hepatocellular carcinoma
- epidemiology
- serological studies
- temporal relationship of HBV infection and cirrhosis to
development of tumour
- animal model (Woodchurch hepatitis virus)
- DNA integration

4) HIV I and 11/

a) HIVI
i) Caribbean lymphoma
b) HIVIII
i) Kaposi's sarcoma in AIDS - Ab to HIV
ii) African KS - 17% Ab to HIV
iii) do not fulfill Koch's postulates
(October 1981, Paper 1, Question 5)

References
1 Taussig, M.J. Viruses and neoplasia. In: Processes in Pathology and
Microbiology, 2nd edition. p776-802. Blackwell Scientific Publications, Oxford
(1984).
2 Brescia, RJ. et al. The role of human papilloma viruses in the pathogenesis
and histologic classification of precancerous lesions of the cervix. Human
Pathol. (1986) 17: 552-558.

Discuss the contribution of epidemiological studies to our

understanding of the causes of malignant tumours

Much of the early insight on cancer causation came from epidemiological studies
and further advances have come from investigation of ideas generated therefrom.
To encompass all epidemiological factors is a difficult task, but could be
approached by illustrating the current theories of cancer development, as in the
previous two examples, but emphasising the components of the theory which
have a base in epidemiological study. Bronchogenic carcinoma is the classic
example, reflecting the work of Professor Sir Richard Doll, but alimentary cancers
and the influence of diet could provide abundant material for consideration in
addition. (November 1969, Paper 1, Question 4)

Comment on the World Health Organisation's statement that

about 80% of human cancer is environmentally induced

This type of question is difficult to answer in an examination because it requires

considerable organisation. In reality such a question can only be attempted
satisfactorily if the candidate has made an effort to be conversant with current
theories of cancer pathogenesis, and their supportive data. One possible approach
50 Advanced Histopathology

would be to briefly outline the multistep theory of neoplasia with emphasis on the
ultimate alteration of the DNA code or alteration of gene expression which
produces an established permanent malignant phenotype. The role in these
processes of chemical carcinogens, radiation and viruses, all of which are
environmental agents, should be highlighted. To complete the answer one or two
individual tumours could be selected to illustrate the points made. Squamous cell
carcinoma of the uterine cervix or bronchus are good well-studied examples of
malignant neoplasms with unquestionable environmental associations.
(October 1979, Paper 1, Question 2)
References
1 Paul, J. Oncogenesis. In: Recent Advances in Histopathology 13. P.P.
Anthony, RN.M. MacSween (eds.), pl3-31. Churchill Livingstone, Edinburgh
(1987).
2 Medline, A., Farber, E. The multistep theory of neoplasia. In: Recent Advances
in Histopathology 11. P.P. Anthony, RN.M. MacSween (eds.) Chapter 6,
pI9-34. Churchill Livingstone, Edinburgh (1981).
3 Robbins, S.L., Cotran, RS., Kumar, V. Neoplasia. In: Pathologic Basis of
Disease, 4th edition. p262-282. W.B. Saunders, Philadelphia (1989).

Discuss the part played by non-biological environmental factors

in the aetiology of human cancer
This question is similar to October 1979, Paper 1, Question 2 and can be
approached in a similar way. The discussion needs to commence with description
of current cancer formation theory highlighting the role of non-biological agents.
Chemical carcinogenesis and radiation of various sorts will form the main
discussion points. Illustration of the above can be provided by discussing
bronchogenic carcinoma or skin cancers, and the neoplastic lesions associated
with asbestos as alternative examples. (April 1977, Paper 1, Question 2)

Reference
1 Gibbs, A.R. Industrial lung disease. In: Recent Advances in Histopathology
13. P.P. Anthony, RN.M. MacSween (eds.) pl09-117. Churchill Livingstone,
Edinburgh (1987).

State one general theory of carcinogenesis. Discuss the main lines

of evidence for and against the theory you choose
The problem here lies with choosing a particular theory, but at the current time
most people would concentrate on the oncogene theory, which is now better
understood. Moreover there is now sufficient data available to call into question
its universal application as the cause of cancer. The essay could be commenced by
defining the term carcinogenesis (malignant transformation), with brief outlines
of other theories such as chemical carcinogenesis, radiation, etc. The conclusion
should reiterate the current idea that abnormal gene expression and its
consequences are considered the main pathway to malignant change.
(April 1972, Paper 2, Question 3)
2. Neoplasia 51

References

1 Robbins, S.L., Cotran, R.S., Kumar, V. Neoplasia. In: Pathologic Basis of

Disease, 4th edition. Chapter 6, p260-296. W.B. Saunders, Philadelphia (1989).
2 Taussig, M.J. Neoplasia. In: Processes in Pathology and Microbiology,
2nd edition. p689-810. Blackwell Scientific Publications, Oxford (1984).

Discuss the oncogene hypothesis

Introduction

Definition
Viral oncogene
Cellular oncogene
Proto-oncogene
Anti-oncogenes

Relationship of v-onc to c-onc with examples (e.g. RSV)

1) Transformation

a) recognition and induction

b) oncogenic retroviruses, 'rapid' vs. 'slow'
c) helper viruses

2) Identification of proto-oncosenes

a) v-onc probes
b) transfection experiments

3) Oncosene activation
a) transduction e.g.
i) FeLV
b) chromosomal rearrangement e.g.
i) Burkitt's lymphoma
ii) ph.Chr 9-22 (ber-abl)
c) point mutation e.g.
i) Ha-ras
ii) c-myc translocated from 8-2, 8-14
iii) 8-22
d) gene amplification e.g.
i) c-myc, N-myc

4) Viraloncosenes

a) DNA viruses e.g. SV40 T antigen

52 Advanced Histopathology

5) Oncogene products
a) regulatory functions
i) growth factors e.g. sis gene (PGDF)
ii) receptors e.g. erb-B (EGF)
iii) G protein (intracellular messenger) e.g. h-ras
iv) Nuclear acting proteins e.g. c-myc

6) Anti-oncogenes
a) chromosome 13 deletion in constitutional retinoblastoma

7) Role of oncogene activation

a) ? stage in multistep process
b) initiation and promotion
c) role of immune suppression
(April 1981, Paper 1, Question 1)

References

1 James, N., Sikora, K. Oncogenes and cancer. Hospital Update (1988) 14:
1261-1270.
2 Paul, J. Oncogenesis. In: Recent Advances in Histopathology 13. P.P. Anthony,
R.N.M. MacSween (eds.) p13-31. Churchill Livingstone, Edinburgh (1987).
3 Goudie, R.B. Editorial: What are anti-oncogenes? J. Pathol. (1988) 154:
297-298.

Discuss the role of oncogenes in carcinogenesis

(October 1986, Paper 1, Question 1)

Discuss the role of growth factors in neoplasia

Introduction

Definition (miscellaneous group of molecules acting in a paracrine fashion)

Relationship to oncogene products
General characteristics (low mw <80 kD; local action; specific cell surface
receptors; affect cell differentiation ± growth)

Types of growth factors (GFs)

1) Epidermal GF

2) Colony stimulatinu factors (C5F)

3) Platelet derived GF

4) Fibroblast GF
2. Neoplasia 53

5) Interleukins

6) Transforming GF

Functions of GFs

'Signal' molecules influencing differentiation and growth

GF binding to membrane receptor activates intracellular pathway
Normal function control ? receptor saturation ± feedback
Excessive production or deficiency influences cellular behaviour

GF in malignancy
11 Mechanisms
a) 'autocrine' hyperstimulation (e.g. bombesin in small cell lung ca)
b) receptor alterations e.g.
i) EGF i in squamous Ca skin + gliomas? gene amplification
ii) i IL2 receptor in T cell leukaemia ? transcriptional deregulation
iii) mutation causing activation e.g. c-erb B1 oncogene product
resembling truncated EGF receptor in breast and gastric ca
c) intracellular pathways - oncogene relations e.g.
i) ras group - signal transducers (activated by mutation)
ii) fos, myc groups - nuclear transcriptional regulators
d) inhibitory function
i) loss 'of gene function
ii) loss of responsiveness to GF e.g. TGF~
(normally inhibits cell growth) receptor deficient in retinoblastoma cell lines
e) induction of other GFs e.g. TNF, ILs
f) unknown e.g. CSFs
(October 1986, Paper I, Question 1)

References

1 Green, A.R. Peptide regulatory factors: multifunctional mediators of cellular

growth and differentiation. Lancet (1989) i: 705-707.
2 Waterfield, M.D. Altered growth regulation in cancer. Br. Med. Bull. (1989)
45: 570-581.
3 Anon. Growth factors in malignancy. Lancet (1986) ii: 317-318.

What factors determine the metastatic potential of tumours~

Introduction

Definition of metastasis
Relationships of morphology to biological behaviour
Historical aspects of 'benign' vs. 'malignant'
Classifications in tumour pathology
54 Advanced Histopathology

Mechanisms of metastasis

1) Cellular detachment from primary

2) Penetration of basement membrane (? Type IV collagenase)

3) Stromal invasion (proteolytic enzymes)

4) Vascular penetration (enzymic/mechanical)

5) Transport to metastatic site

a) aggregation
b) coagulation

6) Endothelial attachment, vascular penetration (?Plasminogen activator)

7) Growth and desmoplasia

'Metastatic inefficiency'

Heterogeneous metastatic capability in primary tumours

(Experimental observations)

Factors influencing metastatic capacity

1) Host immune response

a) specific-MHC expression and tumour Ags
b) non-specific - NK cells, granulocytes

2) Oncogene expression e.g. fos gene increases MHC expression

ras transfection experimentally increases
metastatic ability

3) 7Site specific cellular receptors

a) autopsy studies (Paget (1889) seed/soil hypothesis!)
b) animal models

4) Cell structural alterations

a) membrane
e.g. carbohydrates, enzymes, antigens putative associations (e.g. helix
pomatia lectin binding in breast ca)
b) cytoskeleton - ? 'deformability' t invasive/metastatic ability
2. Neoplasia 55

Histological parameters enabling assessment of metastatic

potential

1) Size (e.g. renal adenocarcinoma. various sarcomas)

2) Differentiation

a) grading systems (e.g. breast, skin, prostate ca)

b) other cytological features (e.g. pleomorphism, cellular maturations,
? 'nucleolar organiser regions'
3) Mitotic index (e.g. uterine smooth muscle tumours)

4) Extent of tumour (e.g. malignant melanoma, colorectal ca)

5) Vascular invasion (e.g. follicular thyroid tumours, breast ca)

6) {Host immune response (e.g. colorectal ca, nasopharyngeal ca)

(October 1988, Paper 1, Question 5)
References
1 Feldman, M., Eisenbach, L. What makes a tumor cell metastatic? Sci. Am.
(1988) 259: 40-47.
2 Hill, R.P. Metastasis. In: The Basic Science of Oncology, Chapter 10, p160-175.
Pergamon Press, Oxford (1987).
3 Robbins, S.L., Cotran, R.S., Kumar, V. Neoplasia. In: Pathologic Basis of
Disease, 4th edition. Chapter 6, p255-260. W.B. Saunders Co, Philadelphia
(1989).

Discuss the value of electron microscopy in the differential

diagnosis of tumours
The introduction to this answer should include some appraisal of the use of EM in
conjunction with conventional microscopy and immunocytochemistry, and
advantages it may offer. Many of the applications hinge on the identification of
subcellular particles which cannot be identified by other means (e.g.
neurosecretory granule presence and morphology, Z-band material, melano-
somes, etc.) and in the delineation of certain tumours which have similar
appearances on conventional microscopy (e.g. synovial sarcoma vs. leiomyo-
sarcoma, or small cell tumour of childhood). Some of the discussion could centre
on the cost effectiveness of EM diagnosis, and the organisation of such a service
for diagnostic purposes. It would also be reasonable to discuss certain research
applications. (April 1982, Paper 2, Question 3)

Reference

1 Mclay, A.L.C., Toner, P.C. Diagnostic electron microscopy. In: Recent

Advances in Histopathology 11. P.P. Anthony, R.N.M. MacSween (eds.)
p241-261. Churchill Livingstone, Edinburgh (1981).
56 Advanced Histopathology

What do you understand by the term 'fibromatosis'~ Give a brief

account of the entities you would include under this heading

The introduction to this answer should clearly define the fibromatoses, as fibrous
tissue proliferations intermediate in behaviour between benign fibrous tumours
and fibrosarcoma. Entities such as fasciitis or localised nodular fibrous prolifer-
ation are clearly excluded. The classification includes the superficial (e.g. palmar
fibromatosis) and deep (e.g. extra-abdominal desmoid tumour) types, but in
addition the fibromatoses characteristic of infancy and childhood should be
described (including infantile digital fibromatosis, infantile myelofibromatosis,
fibromatosis colli and juvenile hyaline fibromatosis). In view of the common
appearances in the superficial and deep forms, one example of each should be
described microscopically, and then the characteristic location and clinical
behaviour outlined for the remainder in each group. The infantile and childhood
forms have fairly characteristic appearances which might merit individual
description. Fibromatoses are a common source of difficulty in pathological
diagnosis, and it is perhaps surprising that this subject has not been chosen more
often in the examination. (October 1978, Paper 1, Question 2)

Reference

1 Enzinger, F.W., Weiss, S.W. Fibromatous and fibrous proliferation of infancy

and childhood. In: Soft Tissue Tumors, 2nd edition. p136-200. C.V. Mosby Co,
St Louis (1988).

Discuss the differential diagnosis in a child with a small cell

tumour involving the maxilla

This question relates to the likelihood of finding a small cell tumour of childhood
in this particular site. Lymphoma might be the most likely diagnosis, especially
over the age of ten years, and the site provides an opportunity to describe Burkitt's
lymphoma and its associations. Embryonal rhabdomyosarcoma may well occur at
this site, whereas Ewing's sarcoma and metastatic neuroblastoma are less likely.
The differential diagnostic considerations should include ultrastructural features
and, as a more recent advance, immunohistochemistry.
(April 1974, Paper 1, Question 4)

Reference

1 Variend, S. Small cell tumours in childhood: a review. J. Pathol (1985) 145:

1-25.

Using illustrative examples, discuss the current clinicopathological

importance of the terms 'histogenesis' and 'differentiation' as
applied to tumour pathology

The terms should be defined in the introductory paragraphs, histogenesis being

the presumed cell or tissue of origin of a tumour, and differentiation being the
2. Neoplasia 57

extent to which the tumour resembles a mature cell or tissue. A current rather
emotive argument concerns whether the expression of what were previously
considered as tissue-specific antigens reflects cell lineage or mere expression of a
particular locus by the neoplastic process, e.g. cytokeratin expression in smooth
muscle tumours. This is a question which requires quite a sophisticated approach
in consideration of these concepts. Examples are fairly easy to think of (e.g.
carcinoid tumours and oat cell carcinoma, ductal and lobular carcinoma of the
breast, leiomyosarcoma and rhabdomyosarcoma, etc.). The first two references
given are excellent overviews of this subject. (April 1987, Paper 1, Question 1)

References
1 Gould, V.E. Histogenesis and differentiation: a re-evaluation of these concepts
as criteria for the classification of tumours. Human Pathol. (1986) 17: 212-215.
2 Mendelsohn, G. et al. Divergent differentiation in neoplasms: pathologic,
biologic and clinical considerations. Path. Ann. (1986) Part 1: 91-119.
3 Gatter, K.C. et al. Human lung tumours: a correlation of antigenic profile with
histological type. Histopathology (1985) 9: 805-823.

Discuss the problems, in principle and in practice, associated

with separating benign from malignant lesions. Use examples of
endocrine tumours to illustrate the points which you make.

This should be a relatively straightforward essay question to answer, without

specific revision, for most histopathologists and may be regarded as another
example of a 'bench-mark' question, since if the examinee cannot provide a
comprehensive answer on the basis of personal experience, then they are probably
not up to the required standard. (April 1986, Paper 1, Question 1)

Discuss critically the concepts of hyperplasia and neoplasia in

relation to endocrine cells

This is a difficult essay to write in terms of achieving a good balance, and avoiding
a long-winded and not very relevant discourse. It is probably better to introduce
with the standard definitions of hyperplasia and neoplasia, and then discuss
various examples in the endocrine system such as thyroid, parathyroid and
adrenal glands, with an example from the diffuse (neuro) endocrine system. The
functional, behavioural and therapeutic implications of the distinction between
hyperplasia and neoplasia should be thoroughly considered in each case.
(April 1983, Paper 1, Question 2)

Discuss the concepts of conditioned (hormone-dependent) and

autonomous neoplasia

In answering this question, the introduction should clearly outline the differences
between hyperplasia and neoplasia, and discussion centred on the tumours,
58 Advanced Histopathology

benign and malignant, which show a response to hormones either experimentally,

during normal physiology or as a result of therapeutic administration, including
uterine leiomyoma, breast fibroadenoma and carcinoma, prostatic carcinoma,
endometrial and ovarian carcinomas. (November 1974, Paper 2, Question 3)

Discuss aberrant ('ectopic') hormone production by tumours

It is clearly important to define what the term 'ectopic' means in this context, and
indeed clearly state what is understood by the term hormone, otherwise there is a
danger of drifting off the topic (e.g. 5H-T synthesis, by carcinoid tumours, which
is not a hormone). The best idea is to list all the hormones which are associated
with inappropriate synthesis, and the tumours which may produce them. A useful
table is found in the reference on page 295. In addition, a brief discussion of the
pathological consequences of these disorders (e.g. ectopic ACTH production) and
the histochemical and immunochemical methods used in their detection would be
useful. (November 1972, Paper 1, Question 2)

Reference

1 Robbins, S.L., Cotran, RS., Kumar, V. Neoplasia and Clinical Aspects of

Neoplasia. In: Pathologic Basis of Disease, 4th edition. Chapters 6 and 7,
p243-245; 294-296. W.B. Saunders, Philadelphia (1989).

What evidence is there in man that immunological factors are

involved in malignant disease~

This is undoubtedly a very difficult question to answer in the light of current

knowledge, as the issues involved are highly complex. The wording of the
question is rather vague (it depends on opinion as to what constitutes an
'immunological factor' or 'involvement' for instance), and it is unlikely that such a
question would emerge again. (November 1970, Paper 1, Question 1)

Discuss the role of the immune process in the development and

spread of neoplasms
This question has rather more information than November 1970, Paper I, Question
I, indicating two separate areas, carcinogenesis and progression of neoplasia.
With respect to the former, while there is little evidence of a direct role in carcino-
genesis, defects in immunity may allow neoplasms to proliferate, e.g.
immunosuppressive states such as AIDS, renal transplantation, etc. The spread of
tumours may be affected by the host response to the tumour, as demonstrated in
breast and rectal carcinomas or melanomas for instance. The role of tumour
antigens and markers should be discussed. (April 1975, Paper 1, Question 3)
2. Neoplasia 59

Discuss the MEN syndromes

The introduction should include an explanation of the term and the general
features present, including an explanation of the differences and difficulties of
distinguishing between hyperplasia and neoplasia. The features of the three major
MEN syndromes, MEN! and MENlIa and lIb should be discussed, with the
pathological features of their components, and some speculation as to the
associations, and ways of investigating these syndromes (e.g. gene mapping).
(April 1988, Paper 1, Question 1)

Reference

1 Robbins, S.c., Cotran, R.S., Kumar. V. Multiple endocrine neoplasia

syndromes. In: Pathologic Basis of Disease, 4th edition. p1007; 1008.
W.B. Saunders, Philadelphia (1989).

Discuss teratomas

This question could still arise, but possibly in a slightly different format, since
there has been a marked increase in the volume of research on this subject in
recent years. As it stands, it would probably be best to approach this in a general
fashion, defining the term and giving data on gonadal and extragonadal
teratomas, with some paragraphs giving the major clinical and pathological
features, and perhaps a comparison of ovarian and testicular teratomas. However,
the rest of the essay should be devoted to a discussion of the theories of the origin
of teratomas, and their relationship to carcinogenesis and embryogenesis.
(April 1970, Paper 1, Question 5)

Reference

1 Fox, H. Biology of teratomas. In: Recent Advances in Histopathology 13. P.P.

Anthony, R.N.M. MacSween (eds.). Chapter 3, p 33-43. Churchill Livingstone,
Edinburgh (1987).

What are the principal similarities and differences between

teratomas and blastomasl Illustrate your answer by examples
from each group

The introduction to this answer should include descriptive definitions of the 'terms
teratoma and blastoma, which may be found in reference 1. The major differences
could be summarised in tabulated form, occupying half to a full A4 page, and
then discussions centred upon the features of the tumours found in the most
common sites e.g. gonads (teratoma), adrenal gland, kidney, lung, liver
(blastomas). The histogenetic theories for each of these entities could be
introduced but should not occupy a major segment of the answer, as the second
half of the question implies considerable emphasis should be given to the
morphological features. (November 1975, Paper 1, Question 5)
60 Advanced Histopathology

References
1 Fox, H. Biology of teratomas. In: Recent Advances in Histopathology 13. P.P.
Anthony, R.N.M. MacSween (eds.). Chapter 3, p33-43. Churchill Livingstone,
Edinburgh (1987).
2 Berry, P.J. Paediatric solid tumours. In: Recent Advances in Histopathology
13. P.P. Anthony, R.N.M. MacSween (eds.). Chapter 12, p203-232. Churchill
Livingstone, Edinburgh (1987)

Discuss the differential diagnosis of an anterior mediastinal mass

in a man aged 17
The differential diagnosis should be strictly related to the age in terms of
likelihood, and weighted according to frequency and clinical importance. Since
this is not a common clinical problem, these decisions require some careful
thought. However, a candidate familiar with the cited reference should be able to
formulate a comprehensive answer. It also lends itself to a rather easier type of
essay plan construction, with a separate subheading for each entity, and this is
one of the better questions on which to practise this technique.
(October 1981, Paper 2, Question 1)

Reference
1 Rosai, J. Mediastinum. In: Ackerman's Surgical Pathology, 7th edition.
p345-390. C.V. Mosby Co, St Louis (1989).

Discuss the problems in the diagnosis of neoplasms of soft tissue

This question should be approached from several aspects. Firstly the problem area
should be defined, excluding the lesions with easily recognisable differentiated
features e.g. rhabdomyomas, well-differentiated fatty tumours, etc. Then the
general aspects of dividing benign from malignant neoplasms in soft tissue are
addressed. It would then perhaps be an idea to divide the problems of the
distinctive childhood tumours and their diagnosis, and then consider the
commoner problems in the adult. A discussion of the more common diagnostic
problems in adults should include an appraisal of subtle diagnostic features on
conventional staining, together with use and limitations of immunohistochemistry
and electron microscopy. Examples of tumours should be given but the overall
discussion kept in a general basis. (April 1983, Paper 2, Question 2)

How do you classify malignant tumours of soft tissue? Discuss the

role of specific techniques in classifying an anaplastic spindle cell
tumour .
Malignant tumours of soft tissue are best classified according to features in the
tumour which resemble differentiation characteristics in adult tissues or their
embryonic precursors. This enables a reproducible classification, with diagnostic
criteria that can be understood and used by the practising histopathologist. In
2. Neoplasia 61

some· cases the differentiation described is only assumed to represent a certain

adult tissue for purposes of classification e.g. malignant fibrous histiocytoma. In
some tumours there is no feature which resembles mature or embryonic non-
neoplastic tissues, these lesions can be classified as SIT of uncertain histogenesis.
In using a classification such as this one does not necessarily imply that the cell of
origin of the neoplastic growth was a committed cell to the lineage, expressed in
the differentiation of the tumour. The most accepted classification is found in the
first reference, but this would only be reproduced somewhat broadly, but the
question does not require a regurgitation of the classification, more a discussion
as above, citing specific examples from the groups selected by Enzinger and
Weiss.

The specific techniques include conventional histochemistry (which is often

overlooked), immunohistochemistry and electron microscopy. Note that the
'anaplastic spindle cell tumour' could be a carcinoma or melanoma (or even rare
spindle cell lymphomas) as much as a sarcoma. In addition, it would not be
appropriate to discuss non-spindle cell sarcomas - a point which might be
overlooked in an examination. (April 1988, Paper 2, Question 4)

References

1 Enzinger, F.M., Weiss, S. General considerations and immunohistochemistry

of soft tissue lesions. In: Soft Tissue Tumors, 2nd edition. pl-18j 83-101. c.V.
Mosby Co, St. Louis (1988).
2 Gatter, K.C., Falini, B., Mason, D.Y. The use of monoclonal antibodies in
histopathological diagnosis. In: Recent Advances in Histopathology 12.
P.P. Anthony, RN.M. MacSween (eds.) p35-67. Churchill Livingstone,
Edinburgh (1984).

What processes underlie hypercalcaemia which may occur in

association with malignant neoplasms~

Introduction

Definition of hypercalcaemia
Paraneoplastic syndrome-incidence (15/100 ODD/year)
Detection/ clinical presentation

Mechanisms

1) Metastatic disease
a) tumour types - lung, breast, renal, endometrial ca
b) patterns
i) osteolytic
- peritumourallysis of bone-hypercalcaemia
- but some lytic bone mets (e.g. oat cell ca) normocalcaemic
c) mechanisms
i) PGE synthesis (e.g. breast ca, melanoma)
ii) TGF alpha and beta (e.g. breast ca)
iii) as for non-metastatic disease
62 Advanced Histopathology

d) osteosclerotic
i) osteoblast stimulation
ii) mechanism unknown

2) Non-metastatic disease
a) 25 - 50% of solid tumours no obvious bony metastases
b) mechanisms
i) PTH-like activity ('ectopic' PTH)
- e.g. squamous/large cell ca lung
renal cell ca
small cell ca ovary
- action of PTH - bone
- kidney
- gut
ii) hypersecretion of PTH
- parathyroid carcinoma

3) Primary bone involvement

Myeloma
a) mechanisms
i) osteoclast activating factors (lymphokines e.g. IL-l)
ii) reduced renal excretion in 'myeloma kidney'
iii) ? increased 1,25 (OH)2 03 production

Non-Hodgkin's lymphoma/leukaemia
a) mechanisms
i) ?1,25 (OH)2, D3 production
ii) osteoclast activating factors
(April 1985, Paper 1, Question 4)

Reference

1 Strewler, G.J., Nissenson, R.A. Non-parathyroid hypercalcaemia. Adv. Intern.

Med. (1987) 32: 235-258.

Describe the pathological conditions that give rise to

hypercalcaemia; discuss the effects on other tissues of the body
This essay encompasses the ground covered in the previous answer, together with
other non-parathyroid causes of hypercalcaemia (e.g. sarcoidosis, milk-alkali
syndrome etc.), which are also covered in the previous reference. A major section
also needs to be included on hyperparathyroidism, where the abnormalities of the
endocrine glands rather than the bony changes require description according to
the wording of the question. In all essays like this, it is usually of value to include
a precis of the control of normal calcium and phosphate absorption and excretion
in the introduction, or even as a line diagram. This will aid the explanation of the
tissue effects (renal complications, metastatic calcification, etc.).
April 1975, Paper 2, Question 5)
2. Neoplasia 63

How would you examine a mastectomy specimen for a suspected

carcinoma? What macroscopic and microscopic criteria do you
use to assess the prognosis of breast cancer?

A question which would be relatively easy for those trainees who had undertaken
a meticulous approach to these specimens in routine practice. Different types of
mastectomy should be described (e.g. simple, radical, etc.) along with procedures
to ensure prompt fixation. The macroscopic features are fairly straightforward
(e.g. size, site, resection margins, etc.) but details of lymph node dissection should
be detailed since this is the most important prognostic indicator. Much of the
information on microscopic features is contained within the previous answers.
Grading of breast carcinoma is contentious but provides an opportunity for
discussion. (October 1984, Paper 1, Question 2)

References

1 Rosai, J. Guidelines for handling of most common and important surgical

specimens. In: Ackerman's Surgical Pathology, 7th edition. 1868-1872.
C.V. Mosby Co, St Louis (1989).
2 Haybittle, J.L. et al. A prognostic index in primary breast cancer. Br. J. Cancer
(1982) 45: 361-366.

What pathological features assist in determining the prognosis in

mammary carcinoma?
(April 1980, Paper 1, Question 1)

Discuss the histopathological (including histochemical and

immunohistochemical) features that may be related to prognosis
in carcinoma of the breast
(April 1981, Paper 1, Question 4)

Give an account of the various types of breast cancer. What role

has the pathologist to play in the management of this
malignancy?
(October 1982, Paper 1, Question 2)

What features enable a pathologist to venture an opinion on

prognosis in a case of carcinoma of the female breast?

These questions require some expansion of the second part of the previous
answer, relating to the classification and its relationship to behaviour (especially
the better prognostic types such as papillary, mucoid, some medullary, tubular
and adenoid cystic carcinomas), location in the breast and staging, and certain
histological features which may have a bearing on behaviour (e.g. vascular
invasion). It is also important to include an assessment of nodal involvement, and
64 Advanced Histopathology

discuss the relevance (or otherwise) of grading systems. More recent advances
such as oestrogen and progesterone receptor status and indeed /EGF receptor
and c-erb B protein expression could also be included within the discussion.
(October 1979, Paper 2, Question 4)

Reference

1 Robbins, S.L., Cotran, R.S., Kumar, V. Carcinoma of breast. In: Pathologic

Basis of Disease, 4th edition. p1192-1201. W.B. Saunders, Philadelphia (1989).

Discuss the correlation between pathological features and

prognosis in mammary carcinoma

Introduction
Incidence of breast carcinoma
Overall mortality rate
Changes in therapy
Influence of breast screening

Role of the Pathologist

Management of specimens
a) naked eye examination
b) specimen radiography
c) resection margins for lumpectomy
d) mastectomy specimens

Classification of breast carcinoma

1) Invasive carcinoma with average or poor prognosis
a) ductal
b) lobular
c) carcinoma NOS

2) Invasive carcinomas with above average prognosis

a) tubular
b) medullary with lymphoid infiltration
c) papillary
d) 'minimal' cancer
e) mucinous/colloid

3) In situ carcinoma
a) ductal
b) lobular
Implications for management and risk of invasive cancer
2. Neoplasia 65

Spread of disease (and staging)

1) Local factors
a) tumour size
b) vascular invasion
c) local invasion and resection margins

2) Metastatic disease
a) local lymph nodes and sites
b) recurrence and extramammary deposits
(April 1971, Paper 2, Question 1)

References

1 Azzopardi, J.G. Problems in Breast Pathology. Chapters 11-13, p240-333. W.B.

Saunders, Philadelphia (1979).
2 Robbins, S.L., Cotran, R.S., Kumar, V. The breast. In: Pathologic Basis of
Disease, 4th edition. Chapter 25, p1192-1201. W.B. Saunders, Philadelphia
(1989).

Describe the appearances of lobular carcinoma of the breast and

give a critical account of its natural history

Introduction

Description of normal breast lobule

Putative 'origin' of lobular and ductal carcinoma

Lobular carcinoma in situ

V Microscopic features
a) uniform cells
b) nucleoli
c) lobular distention
d) 'intracytoplasmic' lumina
e) Pagetoid spread

2) Clinical features
3) Behaviour
a) risk of malignancy
b) bilaterality
c) comparison with intraductal carcinoma
66 Advanced Histopathology

Atypical lobular hyperplasia A

Distinction from LCIS

Invasive lobular carcinoma

1) Macroscopic features

2) Microscopic features
a) LCIS
b) invasive patterns - solid, alveolar, mixed features
i) targetoid spread
ii) indian filing
ii) desmoplasia
iv) intracytoplasmic lumina
v) signet ring cell type
c) immunohistochemistry
d) oestrogen receptors

3) Clinical features

4) Behaviour

5) Identification of metastases

6) Comparison with ductal carcinoma

(October 1983, Paper 2, Question 4)

References

1 Azzopardi, J.G. Underdiagnosis of malignancy, and special problems in breast

pathology. In: Problems in Breast Pathology. p216-233; 278-285. WB
Saunders, Philadelphia (1979).
2 Howell, A., Harris, M. Infiltrating lobular carcinoma of the breast. Br. Med. J.
(1985) 291: 1371-1372.

Discuss critically the evidence which led to the decision to

introduce a national screening programme for breast cancer.
What impact do you think the implementation of such a
programme will have upon the histopathology laboratory~

Introduction

Highest level of breast cancer mortality in UK

'Static' mortality in breast cancer patients in last 50 years
Assessment of screening benefits (Forrest Report)
National programme - one view mammography every three years in 50-64 age
group
2. Neoplasia 67

1) 'Early' detection of breast cancer

2) Assessment and management of premalignant breast disease

Evidence
1) * mortality in 50-65 yr age group (US/Swedish trials) of 30-50%

2) * morbidity (more modest surgery)

Criticisms
1) 'Lead-time'; bias

2) False positive results (mammographic)

3) False negative results

4) Evidence of long term benefit not established

5) ?Theoretical radiation risk

Implications for histopathology laboratories

1) Workload
a) FNA cytology
b) surgical biopsy

2) Management implications
a) funding of laboratory
b) quality control procedures
c) computer processing and registration for regional and national evaluation

3} Specimen radiography
a) liaison with surgeon/radiologist
b) ? laboratory x-ray facilities
c) interpretation of results
d) localisation of lesion (?pre-operative) and sampling procedures
e) excision margins and multifocal disease
f) fixation and dissection
g) staging and classification

'4) Interpretation of histopathological abnormality

a) training programmes and courses
b) evaluation of atypical hyperplasias
c) management of epithelial proliferative diseases
d) assessment of small cancers
(October 1988, Paper 2, Question 2)
68 Advanced Histopathology

References

1 Gad, A. Screening for breast cancer: examination and reporting of

histopathological preparations. Lancet (1988) ii: 953.
2 Anderson, T.J. The pathologist and breast cancer screening. J. Pathol. (1987)
153: 309-310.
3 Reidy, J., Hoskins, O. Controversy over mammography screening. Br. Med. J.
(1988) 297: 932-933.

Give an account of carcinoid tumours

Since the appearance of this question significant advances have been made in this
field. Carcinoid tumours are now generally regarded as a component of the
spectrum of neoplasia arising from the diffuse endocrine and neuroendocrine
system. The biological activity of tumours of this group and their histochemical,
immunohistochemical and ultrastructural features are now extensively described.
An examination question posed today would almost certainly be more specific,
for example - 'Discuss the pathology of diffuse endocrine tumours of midgut
origin'. The question requires an introduction with brief description of the current
concept of the diffuse endocrine and neuroendocrine system together with a
macroscopic and microscopic description of the tumours to include
histochemistry and immunohistochemistry. A discussion of hormone production
and secretion, and a description of the behaviour of the lesions in question must
be included. (April 1972, Paper 2, Paper 4)

References

1 Polak, J.M., Bloom, S.R. Pathology of peptide producing neuroendocrine

tumours. Br. J. Hosp. Med. (1985) 33: 78-88.
2 Dawson, I.M.P. Diffuse endocrine and neuroendocrine cell tumours. In:
Recent Advances in Histopathology 12. P.P. Anthony, R.N.M. MacSween
(eds.) pl11-128. Churchill Livingstone, Edinburgh (1984).

Write an essay on endothelial cell neoplasia

Introduction

Neoplasms vs. malformations/reactive lesions e.g. Masson's tumour,

haemangiomas
Pleomorphic nature of endothelial cell reflected in neoplasia
Exclude leiomyoma and haemangiopericytoma
Endothelial cell markers in diagnosis e.g. laminin
Factor VIIIr Ag, VEAl
2. Neoplasia 69

Benign tumours

1) Epithelioid haemangioma
a) clinical features
b) histological appearance
c) distinction from Kimura's disease
d) confusions in nomenclature

2) eNS haemangioblastoma
a) age, location
b) microscopic appearance
c) associations (phaeochromocytoma, renal cell carcinoma)

Low grade malignancy

1) Epithelioid haemangioendothelioma
a) terminology, (inc IVBA T, 'sclerosing cholangiocarcinoma')
b) clinical features
c) microscopic features
d) differential diagnosis
e) behaviour

2) Malignant endovascular papillary angioendothelioma

a) Dabska tumour
b) clinical and microscopic features

Malignant tumours

1) Angiosarcoma
a) clinical features
b) aetiology (arsenic, vinyl chloride, thorotrast)
c) macroscopic
d) microscopic
e) behaviour

2) Post-mastectomy angiosarcoma
a) chronic lymphoedema
b) microscopic
c) behaviour
70 Advanced Histopathology

3} Kaposi's sarcoma (arguably endothelial in nature)

a) clinical features
b) epidemiological associates
i) (HIV, genetic)
c) microscopy
i) early
ii) late
iii) nodular
d) behaviour
(October 1985, Paper 1, Question 5)

References

1 Enzinger, F.M., Weiss, S.W. Benign tumors and tumorlike lesions of blood
vessels, haemangioendothelioma: vascular tumors of intermediate
malignancy and malignant vascular tumors. In: Soft Tissue Tumors, 2nd
edition, p489-580. C.V. Mosby Co, St Louis
2. Robbins, S.L. Cotran, R.S., Kumar, V. Blood vessels. In: Pathologic Basis of
Disease, 4th edition. p587-593. W.B. Saunders, Philadelphia (1989).
3. Ashley, D.J.B. Tumours of the vascular system. In: Recent Advances in
Histopathology 13. P.P. Anthony, R.N.M. MacSween (eds.) p95-107. Churchill
Livingstone, Edinburgh (1987).

Describe the naked eye and histological appearances of Kaposi's

sarcoma. Give an account of its nature, behaviour and
associations

Cutaneous Kaposi's sarcoma

1} Macroscopic appearances
a) patch (colour, margin, size)
b) plaque
c) nodule
Note tendency of nodules to coalesce and ulcerate in the non-AIDS endemic
patients

2} Microscopic appearances
a) patch
i) upper dermis
ii) proliferation of jagged irregular vascular spaces, avoid normal vessels
iii) blood endothelial cells
iv) dissection of collagen by vessels
v) paucity of spindle cells in stroma
2. Neoplasia 71

b) plaque
i) entire dermis +/ - subcutaneous tissue
ii) greater vascular proliferation
iii) addition of spindle cells in stroma +/- erythrocyte containing clefts
iv) atypia may still be minimal
c) nodule
i) sarcomatous
ii) angiomatoid
iii) mixed

Visceral KS
1) Sites
a) any (except brain)
b) especially CIT, lung, lymph node

Microscopic as before

Clinical setting of KS
1) Endemic
a) Elderly males
i) age >50
ii) epidemiology
iii) site
iv) behaviour indolent
b) African
i) epidemiology
ii) age/sex
iii) behaviour aggressive
iv) metastases - visceral

2) Immunodeficiency-associated
a) AIDS
i) age
ii) HIV status
iii) sites - cutaneous/visceral
iv) behaviour aggressive
v) metastases - visceral and nodal
b) allograft recipients
i) rare
ii) behaviour as AIDS

Nature of KS
1) Histogenesis

Two possibilities
72 Advanced Histopathology

a) ?vascular endothelial cell - morphological features but

i) Factor VIII rAg -ve
ii) no Weibel-Palade bodies
b) ?lymphatic endothelial cell independent regions, association with
lymphoedema, absence in brain

Association with CMV infection

a) antibody studies
b) DNA studies
(October 1984, Paper 2, Question 3)

References

1 Millard, P.R., Chapel, H.M. Immunodeficiency states including AIDS. In:

Recent Advances in Histopathology 13. P.P. Anthony, R.N.M. MacSween
(eds.) p138-142. Churchill Livingstone, Edinburgh (1987).
2 Enzinger, F.M., Weiss, S.W. Malignant vascular tumors. In: Soft Tissue
Tumors, 2nd edition. p561-575. C.V. Mosby Co, St Louis (1988).

Give an account of tumours that may arise in the orbit (including

the eye)

Introduction
Intraocular and extraocular tumours
Benign vs malignant
Incidence

Intraocular tumours
Uveal tract

1) Malignant melanoma
a) choroidal
b) types
i) spindle cell
ii) epithelioid
iii) pure
c) survival
d) prognostic features

2) Leiomyoma
3) Angioma

4) Haemangioendothelioma
2. Neoplasia 73

1) Retinoblastoma
a) age incidence
b) frequency
c) histological types
i) undifferentiated
ii) rosettes
iii) diffuse infiltrating

2) Medul/oepithelioma
3) Astrocytoma
4) Haemangioblastoma
Non-pigmented ciliary epithelium
1) Medulloepithelioma
2) Adenoma/adenocarcinoma
Pigmented ciliary epithelium
1) Adenoma/adenocarcinoma (rare)
Optic disc tumours
1) Melanocytoma
2) Medulloepithelioma
3) Astrocytoma
Secondary deposits
1) e.g. breast, lung, CIT, ovaries

Orbital tumours
1) Optic nerve
a) astrocytoma
b) meningioma

2) Soft tissues
a) embryonal rhabdomyosarcoma
b) cavernous angioma
c) malignant lymphoma
d) Schwannoma
e) histiocytosis X
f) lipoma and liposarcoma
74 Advanced Histopathology

3) Lacrimal B'and
a) adenoid cystic carcinoma
b) others
4) Metastatic carcinoma
(October 1985, Paper 2, Question 1)

References
1 Zimmerman, L.E., Sobin, L.H. Histological Typing of Tumours of the Eye
and Its Adnexa. World Health Organisation International Histological
Classification of Tumours, No 24, Geneva (1980).
2 Rosai, J. Eye and ocular adnexa. In: Ackerman's Surgical Pathology, 7th
edition. p1791-1858. C.V. Mosby Co, St. Louis (1989).
3. lymphoreticular System
76 Advanced Histopathology

Give an account of the role of the Epstein-Barr virus in the

pathogenesis of Burkitt's lymphoma and glandular fever

Introduction

EBV original isolation from African Burkitt lymphoma (BL)

Later isolated glandular fever
Epidemiology - latent infection widespread (serology)

1) Herpes virus (DNA)

2) Structure

3) Replication

4) Transmission

B lymphocytes and EBV

1) In vitro studies
a) transformation
b) C3d receptor binding EBV (on B cells)
c) detection of viral genome vs. expression
d) expression of viral antigens and polyclonal proliferation
e) EBNA

BL and EBV
1) Serology
a) EBV titres
2) Genome in tumour cells (All Africa. 50% Europe)

3) Prospective studies (serum storage)

a) anti capsid Ag = ~ risk
b) Ch 8-14 translocations (c-myc activation)

Influence of other factors

1) Malaria (falciparum)

2) Immunodeficiency and nutrition

3) Clinical features
a) young adults
3. lymphoreticular System 77

GF and EBV

1) Pathology
a) lymph nodes
b) spleen
i) T cell response
c) serological studies.
i) IgM
ii) IgG
d) lymphoblastic cells in circulation + T cells

Immunosuppression and EBV infection

1) Lymphomas
Odober 1984, Paper 2, Question 4

Reference

1) Taussig, M.J. Oncogenic DNA viruses. In: Processes in Pathology and

Microbiology, 2nd edition. p792-796. Blackwell Scientific Publications, Oxford
(1984).

Discuss the structure and function of the spleen in health and

disease
Normal structure
1) ~acroscopjc

a) size
b) weight
c) vascular supply

2) ~icroscopic

a) red pulp
i) sinuses
ii) pulp cords
b) white pulp
i) periarteriolar lymphoid sheath
ii) lymphoid follicles

3) Blood flow
a) arterial supply via arterioles capillaries into
i) 'open' system - cords, sinuses, veins
ii) 'closed' system - sinuses, veins

(Diagrammatic illustration suggested)

78 Advanced Histopathology

Functions
7) Phagocytosis rbcs

2) Iron recycling

3) Platelet pool

4) Immune response

5) Haemopoiesis f< 7 year)

Pathological states
Reduced function

7) Effects
a) immunodeficiencies
b) effects

2) Causes
a) asplenia/hypostasis
b) atrophy/infarction
c) splenectomy
d) coeliac disease

Hyperplasia

7) Effects
a) splenomegaly
b) reduced haemopoietic elements
c) marrow hyperplasia

2) Aetiology

Congestive splenomegaly

7) Causes hepatic cirrhosis, portal vein thrombosis

2) R cardiac failure

3) Pathological appearances
a) weight 0.5-5 kg
b) congestion red pulp and phagocytosis rbcs
c) haemorrhage/fibrosis
d) Gamna-Gandy bodies
3. lymphoreticular System 79

Infections

1) Pathological appearances
a) malaria
b) kala-azar
c) leishmaniasis
d) others

Storage disorders

1) Gaucher's

2) Niemann-Pick

3) Mucopolysaccharides

4) Lymphomalleukaemia
a) CML
b) CLL
c) ?ALL
d) Hodgkin's disease
e) NHL
f) Myelofibrosis (myeloid metaplasia)
April 1986, Paper 2, Question 2

References
1) Robbins, S.L., Cotran, R.S., Kumar, V. Spleen. In: Pathologic Basis of Disease,
4th edition. p747-753. W.B. Saunders, Philadelphia (1989).
2) Scothorne, R.J. The spleen: structure and function. Histopathology (1985) 9:
663-669.
3) Van Krieken, J.H.J.M. et al. The human spleen: a histological study in
splenectomy specimens embedded in methylmethacrylate. Histopathology
(1985) 9: 571-586.

Briefly discuss the normal morphology of the spleen, and outline

the pathological processes which may affect this organ

There are subtle differences in the wording of this question compared to the
previous essay. In this case, the function of the spleen is not a major consideration,
and no great detail is required of the morphology (gross and microscopic). A
diagram would be of great use in both of these essays to eliminate a lot of the
explanation. Outlining the pathological processes would be made in much the
same way as in the previous essay, but with the addition of other entities such as
congenital cysts, minor infections, etc. as given in the useful table in the first
reference above. There is every opportunity to concentrate many facts within this
80 Advanced Histopathology

outline since there are so many different processes which affect the spleen,
producing characteristic changes. (October 1985, Paper 2, Question 2)

Describe briefly and as far as possible explain, the morphological

changes in a) the spleen in typhoid fever b) a lymph node
following antigenic stimulation c) the thymus in myasthenia
gravis
Essentially a 'short notes' type of question, there is a large amount of information
which could be compressed into this answer, especially in section b. Equal
weighting should be given to each part of the question however. The various
appearances can be reviewed from standard texts.
(April 1974, Paper 2, Question 3)

Discuss the role of macrophages in resistance to infection

It would be best to outline the proposed properties and functions of macrophages,
and their mechanisms of interactions with other cells (e.g. lymphocytes,
neutrophils, etc.), before illustrating these principles with various types of
infections producing different tissue responses where the macrophage plays a
major role e.g. bacterial, fungal, viral infections producing acute and chronic
suppuration, granulomatous inflammation, antigen presentation and antibody
production, intracellular parasitisation, etc. This would illustrate all of the roles of
the macrophage in a relatively structured and interesting format.
(November 1971, Paper 1, Question 1)

Reference
1) Taussig, M.J. In: Processes in Pathology and Microbiology, 2nd edition.
p59-62; 114-117; 163-164. Blackwell Scientific Publications, Oxford (1984).

Discuss the common causes of non-neoplastic lymph node

enlargement and describe the histological changes
This question would be best answered by placing the nodal reactive patterns into
broad groups rather than taking a large number of known aetiological agents and
describing each in turn, which would result in undue repetition, with an
unmanageable volume of writing. The main reactive patterns include acute and
chronic non-specific follicular hyperplasia, paracortical hyperplasia, necrotising
and non-necrotising granulomatous lymphadenitis, combined granulomatous/
follicular hyperplasia~

Within the larger groups, the distinctive features associated with each specific
condition can be described (e.g. in necrotising granulomatous lymphadenitis,
tuberculosis, cat-scratch disease). It is important to define what is meant by
'common' in the question, and therefore it may be debatable whether to include
conditions such as syphilis, fungal lymphadenitis, SLE, etc. which are rare at least
3. Lymphoreticular System 81

in the UK. Emphasis should really be placed on the causes related to the frequency
with which they lead to lymph node biopsy.
(October 1978, Paper I, Question 1)

Reference
1) Stansfeld, A.G. Inflammatory and reactive disorders. In: Lymph Node
Biopsy and Interpretation. A.G. Stansfeld (ed.) p85-141. Churchill
Livingstone, Edinburgh (1985).

Discuss the role of the histopathologist in the diagnosis and

management of Hodgkin's disease
One could organise this answer by dividing the histopathologist's contribution
into four parts, 1) diagnosis in lymph node biopsy - pathological features and
immunohistochemical methods, 2) classification (and relation to prognosis), 3)
staging, 4) follow-up - response to treatment and recurrence. Since the question
was set, fine needle aspiration cytology has made it possible to diagnose the
disease before biopsy, and with a good preparation it is possible to make an
informed assessment of the probable type. At the same time, staging laparotomy
has become less popular. The bulk of the answer could be concerned with the
pathological features in the Rye classification and its relation to prognosis.
(April 1976, Paper I, Question 1)

Reference
1) Williams, G.T. Hodgkin's disease. In: Lymph Node Biopsy and Interpretation.
A.G. Stansfeld (ed.) p196-227. Churchill Livingstone, Edinburgh (1985).

Discuss the histological criteria for distinguishing the different

forms of lymphoma
Effectively this question should be answered by choosing the most familiar (or
understandable) lymphoma classification, and outlining the general
morphological features. Once again, Hodgkin's disease should not be forgotten. It
is arguable whether immunocytochemical information should be included in an
answer on purely histological criteria. It might be better to discuss the
architectural and cytological categories of lymphoma based on normal cell types
(e.g. immunoblastic, centroblastic, centrocytic, prolymphocytic, T cell, etc. and
their nodal distribution), and outline the criteria for differentiating them.
(May 1973, Paper I, Question 4)

References
1) Williams, G.T. Hodgkin's disease. In: Lymph Node Biopsy and Interpretation.
A.G. Stansfeld (ed.) p196-227. Churchill Livingstone, Edinburgh (1985).
2) Stansfeld, A.G. Non-Hodgkin's lymphomas, high grade lymphomas and
peripheral T cell lymphomas. ibid p228-276; 277-299; 300-329.
82 Advanced Histopathology

Compare and contrast the pathology of malignant lymphomas

arising in lymph nodes with those that arise elsewhere

A fascinating question which clearly is still topical, although again the advance in
knowledge has resulted in complex lymphoma classifications within the nodal
group. It would be best to consider the concept of the normal extranodallymphoid
tissue distribution, including mucosa-associated lymphoid tissue, spleen, bone
marrow and brain for instance, and then describe the pathology of the lymphoma
types at these sites, highlighting the major differences with nodal lymphomas, it
would be impossible to attempt any detailed description of intranodal
lymphomas. Candidates should remember to include both Hodgkin's disease and
non-Hodgkin's lymphomas in any question of this sort.
(November 1970, Paper 2, Question 5)

Reference

1) Isaacson, P.G., Wright, D.H. Extranodal lymphoma. In: Recent Advances in

Histopathology 13. P.P. Anthony, R.N.M. MacSween (eds.) Chapter 10,
p159-184. Churchill Livingstone, Edinburgh (1987).

Write a descriptive account of extranodal lymphomas

The content is obviously much the same as in the previous question, but the
wording implies there should be only brief references to the nodal lymphomas,
with no descriptive account necessary.
(April 1971, Paper 1, Question 3)

Describe the classification of the non-Hodgkin's lymphomas and

discuss how immunostaining may be of value in their diagnosis

Introduction

1) Reasons for classification

a) morphological diversity
b) clinicopathological correlations
c) retrospective analysis

2) Requirements for classification schemes

a) understandable
b) clinical relevance
c) reproducible
d) scientifically accurate
3. Lymphoreticular System 83

3) Different sYstems in use

a) Rappaport
b) Kiel
c) British National Lymphoma Investigation
d) Working Formulation

4) General observation on complex classification

5) Recommended classification (updated Kie/)

B T

Low grade Lymphocytic-CLL, CLL,PLL

PLL, HCL

Small cerebriform cell - M.F., Sezary

LP immunocytoma Lymphoepithelioid
Plasmacytic AIL
Centroblastic/centrocytic T zone
- Foll/diff
- Diff
Centrocytic Pleomorphic, small cell

High grade Centroblastic Pleomorphic, med/large cell

Immunoblastic Immunoblastic
Large cell anaplastic Large cell anaplastic
Burkitt
Lymphoblastic Lymphoblastic

6) Advantages of single classification

a) clinical relevance
b) scientific assessment
c) functional correlation

7) Use of immunostaininc in diagnosis of NHL

Paraffin section
a) lymphoma vs. carcinoma
i) LCA (PD7, 2B11)
b) B cells (MB2, MBl, L26, LNl)
c) T cells (UCHLl, MTl)
d) clonal plasmacytoid B cells (lgs, light chains)
Frozen section
a) clonal B cells
i) Igs
ii) light chains (surf/cytop)
b) dendritic cells (5100)
i) foIl/diffuse
84 Advanced Histopathology

c) large cell anaplastic lymphoma

i) Ki-1 antigen
d) Pre B cell
i) CALLA
e) T helper IT suppressor
i) T4:T8
f) others
Above identify most lymphomas
(October 1986, Paper 2, Question 2)

Reference

1) Stansfeld, A.G. Lymph Node Biopsy and Interpretation. p 44-66; 228-232.

Churchill Livingstone, Edinburgh (1985).

Discuss the classification of lymphomas and the role of immuno-

histological techniques in establishing and refining the diagnosis
This question also requires a consideration of Hodgkin's disease, which would be
very easy to overlook. The range of available immunohistological reagents was
much smaller in 1982. In future questions there might be some qualifying
statements on the immunohistochemical aspects, such as considering their use in
B cell or T cell lymphomas only. (October 1982, Paper 1, Question 1)

What are your views in the present classifications of non-

Hodgkin's Iymphomasl How far can the classifications be linked
with modern immunological concepts and what value have such
classifications in prognosisl
This is an earlier version of October 1986, Paper 2, Question 2, but the relationship
to cellular phenotype was less well understood at the time.
(November 1975, Paper 1, Question 4)

Describe the current classifications of lymphomas. Which one do

you use in routine practice and whyl
The first part of this operation may be difficult to answer these days (it would be
difficult to describe the Working Formulation in a few lines!), but it is a useful
exercise to assess the Kiel classification outlined previously and its advantages, or
the classification used within a department where the candidate has trained. A
critical approach should be taken. (October 1980, Paper 1, Question 2)
3. Lymphoreticular System 85

Give an account of the tumours which are thought to arise from

histiocytes

This has been a very changeable subject since the time when this question was set,
and some entities previously included within this group have been claimed to be
of lymphoid or other lineage by immunohistochemical analysis or gene
rearrangement studies. Nevertheless, further questions could be envisaged in this
field, such as 'Discuss the concept of neoplastic histiocyte proliferations'.
(October 1981, Paper 2, Question 4)

Describe the necropsy findings in an untreated case of

myelomatosis and discuss their pathogenesis

This question could really be divided into two parts, the appearances of the
tumour itself in the bones and tissues, and their complications such as
pathological fracture or neuropathy, and the results of the tumour function,
including myeloma kidney and systemic amyloidosis. Some mention could be
made of the terminal complications of the disease (e.g. bronchopneumonia) but
the major part of the essay should concentrate on the primary effects of the
myelomatosis itself. (November 1977, Paper 1, Question 3)

Reference

1) Robbins, S.L., Cotran, R.S., Kumar, V. Diseases of white cells, lymph nodes
and spleen - plasma cell dyscrasias and related disorders. In: Pathological
Basis of Disease, 4th edition. p739-743. W.B. Saunders, Philadelphia (1989).
4. Alimentary Tract
88 Advanced Histopathology

Define what is meant by a 'congenitally short oesophagus'.

Describe the histological features and possible complications of
this condition
It is now accepted that this is usually an acquired phenomenon due to gastro-
oesophageal reflux, but it might be useful to include other entities with which it
might be confused, such as heterotopias and hiatus hernia. The bulk of the answer
should be concerned with Barrett's oesophagus, including clinical and
pathological diagnostic criteria, with the three forms of metaplastic epithelium
that may be found, in some detail. Complications include ulceration, stenosis and
malignant change. (November 1972, Paper 2, Question 2)

Reference

1) Jass, J.R. The oesophagus. In: Systemic Pathology. Alimentary Tract. B.C.
Morson (ed.), Volume 3, p130-148. Churchill Livingstone, Edinburgh (1987).

Discuss the value of biopsy and cytology in the diagnosis of

ulceration of the gastric mucosa
This question relates to the differential diagnosis of various gastric ulcers, and
introduction should include the various categories of gastric ulceration such as
acute and chronic peptic ulceration, dysplasia, early and advanced gastric cancer,
gastric lymphoma emphasising the advantages over clinical methods of diagnosis.
The requirements for sufficient biopsies and cytolOgical preparations should be
discussed.

The pathological features need to be covered in more detail than for the more
wide-ranging questions about the value of CIT biopsy, and the particular
advantages of having both biopsy and cytology need to be emphasised, both for
improvement of overall diagnostic rate, and in particular circumstances where
histology may be difficult e.g. deep ulcers covered in slough, or signet ring cells
which may be overlooked (usually better seen on cytology). Other difficult
diagnostic problems on biopsy may be given emphasis (e.g. in gastric lymphoma).
(April 1981, Paper 1, Question3)

Discuss the pathology of the malabsorption syndrome and the

role of the histopathologist in the diagnosis and management of
this condition
Introduction

Definition
Clinical features
Systemic effects
4. Alimentary Tract 89

General principles
Dysfunctions of
1) Digestion
2) Absorption
3) Transport
4) Combinations of above
5) Unknown

1) Digestive abnormalities
a) pancreatic diseases
i) biopsy (bx)
b) hepatic biliary disease
i) bx of liver and CBD
c) bile salt deconjugation
i) blind loop
ii) diverticula
iii) fistula
iv) gastrectomy
v) ? role of histopathologist
2) Absorption
a) metabolic
i) disaccharidase deficiency
ii) a beta lipoproteinaemia - features
iii) vitamin B12 deficiency - gastric bx
b) small bowel disease
i) coeliac disease - role of biopsy
- diagnostic gluten
- response to gluten-free diet
- response to gluten challenge
ii) Whipple's disease
- features - LM, EM, immunocytochemical
- systemic disease
iii) allergic enteritis
iv) chronic ulcerative jejunoileitis - bx
v) Crohn's disease - bx of small and large bowel
vi) infection
- tropical source
- parasites - strongyloidiasis
- giardiasis
- schistosomiasis
c) bx features
3) Transport
a) lymphatic blockage
i) lymphangiectasis
ii) tuberculosis
iii) lymphoma
b) bx features
90 Advanced Hi stopathology

4) Multiple
a) gastrectomy
b) bowel resection
c) radiation

5) Unexplained
a) hypogammaglobulinaemia - bx
b) carcinoid syndrome
c) diabetes mellitus
d) endocrine dysfunction
(April 1977, Paper 1, Question 3)

Reference

1) Robbins, S.L., Cotran, R.S., Kumar, V. The gastrointestinal tract. In: Pathologic
Basis of Disease, 4th edition. Chapter 18, p875-881. W.B. Saunders,
Philadelphia (1989).

Describe the structural alterations in the gastrointestinal tract in

patients with steatorrhoea
This answer covers much of the ground in the previous plan, but excluding some
of the conditions which do not tend to steatorrhoea per se (e.g. Vitamin B12
deficiency, Crohn's disease, radiation enteritis etc.) which essentially result from
inadequate emulsification of fats. As well as the primary pathology, the secondary
effects of fat malabsorption e.g. lipofuscinosis, vitamin D and K deficiency, etc
should also be considered. (November 1973, Paper 2, Question 4)

Discuss the value of endoscopic biopsies in the investigation of

diseases of the gastrointestinal tract
(April 1980, Paper 1, Question 5)

Discuss the problems of processing and interpreting

gastrointestinal biopsies
An example of a subject which has occurred one year, and then repeated in the
subsequent year with alterations in the wording which significantly change the
direction of the answer. In the 1980 example, all that would be required is an
appraisal of the uses of biopsy from the lower oesophagus to the anus, in both
neoplastic and non-neoplastic disease. There is clearly a large volume of
information to be included, but the phrase 'Discuss the value' indicates emphasis
should be paid to those diseases which are effectively diagnosed or monitored by
this technique. This later question has a quite different emphasis, which is more
4. Alimentary Tract 91

concerned with the practical measures necessary in a laboratory - labelling,

wrapping and orientation, etc.) and the requirements for adequate assessment
(e.g. deeper levels, special stains, etc.). The answer could be enlivened by includ-
ing various illustrative examples. The major difference is that the earlier question
calls for an appraisal of the circumstances where a diagnosis can be made, while
the later one is more concerned with the situations where it might not be.
(October 1981, Paper 2, Question 3)

References

1) Talbot, I.c., Price, A.B.P. Biopsy Pathology of Colorectal Disease. p1-3;

373-382. Chapman and Hall, London (1987).
2) Day, D.W., Husain, O.A.N. Biopsy Pathology of the Oesophagus, Stomach
and Duodenum. p1-10. Chapman and Hall, London (1986).

Give an account of iatrogenic disorders of the alimentary tract

This is a rather nebulous question which requires careful organisation. The best
approach would be to consider each part of the alimentary tract, from the mouth
to the anus, and select the lesions which have a characteristic appearance for the
most detailed description. As in other examples, repetition of the descriptive
changes where there is a common iatrogenic cause (e.g. radiation) should be
avoided, except where there are sufficient differences in the tissue response (e.g.
oesophagus vs. large bowel). We suggest that you consider the following
categories as examples:

Antibiotic therapy (e.g. candidal infection, pseudomembranous colitis), anti-

inflammatory drugs (e.g. gastric ulceration), immunosuppressive agents (e.g.
fungal infection), radiation (e.g. enteritis), surgery (e.g. reflux, oesophagitis,
intestinal obstruction, malabsorption). It would not be very appropriate to include
examples resulting from poor technique, but rather the recognised and largely
unavoidable complications. This should provide sufficient material for a
descriptive essay. (November 1973, Paper 2, Question 4)

Reference
1) Morson, B.c. (ed.) Systemic Pathology. Alimentary Tract. Volume 3. Churchill
Livingstone, Edinburgh (1987).

Discuss the mechanisms underlying coeliac disease and its

complications

The introduction should include a definition of coeliac disease and the criteria
necessary for the diagnosis, including response to gluten withdrawal and
challenge. The microscopic features would need to be described in detail before
considering the pathogenesis. The generally accepted modern theory involves a
hypersensitivity response to alpha gliadin, mainly cell mediated but with a
humoral component in addition. The cellular populations in the mucosa should be
92 Advanced Histopathology

described in detail. Complications of coeliac disease include the malabsorption

syndrome and its numerous possible sequelae. The development of malignant B
cell lymphoma of the gut should also be detailed, and brief mention made of the
increased incidence of adenocarcinoma. (April 1988, Paper 1, Question 3)

References

1) Morson, B.C. (ed.) Systemic Pathology. Alimentary Tract. Volume 3.

p272-274; 284-286. Churchill Livingstone, Edinburgh (1987).
2) Stansfeld, A.G. Lymph Node Biopsy and Interpretation. p372-373. Churchill
Livingstone, Edinburgh (1987).
3) Robbins, S.L., Cotran, R.S., Kumar, V. Pathologic Basis of Disease, 4th edition.
p876-878. W.B. Saunders, Philadelphia (1989).

Under what circumstances would you make a diagnosis of

dysplasia in endoscopic gastrointestinal biopsiesl Discuss the
clinicopathological significance of such a diagnosis
Endoscopic biopsies include lower oesophagus, stomach, duodenum and
periampullary region and colon as the main areas to be discussed. Each area has
particular requirements for the diagnosis of dysplasia, the broad definition of
which should be included in an introductory paragraph. Many of the points
should be covered by the essays (April 1987, Paper 2, Question 4 and November
1972, Paper 1, Question 1). This answer clearly calls for an assessment of the
problems of interpreting such biopsies, and this aspect is the major part of October
1981, Paper 2, Question 3, it requires a practical rather than theoretical approach.
The clinicopathological significance relates to the role of histopathological
assessment in the decision as to what stage surgical intervention will be required.
(April 1986, Paper 2, Question 4)

Discuss the concept of pre-cancerous conditions, with particular

reference to the alimentary tract
Introduction

Definition of pre-cancer, relationship to dysplasia

Clinical significance - assessment of dysplasia and reliability
Major sites
a) oral cavity
b) oesophagus
c) stomach
d) large intestine
4. Alimentary Tract 93

Oral cavity
1) Epithelial dysplasias
a) associations
b) diagnosis
i) cytology and biopsy (bx)
c) management
d) progression and diagnosis

Oesophagus
1) Squamous dysplasia
a) aetiology and geographic factors e.g. China
b) diagnosis
i) cytology /bx
c) management

2) Glandular dysplasia
a) associations e.g. reflux
b) diagnosis
i) cytology /bx
c) management
i) risk of progression
d) treatment

Stomach
1) Glandular dysplasia
a) aetiology and geographic factors
b) diagnosis
i) cytology /bx
c) definition and grading (mild and mod/severe)
d) significance
i) relationship to development of carcinoma vs. occult neoplasia
e) management

Large intestine
1) Precancerous lesions

'Adenoma-carcinoma' sequence
a) evidence
i) polyposis syndromes
ii) site of lesions
iii) epidemiology
iv) early cancers
v) rarity of de novo carcinoma
94 Advanced Histopathology

b) inflammatory bowel disease

i) evidence of association
ii) diagnostic problems
iii) management
(November 1972, Paper 1, Question 3)

Reference
1) Morson, a.c. (ed.) Systemic Pathology. Alimentary Tract. Volume 3. Churchill
Livingstone, Edinburgh (1987).

Discuss pre-cancerous lesions of the gastrointestinal tract

(April 1987, Paper 2, Question 4)

Describe the morphology and behaviour of intestinal polyps

This would be a difficult question to answer in the time available unless brief and
succinct reviews were given. In the light of recent advances in knowledge, it
would probably not be as wide ranging. (If set today, in questions such as this, it
is easy to overlook the two aspects of the question, morphology and behaviour.
Equal weighting should be given to each.) (April 1970, Paper 2, Question 1)

Give an account of the pathology of colorectal polyposis

syndromes. How do the pathological findings influence the
clinical managemenH
(April 1985, Paper 2, Question 5)

Discuss the histological classification of polypoid lesions of the

colonic mucosa

Introduction

Inherited syndromes/acquired disease

Types of lesion present
Systemic/localised distribution - colonic involvement
Clinical implications - risk of malignancy in generalised polyposis
4. Alimentary Tract 95

Types of colonic polyposis

Inherited
1) Familial adenoma to us polxposis
a) macroscopic features
i) number of polyps (> 100)
ii) size and distribution incl. extracolonic lesion
iii) tubular adenomas - morphology
b) microscopic
i) adenomatous polyps
ii) cryptal changes
iii) dysplasia
c) clinical management
i) risk of malignancy
ii) monitoring of disease
iii) genetic counselling
d) Gardner syndrome
i) polyposis with additional features (e.g. desmoid tumours, jaw cysts,
osteomas, etc.)
e) Turcot syndrome
i) polyposis with CNS changes

2) Luvenile polyposis
a) macroscopic features
i) number of polyps
ii) size and distribution
iii) appearances
iv) extracolonic lesions
b) microscopic
i) hamartomatous
ii) descriptive detail
c) clinical management
i) ?risk of malignancy
ii) counselling

3) Peutz-Ieghers' syndrome
a) macroscopic features
i) predominantly small intestinal
ii) colonic and rectal polyposis occurs
b) microscopic features
i) hamartomatous (c/w juvenile polyps)
c) clinical management
i) risk of malignancy

4) Others
Colonic involvement in systemic disease, e.g. ,neurofibromatosis or blue
rubber bleb naevus syndrome '
96 Advanced Histopathology

5) Multiple colonic adenomatosis

a) macroscopic features
i) fewer than FAP «50)
b) clinical management
i) risk of malignancy
ii) possible genetic inheritance

Acguired
1) Inflammatory polyposis - inflammatory bowel disease
a) macroscopic features
b) microscopic features
c) clinical management
i) as for U.C. or Crohn's disease
ii) differential diagnostic problem

2) Metaplastic pol't{JOsis

3) BeniBn lymphoid polyposis

a) differential diagnosis problem

4) MaliBnant lymphomatous pol't{JOsis

5) Lipomatous polxeosis

6) Pneumatosis coli

References
1) Bussey, H.J.R. Gastrointestinal polyposis syndromes. In: Recent Advances in
Histopathology 12. P.P. Anthony, R.N.M. MacSween (eds.) p169-177.
Churchill Livingstone, Edinburgh (1984).
2) Morson, B.C., Dawson, I.M.P. Adenomatosis and the adenoma-carcinoma
sequence. In: Gastrointestinal Pathology. Chapter 38. Blackwell Scientific
Publications, Oxford (1979) (April 1978, Paper 1, Question 1)

Give a brief account of how you would investigate a colectomy

specimen removed for malignant disease. Discuss the various
staging and grading systems used in this disease mentioning their
prognostic significance
A question designed to assess the ability to describe the practical approach to
dissection of a common surgical specimen. It would be desirable to indicate the
common types of partial and total colectomy, and briefly justify the location and
number of blocks to be taken in the ideal situation. Other techniques such as
macroscopic photography, localisation of lymph nodes or vascular injection might
also be included.
4. Alimentary Tract 97

Dukes' classification should be discussed in detail, together with the clinical

correlation. The American and TNM classifications should be compared, and the
recent criteria proposed by Jass et al., (1987) which have emerged since this
question was set should be discussed and evaluated.
(October 1983, Paper 1, Question 5)

References

1) Jass, J.R. The large intestine. In: Systemic Pathology. Alimentary Tract. B.C.
Morson (ed.) Volume 3. 3rd edition, p365-377. Churchill Livingstone,
Edinburgh (1987).
2) Rosai, J. Appendix-guidelines for handling of most common and important
surgical specimens. In: Ackerman's Surgical Pathology. Volume 2. 7th edition,
appendix A; p1902-1905. C.V. Mosby Co, St Louis (1989).

Give an account of the pathology of ulcerative colitis and discuss

its aetiology

A straightforward description of this disease should include macroscopic

appearances, microscopic patterns on resection and biopsy specimens, and
complications of the disease such as toxic dilatation, dysplasia and malignancy.
The aetiology is more difficult, but several theories have been advanced and
should be critically evaluated. It is important not to stray into a discussion of the
differentiation of ulcerative colitis from Crohn's disease.
(April 1981, Paper 1, Question 1)

Discuss the principal microscopic and macroscopic features that

may help you to differentiate between ulcerative colitis and
Crohn's disease of the colon
(November 1975, Paper 1, Question 1)

Discuss the problems of differentiating between the lesions of

Crohn's disease and ulcerative colitis

These questions should be answered easily by a candidate for the final

examination, without the necessity for revision. It may account for the reason why
this comparison has not been set since 1975, since it will be a poor discriminator.
(April 1969, Paper 2, Question 4)

Reference

1) Jass, J.R. The large intestine. In: Systemic Pathology. Alimentary Tract. B.c.
Morson (ed.) Volume 3. 3rd edition, p334-346. Churchill Livingstone,
Edinburgh (1987).
98 Advanced Histopathology

How would you attempt to establish a diagnosis of

pseudomembranous colitis? Discuss its pathogenesis

I ntroducti on

Causation - associations with antibiotic therapy and C. difficile

Distinction between PMC, antibiotic-associated diarrhoea, antibiotic-associated
colitis

Clinical features

Pathological features

1) Gross
a) mucosal plaques
b) distribution
c) morphology

2) Microscopic
a) 'summit' lesion
b) plaques
c) mucosal ulceration and submucosal oedema

Diagnosis
1) Clinical history

2) Toxin estimation
a) reliability

3) Sigmoidoscopy
a) gross features
b) rectal biopsy
i) techniques and limitations
c) differential diagnostic problems (e.g. lBO, infective colitis)

Pathogenesis
1) Early theories
a) ischaemia
b) C. difficile
i) pathogen or commensal?
c) toxin
i) cytopathic properties
d) animal studies
4. Alimentary Tract 99

2) Epidemi%fl,Y
a) susceptibility to C. difficile colonisation
b) ? changes in gut flora, growth factors, mucosal adhesiveness of organism
c) ? role of host factors
(Odober 1980, Paper 2, Question 2)

Reference
1) Price, A.B., Day, D.W. Pseudomembranous and infective colitis. In: Recent
Advances in Histopathology 11. Anthony, P.P., MacSween, R.N.M. (eds.)
p99-117. Churchill Livingstone, Edinburgh (1981).

Discuss the role of histopathology in the diagnosis and

management of infective disorders of the small and large intestine

This question has a fairly broad scope, although the use of histopathology in
diagnosis and management means that relevant weight must be given to these
specific aspects; hence a detailed description of typhoid would not be appropriate
(although some mention of the changes could be made). The role of endoscopic
biopsy should be emphasised, both in the small intestine in conditions such as
giardiasis, cryptosporidiosis or even putative infections such as tropical sprue,
and in the large bowel in pseudomembranous and infective colitis. It may also be
useful to subdivide infection into parasitic (e.g. amoebiasis, strongyloides),
bacterial (e.g. Whipple's disease, actinomycosis, tuberculosis), fungal (e.g.
candida) or viral (e.g. CMV).
(Odober 1988, Paper 2, Question 4)

References
1) Dawson, I.M.P. The small intestine. In: Systemic Pathology. Alimentary Tract.
3rd edition, Chapter 6. B.C. Morson (ed.) p229-291. Churchill Livingstone,
Edinburgh (1987).
2) Jass, J.R. ibid. Chapter 8, p313-395.

Discuss primary lymphoid tumours of the gastrointestinal tract

This subject has been intensively studied in the intervening years since this
question was set, and many new entities have emerged with the use of
immunohistochemistry and molecular biology (and have sometimes been
reclassified more than once). Excellent reviews are available in the given
references, and the advantage of the questions beginning 'Discuss .......' is that
one's own views, or those of others, can be given and contrasted if required. The
question as worded may be very difficult to answer in the set time nowadays, and
to be comprehensive should encompass the stomach to the anal region.
(April 1978, Paper 2, Question 5)
100 Advanced Histopathology

References
1) Isaacson, P.G., Wright, D.H. Extranodallymphoma. In: Recent Advances in
Histopathology 13. P.P. Anthony, R.N.M. MacSween (eds.) p159-184.
Churchill Livingstone, Edinburgh (1987).
2) Morson, B.c. The stomach, the small intestine, the large intestine. In: Systemic
Pathology. Alimentary Tract. Volume 3. 3rd edition, p216-217; 284-286;
382-384. Churchill Livingstone, Edinburgh (1987).

Discuss the differential diagnosis of ulceration of the large

intestine
A question which includes a consideration of neoplasia, inflammatory bowel
disease, infections and pseudomembranous colitis, ischaemia and less common
causes of ulceration such as mucosal prolapse syndrome. The best approach
would be a brief description of the clinical, macroscopic and microscopic features
of each category, laying emphasis on the distinguishing characteristics of each
condition to avoid tedious repetition. (April 1976, Paper 2, Question 2)

Reference
1) lass,l.R. The large intestine. In: Systemic Pathology. Alimentary Tract. B.c.
Morson (ed.) Volume 3. 3rd edition, p325-354. Churchill Livingstone,
Edinburgh (1987).

Discuss the value and limitations of hepatic biopsy as a

diagnostic tool
Since the time that this question was set, liver biopsy has been an increasingly
used technique and the associated descriptions of disease states have become
correspondingly more sophisticated. Thus the value has increased greatly and a
large number of conditions can be diagnosed on biopsy. It might be an idea to
concentrate on those conditions which have pathognomonic features on liver
biopsy (e.g. Wilson's disease, storage diseases, etc.) and those where liver biopsy
may resolve a clinically based differential diagnosis (e.g. alcoholic liver disease
versus chronic hepatitis), contrasted with situations where liver biopsy often fails
to provide a diagnosis, either through the nature of the disease or due to technical
factors. (November 1975, Paper 1, Question 3)

Discuss the value of liver biopsy in the diagnosis and

understanding of hepatic disease
Another question where the accumulated knowledge in the last 20 years means
that it would be difficult to compress into an essay format, but again construction
of a lengthy notation form overview of the advantages and limitations of liver
biopsy can only be of value in revision. (April 1969, Paper 1, Question 2)
4. Alimentary Tract 101

Discuss the factors concerned in the accumulation of abnormal

amounts of triglyceride in the liver

Introduction

Types of lipid
Morphological changes - steatosis
Accumulations due to imbalance in production, utilisation or mobilisation
Significance of fatty change

Normal lipid metabolism

1) Lipid derived from
a) diet - FFA + chylomicrons
b) adipose tissue - FFA

2) FFA in liver cell-esterified

a) triglyceride
b) cholesterol (minor)
c) phospholipid (minor)
Acetate in liver forms FFA

3) Secretion by apoprotein comp/exine - 'lipoproteins'

Causes of triglyceride accumulation

1) Excess FFA
a) dietary
b) starvation
c) corticosteroids

2) ! FA synthesis from acetate

3) ! esterification of FA
a) alcohol

4) ~ lieQprotein synthesis
a) malnutrition
b) ? fatty liver of pregnancy
c) ? tetracycline
d) ? Reyes' syndrome
e) Na valproate

5) Impaired lipoprotein secretion

a) orotic acid
102 Advanced Histopathology

Complex factors

1) Alcohol
Effects
a) Extrahepatic FFA mobilisation
b) decreased FA oxidation
c) block in lipoprotein secretion
d) direct damage to endoplasmic reticulum
e) decreased protein synthesis
Result
a) steatosis
(November 1971, Paper 1, Question 4)

Reference

1) Hall, P. de la M. Alcoholic liver disease. In: Pathology of the Liver. R.N.M.

MacSween, P.P. Anthony, P.I. Scheuer (eds.) 2nd edition, p281-285. Churchill
Livingstone, Edinburgh (1987).

Discuss the relationship of the hepatitis-associated (Australia)

antigen to human liver disease
A great deal of information now exists that was not available at the time this
question was set, but it essentially covers much the same ground as the
following answers (April 1983, Paper 1, Question 1 and November 1977, Paper 1,
Question 4).
(April 1971, Paper 2, Question 3)

References

1) Bassendine, M.F. Aspects of Liver Disease. Hepatitis B virus and liver cell
carcinoma. In: Recent Advances in Histopathology 12. P.P. Anthony, R.N.M.
MacSween (eds.) Churchill Livingstone, Edinburgh (1984).
2) Gerberg, M.A., Thung, S.N. The diagnostic value of immunohistochemical
demonstration of hepatitis viral antigens in the liver. Human Pathol. (1987)
18(8): 771-774.

Discuss the pathogenesis of hepatitis

This would today be a very difficult question to answer within the available time.
However, it would be a useful revision exercise to extract all the pathogenetic
mechanisms (known and hypothetical) for each type of hepatitis, both acute and
chronic. By the end of this, you would not only have resulted in an active review
of many important diseases, but should certainly ensure familiarity with the
distinction between aetiology and pathogenesis!
(April 1970, Paper 1, Question 1)
4. Alimentary Tract 103

Give an account of the possible effects on the liver of infection

with hepatitis B virus

This essay involves expanding the aspects answered partly in the previous
question with additional consideration of acute liver disease, histological features
of chronic HBV infection, and more detailed accounts of the association with
neoplasia. It would be pertinent to consider the additional consequences of delta
agent infection. (April 1983, Paper 1, Question 1)

Describe the pathology and aetiology of chronic active hepatitis.

What laboratory tests are useful in the differential diagnosis of
this condition~

The best approach would be to describe the major diagnostic features in chronic
active hepatitis, the periportal inflammation with piecemeal necrosis, and the
progression of the disease, describing the microscopic features in detail. Consider
each of the accepted aetiologies of chronic active hepatitis; viral induced, auto-
immune, drug induced and cryptogenic, and indicate the additional diagnostiC
features which may be of use. The laboratory tests include viral antibody studies,
autoantibodies, and hypergammaglobulinaemia in true CAH, versus the findings
in primary biliary cirrhosis, Wilson's disease, alpha-I-antitrypsin deficiency,
sclerosing cholangitis and alcoholism. (April 1977, Paper 1, Question 1)

Reference
1) Bianchi, L., Spichtin, H.P., Gudat, F. Chronic hepatitis. In: Pathology of the
Liver. R.N.M. MacSween, P.P. Anthony, P.]. Scheuer (eds.). Chapter 10,
p31O-341. Churchill Livingstone, Edinburgh (1987).

Discuss the early diagnosis of primary biliary cirrhosis. Give an

account of the natural history of the disease

Introduction
7) Primary vs. secondary disease

2) Clinical features
a) early and late
b) associated features
c) biochemical tests
d) autoantibody production

3) Aetiology
a) ? AI disease
b) MHC expression and 'self antigens'
104 Advanced Histopathology

4) PatholoBY
a) early lesions
i) bile ducts 45 to 75 mm
ii) segmental distribution
iii) epithelial changes
iv) inflammatory infiltrate
v) granulomas
vi) small ductal changes (focal cell loss)
vii) absence of bile ducts
viii) parenchymal changes

Natural history

1) Clinical proBression
a) asymptomatic
b) jaundice
c) portal hypertension
d) cirrhosis and liver failure

2) PatholoBical evolution
a) inflammatory extension
i) limiting plate
ii) parenchymal extension
iii) cholangiocytic metaplasia
iv) ductular proliferation
v) portal-portal linkage
b) cholestasis
i) periportal/paraseptal
ii) hepatocyte changes 'cholate stasis'
iii) Mallory bodies and copper
iv) associated protein
c) fibrosis
i) following inflammatory patterns - 'monolobular'
d) regeneration and cirrhosis
i) irregular
ii) micronodular
e) portal hypertension
i) effects
f) ?? malignant transformation
(October 1982, Paper 2, Question 2)

Reference

1) Portmann, B.C., MacSween, R.N.M. Diseases of the intrahepatic bile ducts. In:
Pathology of the Liver. R.N.M. MacSween, P.P. Anthony, P.]. Scheuer (eds.)
p424-436. Churchill Livingstone, Edinburgh (1987).
4. Alimentary Tract 105

Discuss the mechanisms by which alcohol may produce damage

to the liver

This sort of question is often a problem for histopathologists in examinations. The

subject is quite complex (as is usual when the exact mechanism is not entirely
clear) and requires a logical approach and good memory. The danger is the natural
tendency to drift away from the mechanism (e.g. metabolic disturbance, cyto-
skeletal derangement, immunological injury, etc.) for each category of histological
injury and start to describe the perhaps more familiar territory of histological
features instead, when only brief categorisation of the alcoholic-induced injury is
required. (April 1985, Paper 1, Question 5)

Describe the histological features found in the liver in alcohol-

induced disease

Introduction

Prevalence
Clinical features
Definition of alcoholism

1) Fatty change
a) macrovesicular steatosis
b) lipogranulomas
c) cholestasis

2) Alcoholic hepatitis
a) liver cell damage
i) ballooning degeneration
ii) liver cell necrosis
iii) Mallory body formation
b) neutrophil infiltrate
c) pericellular fibrosis (perivenular) - sclerosing hyaline necrosis
d) fatty change
e) megamitochondria
o cholestasis
g) bridging hepatic necrosis
Variable picture from minimal to fully developed disease

3) Alcoholic cirrhosis
a) early micronodular
b) late macronodular
c) fibrosis and inflammation in septa
d) features of alcoholic hepatitis
106 Advanced Hi stopathology

4) Hepatocellular carcinoma
a) frequency
b) sex incidence (M>F)

5) Siderosis
a) ? heterozygotes with haemochromatosis
b) dietary
c) haemolysis
(October 1981, Paper 1, Question 3)

References

1) Review by an International Group. Alcoholic liver disease: morphological

manifestations. Lancet (1981) i: 706-711.
2) Hall, P. de la M. Alcoholic liver disease. In: Pathology of the Liver. R.N.M.
MacSween, P.P. Anthony, P.]. Scheuer (eds.) 2nd edition, p281-309. Churchill
Livingstone, Edinburgh (1987).

How is cirrhosis of the liver classified~ Discuss the aetiology of

the various types included in your classification
Some things do not change, this question being equally pertinent today, and lends
itself well to a plan-style outline. There is a large amount of information to be
included, and the comparison of the aetiological classification versus the
morphological one may be awkward to combine, since more than one morphology
is produced by the same aetiological agent, so it is better nowadays to base the
classification on the aetiology, as provided in the reference.
(November 1969, Paper 2, Question 3)

Reference

1) Millward-Sadler, G.H. Cirrhosis. In: Pathology of the Liver. R.N.M.

MacSween, P.P. Anthony, P.]. Scheuer (eds.) 2nd edition, p342-363. Churchill
Livingstone, Edinburgh (1987).

How would you try to discover the underlying cause of a

granuloma found in a liver biopsy of an adult patienH
Introduction

Definition
Epithelioid vs. lipo-granuloma
Frequency
General appearances
4. Alimentary Tract 107

Causes

Infection
1) Bacterial
a) identification
i) Gram (Actinomyces), Levaditi (typhoid, syphilis),
ii) serology (Brucella)

2) Mycobacterial
a) identification
i) stains: Ziehl-Neelsen, Wade-Fite

3) Fungal
a) identification
i) stains: PAS, Grocott

4) Viral
a) identification
b) morphological pattern, nuclear features (CMV)

5) Parasites
a) identification
b) eosinophils, parasite (Toxoplasma, Leishmania & others), ova
(Schistosoma, Fasciola & others)

6) Rickettsia
a) identification
i) (Q fever), granuloma morphology

7) Identification
a) eosinophils, history/follow up

Vasculitis
7) Identification
a) clinical features

Neoplasia
7) Identifica tion
a) morphology (Hodgkin's disease), history
108 Advanced Histopathology

Forei~n body
1) Identification
a) stains - Sudan black (oil), (PVP), - Congo red
b) birefringence - silica, starch, suture, barium
c) minerals - EDAX

Miscellaneous
1) Sarcoidosis
a) Kveim test
i) identification
ii) morphology
b) PBC
i) identification
ii) morphology
iii) serology
c) biliary obstruction
i) identification - bile pigment
d) Whipple's disease
i) portal changes
ii) identification - stain - PAS

Idiopathic
1) Frequency

2) Diagnosis of exclusion
(November 1976, Paper 2, Question 3)

Reference

1) MacSween, R.N.M. Liver pathology associated with diseases of other organs.

In: Pathology of the Liver. R.N.M. MacSween, P.P. Anthony, P.]. Scheuer
(eds.) 2nd edition, p64~88. Churchill Livingstone, Edinburgh (1987).

Give an account of the pathology of: a) veno-occlusive disease of

the liver b) pulmonary veno-occlusive disease

These should be straightforward accounts of two rare conditions, which have

relatively different appearances despite the similarity of the names. It would be in
order to describe the aetiological factors, clinical setting and complications, which
would justifiably be included in the 'pathology'. The macroscopic and microscopic
features are relatively limited in any case, and would probably not be sufficient to
provide a full answer for the majority of candidates.
(Odober 1984, Paper 2, Question 5)
4. Alimentary Tract 109

References
1) Bras, G., Brandt, K.H. Vascular disorders. In: Pathology of the Liver. R.N.M.
MacSween, P.P. Anthony, P.]. Scheuer (eds.) 2nd edition, p485-488. Churchill
Livingstone, Edinburgh (1987).
2) Dunnill, M.S. Pulmonary vascular disease. In: Pulmonary Pathology.
p281-284. Churchill Livingstone, Edinburgh (1982).

Write a brief essay on the pathogenesis of primary tumours and

tumour-like lesions of the liver, briefly describing the histological
appearances of the conditions you mention
This is a difficult question to answer unless great care is taken to organise the
essay into a review of the various hypotheses for some of the entities. In many
cases, especially benign lesions, the pathogenesis is unknown, and these should
be listed early on in an introductory paragraph, and then lesions which have some
proposed pathogenesis concentrated on e.g. liver cell adenoma and pre-neoplastic
changes, hepatocellular carcinoma and its relationship to cirrhosis, hepatitis B
infection and other factors which may be related to the pathogenesis, bile duct
carcinoma and liver parasitic infestation and haemangiosarcoma and vinyl
chloride or arsenic. It should be noted that the question refers to pathogenesis, the
mechanisms and changes which may lead to a particular disease state. It would be
all too easy to start listing the epidemiological and aetiological factors in this
question, without considering the way in which these agents may act. Brief
descriptions of the conditions mean that no more than one or two paragraphs
should be devoted to each pathology, emphasising the changes during patho-
genesis rather than long descriptions of the resulting tumour.
(April 1982, Paper 2, Question 5)

Discuss the relation between hepatitis, cirrhosis and tumours of

the liver
This question mainly relates to the well defined linkage and progression of some
forms of hepatitis to cirrhosis and the complicating development of hepatocellular
carcinoma. Other liver tumours are not clearly related to this sequence, and this
should be mentioned in the opening paragraph. Consideration should be given to
those forms of hepatitis which are often associated with cirrhosis (e.g. Hepatitis B
infection, alcoholism, etc.) and those which do not (Hepatitis A, etc.) and how the
pathology of these diseases differs. Following on from this, the relationship
between Hepatitis B infection and cirrhosis requires illumination (including
epidemiological studies). Some speculation on the incidence of malignant change
in other forms of cirrhosis, such as alpha-I-antitrypsin deficiency, primary biliary
cirrhosis, Wilson's disease, etc. would be of value.
(October 1979, Paper 1, Question 1)
110 Advanced Histopathology

Evaluate critically the factors which may be of importance in the

aetiology of primary malignant tumours of the liver

This question has a somewhat broader scope than the preceding one, and in which
the major emphasis should be on hepatocellular carcinoma, along with bile duct
carcinoma and its association with liver flukes, inflammatory bowel disease and
congenital abnormalities, haemangiosarcoma with vinyl chloride monomers,
thorotrast and arsenic. Consideration of rarer entities with less well known factors
(e.g. bile duct cystadenocarcinoma developing in a cystadenoma) should only be
attempted if there is sufficient time, in a fully developed answer the first three
groups should provide more than enough material, remembering that factors
such as age, sex, genetic diseases, alcohol, carcinogens, hepatitis B virus and
cirrhosis should all be included for liver cell carcinoma alone. The word critically
means a weighting should be applied to the degree of importance of each
aetiological factor. (October 1978, Paper 2, Question 1)

Reference
1) Anthony, P.P. Tumours and tumour-like lesions of the liver and biliary tract.
In: Pathology of the Liver. R.N.M. MacSween, P.P. Anthony, P.}. Scheuer
(eds.). 2nd edition, p574-645. Churchill Livingstone, Edinburgh (1987).

Describe the pathology of liver tumours. What is know of their

aetiology and pathogenesisl
The use of the term 'tumour' is unqualified in this question, and thus there is
scope for describing benign and malignant neoplasms along with 'tumour-like
lesions', the groundwork for which can be laid in a sensibly outlined introduction.
(October 1988, Paper 2, Question 3)

Discuss the pathology of the intra-hepatic bile ducts

This covers a large spectrum of disease, both congenital and acquired. In order to
cover the subject and avoid repetitious detail, choose the major commoner lesions
in each group, and then outline the major differential diagnostic features in other
conditions. Make sure the emphasis is balanced, avoiding undue emphasis in rare
conditions or secondary involvement of bile ducts in hepatic disease. There is
clearly no time to go into the fine detail of each disease mentioned so you would
have to estimate the balance of the essay fairly closely when compiling the initial
plan. (October 1985, Paper 2, Question 3)

References
1) Desmet, V.}. Cholestasis. In: Recent Advances in Histopathology 12. P.P.
Anthony, R.N.M. MacSween (eds.) Churchill Livingstone, Edinburgh (1984).
2) Portman, B.C., MacSween, R.N.M. Diseases of the intrahepatic bile ducts. In:
Pathology of the Liver. R.N.M. MacSween, P.P. Anthony, P.}. Scheuer (eds.)
2nd edition. Churchill Livingstone, Edinburgh (1987).
4. Alimentary Tract 111

Acute pancreatitis: enumerate the causes, describe the

pathological features and discuss the pathogenetic mechanisms

Causes

1) Gallstones
2) Alcohol abuse
3) Hypothermia
4) Viral infection
5) Diabetes mellitus
6) Hyperparathyroidism
7) Trauma (surgery)
8) Shock
9) Gastrectomy

Pathological features

1) Macroscopic
2) Microscopic
a) periductal
b) perilobular
c) pan lobular

Pathogenetic mechanisms

Periductal necrosis
7) Gallstones
a) common channel theory
b) duodenal biliary reflex

Pathogenesis - conversion of primary bile acids to 2° bile acids - role of

infection and trypsin

2) Alcohol
a) ductal inflammation
Pathogenesis - via stone formation

Panlobular necrosis
1) Hypotensive episodes
a) shock
b) hypothermia
c) surgery
112 Advanced Histopathology

Perilobular necrosis
1) Extension of necrosis by vascular compromise

2) Combined aetiologies
3) Unknown aetiolol:)!
a) diabetes mellitus
b) hyperparathyroidism
c) alcohol
(April 1983, Paper 3, Question 5)

Reference

1) Foulis, A.K. Gastrointestinal pathology. Acute pancreatitis. In: Recent

Advances in Histopathology 12. P.P. Anthony, R.N.M. MacSween (eds.)
pl88-196. Churchill livingstone, Edinburgh (1984).
5. Cardiovascular and Respiratory Systems
114 Advanced Histopathology

Discuss the contribution of bronchial biopsy and cytology in

investigation of diseases of the lungs and bronchi
The most important contribution bronchial cytology and biopsy make is in
diagnosis of malignant epithelial tumours. Useful cytological specimens include
sputum, bronchial aspiration and washing, bronchial brushing and in certain
cases trans-thoracic fine needle aspiration of bronchial and parenchymal lesions.
The use of these techniques in detection of neoplastic lesions should be discussed
with comments made about advantages and disadvantages of each. Biopsy
specimens are especially useful in accurately diagnosing and typing bronchial
tumours, again there are some limitations which should be discussed.

Other uses of cytological preparations include diagnosis of infectious disease

particularly viral, parasitic and fungal, but the limitations should be highlighted.
The assessment of allergic reactions in the respiratory tree can also be made
cytologically. An assessment of pneumoconiosis processes may be possible by
identifying the dust particles in sputum or localised collection specimens.

Biopsy uses other than malignant disease include benign neoplastic lesions and
inflammatory lesions including those of an infectious nature. Transbronchial
biopsies are useful to assess interstitial lung disease.
(April 1979, Paper 2, Question 4)

References

1) Churg, A. Lung biopsy handling and diagnostic limitations. In: Pathology of

the Lung. W.M. Thurlock (ed.) p67-78. Thieme Medical Publications, London
(1988).
2) Farrell, L., Saccommona, G. Diagnostic cytology techniques including fine
needle aspiration: practical consideration. In: Pathology of the Lung. W.M.
Thurlock (ed.) p105-146, Thieme Medical Publications, London (1988).

What are the mechanisms that normally present pulmonary

infectionl Discuss the pathogenesis of bacterial viral and fungal
pneumonia in relationship to these mechanisms
Defence mechanisms

Inhaled pathogens and particulate matter

Proximal
7) Mechanical
a) nasal passages
b) mucociliary clearance proximal airways
5. Cardiovascular and Respiratory Systems 115

2) Immunological mucosal defence

a) humoral (lgA, IgE)
b) cellular reactions
i) early - polymorphs, phagocytes
ii) later - cell-mediated immunity

1) Macrophage clearance

2) Mucosal and interstitial immunological defence mechanisms

Pathogenesis of pneumonia

Bacterial
1) Interference with normal clearing mechanisms
a) cough reflex
i) coma
ii) anaesthesia
iii) drugs
iv) chest pain
v) neuromuscular disorders
b) injury to mucociliary apparatus
i) tobacco smoke
ii) viral diseases
iii) inhalation of hot or corrosive gases
iv) immobile cilia syndrome
c) bactericidal or phagocytic action of alveolar macrophages
i) alcohol
ii) tobacco smoke
iii) anoxia
iv) oxygen toxicity
d) pulmonary congestion and oedema - especially important in
bronchopneumonia

2) Decreased systemic immunity

a) chronic diseases
b) immunological deficiencies
i) congenital
ii) acquired
c) immunosuppressive therapy
d) leucopenia - usually virulent organisms

Viral and fun~al

Decreased immunological defence, which favours these opportunistic organisms

116 Advanced Histopathology

1) Immunocompromisation
a) congenital
b) acquired
i) iatrogenic (immunosuppressive therapy)
ii) AIDS
iii) associated with chronic disease states and disseminated malignancy
(April 1969, Paper 1, Question 3)

Reference
1) Dunnill, M.S. Pulmonary defence mechanisms. In: Pulmonary Pathology.
pl-16. Churchill Livingstone, Edinburgh (1982).

Describe the various sorts of cells lining the pulmonary alveoli.

How may they be altered in diseasel

This question is restricted to alveolar lining cells, the type I and type II
pneumocytes, the morphological, immunohistochemical and ultrastructural
features of which should be described. (Neuroendocrine cells are not considered
to form part of the alveolar lining.) It is generally considered that type II
pneumocytes give rise to type I cells, acting as a stem cell compartment. As the
type I pneumocytes are so vulnerable to injury their loss is a feature of any cause
of diffuse alveolar damage (shock lung). Thus, type II hyperplasia is a non-specific
reparative response to injury to type I cells. The features of diffuse alveolar
damage thus need to be well described in this answer. Type II pneumocyte
hyperplasia is also seen in more chronic disease states, in association with
interstitial damage and disorganisation. Mention should be made of some
examples such as usual interstitial pneumonia, desquamative interstitial
pneumonia, alveolar proteinosis and extrinsic allergic alveolitis for instance, but it
is important not to digress into descriptions of the bronchiolar and vascular
changes associated with such diseases. The replacement of normal alveolar lining
cells by neoplastic glandular cells in bronchioloalveolar carcinoma at the growing
edge of adenocarcinomas could also be mentioned. This question is relatively
stringent in its requirements and poses considerable difficulties for those who did
not have particularly detailed knowledge about this subject.
(November 1977, Paper 1, Question 1)

Reference
1) Spencer, H.S. The anatomy of the lung, and various headings. In: Pathology of
the Lung, 4th edition. p37-48; 726-730; 536-541; 788-798. Pergamon Press,
Oxford (1985).

List the types of pulmonary emphysema. Discuss their

pathogenesis

The list of the various types should include a brief explanation of the terms used
but no more. This question requires a detailed consideration of the pathogenesis
5. Cardiovascular and Respiratory Systems 117

and it would be important not to digress into morphometry, pathological features,

etc. It is the sort of question where there is not a great deal of factual information
to be extracted for the average candidate to comfortably complete a 45 minute
answer. (April 1975, Paper 1, Question 4)

References
1) Dunnill, M.S. Emphysema. In: Pulmonary Pathology. p81-112. Churchill
Livingstone, Edinburgh (1982).
2) Spencer, H.S. Emphysema. In: Pathology of the Lung, 4th edition. p557-594.
Pergamon Press, Oxford (1985).

How is emphysema classified and what morphometric methods

are available to quantify iH Discuss the aetiology and
pathogenesis

This is a fairly precise question which lends itself well to an essay plan. It should
start with a definition of the term emphysema and classification into the well-
recognised types with a brief explanation relating to the anatomy of the
pulmonary lobule (in which diagrammatic representations may be helpful).
Morphometric analysis is straightforward but the methods of lung preparation
should be described in addition. The aetiology and pathogenesis, including a
consideration of the role of neutrophils and anti-proteases (alpha-I-antitrypsin),
have been covered in other questions. (November 1976, Paper 2, Question 5)

Describe the post-mortem examination of the respiratory tract in

a case of chronic obstructive airways disease. How may the
findings explain the patients' symptoms and signs

Introduction
Definition COAD (NB Bronchiectasis and asthma included in US but not in UK)
Association of chronic bronchitis and emphysema

Emphysema

Definition

1) Macroscopic
a) dissection and fixation of lungs
i) formal saline (under pressure)
ii) formal vapour
b) morphometric analysis
i) Gough-Wentworth slices
ii) subgross techniques
118 Advanced Histopathology

c) features
i) centrilobular
ii) panlobular
iii) periseptal
iv) bullae

2) Microscopic
a) features of emphysema
b) secondary pulmonary hypertension (hypoxic type)
c) morphometric analysis

3) Clinicopathological correlation
a) panlobular
i) '[ink puffer' - normal 02 J, CO2
ii) alveolar surface area
iii) V /P
iv) J, elasticity leads to t expiration phase
b) centrilobular
i) 'blue bloater' - J, 02 t CO2
ii) n alveolar surface area
iii) J, alveolar ventilation
iv) ? role of peribronchial fibrosis
c) mixed

Chronic bronchitis

Clinical definition

1) Macroscopic

2) Microscopic
a) goblet cell hyperplasia
b) bronchial gland hyperplasia
c) inflammatory pattern in bronchi/bronchioles

3) Clinicopathological correlation - features due to

a) Mucous gland hypertrophy
b) Mucus plugs
c) Peribronchial-fibrosis - cough due to
i) mucus over-production
ii) ? mucosal inflammation - inflammatory mediators
(April 1988, Paper 1, Question 4)

Reference

1) Dunnill, M.S. Chronic bronchitis and emphysema. In: Pulmonary Pathology,

p33-49; 81-112. Churchill Livingstone, Edinburgh (1982).
5. Cardiovascular and Respiratory Systems 119

Discuss the pathogenesis and pathology of bronchiectasis

This is an example of a subject which appeared in two consecutive years, where

alterations in the wording completely altered the approach to and content of the
answer. In this case, after the introduction where bronchiectasis should be
defined, the pathogenesis is considered under collapse of the lung parenchyma
and infection. The various aetiological factors which lead to these pathways could
be introduced, including obstructive lesions (bronchial tumours, mucus, foreign
bodies, etc.) congenital diseases which predispose to infection (e.g. Kartagener's
syndrome, immunodeficiency states, cystic fibrosis, etc.), but it is important not to
become obsessed with the aetiological factors at the expense of the common
pathogenetic mechanisms. The pathological features could be discussed under the
classification outlined in the preceding essay plan. It is important not to digress
into description of the association aetiological agents rather than concentrating on
the pathology of bronchiectasis in general. (October 1983, Paper 2, Question 1)

References

1) Dunnill, M.S. Bronchiectasis. In: Pulmonary Pathology. p67-80, Churchill

Livingstone, Edinburgh (1982).
2) Robbins, S.L., Cotran, R.S., Kumar, V. Bronchiectasis. In: Pathologic Basis of
Disease, 4th edition. p777-779. WB Saunders, Philadelphia (1989).

How would you classify the different types of bronchiectasis and

what are the pathological consequences of this condition?

Introduction

Definition
Associations
Clinical features

Classification

Congenital - Williams-Campbell syndrome

Acquired - Whitwell

Pathological features of each group

1) Saccular
a) lower lobes (bR)
b) distal to 3/4 segmental branches
c) macroscopic features

2) Atelectasis
a) R middle commonest
b) all segmental branches
c) usually obstruction (e.g. ca, lymph nodes, etc.)
120 Advanced Histopathology

3) Follicular
a) lymphoid infiltrate and follicles
b) otherwise resembles saccular type

Pathological consequences
1) Infection
a) recurrent bronchopneumonia
b) pulmonary abscess/emphysema
c) infective endocarditis
d) 'metastatic' abscess

2) PulmonaC¥. fibrosis
3) Mucosal ulceration
a) squamous metaplasia
b) haemorrhage

4) PulmonaO! hmertension
a) hypoxic
b) obstructive (fibrotic)

5) H~rtrol2hic osteoarthrol2ath~

6) Amyloidosis
a) reactive systemic
(April 1984, Paper 2, Question 1)

Reference

1) Dunnill, M.S. Bronchiectasis. In: Pulmonary Pathology. p67-80. Churchill

Livingstone, Edinburgh (1982).

What are the causes of pulmonary hypertensionl Describe the

pathological changes which are seen in the lungs

Introduction

Pulmonary circulation
Definition of pulmonary hypertension
Clinical features
5. Cardiovascular and Respiratory Systems 121

Major causes
1) Increased blood flow
a) pre tricuspid shunt
i) ASD
ii) TAPVD
b) post tricuspid shunt
i) VSD (cong)
ii) PDA
iii) Transposition

2) Pulmonary venous congestion

a) severe LVF
b) mitral valve stenosis/regurgitation
c) L atrial myxoma
d) pulmonary venous compression
e) pulmonary veno-occlusive disease

3) Pulmonary arterial obstruction

a) recurrent thromboembolism
b) emboli (e.g. tumour, particulate material in drug abuse, schistosomal ova)
4) Alveolar hwoxia
a) high altitude
b) upper airway obstruction
c) lower airway obstruction (chronic asthma, chronic bronchitis)
d) obesity (Pickwickian syndrome)

5) Destruction of distal capillary bed

a) interstitial lung disease
b) emphysema
6) Idiopathic
a) primary pulmonary HT
7) Miscellaneous
a) hepatic disease/portal HT
b) collagen vascular disease
c) drugs

Pathological changes
1) Macroscopic
a) pulmonary atheroma
b) focal interstitial haemorrhage
c) changes of underlying disease
122 Advanced Histopathology

2) Microscopic
a) Reversible changes
Grade I - hypertrophy muscular pulmonary arteries
- muscularisation of arterioles (<100Ilm vessels)
Grade II - I and internal cellular proliferation in small arteries (smooth
muscle)
Grade III - II and lamellar fibrosis
- obliterative lesions in muscular arteries
b) Irreversible changes
Old grades IV - VI

3) Dilatation lesions
a) associations
i) primary pulmonary HT
ii) congenital heart disease
iii) hepatic cirrhosis
b) pathological features
i) venous-like branches
ii) plexiform lesions
iii) angiomatoid lesions

4) Late sequelae

a) fibrinoid vasculosis/necrosis
b) interstitial haemorrhage/fibrosis
(April 1983, Paper 2, Question 4)

References

1) Dunnill, M.S. Pulmonary pathology. In: Pulmonary Vascular Disease. Chapter

14, p245-292. Churchill Livingstone, Edinburgh (1982).
2) Spencer, H.S. Chronic pulmonary hypertension. In: Pathology of the Lung,
4th edition, p631-704. Pergamon Press, Oxford (1985).

Discuss the causes of pulmonary hypertension, describe the

histopathological features of the lungs in this condition
(April 1977, Paper 1, Question 5)

What pathological changes may be induced in the pulmonary

arterial tree by diseases of the heart and lungs. How may these
changes influence the clinical course of the predisposing disease~

This question requires a description of the pathological changes of pulmonary

hypertension (see April 1983, Paper 2, Question 4). The changes of pulmonary
hypertension induce a compensatory hypertrophy of the right ventricle, which
may result in terminal right sided cardiac failure. In cases where cardiac shunts
5. Cardiovascular and Respiratory Systems 123

have resulted in pulmonary hypertension, the shunt may ultimately reverse with
increased load on both ventricles which speeds the path to failure. Brief comments
may be made about the exact changes induced by the pulmonary hypertension for
the separate aetiological groups. (April 1972, Paper 1, Question 1)

Discuss the aetiology of chronic pulmonary hypertension and

describe the pathological changes that may be found in the lungs

As there are so many causes of pulmonary hypertension, it is doubtful whether

any candidate could attempt to provide a comprehensive list, but all three
questions on this subject allow for some selective expansion of various aspects,
and particular attention might be paid to be differences between the changes
found in chronic hypoxia, in severe pulmonary venous hypertension (e.g. tight
mitral stenosis), and in the rather restricted group of conditions leading to
plexogenic pulmonary arteriopathy, areas which cause particular confusion. Note
also that while the Heath and Edwards Grades 1-3 still reflect increasing severity
of disease, Grades 4 and 5 are not found in all conditions and Grade 6 (necrotising
arteries) indicates severe and/or prolonged disease which is irreversible and so
the changes in these grades are not necessarily sequential.
(April 1976, Paper 2, Question 5)

References
1) Dunnill, M.S. Pulmonary vascular disease. In: Pulmonary Pathology. Chapter
14. Churchill Livingstone, Edinburgh (1982).
2) Spencer, H.S. Chronic pulmonary hypertension. In: Pathology of the Lung.
4th edition. p631-704. Pergamon Press, Oxford (1985).

Describe the histological features and pathogenesis of the

plexiform lesion in the lung. In what conditions does it occurl
What are its prognostic implications when found in a lung biopsy
specimen

This is a much more specific question on pulmonary hypertension, and requires a

detailed consideration of the conditions associated with this lesion, usually post-
tricuspid shunts in congenital heart disease, primary pulmonary hypertension
and pulmonary hypertension associated with cirrhosis. It is useful to describe the
associated changes of pulmonary hypertension (as outlined previously) is that the
pathogenesis of the plexiform lesion, a cellular intimal proliferation, can be
explained. (April 1987, Paper 2, Question 1)

References

1) Spencer, H.S. Chronic pulmonary hypertension. In: Pathology of the Lung.

4th edition. p631-704. Pergamon Press, Oxford (1985).
124 Advanced Histopathology

Discuss the criteria for a pathological diagnosis of cor pulmonale.

Describe the changes in the pulmonary vasculature and how you
would assess their severity at autopsy
The introduction to such an answer requires a definition of the term cor
pulmonale, and its clinical setting. The criteria for the pathological diagnosis
should be outlined, and in particular the practical measures necessary in the
accurate measurement of right ventricular weight. The effects of right ventricular
failure should also be mentioned (e.g. in the liver) The question does not call for a
discussion of the numerous causes of cor pulmonale, but there needs to be some
consideration of the various causes of pulmonary hypertension, both hypoxic and
primary vascular types. The assessment at autopsy includes both macroscopic and
microscopic features. (October 1980, Paper 2, Question 3)

Reference

1) Dunnill, M.S. Pulmonary vascular disease. In: Pulmonary Pathology.

p245-292. Churchill Livingstone, Edinburgh (1982).

Give a concise account of those diseases of lung parenchyma

which are brought about by occupation
The bulk of the answer should be concerned with those diseases caused by dust
inhalation and noxious fumes. The ducts could be divided into the inorganic (e.g.
silicosis (acute and chronic), coal-miner's pneumoconiosis, asbestosis and
berylliosis among others) and organic (extrinsic allergic alveolitis, e.g. farmer's
lung, bagassosis). Noxious fumes include cadmium, bauxite and gases
Development of bronchial carcinoma (e.g. in uranium mining or asbestosis) does
not strictly fall within the bounds of a parenchymal disease, but pulmonary
adenocarcinoma in asbestosis would be a justifiable inclusion. Likewise
mesothelioma is not a parenchymal disease, and only brief mention should be
made. Note that the question indicates that all of the occupation diseases require
consideration, instead of describing one in detail from each group and mentioning
the main differences in the remainder. (October 1979, Paper 1, Question 3)

Reference

1) Spencer, H. The pneumoconioses and other occupational lung diseases. In:

Pathology of the Lung, 4th edition. Chapter 11, p413-450. Pergamon Press,
Oxford (1985).

What is meant by extrinsic allergic alveolitis~ Give an account of

the pathology of this condition

Introduction
EAA (Hypersensitivity pneumonitis)
5. Cardiovascular and Respiratory Systems 125

Provoking antigens a) thermophilic actinomycetes (e.g. farmer's lung)

b) moulds (e.g. suberosis)
c) animal proteins (e.g. bird fancier's lung)

Clinical features

Relapsing acute condition on exposure

Chronic interstitial disease

Pathological features
1) Acute
a) unknown

2) Subacute
a) miliary nodules
i) epithelioid granulomas
ii) bronchiolar damage and obstruction
iii) foamy intra-alveolar macrophages
iv) interstitial inflammatory infiltration
v) crystalline intracellular inclusions

3) Chronic
a) fibrosis and obliterated airspaces
b) 'honeycomb'lung
c) diffuse interstitial fibrosis
d) few subacute changes
e) pulmonary vascular disease

Pathogenesis

1) Antigen in wall of bronchioles

2) IgG in plasma cells

3) C3 in histioc;ytes
a) ? complement activation via alternative pathway unlike type III
hypersensitivity
b) ? type IV reaction - T lymphocytes in alveoli
c) ? granulomatous disease resulting from lymphokine release
(May 1973, Paper 2, Question 5)

References

1) Dunnill, H.S. Extrinsic allergic alveolitis. In: Pulmonary Pathology. pl13-124.

Churchill Livingstone, Edinburgh (1982).
2) Spencer, H.S. The pneumoconioses and other occupational lung diseases. In:
Pathology of the Lung, 4th edition. p497-510. Pergamon Press, Oxford (1985).
126 Advanced Histopathology

Describe the changes found in the lung in fibrosing alveolitis and

extrinsic allergic alveolitis. What mechanisms may be involved in
the causation of these diseasesl
Most of the information is contained within the two preceding essay plans. The
mechanisms involved in both diseases appear to have a very similar
immunological basis, at least in the light of current knowledge, although extrinsic
allergic alveolitis has a more acute course in general than the insidious progress of
fibrosing alveolitis. (April 1975, Page 2, Question 2»

Describe the gross and microscopic features of pulmonary

fibrosing alveolitis and discuss the pathogenic mechanisms
Introduction
Definition of terms
Variants (DIP, VIP, LIP, etc)

Macroscopic features
1) Early
a) parenchymal fibrous thickening
2) Late

a) bilateral shrunken, firm lungs

b) bosselated pleural surface
c) loss of normal pattern with enlarged airspaces bound by fibrous tissue -
'honeycomb' lung

Microscopic features
Patchy process, both inter and intra-lobular

1) Early
a) ? diffuse alveolar damage or interstitial disease

2) Established
a) interstitial fibrosis
b) chronic inflammation
c) smooth muscle hyperplasia
d) metaplastic changes
i) type II pneumocyte hyperplasia
ii) bronchiolar-type columnar
e) hyaline membranes +/- alveolar macrophages
f) pulmonary hypertensive vascular changes
5. Cardiovascular and Respiratory Systems 127

Pathogenesis

1) Aetiology
a) unknown
2) Genetic influences (M>F)

3) Immunological factors
a) increased circulating immune complexes
b) cryoglobulinaemia
c) IgG (granular) in septal wall
d) associations
i) RA
ii) SLE
iii) systemic sclerosis
4) Complexed antigen unknown

5) Broncho-alveolar lavage - increased neutrophil count

6) Possible sequence
a) intrapulmonary accumulation of immune complexes
b) macrophage activation
c) neutrophil chemotaxis
d) protease release
e) death of type I pneumocytes
f) structural damage and regenerative changes
(November 1976, Page 2, Question 4)

References

1) Robbins, S.L., Cotran, R.S., Kumar, V. The respiratory system. In: Pathologic
Basis of Disease, 4th edition. p789-793. W.B. Saunders, Philadelphia (1989).
2) Dunnill, M.S. Pulmonary fibrosis. In: Pulmonary Pathology. p216-244.
Churchill Livingstone, Edinburgh (1982).

Discuss the pathogenic mechanisms involved in diffuse

pulmonary fibrosis
Diffuse pulmonary fibrosis is a non-specific reaction to injury of the lung and is
associated with a wide range of diseases and injurious agents. The pathogenic
mechanisms are poorly understood, however the best method to cover what is
known is to use a classification of interstitial fibrosis and consider the mechanisms
for each. The idiopathic group (usual interstitial pneumonia or fibrosing alveolitis)
has been considered in the answers previously on this subject (see November
1976, Paper 2, Question 4). Those pulmonary interstitial fibroses where aetio-
logical factors are known, and pathogenic mechanisms may be better understood,
128 Advanced Histopathology

include drug reactions (especially chemotherapeutic agents), diffuse pulmonary

infections (viruses, mycoplasma), industrial or environmental. inhalants
(especially asbestos) and the interstitial changes seen in collagen-vascular
diseases. Comments can be made about each of these in tum, using them to
highlight possible pathogenic mechanisms. It is important to only consider states
resulting in diffuse pulmonary fibrosis, and although there is a temptation to
include the pneumoconiosis group, apart from pulmonary asbestosis these
diseases tend to result in parenchymal nodules of varying size, thus the changes
are not diffuse. Extrinsic allergic alveolitis may result in a diffuse interstitial
fibrosis and can be considered in the environmental inhalant group.
(April 1980, Paper 2, Question 3)

Describe the pathological features of adult shock lung syndrome

and discuss their pathogenesis
Introduction
1) Definition
a) non-specific but predictable sequence of events
b) aetiologies

Pathological changes
1) Acute exudative phase (up to 7 days)
Early
a) oedema - interstitial/alveolar
b) alveolar haemorrhage/fibrin deposition
Intermediate
a) 'hyaline' membrane (pneumocyte necrosis/fibrin)
b) interstitial infiltrate - lymphocytes, plasma cells, macrophages
c) capillary/small arterial thrombi
Late
a) type II pneumocyte hyperplasia
b) squamous metaplasia of regenerative bronchiolar epithelium

2) Organisinc phase (7-14 days)

Early
a) loose interstitial fibrosis
b) macrophage digestion of hyaline membrane
c) florid type II pneumocyte hyperplasia
d) focal alveolar fibrosis
s. Cardiovascular and Respiratory Systems 129

Late
a) interstitial expansion by fibrosis
b) distortion of air spaces
c) progression to chronic phase or
d) resolution

Pathogenesis
Toxic injury to pneumocytes and/or capillary endothelium

1) Aeti%Bica/ aBents
a) infection - virus, mycoplasma
b) inhaled gases- oxygen, nitrogen, sulphur dioxide, smoke, or other
noxious fumes
c) drugs - narcotics, paraquat, chemotherapy
d) 'shock' states - septicaemia, injury etc.
e) miscellaneous - radiation, high altitude, uraemia, aspiration pneumonitis

2) Mechanisms
a) superoxide radicals
i) oxygen toxicity
ii) paraquat
b) neutrophil aggregation in capillaries

Postulated sequence:- complement activation (sepsis, bacterial toxin, bypass

surgery, etc.) -+ leucocyte aggregation/activation -+ free radical generation and
enzymes -+ vascular permeability -+ interstitial oedema -+ protease digestion of
interstitium -+ pneumocyte death and fibrin formation.
Also microthrombosis due to kinin activation/prostaglandin release.
(April 1985, Paper 1, Question 2)

References
1) Dunnill, M.S. Pulmonary oedema and shock lung. In: Pulmonary Pathology.
p17-32. Churchill Livingstone, Edinburgh (1982).
2) Robbins, S.L., Cotran, R.S., Kumar, V. The respiratory system. In: Pathologic
Basis of Disease, 4th edition. p760-762. W.B. Saunders, Philadelphia (1989).

Describe the various lesions which may be produced in the lungs

by therapy including drugs, and by other toxic chemical
substances of a non-particulate nature

This question primarily calls for a consideration of diffuse alveolar damage (shock
lung) and the more chronic process of diffuse pulmonary interstitial fibrosis,
despite the initial impression that there might be a wide spectrum of diseases to
consider. Both are associated with drugs, (including chemotherapeutic agents,
130 Advanced Histopathology

antibiotics, penicillamine) medical radiation and gas inhalation (both therapeutic,

e.g. oxygen, or toxic, e.g. sulphur dioxide). The pathological features are described
in the preceding two answers. (November 1973, Paper 1, Question 1)

Describe the possible effects on the lungs of exposure to

asbestos. What are the medicolegal complications?

In the introduction the point should be made that the pleura do not strictly form
part of the lungs, and a decision has to be made about whether to include these
effects in the answer. Most authorities would accept that the pleura would be
considered a part of the lungs, just as the bronchi would be also. The types of
asbestos should be described, and then descriptions made of the various
pathologies, including pulmonary fibrosis, and bronchial carcinoma, pleural
plaques, pleural effusion and malignant mesothelioma. The medicolegal
implications result from the compensation payable to victims and dependents,
and are affected by the diagnostic acumen of the pathologist, especially in the
assessment of interstitial fibrosis. The role of the Pneumoconiosis Medical Panel
should also be considered. (April 1988, Paper 2, Question 1)

Reference

1) Gibbs, A.R. Industrial lung disease. In: Recent Advances in Histopathology

13. P.P. Anthony, RN.M. MacSween (eds.) p109-117. Churchill Livingstone,
Edinburgh (1987).

What detailed and logical arguments could you use to convince a

sceptical scientist of a causal relationship between smoking and
lung disease?

Since 1971 there has been overwhelming evidence for this linkage from
epidemiological and experimental studies, and it is unlikely that the sceptical
scientist still exists. (November 1971, Paper 1, Question 2)

'While many pulmonary cancers consist predominantly,

sometimes exclusively, of growth of a particular type, it must be
emphasised that there is only one entity, carcinoma of the lung'
(Willis, 1960). Discuss this statement with reference to aetiology,
pathogenesis and classification of lung cancer.

Behind this question lies a paper in the Journal of Pathology (Gauer et a1., 1986)
suggesting that, because careful examination of lung carcinomas reveals evidence
of differentiation along most of the lineages represented in pulmonary
malignancy, these tumours arise from a pI uri potential stem cell. Thus there is
'only one entity' but showing cell lineage representation in differing amounts.
5. Cardiovascular and Respiratory Systems 131

Introduction
Observation confined to carcinomas
Classifications - morphological (WHO)
Histogenesis - definition - relation to differentiation
Differentiation - definition - relation to morphology

Classification (WHO)

Sauamous cell carcinoma

1) Microscopic
a) 1 or more features of squamous differentiation

2) Aetiology
a) tobacco
b) radiation

3) Pathogenesis
a) squamous metaplasia carcinogens in tobacco

4) Behaviour

Adenocarcinoma
1) Microscopic
a) glandular differentiation +/- mucin production
b) ? scar cancer
c) peripheral vs. hilar

2) Aetiology
a) tobacco
b) pulmonary scarring - diffuse and ? focal

3) Pathogenesis
a) scarring may increase epithelial turnover
b) susceptible to carcinogenesis

4) Behaviour
a) solid vs. bronchioloalveolar

Small cell (oat cell) carcinoma

1) Microscopic
a) oat cell, intermediate, mixed, ultrastructure
132 Advanced Histopathology

2) Functional characteristics

3) Aetiology
a) tobacco
b) radiation

4) Behaviour

Lar~e cell carcinoma

1) Distinction from above groups

1) Evidence for single entity

a) mixed carcinomas and tumour heterogeneity (LM)
b) ultrastructural heterogeneity
c) the ideal evidence would be a cloned cell line(s) with ability to
differentiate along any lineage!

2) Evidence against
a) differences in behaviour - clinical and metastatic pattern
b) chemotherapeutic responses
c) lack of pluripotential cloned cell line
(April 1986, Paper 1, Question 4)

References

1) Lamb, D. Lung cancer and its classification. In: Recent Advances in

Histopathology 13. P.P. Anthony, R.N.M. MacSween (eds.) p45-59 (1987).
2) Gatter, K.c. et al. Human lung tumours: a correlation of antigenic profile with
histological type. Histopathology (1985) 9: 805-823.

Write an essay on small cell (oat cell) carcinoma of the lung

Introduction

Definition of terms
Incidence
Relation to other lung carcinomas

Aetiology
1) Tobacco

2) Radiation
5. Cardiovascular and Respiratory Systems 133

Clinical features
1) Pulmonary carcinoma presentation

2) Spread

3) Prognosis

4) Ectopic hormone
a) ACfH - Cushing's
b) ADH - hyponatraemia
c) 5HT - carcinoid syndrome

Macroscopic
1) Site
a) bronchial wall

2) Size, colour, infiltration

3) Spread
a) local
b) nodal

Microscopic
1) Cellular
a) nuclear
b) cytoplasmic
c) classification - oat, intermediate, mixed

2) Stroma
a) vasculature
b) haematoxyphilic fibre staining ('Azzopardi' effect)

3) Special stains
a) argyrophilia (rare)
b) immunostaining
i) chromogranin
ii) ACfH
iii) Cytokeratin
iv) LCA (negative)
v) others

4) Cytological diallnosis
134 Advanced Histopathology

5) Ultrastructure
a) neuroendocrine granules
b) paranuclear intermediate filaments
c) lack of desmosomes

Differential diagnosis

7) Atypical carcinoid

2) Poorly differentiated squamous carcinoma

3) Lymphoma

4) Mixed pulmonary carcinoma

Spread

2) Nodal

3) Dissemination
a) liver - sinusoidal infiltration
b) brain
c) adrenal (>50%)
d) bone marrow - osteoblastic/fibroblastic response
(April 1985, Paper 2, Question 2)

Reference

1) Spencer, H. Carcinoma of the lung. In: Pathology of the Lung, 4th edition.
p837-932. Pergamon Press, Oxford (1985).

Give an account of the changes that you would expect to find in

the heart and systemic vasculature at necropsy in a case of
coarctation of the aorta

It would first be advisable to clarify the major differences between so-called

'infantile' and 'adult' forms of coarctation, a situation where diagrammatic
comparison would definitely enhance the answer. In the main part of the answer,
it would be reasonable to assume that the case was untreated, or succumbed to
known complications such as infective 'endocarditis'. As well as the effects on the
heart and pressure effects on vessels, it is important to remember to include
associated congenital defects such as berry aneurysms, other forms of congenital
heart disease and association such as Turner's syndrome. In the more protracted
distal (postductal) forms, aortic aneurysmal dilatation and dissection may
develop, as well as atherosclerosis, complications which all require description.
5. Cardiovascular and Respiratory Systems 135

Some comment should also be made on the vessels distal to the coarctation, with
a brief description of the microscopic structure of the coarctation.
(April 1987, Paper 2, Question 3)

References

1) Robbins, S.L., Cotran, R.S., Kumar, V. The heart - congenital heart disease. In:
Pathologic Basis of Disease, 4th edition. p618-626. W.o. Saunders,
Philadelphia (1989).
2) Berry c.L. Congenital heart disease. In: Paediatric Pathology, p63-123.
Springer-Verlag, Berlin (1989).

Describe the effects of sustained systemic hypertension on blood

vessels

This answer requires a definition of hypertension with some general

epidemiological and clinical features to provide a broad introduction. The
remainder of such an essay would be very straightforward and logical, to consider
the macroscopic and microscopic features affecting large elastic arteries, large and
small muscular arteries, and arterioles in turn. Although atherosclerosis should be
considered and described, it would be important not to digress too much into this
subject. Malignant (accelerated) hypertension should also be described in detail,
as it affects the smaller calibre vessels in particular.
(May 1973, Paper 2, Question 1)

Reference

1) Robbins, S.L., Cotran, R.S., Kumar, V. The kidney. In: Pathologic Basis of
Disease, 4th edition. pI 062-1 069. W.B. Saunders, Philadelphia (1989).

Discuss the pathogenesis of atherosclerosis

Introduction
Definition
Epidemiology, historical and current concepts
Clinical and experimental observations
'Response to injury' hypothesis

Pathological observations

1) Atheroma
a) macroscopic
b) microscopic
i) fibrolipid plaque
136 Advanced Histopathology

2) 'Precursor' lesions
a) fatty streak
b) features against precursor status
i) ubiquitous occurrence
ii) distribution and location
iii) lipid content - cholesterol oleate vs. linoleate
c) unknown role
d) gelatinous lesion
i) pathology
ii) composition - LBL and fibrinogen - little cholesterol

Historical theories
1) Insudation Mrchow)

2) Encrustation (Rokitansky)
a) endothelial injury

'Risk factors' and endothelial injury

1) Smoking

2) Hypertension

3) Diabetes mellitus

4) Hyperlipidaemia

Role of plasma lipids

1) High risk
a) LOL and VLOL

2) Low risk
a) HOL

3) Familial/epidemiological studies and risk

Pathogenesis
1) Endothelial injury and platelet dep-osition

2) Release of PGDF
a) platelets
b) activated macrophages

3) Migration of smooth muscle cells

4) Insudation of plasma lipids

5. Cardiovascular and Respiratory Systems 137

Progression

1) Persistent endothelial injury

2) Hyperlipidaemic states

Com pi i cati ons

1) Ulceration and thrombosis

2) Ischaemia, embolism

Monoclonal theory of Benditt

1) G6PD Iclonality'

2) Recent evidence? oligoclonal

(October 1982, Paper 1, Question 4)

References

1) Ross, R. The pathogenesis of atherosclerosis - an update. New Eng!. J. Med.

(1986) 314: 488-499.
2) Martinet, Y., et al. Activated human monocytes express the c-sis proto-
oncogene and release a mediator showing PDGF-like activity. Nature (1986)
519: 158-160.
3) Taussig, M.J. Processes in Pathology and Microbiology. 2nd edition. p649-672.
Blackwell Scientific Publications, Oxford (1984).

Describe current views in the pathogenesis of atherosclerosis

(October 1980, Paper 1, Question 1)

Discuss the current views on the relationship between lipids and

atherosclerosis
This essay would provide an opportunity to go into more detail on the
pathological and epidemiological data, as well as outlining the pathogenetic
mechanisms. There is still a large amount of factual information to be compressed
into this essay, which should be kept as succinct and relevant as possible.
(April 1971, Paper 1, Question 2)

The geographical variations in the incidence of a disease may be

of significance. Discuss this statement in relation to ischaemic
heart disease
One of the more uncommon type of questions which is largely based on
epidemiology, but nevertheless relevant as pathologists have a major
138 Advanced Histopathology

responsibility in the assessment of the prevalence and severity of ischaemic heart

disease by ensuring detailed necropsy information is available and more
importantly in the accurate death certification from which this may be assessed. In
the specific answer much of the detailed pathological information is presented in
the previous questions on atherosclerosis, but in this case it should be presented
in the light of the social and epidemiological data available, such as differences in
smoking habits, diet, possible genetic differences, etc. This information is largely
derived from national studies (e.g. Scotland vs. England, Japan vs. US) and from
intensive population studies, such as the Framingham experiment. It may be
difficult for some pathologists to concentrate sufficient information in this sort of
answer, unless they have experience of integrating epidemiological and
pathological data. (November 1988, Paper 1, Question 3)
References

1) Kaunel, W.B., Thorn, T.J. Implication of the declining mortality rate of

cardiovascular disease in the USA. In: Recent Advances in Cardiology,
Volume 10 p49-69. OJ Rowlands (ed.) Churchill Livingstone (1987).
2) Stebbens, W.E. An appraisal of the epidemic rise of coronary heart disease
and its decline. Lancet (1987) i: 606-611.

Discuss the aetiology and pathology of aneurysms

Introduction
Definition
Sites
Incidence and aetiologies

Aorta and major vessels

1) Atherosclerotic
a) aetiological factors
b) haemod ynamic effects
c) pathology
i) gross
ii) microscopic
iii) complications

2) Luetic
a) aetiology (tertiary syphilis)
b) pathology
i) gross
ii) microscopic
iii) complications
5. Cardiovascular and Respiratory Systems 139

3) Dissecting
a) aetiology (trauma, atherosclerosis, cystic medial degeneration,
hypertension)
b) gross
c) microscopic

Cerebral arteries

1) 'Berry' aneurysm
a) gross
b) microscopic
c) complications

Other sites
1) Infective
a) localised suppuration
b) embolic

2) Vasculitis
a) PAN
b) Kawasaki disease (coronary)

3) Rarely
a) post radiation
b) surgery
c) neoplastic invasion
(November 1970, Paper 2, Question 1)

Reference

1) Robbins, S.L., Cotran, R.S., Kumar, V. Blood vessels. In: Pathologic Basis of
Disease, 4th edition. p579-585. W.B. Saunders, Philadelphia (1989).

Describe how you would examine the atrioventricular bundle.

What changes may be found in the bundle in heart block~

This question requires the candidate to be familiar with a method of examining

the cardiac conduction system, from the atrioventricular node to the bundle
branches. A good method is described in the reference.

One way is to take a block of tissue including low interatrial septum and upper
interventricular septum at autopsy. This is divided horizontally below the
tricuspid valve ring. The upper block is sectioned vertically, while the lower is
sectioned horizontally. This will require hand processing. Every 30 sections are
then examined, keeping the intervening sections to examine if required. The upper
140 Advanced Hi stopathology

block will contain the AV node and proximal atrioventricular bundle, while the
lower block features the more distal bundle and its branches. It is much easier to
answer this question with personal experience. The changes which may be found
in heart block are manifold. The main ones include idiopathic bundle branch
fibrosis (three types A, B and C) ischaemic destruction of bundle (usually
associated with a large septal myocardial infarct), myocarditis, heavy calcification
of mitral and/or aortic valve rings, syphilitic gumma, fibrosis occurring in
association with connective tissue diseases, amyloidosis, haemochromatosis,
'interatrial mesothelioma', metastatic carcinoma, lymphoma/leukaemia tissue
infiltrates and fibrosis in cardiomyopathy. These can all be briefly described.
However, this is regarded as a particularly difficult examination question for the
average candidate. (April 1972, Paper 2, Question 2)

Reference

1) Lamb, D. Examination of the conducting system. In: Pathology of the Heart.

A. Pomerance, M.J. Davies (eds.) p26-31. Blackwell Scientific Publications,
Oxford (1975).

Discuss the changing pattern of infective endocarditis

April 1970, Paper 2, Question 2

Give an account of the changing pattern of infective endocarditis

It is important to point out that much of the change relates to Western countries,
where there has been a shift from the young adult with rheumatic heart disease to
older adults with normal or slightly abnormal valves, with reduced distinction
between acute and subacute endocarditis. Another factor has been the emergence
of unusual forms of endocarditis with increasing foreign travel and
immunosuppressive treatment regimes. (April 1980, Paper 1, Question 4)

Reference

1) Pomerance, A. Infective and non-bacterial thrombotic endocarditis. In:

Pathology of the Heart. A. Pomerance, M.J. Davies (eds.) p343-366. Blackwell
Scientific Publications, Oxford (1975).

Discuss the aetiology and pathology of conditions causing

functional disturbance of the mitral valve
This question could either be approached from the point of view of the
pathologies leading to stenosis, regurgitation, or both, or from an anatomical
point of view, such as abnormalities of the valve leaflet, chordae tendinae,
papillary muscles, mitral valve annulus or generalised cardiac disease. From a
practical point of view the first approach is probably simpler, and it would be
possible to divide each section into possible causes, congenital and acquired. It
5. Cardiovascular and Respiratory Systems 141

would be a mistake to concentrate purely on diseases of the valve only, such as

rheumatic heart disease or mucoid degeneration, without including the many
disorders of the endocardium (e.g. endocardial fibroelastosis) or myocardium
(e.g. ischaemic rupture of papillary muscle, cardiomyopathies, etc.) which can
interfere with normal function. It is important to place the correct emphasis on
each condition according to its relative frequency and morbidity in clinical
practice (e.g. overemphasising congenital fibroelastosis at the expense of
rheumatic heart disease). (October 1984, Paper 1, Question 3)

Reference

1) Davies, M.J. Non-rheumatic disorders of the heart valves. In: Recent Advances
in Histopathology 10. p139-158. Churchill Livingstone, Edinburgh (1978).

Give an account of the changing patterns in the United Kingdom

of the pathology of mitral incompetence

It is best to define what is understood by mitral incompetence (generally

regurgitation) prior to a general overview of the disease prevalence in the
population. Note that the question does not ask for detailed description of the
pathology (which can be mentioned briefly however), but for the patterns of
disease, i.e. aetiology and to a lesser extent pathogenesis. The major shifts have
been in rheumatic heart disease and a lesser rise in ischaemic heart disease and its
complications, and a rise in infective endocarditis due to several factors which all
require detailing. Those conditions which have remained relatively static should
also be mentioned (e.g. floppy valve, congenital heart disease, etc.). This is a
deceptively difficult question to answer in as much as there remains a great
temptation to digress into detailed pathological description.
(April 1982, Paper 1, Question 5)

Reference

1) Davies, M.J. Non-rheumatic disorders of the heart valves. In: Recent Advances
in Histopathology 10. p139-158. Churchill Livingstone, Edinburgh (1978).

Write an account of the non-rheumatic lesions of the aortic valve

This essay requires an introduction which covers the prevalence of these disorders
in the population, and a consideration of the clinical features including sudden
death. It would be best to describe the major congenital abnormalities first, then
consider the acquired disorders in various age groups, including a description of
aetiology, pathogenesis and complication as well as the pathological features.
Disorders such as aortic root dilatation, which are technically part of the function-
ing valve, could also be included. (October 1982, Paper 2, Question 3)
142 Advanced Histopathology

Write an essay on tricuspid valve disease of the heart

The main feature of tricuspid valve disease is that it is much less common than
diseases involving the mitral and aortic valves, much of this difference relates to
the lower pressures in the right side of the heart. Congenital abnormalities of the
tricuspid valve should be considered first, and then the rare diseases which
primarily involve the tricuspid valve. Carcinoid heart disease and infective
endocarditis in intravenous drug abusers are the two main disease processes.
Libman-Sacks endocarditis seen in patients with systemic lupus erythematosus,
rheumatic heart disease, non-bacterial thrombotic and infective endocarditis and
mucoid degeneration are all conditions which occur in association with similar
and sometimes more severe changes in the mitral valve. Tricuspid valve
involvement in the rare restrictive cardiomyopathies, endomyocardial fibrosis,
Loeffler's syndrome and endocardial fibroelastosis would also be included in a
comprehensive answer. (November 1972, Page 2, Question 5)

References
1) Pomerance, A. Chronic, rheumatic and other inflammatory valve disease; and
rarities and miscellaneous endocardial abnormalities. In: Pathology of the
Heart. A. Pomerance, M.J. Davies (eds.) p313-4; 504-7. Blackwell Scientific
Publications, Oxford (1975).
2) Robbins, S.L., Cotran, R.S., Kumar, V. The heart. In: Pathologic Basis of
Disease, 4th edition. p626-640. W.B. Saunders, Philadelphia (1989).

Describe critically the examination of the heart in cases of

sudden death
This question requires an introduction defining the meaning of sudden death, and
a consideration of the major cases where the heart is primarily involved. The word
critically is included to indicate that a flexible approach is necessary to enable the
demonstration of the various causes which may be obscured if a standard protocol
is followed without due regard to clues which may be gathered during the course
of the examination. It is therefore probably best to list the cause as primary cardiac
sudden death, and then describe how the changes may be manifest at each stage
of the examination, and how it might alter the direction of the dissection. The
main stages are: a) in situ and pericardial inspection, b) external examination, c)
valve inspection, d) right atrium and ventricle, e) coronary circulation, f) left
atrium, g) left ventricle, h) conducting system. (April 1986, Paper 1, Question 3)

Reference
1) Davies, M.J., Anderson, R.H. Pathology of the conducting system. In:
Pathology of the Heart. A. Pomerance, M.J. Davies (eds.) p404-406. Blackwell
Scientific Publications, Oxford (1975).
5. Cardiovascular and Respiratory Systems 143

Describe the pathology of subendocardial myocardial necrosis

and discuss its pathogenesis
The introduction to this essay must define precisely what is meant by the term
subendocardial myocardial necrosis, and its major associations. Pathological
considerations also include the clinical features and conditions which may
predispose to left ventricular hypertrophy. The macroscopic appearances with
detailed description of the acute and chronic forms, macroscopic demonstration of
the necrosis, together with the microscopic appearances and evolution of the
lesion all require description along with the complications that may occur such as
papillary muscle rupture, thrombus formation, etc. In respect of the pathogenesis,
the normal high metabolic demand of the subendocardial myocytes needs to be
emphasised and that they are compromised in hypertrophic states,
hypercirculation for any cause, or susceptibility to metabolic disturbance and how
vascular compromise may tip the balance. This should provide material for a
relatively circumscribed essay. Much of the detail would already be familiar to a
pathologist who has performed necropsies on patients with sudden death.
(October 1983, Paper 2, Question 2)

Reference

1) Davies, M.J. Pathology of ischaemic heart disease. In: Recent Advances in

Histopathology 13. P.P. Anthony, R.N.M. MacSween (eds.) p185-201.
Churchill Livingstone, Edinburgh (1987).

Discuss the pathology of the cardiomyopathies

(April 1978, Paper 2, Question 4)

Classify the cardiomyopathies and describe the pathology of the

heart in each case (October 1988, Paper 2, Question 5)

Discuss the classification and pathology of cardiomyopathies

Introduction

Definition
Primary vs. secondary (specific)
Incidence
144 Advanced Histopathology

Primary

Con~estive (dilated)
1) LV dilatation (myocardial failure)
Macroscopic
a) endocardium
i) thrombi
b) myocardium
i) flabby, thin
ii) fibrosis

Microscopic
a) endocardium
i) smooth muscle
ii) hypertrophy
b) myocardium
i) degenerative change

Secondary effects
a) LV failure
b) emboli

HllPertro.phic
1) L V compliance decreased
Macroscopic
a) LV thickening symmetrical/asymmetrical endocardial fibrosis (Ant. M.V.
leaflet)
Microscopic
a) fibre changes and degeneration
EM
a) myofibrillary disarray

Restrictive
1) Endocardial fibroelastosis
Clinical
a) congenital abnormalities
Macroscopic
a) porcelain fibrosis
MiCroscopic
a) hyaline collagen deposition
5. Cardiovascular and Respiratory Systems 145

2) Endomyocardial fibrosis
Clinical
Macroscopic
a) RV > LV
b) Apex> base

Microscopic
a) fibrosis, eosinophils (Loeffler's syndrome)

Secondary

1) Toxic
a) alcohol
b) cobalt
c) catecholamines
d) Co
e) Li
f) As
g) anthracyclines
h) cyclophosphamide

2) Metabolic
a) hypo- and hyperkalaemia
b) hypo- and hyperthyroidism
c) nutritional deficiencies
i) Vitamin Bl
d) haemochromatosis

3) Infiltrative
a) sarcoidosis
b) amyloid
c) tumour

4) Neuromuscular
a) Friedreich's ataxia
b) muscular dystrophy
c) congenital atrophies

5) Storage disorders
a) Fabry's
b) Pompe's diseases
(October 1980, Paper 2, Question 1)
146 Advanced Histopathology

Reference
1) Davies, M.J. The cardiomyopathies: a review of terminology, pathology and
pathogenesis. Histopathology (1984) 8: 363-393.

Discuss classification and pathology of the primary

cardiomyopathies
This question is very similar but the causes of secondary cardiomyopathy do not
need consideration. It is important not to overlook these when questions are set
on cardiomyopathy without specification. (April 1976, Paper 2, Question 3)

Define right ventricular hypertrophy and discuss its pathogenesis

This is a similar question, but includes all causes of pulmonary hypertension
including shunts, vascular disease and pressure effects due to left heart failure as
well as the previously cited causes of pulmonary hypertension. It might be better
to discuss the diagnosis of right ventricular hypertrophy in detail, and then take
one or two examples of each group to illustrate the different pathogenetic
mechanisms. (April 1971, Paper 2, Question 4)

What is a cardiac myxomal How may it give rise to clinical signs

and symptomsl
This requires a straightforward pathological description of this entity, to include
macroscopic, microscopic, histochemical, immunohistochemical and ultrastruct-
ural features, with speculation on the histogenesis. The complications of cardiac
myxoma are well defined and largely predictable. This type of question could be
answered with relative ease by a candidate who has reached the required standard
for the examination. (November 1974, Paper 1, Question 2)

References
1) Davies, M.J. Tumours of the heart and pericardium. In: Pathology of the
Heart. A. Pomerance, M.J. Davies (eds.) p428-433. Blackwell Scientific
Publications, Oxford (1975).
2) Landon, G. et al. Cardiac myxoma. An immunocytochemical study using
endothelial, histiocytic and smooth muscle markers. Arch. Pathol. Lab. Med.
(1986) 110: 116-120.
6. Endocrine System
148 Advanced Histopathology

Discuss the aetiology and pathology of Cushing's syndrome

(April 1979, Paper 1, Question 3)

Describe the macroscopic and microscopic changes which may

be found in the adrenals in patients with Cushing's syndrome.
What bearing may the changes have in the treatment of the casel
(November 1971, Paper 2, Question 2)

Discuss the pathological basis of Cushing's syndrome

(April 1970, Paper 2, Question 3)

Give a detailed description of the changes that may be found in

the adrenal glands in Cushing's syndrome. Discuss the changes
that may occur in the other tissues and organs
These essays are substantially the same in terms of basic content, but each requires
a different emphasis. The earliest question requires only the primary adrenal
causes to be considered, but secondary changes from an ectopic source of ACfH
need to be mentioned. The effect on other tissues in Cushing's syndrome is wide
ranging and requires careful planning.

In the 1970 question, division should be made on the basis of abnormal

stimulation of the adrenal glands by ACfH, from pituitary, ectopic and iatrogenic
sources, and adrenal causes including hyperplasia and neoplasia.

The 1971 question requires a discussion on the aetiology and pathogenesis of the
changes as this information is required for appropriate treatment.

The 1979 question requires a discussion rather than a description and problems in
diagnosis and histological assessment should be considered.
(November 1969, Paper 2, Question 1)

Give an account of the structure and behaviour of tumours

arising in the adrenal medulla and the sympathetic nervous system
The 'structure' in this question presumably relates more to the microscopic and
the ultrastructural features than the macroscopic appearance. Phaeochromocyt-
oma, neuroblastoma and ganglioneuroma are the main tumours to be considered,
and their systemic effects as well as benign or malignant behaviour should be
described. The sympathetic nervous system may give rise to similar extra-adrenal
tumours, and their principal sites and behaviour should be summarised in one or
two paragraphs. In addition, it would be appropriate to include description of
paragangliomas arising in the carotid body and other sites, comparing and
contrasting features with phaeochromocytoma.
(November 1973, Paper 1, Question 4)
6. Endocrine System 149

References
1) Robbins, S.L., Cotran, R.S., Kumar, V. Adrenal medulla. In: Pathologic Basis
of Disease, 4th edition. pI262-1267. W.B. Saunders, Philadelphia (1989).
2) Enzinger, F.M., Weiss, S.W. Tumors of the sympathetic nervous system and
paraganglioma. In: Soft Tissue Tumors, 2nd edition. p816-860. C.V. Mosby
Co, St Louis (1988).

Write a short essay on the pathology of the carotid bodies

While most pathologists should be familiar with the neoplasms which arise from
the carotid bodies, the normal structure and the alterations encountered in cases
of chronic hypoxia, systemic hypertension and pulmonary hypertension are less
well known, and the information is not provided to any major degree in the more
basic pathology texts. The question requires some consideration of these states.
The information is provided in the first reference in fairly detailed form, but
otherwise a lecture in a symposium or teaching course including non-neoplastic
disease of the carotid body may be the only way to acquire this knowledge for the
average candidate. (April 1981, Paper 1, Question 2)

References
1) Heath, D., Smith, P. The Pathology of the Carotid Body and Sinus. Edward
Arnold, London (1985).
2) Enzinger, F.W., Weiss, S.W. Paraganglioma. In: Soft Tissue Tumors, 2nd
edition. p836-860. C.V. Mosby Co, St. Louis (1988).

Give an account of the structure and behaviour of tumours

arising in the adrenal medulla and the sympathetic nervous system

This essay requires a concentration on phaeochromocytoma as well as neuro-

blastoma and ganglioneuroma, with less detailed mention of the paragangliomas
described in the preceding answer. (Although the latter might be argued to arise
from the parasympathetic rather than ortho-sympathetic system, they could still
be justifiably included. Subtle distinctions such as this would not cause a
candidate to be marked down, especially if they had discussed and qualified the
terminology in an introduction.) Other entities such as myelolipoma could be
mentioned, but secondary carcinoma should not be discussed, as the question
requires only those lesions arising in the adrenal gland.
(November 1973, Paper 1, Question 4)

Reference
1) Rosai, J. Adrenal gland and other paraganglia. In: Ackerman's Surgical
Pathology. Volume 1, 7th edition. Chapter 16, p789--818. C.V. Mosby Co, St.
Louis (1989).
150 Advanced Histopathology

Give an account of the histological and ultrastructural features of

the chemodectoma. How does this tumour behavel What
tumours with the same microscopic appearance occur elsewhere
in the body

Introduction
Syn. carotid body paraganglioma
Sites of paraganglia
Function of paraganglion cells
General features

Histological appearances

1) Benign
a) capsule
b) zellballen
c) nuclear features inc. pleomorphism
d) cytoplasm (spindle cell change)

2) Malignant?
a) irregular cell clusters
b) mitotic activity
c) necrosis

3) Special stains
a) grimelius
b) formalin-induced fluorescence

4) Ultrastructure of
a) chief cell
b) dark and light cells
c) cell junctions
d) dense core granules 100-200J.l.m

5) Clinical behaviour
a) local recurrence
b) metastasis (<10%)
i) lymph nodes
ii) lung and bone
6. Endocrine System 151

6) Other tumours
a) phaeochromocytoma of adrenal gland
b) glomus jugulare tumour
c) vagal paraganglioma
d) mediastinal paraganglioma
e) retroperitoneal paraganglioma
f) others e.g. larynx, orbit, bladder
(April 1986, Paper 2, Question 1)

Reference
1) Enzinger, F.W., Weiss, S.W. Paraganglioma. In: Soft Tissue Tumors. 2nd
edition. p836-860. C.V. Mosby Co, St. Louis (1988).

Discuss the concept of the diffuse endocrine system and the

neoplasms that can arise from it
(November 1977, Paper 2, Question 3)

What are APUD cells~ How may they be identified~ Give a short
account of the tumours ('apudomas') which can arise from these
cells

The second of these two questions was clearly related to the publication of the
first reference. Since that time there has been considerable discussion in the
literature as to the proposed 'neural crest' origin of these cells, but this issue is to
some extent peripheral to the concerns of a diagnostic pathologist, and certainly in
relation to the content of these answers. So also is the expanding body of
knowledge on various peptides (and combination of peptides), which may prove
confusing for the average trainee trying to keep up with the literature. It is much
better to read the simpler review articles on the subject, so that the problem of 'not
seeing the wood for the trees' is avoided! (October 1978, Paper 2, Question 4)

References

1) Gould, R.P. The APUD cell system. In: Recent Advances in Histopathology 10.
P.P. Anthony, N. Woolf (eds.) pl-22. Churchill Livingstone, Edinburgh (1978).
2) Dawson, I.M.P. Diffuse endocrine and neuroendocrine cell tumours. In:
Recent Advances in Histopathology 12. pl11-128. Churchill Livingstone,
Edinburgh (1984).
3) Polak, J.M., Bloom, S.R. Pathology of peptide-producing neuroendocrine
tumours. Br. J. Hosp. Med. (1985) 33: 78-88.
152 Advanced Histopathology

Give an account of inflammatory and inflammatory-like diseases

of the thyroid gland
The conditions which could be described in these answers include acute
thyroiditis, and more chronic diseases such as primary thyrotoxicosis (which
could be included as a form of 'auto-immune' disease), Hashimoto's disease,
granulomatous (De Quervain's) thyroiditis, lymphocytic and chronic atrophic
thyroiditis. Riedel's thyroiditis could also justifiably be included (especially as an
'inflammatory-like disease') even though it is probably a form of fibromatosis (or
even sclerosing carcinoma). (October 1985, Paper 2, Question 4)

References

1) Robbins, S.L., Cotran, R.S., Kumar, V. Thyroid gland. In: Pathologic Basis of
Disease. 4th edition. pl220-1227. W.B. Saunders, Philadelphia (1989).
2) Rosai, J. Thyroid gland. In: Ackerman's Surgical Pathology. Volume 1. 7th
edition. Chapter I, p391-448. C.V. Mosby Co, St Louis (1989).

Write an essay on inflammatory lesions of the thyroid gland

(November 1977, Paper 1, Question 5)

Discuss the pathology of the clinically solitary thyroid nodule

Introduction
Definition - discrete palpable mass in thyroid
Prevalence
Significance

Pathological categories

Colloid ('involutional') nodule

1) Macroscopic features

2) Microscopic

Adenoma
1) Macroscopic features

2) Microscopic
a) follicular
b) foetal
c) trabecular/embryonal
d) oxyphil
e) ?atypical adenoma.
6. Endocrine System 153

1) Decenerative

2) Developmental

Carcinoma
1) Follicular
a) well differentiated
i) macroscopic
H) microscopic
Hi) variants
iv) clear cell ca
v) oxyphil
b) poorly differentiated
2) Papillary
a) macroscopic
i) unifocal and multifocal
b) microscopic
c) variants
3) Medullary
a) localised
i) macroscopic
ii) microscopic
b) multifocal
i) genetic association (MEA)
ii) C cell hyperplasia

4) Undifferentiated
a) macroscopic
b) microscopic
i) small cell ca
ii) giant cell ca
(October 1982, Paper 2, Question 5)

References
1) Brown, C.L. The solitary thyroid nodule. In: Recent Advances in
Histopathology 11. P.P. Anthony, R.N.M. MacSween (eds.) p203-212.
Churchill Livingstone, Edinburgh (1981) .
2) Robbins, S.L., Cotran, R.S., Kumar, V. Thyroid gland. In: Pathologic Basis of
Disease, 4th edition. pl227-1242. W.B. Saunders, Philadelphia (1989).

Write an essay on thyroid cancer

(April 1976, Paper 1, Question 4)
154 Advanced Histopathology

Give a classification of malignant tumours of the thyroid and

describe briefly the behaviour of each type of tumour
This answer requires an expansion of the relevant section from the previous plan,
and should provide relatively little problem for the average candidate, since most
of these entities are regularly encountered in diagnostic practice, and are
frequently discussed in the literature. There are several good accounts of thyroid
malignancies but there is more than enough detail in the given reference.
(April 1969, Paper 2, Question 3)

Reference
1) Rosai, J. Thyroid gland. In: Ackerman's Surgical Pathology, Volume 1. 7th
edition, Chapter 9, p391-448. C.V. Mosby Co, St. Louis (1989).

Give an account of malignant thyroid neoplasms and relate this

to their clinical behaviour
(April 1980, Paper 2, Question 1)
7. Renal Pathology
156 Advanced Histopathology

Describe the alterations that may be found in the kidney in a)

polyarteritis nodosa b) scleroderma c) renal artery stenosis

This is really a 'short notes' type of question, although the wording indicates that
formal sentence construction is required. Each section therefore constitutes a small
essay, and in view of the relatively brief nature of each section all that is really
required as a plan is a few key words and notes under each heading, especially as
each of these subjects is circumscribed and straightforward.
(April 1980, Paper 2, Question 2))

What correlation is found between renal function tests and

morphological appearances of renal biopsies

A difficult question to answer, there being great potential to digress without a

structured plan and it is essential to try to be concise as well as thorough. Normal
function is obviously dependent on the presence of sufficient nephrons being able
to carry out their role, and thus one simple scheme might be to take various
components of the nephron in turn. Abnormalities at each level could then be
highlighted and their functional significance considered. A possible sequence to
consider would be vascular supply; muscular arteries, arterioles, glomerular
capillaries, efferent arterioles, vasa recta and renal veins; glomeruli; capillary
walls, mesangial support, tubules, collecting ducts and finally interstitium. Each
of the above can be briefly considered in the light of various pathological
abnormalities and their effects on functional tests at the clinical level.
No specific references are provided, as the information to answer this question
has to be derived from a number of sources. This has been a particular feature of
the questions in this section, and there is a particular emphasis on broad
overviews on several subjects in renal pathology. While this is usually straight-
forward for candidates who have wide-ranging practical experience, other
candidates may find difficulty in coordinating and comparing all of these entities
within an examination - these points should be borne in mind when revising
renal pathology, when extra effort should be made to compare and contrast
different diseases. (May 1973, Paper 1, Question 3)

Discuss the value of renal biopsy in the diagnosis and prognosis

of renal disease

This question is so wide-ranging the problem arises from selecting those

conditions which could be discussed under this heading. Perhaps the best way is
to select those diseases whose prompt and accurate diagnosis would significantly
alter the clinical management to the benefit of patients, illustrating (he particular
features which are most important. Examples could include biopsy diagnosis in
the nephrotic syndrome, in glomerulonephritis or in management of allograft
rejection, there are clearly many areas which could be covered. This is another
example where a 'global' knowledge of renal pathology is required to answer the
question. (November 1977, Paper 2, Question 4)
7. Renal Pathology 157

How would you handle the investigation of a renal biopsy

specimen in the laboratoryl What techniques would you use and
what information would you hope to derive from theml

Essentially a question directed to the candidate experienced in diagnostic work, it

also illustrates the importance of considering more than just interpretation of
stained sections. The handling of a biopsy is critical, and methods for the division
of biopsies for processing, cryostat sectioning for immunofluorescence and
electron microscopy, all of which should ideally contain glomeruli, require
description. Fixation and storage methods should be considered, and the range of
special staining techniques (including methanemine silver, toluidine blue, PAS
and trichrome stains all have applications), along with immunohistochemical
studies and the range of abnormalities present in the commoner forms of
glomerulonephritis could be described. In addition, other diseases such as
amyloidosis can also be considered and the range of stains detailed. Electron
microscopic analysis could also be reviewed, and selected diseases which have a
characteristic appearance described. The range of options in such an answer is
very wide, and it would be difficult to provide a balanced answer without a
carefully thought out plan. No reference is given because this answer more or less
encompasses the whole of renal biopsy pathology.
(April 1987, Paper 2, Question 5)

Discuss the pathology of renal diseases occurring in pregnancy

A difficult question if the problems of renal disease in pregnancy have not been
specifically considered prior to the examination! There are two broad groups of
renal disease in pregnancy - those specific to pregnancy, and those which occur
in other circumstances but are predisposed to by pregnancy. The former can be
discussed first and include pre-eclampsia/eclampsia, idiopathic post-partum
acute renal failure, cortical necrosis and fatty liver with acute renal failure. Details
of these conditions can be obtained from the reference below. Those diseases
predisposed to but not specific for pregnancy include urinary tract infection/
acute pyelonephritis and essential hypertension.
(October 1977, Paper 2, Question 1)

Reference

1) Heptinstall, R.H. Renal diseases in pregnancy. In: Pathology of the Kidney,

3rd edition. p963-991. Little, Brown & Co, Boston (1983).

Discuss the possible autopsy findings in a patient who has died

from chronic pyelonephritis

Renal
158 Advanced Histopathology

1) Macroscopic features
a) kidneys reduced in size (except when secondary to distal obstruction -
PN and hydronephrosis)
b) pathognomonic change - irregular coarse discrete corticomedullary scars
overlying distorted calyx
c) predilection for poles
d) unscarred areas normal or secondary hypertensive changes

2) Microscopic features
a) tubules
i) atrophic shrinkage
ii) atrophic dilated + / - colloid casts 'thyroidisation'
b) interstitium
i) fibrosis, inflammation - variable predominantly chronic
c) glomeruli
i) variable from essentially normal - periglomerular fibrosis - global
sclerosis - loss with incorporation into fibrotic scar
d) pelvicalyceal region
i) chronic inflammatory and submucosal fibrosis
e) non-scarred regions
i) variety of changes including ischaemic, hypertensive and
hyperfiltration changes
o vasculature
i) changes secondary to hypertension
No specific ultrastructural or immunofluorescent changes

Systemic
1) CVS
a) pericardium
i) fibrous pericarditis, pericardial effusion
b) heart
i) LVH
ii) LVF changes
iii) myocardial calcification (secondary to hyperparathyroidism)
iv) oxalate deposition (including conducting system)
c) systemic arteries
i) hypertensive changes
ii) medial calcification
iii) oxalate deposition
iv) accelerated atherosclerosis

Respiratory system
1) Pleura
a) fibrinous pleurisy
b) effusion
7. Renal Pathology 159

2) Lungs
a) heavy, features of uraemic pneumonitis

Skeletal system
1) Renal osteodystrophy (including changes of secondary hyperparathyroidism)

Endocrine
1) Secondary hyPerparathyroidism
a) diffuse parathyroid hyperplasia

2) Tertiary hyperparathyroidism
a) exaggerated changes in gland (functional autonomy)

Alimentary tract
1) Mucosal inflammatory changes +/- ulceration and haemorrhage at all levels

2) Pancreatic duct dilatation

3) Ascites +/- uraemic fibrinous peritonitis

Central nervous system

1) Cerebral haemorrhage secondary to hypertension and vascular changes

2) Changes of terminal infection may involve any system, especially respiratory

3) Other changes, microscopic only e.g. hypoplastic bone marrow

(April 1981, Paper 2, Question 2)

References

1) Robbins, S.L., Cotran, R.S., Kumar, V. The kidney. In: Pathologic Basis of
Disease, 4th edition. pl015-1017; 1055-1057. W.B. Saunders, Philadelphia
(1989).
2) Kashgarian, M., Rosai, J. The urinary tract. In: Ackerman's Surgical Pathology,
Volume 1, 7th edition. p819-922. C.V. Mosby Co, St Louis (1989).

Discuss the aetiology and pathogenesis of chronic pyelonephritis

The introduction should include an adequate definition of chronic pyelonephritis,
primarily that it is a chronic tubulointerstitial disorder in which renal scarring is
associated with pathological involvement of calyces and pelvis. Emphasis is
placed on bacterial infection associated with vesicoureteric reflux or obstruction
distal to the pelvis which is considered to play the major role in the development
of chronic pyelonephritis. Thus pathogenically there are two major causes of
160 Advanced Histopathology

chronic PN - chronic obstructive PN and the more common chronic reflux

associated PN. In chronic obstructive PN a haematogenous route of infection is
favoured, as the obstructed kidney is much more vulnerable to circulating
organisms that are potentially pathogenic than the normal kidney. Chronic reflux
associated PN is thought to be associated with ascending infection. The
importance of vesicoureteric reflux in childhood should be described in detail,
along with the significance of compound refluxing renal papillae leading to intra-
renal reflux. (November 1972, Paper 2, Question 1)

References
1) Heptinstall, R.H. Urinary tract infection, reflux and pyelonephritis. In:
Pathology of the Kidney, 3rd edition. p1257-1304. Little Brown & Co, Boston
(1983).
2) Risdon, R.A. Cystic disease of the kidney and reflux nephropathy. In: Recent
Advances in Histopathology 11. R.N.M. MacSween, P.P. Anthony (eds.)
Churchill Livingstone, Edinburgh (1981).

Discuss the pathology and pathogenesis of interstitial nephritis

This may be a difficult question for those candidates who have not worked within
a Department receiving biopsies from a renal specialist unit, as the possible
aetiological factors are quite wide ranging. It would be best to define acute and
chronic interstitial nephritis and discuss the gross and microscopic changes in
both, including the nature of the interstitial changes (and their consequences) and
the composition of the cellular infiltrate. Since there are a large number of
aetiological and associated conditions, it would be best to list the main aetiologies
in each (e.g. the acute group includes infection, drugs and toxins,
glomerulonephritis, SLE, transplantation and the chronic group includes
infection, obstructive uropathy, ischaemia, papillary necrosis, radiation injury,
sarcoidosis and several others). The major differences in pathogenesis between
the groups should be emphasised to avoid repetition of the common features.
(October 1983, Paper 2, Question 3)

Reference
1) Risdon, R.A., Turner, D.R. Interstitial nephritis. In: Atlas of Renal Pathology.
p35-39. J.B. Lippincott Co, Philadelphia (1980).

Discuss how therapeutic agents may induce kidney disease and

how they can modify lesions of pre-existing disorders
A very broad question which covers many fields. The renal diseases induced by
therapeutic agents include acute tubular necrosis (e.g. antibacterials, anaesthetic
agents), interstitial nephritis (e.g. antibiotic or diuretics), analgesic nephropathy,
nephrocalcinosis (Vitamin D), radiation nephritis, urate nephropathy (e.g.
treatment of leukaemias), and glomerulonephritis (e.g. gold salts, penicillamine).
Therapeutic agents modifying renal disease include antibiotics in pyelonephritis
7. Renal Pathology 161

and ureteric reflux, steroids in some forms of glomerulonephritis, antibiotics in

post-streptococcal glomerulonephritis and cytotoxic drugs in crescentic glomer-
ulonephritis and lupus nephritis, or antihypertensive agents in hypertensive
disease. There are several other examples which could be considered. It is difficult
to provide specific references to these broad categories of disease, which are
drawn from many sources in the major renal texts.
(April 1969, Paper 2, Question 1)

Describe the changes found in necrosis of the renal papillae.

Discuss the aetiology and pathogenesis of this condition

Renal papillary necrosis occurs in two main settings, analgesic abuse and acute
pyelonephritis, and since the changes are sufficiently distinctive in each case they
could be described separately. For analgesic nephropathy, the macroscopic
appearances should be given in detail, along with the microscopic features, in
both early and late stages. As expected, superimposed suppurative changes are
important in the pyelonephrotic cases.

As regards aetiology and pathogenesis, there is experimental and epidemiological

evidence for analgesias leading to renal papillary necrosis, thought to be due to
acetaminophen binding to cellular proteins and depleting renal glutathione,
which normally prevents oxidative damage, exacerbated by interference with
prostaglandin synthesis by aspirin. In pyelonephritis and obstructive uropathy,
pressure effects and interference with local vascularity are proposed, and these
hypotheses should be discussed and criticised as appropriate.
(April 1975, Paper 2, Question 4)

Reference

1) Robbins, S.L., Cotran R.S., Kumar, V. The kidney-tubulointerstitial diseases.

In: Pathologic Basis of Disease, 4th edition. p1051-1061. W.B. Saunders,
Philadelphia (1989).

Discuss the nature of the relationship between stenosis of the

renal artery and arterial hypertension

This is one of the most thoroughly investigated mechanisms of hypertension,

although the explanation is far from complete and can't be applied to every case
of renal artery stenosis. The answer should concentrate on the relationship and
not provide a lengthy description of the various lesions which can produce the
stenotic lesion. A brief mention of the pathological lesions producing renal artery
stenosis would be all that is required. In discussing the relationship between
stenosis and hypertension the pioneering experiments of Goldblatt should be
highlighted. This leads on to a description of the renin angiotensin system which
best explains the development of arterial hypertension after renal artery stenosis
including the means by which stenosis leads to increased renin release by the
juxtaglomerular apparatus in the kidney rendered relatively ischaemic by the
stenosis. A line diagram of the renin angiotensin system may help in this answer.
162 Advanced Histopathology

In concluding this discussion it should be noted that only 50% of patients with
long term arterial hypertension secondary to renal arterial stenosis have elevated
renin levels. This implies that there are additional mechanisms, which may
include sodium retention, altered peripheral vascular reactivity to vasopressor
substances and changes in prostaglandin and kinin systems. There is no need to
discuss morphological changes in the kidney secondary to renal artery stenosis, as
these have not been requested. (November 1969, Paper 2, Question 5)

References

1) Robbins, S.L., Cotran, R.S., Kumar, V. The kidney. In: Pathologic Basis of
Disease, 4th edition. p1062-1069. W.B. Saunders, Philadelphia (1989).
2) Heptinstall, R.H. Hypertension - III secondary forms. In: Pathology of the
Kidney, 3rd edition. p248-267. Little, Brown & Co, Boston (1983).

Discuss the pathogenesis and pathology of immune complex

nephritis

Introduction
Explanation of terms used
Experimental models vs. human disease

Experimental nephritis
7) In situ immune complex formation
a) anti GBM
i) nephrotoxic (Masugi) heterologous anti GBM antisera injection
heterologous/autologous phases
ii) AI (Steblay)
b} Other fixed Ag
i) Heymann nephritis
c) 'Planted' antigens
i) endogenous
ii) exogenous

2) Circulatinc immune complex

Localisation due to physicochemical/haemodynamic factors

a) acute serum sickness
b) chronic serum sickness

Human disease
7) Goodpasture's syndrome
a} ?nephrotoxic
7. Renal Pathology 163

2) Membranous GN
a) ?chronic serum sickness

3) Lupus nephritis
a) various

4) Acute proliferative
a) ?acute serum sickness
(Odober 1982, Paper 1, Question 3)

References

1) Heptinstall, R.H. Immunologic mechanisms in glomerular disease. In:

Pathology of the Kidney, 3rd edition. p301-386. Little, Brown & Co., Boston
(1983).
2) Robbins, S.L., Cotran, R.S., Kumar, V. The kidney. In: Pathologic Basis of
Disease, 4th edition. pI 022-1 042. W.B. Saunders, Philadelphia (1989).

Describe the various forms of glomerulonephritis that may be

found in the nephrotic syndrome. Indicate the clinical course of
the various types

Introduction
Nephrotic syndrome NS - proteinuria (>3.5 g/day), hypoalbuminaemia,
oedema, hyperlipaemia, lipiduria

Frequency - adults vs. children

GN associated with NS

Proliferative
Acute diffuse (rare)
Crescentic (rare)
Mesan~al proliferation
Focal
Histolo~cal features
1) Clinical
a) response to Px
b) Focal sclerosing glomerulosclerosis (FSGS) in 50-70%
i) crescentic
ii) prognosis
164 Advanced Histopathology

Membranous

Histolo~cal features (EM + immunocytochemistry)

1) Clinical
a) children 10 YSR 90%
b) adult 20% remission
25% partial remission
15% relapsing
50% die within 15 years

Mesangiocapi lIary

Histolo~cal features (EM + immunocytochemistry) (type I and type II)

1) Clinical
a) type I
i) persistent NS 40%
ii) 10 YSR
iii) proteinuria
iv) 85% 10 YSR
b) type II
i) worse prognosis

Histolo~cal features (+EM)

1) Clinical
a) remission 37%
b) relapsing 14%
c) chronic renal failure 50%

Minimal change

Histolo~cal features (EM)

1) Clinical

a) remission 7-40%
b) relapsing 60%

2) Other causes of NS with GN picture

a) SLE, HSP
b) drugs e.g. penicillamine, Au
c) infection e.g. syphilis, malaria, SBE
d) miscellaneous e.g. transplantation glomerulopathy, sarcoid
(April 1972, Page 2, Question 1)
7. Renal Pathology 165

Reference

1) Turner, D.R. Glomerulonephritis. In: Recent Advances in Histopathology 10.

P.P. Anthony, N. Woolf (eds.) p240-259. Churchill Livingstone, Edinburgh
(1978)

Discuss the renal changes and discuss the aetiology of focal

glomerulonephritis. What factors determine prognosisJ

Classification

Focal and segmental proliferative glomerulonephritis (FSPGN)

Focal and segmental glomerulosclerosis (FSGS)
Focal global sclerosis

FSPGN
1) Primary (lgA and non IgA)
2) Secondary part of systemic disorders: SLE; PAN; HSP; bacterial endocarditis;
shunt nephritis; Wegener's granulomatosis; Goodpasture's syndrome

1) Morphology
Similar for 10 and 20
a) changes focal (only some glomeruli) and segmental (only part of
glomerulus)
b) + / - mesangial
c) segmental cellular proliferation +/- necrosis
d) + / - small crescents anatomically related to segmental damage
e) 'mature' lesions solidified +/- adherence to Bowman's capsule
f) tubules, interstitium and blood vessels, minor changes - focal tubular
atrophy /interstitial fibrosis

2) Immunofluorescence
a) 10
i) IgA nephropathy - diffuse (all glomeruli) mesangial IgA + / - lesser
mesangial IgG, C3
ii) non IgA nephropathy - diffuse mesangial C3 + / - other Igs
b) 20
i) depends on disease, e.g. SLE vs. Goodpasture's
c) TEM variable depending on specific disease and stage

3) Aetiology

Immunological mechanisms almost certainly involved in most cases

166 Advanced Histopathology

4) IgA nephropathy
a) IgA production deposits, some alteration in normal regulation and
primary environmental stimulus e.g. virus
b) alternative pathway complement activations in mesangium
c) ? mesangial overload leading to focal and sequential lesions at sites of
overload

5) SLE
a) deposition of circulating complexes, complement activation, variety of
possible lesions depend on
i) level of complexes
ii) local activation mediators of inflammation

1) Morphology
a) early glomeruli
i) most normal
ii) juxtamedullary glomeruli - segmental solidification of one or more
lobules especially perilobular + / - hyalinosis
b) later glomeruli
i) segmental solidification + / - global sclerosis, hyalinosis and foam
cells
c) tubules
i) focal atrophy
d) interstitium
i) focal fibrosis
e) advanced
i) global glomerular sclerosis, esp. juxtamedullary region. Extensive
tubular atrophy and accompanying interstitial fibrosis

2) Immunofluorescence
a) diffuse mesangial IgM, G and C3
b) sclerotic areas secondary entrapment of IgM and C3

3) TEM
a) segmental sclerosis, overlying epithelial swelling podocyte effacement and
separation
b) subendothelial hyalinosis

Prognosis
1) % of glomeruli showing sclerotic lesions at initial biopsy significant, if >20%
then high probability of terminal RF
2) Individuals with associated diffuse mesangial hypercellularity progress more
rapidly
3) Allograft recurrence
7. Renal Pathology 167

Aetiology
Unclear - disputed claim FSGS phase of minimal change disease
(April 1978, Paper I, Question 4)

References

1) Turner, D.R. Glomerulonephritis. In: Recent Advances in Histopathology 10.

P.P. Anthony, N. Woolf (eds.) p249-254. Churchill Livingstone, Edinburgh
(1978).
2) Heptinstall, RH. Focal glomerulonephritis. In: Pathology of the Kidney. 3rd
edition, p557-600. Little, Brown & Co, Boston (1983).

Give an account of the changes that may be found in the kidney

in systemic lupus erythematosus

Introduction
Clinical features of renal involvement frequency and severity

Pathological features
1) Gross

a) granular, contracted
b) cortical infarction and haemorrhages in accelerated HT
c) superimposed pyelonephritis

2) Microscopic
a) glomeruli (lupus nephritis)
i) normal
ii) mesangial (5-10%)
iii) focal proliferative (33%)
iv) diffuse proliferative (50%)
v) membranous (10%)
additional features
i) hyaline (fibrin) thrombi
ii) tubuloreticular structures
iii) fingerprint deposits
iv) haematoxylin bodies
v) wire looping
b) tubules
i) hyaline droplets (proteinuria)
ii) haematoxylin bodies in lumina
iii) tubular atrophy
c) interstitium
i) fibrosis with tubular atrophy
ii) inflammatory infiltrate
168 Advanced Histopathology

d) vessels
i) vasculitis
ii) HT changes - benign
- accelerated
iii) renal vein thrombosis (membranous GN with nephrotic syndrome)
(October 1982, Paper2, Question 2)

Reference

1) Robbins, S.L., Cotran, R.S., Kumar, V. Diseases of immunity. In: Pathologic

Basis of Disease, 4th edition. p197-200. W.B. Saunders, Philadelphia (1989).

Discuss the mechanisms underlying the rejection of transplanted

kidneys

Introd ucti on
Clinical features
Types of rejection

Mechanisms
1) Sensitisation
a) MHC Ags
b) blood group Ags
c) minor He Ags
2) Source of Ag
a) subcellular, into host RE cells
b) donor lymphoid/haemopoietic cells
c) allograft endothelium
3) Effector mechanisms
a) cell mediated
i) macrophages (Ag presentation)
ii) T helper (Abs, lymphokines)
iii) T cytotoxic

Types of rejection
1) Hyperacute
a) pre-existing host Ab to
i) donor endothelium
ii) MHC Ag
b) effect
i) activation oJ clotting cascade
ii) ischaemic necrosis
7. Renal Pathology 169

2) Acute (two forms)

a) interstitial cellular
i) T cytotoxic cells
ii) Ab-mediated cytotoxicity
b) vascular
i) Ab deposition
ii) complement activation
iii) T cytotoxic resection to endothelium

3) Chronic
a) arterial intimal changes
i) repeated acute damage
ii) continuous platelet/ fibrin deposition
b) glomerular changes
i) subendothelial Ig
ii) plasma protein
(April 1985, Paper 1, Question 1)

References

1) Heptinstall, R.H. Renal transplantation. In: Pathology of the Kidney.

p1455-1511. Little, Brown and Co, Boston (1983).
2) Robbins, S.L., Cotran, R.S., Kumar, V. Diseases of immunity - transplant
rejection. In: Pathologic Basis of Disease, 4th edition. p183-187. W.B.
Saunders, Philadelphia (1989).

Describe the changes in the kidney when rejection follows renal

transplantation and discuss the significance of the features you
describe
(November 1973, Paper 1, Question 3)

Write a critical account of the pathogenesis and pathological

features of rejection of a transplanted kidney

This answer requires morphological changes to be discussed in addition to the

mechanism. If the question is approached considering in turn hyperacute, acute
and chronic rejection and describing morphological changes, and the underlying
mechanisms in less detail, then a full coverage can easily be provided.
(April 1969, Paper 1, Question 1)

Discuss the significance of the changes that may be found in a

human allograft

This question can be answered using kidney allografts to illustrate the answer, as
in the preceding examples.
(May 1973, Paper 2, Question 3)
170 Advanced Histopathology

Discuss the changes which have occurred in the blood vessels of

transplanted organs and discuss their significances

This question can also be answered using kidney allografts as the main
consideration. The vascular changes characterising hyperacute, acute vascular
and chronic rejection should be described. These changes are of prime pathogenic
importance in kidney rejection and their pathogenesis should be outlined.
(April 1970, Paper 1, Question 5)

Discuss the role of the mesangium in health and disease

An interesting question which highlighted the importance of this area which had
been relatively neglected in conventional teaching until recently. The morphology,
function and biochemical activity should occupy about a third of the essay, with
the remainder considering the changes in various types of glomerulonephritis,
including mesangial proliferative, mesangiocapillary, focal and diffuse prolif-
erative types, together with diabetic glomerulosclerosis and amyloidosis. It is
important to avoid a digression into the 'extramesangial' features as far as
possible. (November 1975, Paper 2, Question 3)

Reference

1) Michael, A.F. The glomerular mesangium. Contr. Nephrol. (1984) 40: 7-16.

Describe the changes in renal blood vessels and glomeruli in

diabetes mellitus and discuss their pathogenesis

Glomerular changes
1) Histopathology (+ histochemistry, EM)

2) Glomerulosclerosis
a) nodular
b) diffuse

3) Fibrin caps

4) Capsular drops

5) Thickened GBM

Arterial changes
1) Large vessels
a) atheroma
b) intimal fibrosis
7. Renal Pathology 171

Pathology + EM
1) Small vessels
a) hyalinosis (afferent & efferent arterioles)

Patho~enesis of ~lomerulosclerosis
1) Animal studies
a) injection glycosylated proteins produce changes
b) mesangial changes - response to protein accumulation
c) glomeruli increased content of PGE2 and prostacyclin
d) cultured diabetic mesangial cells produce more prostacyclin, fibronectin,
collagen I, II, IV, V.

Patho~enesis of thickened GBM

a) seen within months of onset of insulin-dependent DM
b) i glycosylated hydroxylysine-rich subunits
c) ? influence on cross-linking
d) inhibits packing of structural proteins
e) reduces proteolytic turnover
f) normal ageing of collagen i in diabetics

Patho~enesis of lar~e vessel chan~es

a) cultured medial cells - i proliferation in diabetic serum
b) also in presence of GH
c) hyperglycaemic serum
i) cytopathic to endothelial cells
ii) reduces PG secretion
(November 1969, Paper 2, Question 4)

References
1) Morley A.R. Invited review: Renal vascular disease in diabetes mellitus.
Histopathology (1988) 12: 343-359.
2) Robbins, S.L., Cotran, R.S., Kumar, V. The kidney. In: Pathologic Basis of
Disease, 4th edition. pl043-1047. W.B. Saunders, Philadelphia (1989).

Discuss the pathology of the renal complications of diabetes

mellitus
(November 1970, Paper 1, Question 2)

Discuss the pathology of the kidney in diabetes mellitus

(April 1979, Paper 1, Question 1)
172 Advanced Histopathology

Describe the changes which may be found in the kidney in

diabetes mellitus and discuss their pathogenesis
These three questions have a much broader scope, and are to some extent less
satisfactory, because there is a vast amount of information which could be covered
in addition, so the answer should be compiled in small sections, probably covering
each component of the kidney to be affected, so that blood vessels and glomeruli
are involved as in the previous essay (in less detail), tubular changes, interstitial
nephritis and acute pyelonephritis with renal papillary necrosis. An essay plan
can be formulated along these lines.
(October 1986, Paper 2, Question 3)

Discuss the pathogenesis of acute renal failure

Definition ARF

Reduction in daily urine production to less than 400 ml

Causes - six groups

1) Acute tubular necrosis (two forms) (Oliver)
a) ischaemic (tubulorrhectic) complicated shock states
b) nephrotoxic - direct damage to tubular cells
c) pathogenetic mechanisms -
i) failure of glomerular filtration due to decreased renal perfusion
ii) loss of tubular integrity
iii) tubular obstruction (interstitial oedema or intratubular casts)
iv) glomerular capillary changes - short circuit outer capillaries or
decrease capillary wall permeability
More than one of the above may occur in each case

2) Renal infarction
a) arterial
i) embolism (heart, atherosclerotic aorta)
ii) proximal disease of renal artery
iii) cortical necrosis
iv) trauma or surgical ligation of renal artery
b) venous
i) renal vein thrombosis

3) Organic occlusion of small renal vessels

Malignant hypertension, microangiopathic polyarteritis, scleroderma,

haemolytic uraemic syndrome, idiopathic post-partum acute renal failure,
sickle cell disease.
7. Renal Pathology 173

4) Severe forms of glomerulonephritis

5) Severe infections
a) acute PN
b) DIC in septicaemia

6) Obstruction to outflow
a) intraluminal causes
i) neoplasms, calculi, blood clots, sloughed renal papillae
b) extraluminal causes
i) prostatic hyperplasia, neoplastic compression, retroperitoneal fibrosis
(April 1974, Paper 2, Question 5)

Reference

1) Heptinstall, R.H. Acute renal failure. In: Pathology of the Kidney, 3rd edition.
p1069-1133. Little, Brown and Co, Boston (1983).

Write an account of the histopathology of acute renal failure.

Discuss the aetiology and pathogenesis of this condition and
relate histopathological change to pathophysiology

This question is very similar to April 1974, Paper 2, Question 5 but is more specific
and directs the candidate to headings for the essay plan. It appears slightly
ambiguous asking for histopathology of acute renal failure (ARF) which could be
either renal changes, systemic changes or both. The second sentence in the
question concentrates on the different renal changes causing acute renal failure,
these cannot be easily discussed without reference to histopathological changes.
Therefore an outline similar to that provided for April 1974, Paper 2, Question 5 is
appropriate. Each group of causes of ARF should be discussed providing brief
details of histopathological change, aetiology and pathogenesis. At the conclusion,
a brief note can be made about systemic changes in acute renal failure, these will
include oedema - especially pulmonary, sterile fibrinous pericarditis, uraemic
colitis and other possibilities e.g. secondary changes after vomiting (aspiration
pneumonitis), changes secondary to pruritus scratching, and changes associated
with liver failure often seen in severe renal failure.
(April 1976, Paper 1, Question 2)

Give an account of renal neoplasms and their effects

Benign

Rare 5% of all renal tumours

174 Advanced Histopathology

1) Mesoblastic nephroma.
a) congenital (c.f. Wilm's)
b) gross - solid yellow to grey
c) resembles fibroid
d) microscopic - cellular spindled
e) entrapped tubules and glomeruli
f) no capsule

2) An~iomyolipoma

a) 1/3 patients tuberous sclerosis, also with lymphangiomyomatosis

b) macro, yellow with haemorrhage and frequent extrarenal growth
c) micro, extrarenal lymph nodes may be involved

3) Multicystic nephroma
a) clinical - urinary obstruction by daughter lobules
b) gross - sharply defined lesion
c) microscopic - cyst wall of smooth muscle
d) stroma (striated muscle cells)

4) Adenoma
a) frequency
b) significance
c) association with dialysis kidney
d) gross
e) microscopic
f) behaviour

5) luxta~/omerular cell tumour

a) renin secreting
b) microscopic
c) EM

Malignant
1) Wilm's tumour
a) infants, occasionally congenital
b) associations
c) gross
d) microscopic

Bone metastasising renal tumour of childhood = clear cell sarcoma

- c.f. Wilm's
- prognosis
7. Renal Pathology 175

2) Renal cell carcinoma

a) gross
b) microscopic - clear cell, tubulopapillary, sarcomatoid
c) spread
d) prognosis
e) effects
f) local
i) pain
ii) mass
iii) haematuria
g) systemic
i) fever
ii) malaise
iii) weakness
iv) weight loss
v) amyloidosis
vi) anaemia
vii) polyneuromyopathy
viii) leukaemoid reaction and eosinophilia
ix) endocrine - Cushing's
- feminisation
- hypertension
- hypercalcaemia
- polycythaemia
h) metastatic

NB RCC most common recipient of metastasis from one cancer into another
(April 1983, Paper 2, Question 1)

References
1) Kashgarian, M., Rosai, J. Urinary tract. In: Ackerman's Surgical Pathology. J.
Rosai (ed.) 7th edition. p819-922. C.V. Mosby Co, St. Louis (1989).
2) Beckwith, J.B. Wilm's tumour and other renal tumours of childhood. Human
Pathol. (1983) 14: 481-492.

Discuss the pathological features, classification and possible

causation of epithelial tumours of the urinary bladder
Classification and pathological features (Mostofi - WHO)

Beni~n

1) Transitional cell papilloma (exophytic/inverted)

2) Squamous cell papilloma

3) 'Nephrogenic' adenoma
176 Advanced Hi stopathology

Malisrumt
7) Transitional cell carcinoma
a) papillary
b) flat
i) non-invasive
ii) invasive
iii) grading (1-3)
iv) behaviour
c) variants
i) squamous and glandular metaplasia

2) Squamous cell carcinoma - associated features (e.g. calculus,

schistosomiasis etc.)

3) Adenocarcinoma
a) ? metaplasia
b) ? urachal origin

4) Undifferentiated carcinoma

Causation
a) aniline dyes
i) beta-naphthylamine and biphenyls
ii) risk in dye, rubber and other workers
b) schistosomiasis
i) ? local effect - usually squamous
ii) also in bladder calculi
c) tobacco
d) tryptophane
(April 1974, Paper 1, Question 1)

References

1) Robbins, S.L., Cotran, R.S., Kumar, V. The lower urinary tract. In: Pathologic
Basis of Disease, 4th edition. pl090-1094. W.B. Saunders, Philadelphia (1989).
2) Kashgarian, M., Rosai, J. Bladder and urethra. In: Ackerman's Surgical
Pathology. Volume 1, 7th edition. p898-922. C.V. Mosby Co, St Louis (1989).

Give a classification of bladder tumours and discuss its value in

prognosis
The previous plan would include a description of the classifications of epithelial
tumours of urinary bladder, and the WHO classification referenced in this answer
is comprehensive in this respect. This classification is used by most diagnosticians
and although proposed in 1972 is still the best to use in your answer. The
prognosis of malignant bladder tumours depends on the type of tumour (e.g.
7. Renal Pathology 177

squamous cell carcinoma is much worse than transitional cell carcinoma). Other
factors to emphasise in the answer include the grade of tumour (i.e. degree of
differentiation), depth of invasion of bladder wall (and a detailed description of
the various stages) and the presence or absence of disease spread beyond bladder-
direct spread and lymphatic/haematogenous metastases. In transitional cell
tumours the separation of non-invasive from invasive carcinomas, papillary vs.
flat and the grade must be emphasised as all have great prognostic Significance.
(November 1969, Paper 2, Question 2)

Reference
1) Mostofi, F.F. et al. Histological typing of urinary bladder tumours. In:
Cassification of Tumours 19. WHO Geneva (1972).
8. Central Nervous System
180 Advanced Histopathology

Describe the likely pathological findings in a patient with

dementia
Introduction

Definition
Clinical features
Incidence

Pathology

Alzheimer's disease
1) Macroscopic
a) weight reduction
b) 'shrinkage' especially hippocampus

2) Microscopic
a) neurofibrillary tangles
i) LM
ii) EM

Other diseases with neurofibrillary tangles - Down's syndrome, boxing, Steele-

Richardson-Olszewski syndrome
b) senile plaques
i) LM - early
-late
ii) EM
c) Hirano bodies
d) neural processes

Pick's disease
1) Macroscopic

2) 'Knife-edge' Iyral atrophy

3) Microscopic

4) Pick bodies

Cerebrovascular diseas,
Difficulty in categorisation
Association with hypertension (Binswanger's disease)
8. Central Nervous System 181

1) Microscopic
a) diffuse gliosis
b) loss of myelinated fibres
c) + / - focal infarcts
d) vascular changes

Creutzfeldt-lakob Disease
1) Sponfiiform encephalopathy

2) Incidence and aetiology

3) Microscopic
a) spongiform change
b) astrocytosis
c) nerve cell degeneration and loss

Cerebral injury/anoxia
1) Microscopic
a) focal or diffuse gliosis
b) maximal in vascular boundary zones
c) ischaemic cell change
(April 1984, Paper 2, Question 5)

References

1) Janota, I. Pathology of dementia. In: Recent Advances in Histopathology II.

P.P. Anthony, R.N.M. MacSween (eds.) p49-63. Churchill Livingstone,
Edinburgh (1981).
2) Adams, J.H., Graham, 0.1. Diffuse brain damage in non-missile head injury.
In: Recent Advances in Histopathology 12. P.P. Anthony, R.N.M. MacSween
(eds.) p241-257. Churchill Livingstone, Edinburgh (1984).

Describe the naked eye and microscopical changes that may be

found post mortem in virus infections of the nervous system and
mention what investigations would be helpful in establishing the
diagnosis in each case
Introduction

Incidence
Tropism
Latency
Diagnosis - brain biopsy, immunohistology, viral probes, serology
182 Advanced Histopathology

General features of viral infection

1) Perivascular infiltrate

2) Glial nodules

3) Inclusion bodies
a) Cowdry A
b) Cowdry B
c) Negri

4) Neuronol2.hagia

Causes of viral encephalitis

1) Childhood infection - measles, mumps, rubella, varicella zoster

2) Respiratory viruses
3) Enteroviruses
4) CMV, herpes zoster, herpes simplex, arboviruses

Specific features of some viruses

1) Herl2.es siml2.lex
a) adult
i) localisation
ii) microscopic features
iii) resolution
b) neonatal
i) global
c) meningitis
d) herpes labialis
i) localisation
ii) histology

2) Herpes zoster
a) localisation
i) brain
ii) spinal cord
b) histology

3) Poliomyelitis
a) acute
i) macroscopic
b) chronic
ii) microscopic
8. Central Nervous System 183

4) Rabies
a) localisation
b) microscopic

5) Slow viruses
a) subacute sclerosing panencephalitis
i) gross
ii) microscopic
iii) EM and immunohistology
b) progressive multifocalleucoencephalopathy
i) associations
ii) gross
iii) microscopic
iv) EM
c) ?Jakob-Creutzfeldt disease - microscopic
i) EM
(November 1973, Paper 2, Question 2)

Reference

1) Morris, J.H. The nervous system - viral diseases. In: Pathologic Basis of
Disease. S.L. Robbins, R.S. Cotran, V. Kumar (eds.) 4th edition. p1382-
1388. W.B. Saunders, Philadelphia (1989).

What are the pathological effects of viruses on the nervous

system?
(April 1983, Paper 2, Question 3)

Describe the pathological changes that may occur in the brain

after infection by
1) Toxoplasma gondii
2) Cryptococcus neoformans
3) Mycobacterium tuberculosis
There is abundant information which can be introduced into each of these
categories, and would probably best be laid out by short side headings with
concentrated information. It is important to include congenital disease in these
conditions, and the effect of immunosuppression on disease patterns.
(November 1976, Paper 1, Question 5)

Describe the changes that occur in the central nervous system in

demyelinating diseases and discuss the causes and mechanisms
that are implicated

It is important to define what the term 'demyelinating diseases' actually refers to.
Demyelination may occur in other conditions where there is white matter
184 Advanced Histopathology

degeneration (such as motor neurone disease, subacute combined degeneration of

the cord etc.), but the demyelinating diseases primarily include multiple sclerosis
and its variants (see following paragraphs for pathogenetic considerations); acute
disseminated encephalomyelitis as a hypersensitivity autoimmune phenomenon
along with necrotising haemorrhagic leucoencephalitis (primary vasculitis),
leucodystrophies (unborn errors in myelin metabolism) and progressive multi-
focalleucoencephalopathy (viral infection). There are other rare conditions such
as central pontine myelinolysis or Marchiafava-Bignami disease in alcoholics
which might be mentioned. Thus, there is a lot of ground to be covered in this
answer. One example from each group should be chosen to illustrate the changes
both macroscopic and microscopic, since they are individually distinctive, before
considering pathogenesis. (April 1981, Paper 1, Question 5)

References

1) McDonald, W.1. The pathogenesis of multiple sclerosis: the Bradshaw lecture

1986. Journal Royal ColI. Phys. London (1987) 21(4): 287-294.
2) Robbins, S.L., Cotran, R.S., Kumar, V. In: Pathologic Basis of Disease, 4th
edition. p1422-1426. W.B. Saunders, Philadelphia (1989).

Describe the pathology of multiple sclerosis and discuss its

pathogenesis
This would be a straightforward account, considering the gross and microscopic
changes in the various stages of the disease, including immunohistochemical
studies on the lymphoid populations. The various theories of pathogenesis can be
considered in some depth, including currently topiC aspects of primary venulitis
or relation to human immunodeficiency virus infection. In the earlier question, the
aetiological factors are considered in relation to the pathogenetic mechanisms.
(April 1977, Paper 2, Question 2)

Reference

1) McDonald, W.1. The pathogeneSis of multiple sclerosis: the Bradshaw Lecture

1986. Journal Royal ColI. Phys. London (1987) 21(4): 287-294.

Describe the lesions in the central nervous system in multiple

(disseminated) sclerosis. Discuss modern concepts in aetiology
(November 1970, Paper 2, Question 4)

Give a critical review of the theories of the aetiology of multiple

(disseminated) sclerosis
This question is somewhat more difficult to answer, as the aetiological agents are
unknown, and thus the pathogenetic hypotheses still have to be considered in
depth. It would be justifiable to discuss these as before, pointing out the support
8. Central Nervous System 185

each hypothesis lends for a particular aetiological agent. Questions phrased in this
fashion are responsible for much of the failure to appreciate the distinctions
between aetiology and pathogenesis in the minds of examination candidates.
(November 1976, Paper 1, Question 2)

Discuss the aetiology and pathogenesis of the lesions found in

Alzheimer's disease
Description of lesions
1) Macroscopic
a) weight down
b) cortical atrophy - frontal temporal, posterior parietal

2) Microscopic
a) neuronal loss
i) neocortical large pyramidal cells of layers III and V
ii) hippocampal pyramidal cells in Sommer's sector
iii) para hippocampal cortical stellate neurones of lamina II
iv) nucleus basalis of Meynert (quantitative study)
v) locus ceruleus
b) results of neuronal loss
i) neurofibrillary tangles (Nfl)
ii) senile plaques (SP)
iii) granulovacuolar degeneration
iv) Hirano bodies

Aetiology
Unknown

1) Possibilities
a) toxic environmental agent
i) virus
ii) aluminium
iii) others
b) hereditary factors
c) Down's syndrome - ?gene location

Pathogenesis
1) Down's syndrome studies
a) SP - amyloid protein precedes peripheral plaque neurites
b) Nfl - in all damaged cell types
- ? reactive to toxic change
Aluminium levels in diet and within affected brains? toxic
186 Advanced Histopathology

Interference with nerve function by NFfs by

a) crowding out of cell organelles
or
b) interruption axoplasmic flow

Significance of granulovacuolar degeneration and Hirano bodies unclear

(April 1987, Paper 1, Question 5)

References

1) Mann, D.M.A. The neuropathology of dementia. Bull. Royal ColI. Pathol.

(1988) 64: 8-10.
2) Glenner, G.G. Current topics - on causative theories in Alzheimer's disease.
Human Pat hoI. (1985) 16: 433-435.

What changes may be found at necropsy in a subject who died

with a significant increase in intracranial pressurel
Introduction
Clinical features
Definition (CSF > 15 mm Hg)

General features
1) Herniation
a) subfalcine herniation
b) uncinate or tentorial herniation
c) cerebellar tonsils ('coning')
d) contralateral damage
2) Compression effects on brain and ventricles

Secondary effects
Vascular compression
Pontine haemorrhages
e.g. Posterior occipital artery occlusion and calcarine infarction

Causes of raised intracranial pressure

1) Tumours - intra and extracerebral
Macroscopic features
a) meningioma
b) glioma
c) lymphoma
d) secondary carcinoma
8. Central Nervous System 187

2) Cerebral abscess

3) Intracerebral haemorrhage

4) Extra cerebra I haemorrhage

5) Cerebral oedema
a) infections
b) lead encephalopathy
c) trauma

6) Adult hydrocephalus
a) neoplasms
b) inflammation
(April 1986, Paper 2, Question 2)

Reference

1) Morris, J.H. The nervous system. In: Pathologic Basis of Disease.

S.L. Robbins, R.S. Cotran, V. Kumar (eds.) 4th edition. p1388; 1389.
W.B. Saunders, Philadelphia (1989).

Describe in detail the effects on the intracranial contents of an

expanding lesion in the left cerebral hemisphere
(April 1972, Paper 1, Question 3)

Describe the findings at necropsy in a subject who died with

greatly raised intracranial pressure due to a rapidly-expanding
lesion of the left cerebral hemisphere

Similar questions but which need more detailed consideration of circumscribed,

rapidly expanding lesions, predominantly haemorrhagic or perhaps infective.
(October 1979, Paper 2, Question 3)

Reference

1) Morris, J.H. The nervous system. In: Pathologic Basis of Disease.

S.L. Robbins, R.S. Cotran, V. Kumar (eds.) 4th edition. p1388; 1389.
W.B. Saunders, Philadelphia (1989).

A man of 60 develops a right hemiplegia and some impairment of

consciousness over 2-3 days. What are the likely causesl
Describe the pathology of one of these

A question along similar lines to the preceding ones, with the addition of
cerebrovascular disease, cerebral infarction being the most likely cause. In view of
188 Advanced Histopathology

the familiarity of most pathologists with these appearances, it is suggested that

this be developed for the final part of the question.
(November 1974, Paper, 2, Question 4)

Discuss the pathogenesis of intracranial haemorrhage and

describe the relevant post-mortem appearances

Introduction
1) Classification
a) cerebral
b) subarachnoid
c) subdural
d) mixed

Cerebral
1) Pathouenesis
a) hypertension
b) trauma
c) aneurysm
d) vascular malformation
e) bleeding diathesis

2) Macroscopic features
a) location
b) early
i) secondary effects of intracranial expansion
ii) location in trauma
c) late
i) changes in hypertensive disease

3) Microscopic features

Subarachnoid
1) Pathouenesis
a) Berry aneurysms
i) location
ii) structure
iii) cause of rupture - HT
-trauma
b) hypertensive
c) 'mycotic' aneurysms
8. Central Nervous System 189

2) Macroscopic features
a) early
b) late

3) Microscopic features
a) aneurysm structure

Extradural

1) Pathogenesis
a) trauma to middle meningeal artery

2) Macroscopic features

Subdural

1) Pathogenesis
Acute
a) bridging vein tear

2) Macroscopic features
Chronic
a) clinical features

3) Microscopic features

Mixed

1) Tumours

2) Arteriovenous malformations
(October 1983, Paper 1, Question 1)

Reference

1) Morris, J.H. The nervous system - intracranial haemorrhage. In: Pathologic

Basis of Disease. S.L. Robbins, RS. Cotran, V. Kumar (eds.) 4th edition.
p140S-1411. W.B. Saunders, Philadelphia (1989).

Discuss the aetiology and pathogenesis of strokes

This is the type of question which all pathologists should be able to answer
adequately without any revision, since it is an important cause of morbidity and
mortality. For the same reasons, such questions tend to be poor discriminators,
which may account for their non-appearance in subsequent examinations.
(May 1973, Paper 1, Question 1)
190 Advanced Histopathology

A patient suffered several transient cerebral ischaemic attacks

before death. Describe how you could demonstrate the cause of
the attacks' at post mortem laying special emphasis on the
methods of examination of the cerebral circulation

Introduction
Definition of TIA
Clinical features
Association with cerebral infarction

Pathogenesis
1) Atherosclerosis
a) emboli
b) flow reduction

2) Thrombosis in atherosclerosis

3) Emboli
a) heart (SABE, atria in AF, ventricles, MI)
b) bone marrow (trauma)
c) sites of lodgement
i) middle cerebral (90%)
ii) others

4) Pathology
a) lacuna stroke
i) motor paresis
ii) sensory paresis
b) cerebral haemorrhage - macroscopic
c) embolic infarct - macroscopic appearance

Vascular dissection
1) Aorta
a) orifices of carotid and vertebral arteries

2) Carotid arteries
Sites
a) bifurcation
b) carotid sinus

3) Vertebral arteries
a) anatomy
b) method of dissection
8. Central Nervous System 191

Removal of brain

Vascular supply to brain

(October 1986, Paper I, Question 3)

Reference

1) Morris, J.H. The nervous system - vascular disease. In: Pathologic Basis of
Disease. S.L. Robbins, R.S. Cotran, V. Kumar (eds.) 4th edition. pl402-
1411. W.B. Saunders, Philadelphia (1989).

Discuss the factors which determine the distribution of infarcts of

the brain
It would be important to avoid the temptation to go into macroscopic and
microscopic features in the evolution of cerebral infarction, as the question clearly
calls for an account of the vascular pathology, including local arterial disease, (e.g.
atherosclerosis, thrombosis) abnormality in the supply to the cerebral vessels
(carotid, vertebral or aortic disease), cerebral infarction secondary to cardiac
disease, and embolic phenomena. A description of the arterial supply to the brain
would be of great value, including an outline of collateral supply, and a diagram
may help in this respect. Infarction due to venous occlusion also deserves
consideration, and is easily overlooked. (April 1969, Paper 2, Question 2)

Reference

1) Morris, J.H. The nervous system - vascular disease. In: Pathologic Basis of
Disease. S.L. Robbins, R.S. Cotran, V. Kumar (eds.) 4th edition. p1402-
1411. W.B. Saunders, Philadelphia (1989).

Describe and discuss the morbid anatomical changes in the brain

that may be produced by chronic hypoxia
Hypoxia is a term embracing several states which impair the consumption of
oxygen by the brain, namely stagnant hypoxia (with ischaemia) pure hypoxia
(seldom occurring naturally except at birth and at high altitude), anaemic hypoxia,
and hypoglycaemia (lack of glucose impairs uptake of oxygen by neurons). By
approaching the answer in this manner most candidates should be able to
formulate a reasonable answer, but this is regarded as one of the more difficult
questions which have been set. (November 1972, Paper 2, Question 4)

Reference

1) Blackwood, W., Corsellis, J. Cerebral hypoxia. In: Greenfield's Neuropathology.

W. Blackwood (ed.) p43-85. Edward Arnold, London (1976).
192 Advanced Histopathology

Describe the changes which occur in the central nervous system,

and elsewhere, in syringomyelia, and speculate as to how the
changes may be caused

A very interesting question, requiring more than usual thought in its preparation.
Initially this seems to be a narrow, rather specialised pathology, but the secondary
effects due to the dissociated sensory loss and motor weakness may be wide-
ranging. A diagram illustrating the distribution of the lesions in a cross section of
a spinal cord could be included. There is ample scope for speculation on
mechanisms in 'primary' and 'secondary' syringomyelia. Having said this, it
would probably be better to avoid this type of question if easier options are
available. (October 1978, Paper 2, Question 5)

Give an account of the primary tumours located in the posterior

cranial fossa in children and adults

A fairly straightforward question especially for candidates who have completed a

neuropathology attachment. One way of approaching this is to consider the
anatomical contents of the posterior fossa, i.e. cerebellum, pons and medulla,
choroid, nerves (including the auditory nerve) meninges, blood vessels, and then
describe the most important tumours arising from them in each group. Where
there is some overlap (e.g. adult medulloblastomas), only describe the major
differences rather than duplicating the common features. Tumours that require
description include in children, astrocytoma, ependymoma, medullobastoma and
haemangioblastoma, and in adults ependymoma, astrocytoma, glioma, choroid
plexus papilloma, neurilemmoma and meningioma.
(October 1986, Paper 2, Question 5)

Reference

1) Rosai, J. Neuromuscular system - tumors. In: Ackerman's Surgical

Pathology. Volume 2, 7th edition, p1724-1771. C.V. Mosby Co, St Louis (1989).
9. Osteoarticular Pathology
194 Advanced Histopathology

Discuss genetic diseases of bone

It is probably best to approach this by briefly explaining the difference between

congenital disease of bone, which often has an environmental influence (e.g. spina
bifida, congenital syphilis, etc.) and those which have a defined genetic and
hereditary component. Then explain the different types of disease, including
clinical features, mode of transmission, pathological abnormalities and complicat-
ions and pathogenesis if known. Suggested entities are osteogenesis imperfecta,
achondroplasia, osteopetrosis, osteochondromatosis, enchondromatosis. Also
involvement of the bones as a major feature in hereditary disorders such as
storage diseases or Maffuci's syndrome should be considered, without expanding
on the extraskeletal manifestations. Polymorphisms closely linked to the gene for
some disorders, e.g. osteogenesis imperfecta are available for diagnosis, and
should also be mentioned briefly. (April 1980, Paper 2, Question 5)

Reference
1) Robbins, S.L., Cotran, R.S., Kumar, V. The musculoskeletal system. In:
Pathologic Basis of Disease, 4th edition. p1315-1345. W.B. Saunders,
Philadelphia (1989)

Describe the possible macroscopic and microscopic findings in an

autopsy on a 60 year old woman who had refused further
investigation or treatment after repeated findings of
hypercalcaemia and hypophosphataemia over a period of four
months before death
Hypercalcaemia (and consequent hypophosphataemia) may result from several
conditions, of which malignancy is probably the commonest cause. Tumours
include myelomatosis and secondaries from breast or lung cancers for example,
and a brief comparison of the findings in such cases may be made. Although some
tumours elaborate calcium mobilising substances without skeletal metastases,
these should not be discussed in great detail as it is not something which can be
surmised from the macroscopic or microscopic findings, except from a negative
aspect. Hyperparathyroidism should be discussed in detail, including both the
various features of the parathyroid glands, in primary hyperparathyroidism, and
the effects on the bones and kidneys. The period of four months cited in the
question may indicate that the gross changes (osteitis fibrosa cystica) would
probably not be apparent, but microscopic diagnpsis may be made. Renal changes
in primary (calculus formation, nephrocalcinosis) and tertiary hyperparathy-
roidism (primary renal disease) may be described. Mention should be made of
multiple endocrine neoplasia syndromes. Other causes of hypercalcaemia could
be discussed such as milk alkali syndrome, sarcoidosis, etc, but again it should be
noted that the mechanisms are not required, only relevant pathological features.
This is the type of question where very close attention must be paid to the
wording. (April 1974, Paper 1, Question 3)
9. Osteoarticular Pathology 195

Reference

1) Robbins, S.L., Cotran, R.S., Kumar, V. The endocrine system. In: Pathologic
Basis of Disease, 4th edition. p1243;1244. W.B. Saunders, Philadelphia (1989).

Describe the various changes that may be found in the bones in

chronic renal failure including patients on haemodialysis. Discuss
the pathogenesis of the various lesions
Introduction

Types of bone disease in CRF

Incidence
Symptomatology

Osteitis fibrosa
1) Accelerated bone resorption

2) Paratrabecular marrow fibrosis

3) Osteocytic osteolysis

4) Increased bone function with osteoid and woven bone

Quantitative measurements
a) excessive osteoid covered trabeculae
b) normal seam width
c) normal mineralisation rate

Osteomalacia
1) Increased extent of osteoid seams (undecalcified bone)

2) Reduced mineralisation front (toluidine blue)

Quantitative measurements
a) increased osteoid seam thickness
b) reduced mineralisation rate (double tetracycline labelling)

Osteosclerosis

Increased mineralised woven bone

Osteoporos i s
Rare - in steroid therapy or elderly
196 Advanced Histopathology

Pathogenesis
1) Hypocalcaemia due to
a) renal retention of P04
b) intestinal malabsorption of Ca2+ in CRF
c) ? defective Vit 03 suppression of parathyroids compensatory i in PTH
2) Osteomalacia due to
a) ? defective In hydroxylation of 250HCC
b) systemic acidosis in CRF alters Vit 0 metabolism
c) hypophosphataemia in Fanconi syndrome, renal tubular acidosis, etc.

Haemodialysis
1) Osteitis fibrosa and osteomalacia

Pathogenesis
a) P04 binding resin
b) dialysis
c) anticonvulsants
d) unknown

2) Dialysis and osteomalacia

a) symptoms
b) osteomalacia with little osteitis fibrosa
c) inactive osteoid seams, ..t. mineralisation front
d) normal alkaline phosphatase

Pathogenesis
a) aluminium toxicity
b) bone measurements, animal toxicity
c) reduction after deionisation
(October 1982, Paper 2, Question 1)

Reference

1) Ellis, H.A. Metabolic bone disease. In: Recent Advances in Histopathology 11.
P.P. Anthony, R.N.M. MacSween (eds.) pI85-202. Churchill Livingstone,
Edinburgh (1981).

What lesions of bone may be found in chronic renal failurel

Discuss their pathogenesis
(November 1973, Paper 1, Question 2)
9. Osteoarticular Pathology 197

Describe the macroscopic and microscopic changes which may

develop in bone secondary to renal disease
There is abundant material to write on in this answer ranging from the clinical
and radiological features of renal osteodystrophy and its pathological
consequences, to the microscopic features best described in the earlier stages on
bone biopsy, including osteomalacia, secondary hyperparathyroidism and osteo-
sclerosis, with a detailed description of morphometric analysis (including
dynamic measurements such as tetracycline labelling). A discussion on dialysis
osteomalacia should also be included. (April 1972, Paper 1, Question 4)

Describe the macroscopic and microscopic changes in bone

affected by Paget's disease (osteitis deformans). What are the
complications of this disease?
(April 1971, Paper 2, Question 2)

Write an essay on Paget's disease of bone

(NB Good writing style and paragraph construction required)

Introduction
Osteitis deformans
General features
Pathological definition - remodelling of bone in a coarser mould
Incidence and epidemiology

Clinical features

Monostotic/polyostotic

2) Symptoms
a) asymptomatic
b) deformity
c) arthritis
d) pain
e) fractures
f) nerve compression (optic, auditory, vertebral, etc.)
g) heart failure

3) Investigations
a) i alkaline phosphatase, normal calcium, phosphorus, and PTH
b) radiographic features - osteolytic, mixed, sclerotic
198 Advanced Histopathology

4) General patholoBY
a) sites - pelvis> skull> femur> spine> tibia> humerus> jaw
b) loss of corticomedullary distinction and enlargement
c) consistency - early - porous late - sclerotic
d) deformity

5) Microscopic
a) osteolytic phase
i) disorganised osteoclastic activity
ii) morphology of osteoclasts
b) osteoblastic response
i) stromal vascularisation
ii) haphazard matrix deposition
iii) 'mosaic' reversal lines with osteoid persistence at margins
iv) subperiosteal
c) sclerotic phase
i) J, osteoclasis
ii) osteoblastic activity leads to bone thickening

Com pi ications
1) Pathological fractures

2) Haemodynamic changes
a) bone hypervascularity
b) arteriovenous shunting
c) osteogenic sarcoma
i) incidence 1%
ii) distribution
iii) pathology
iv) behaviour

Aetiology
1) Previous theories
a) inborn error of connective tissue
b) autoimmune disorder

2) Recent? 'slow' viral infection

a) tubular viral structures in osteoclasts on EM
b) immunocytochemistry
Absence of antibody response or isolation of virus
(April 1983, Paper 1, Question 4)

Reference
1) Ellis, H.A. Metabolic bone disease. In: Recent Advances in Histopathology 11.
P.P. Anthony, R.N.M. MacSween (eds.) p185-202. Churchill Livingstone,
Edinburgh (1981).
9. Osteoarticular Pathology 199

Discuss the mechanisms involved in the pathogenesis of

osteomalacia and outline the histopathological techniques used in
its assessment
Introduction
Vitamin 0 deficiency in adults
Clinical features
General functions of Vitamin 0

Metabolism of Vitamin D
1) Skin
a) 70HC converted to 03 (UV light)

2) Diet
a) 03 (animal products)

3) Absorption
a) small bowel
b) transported to liver
c) 25 hydroxylation
d) la hydroxylation
e) 1,25 (OH)203 in kidney

4) Receptors
a) small intestine villus cells for 1,25 (OH)203
b) osteoblasts
c) renal tubular cells

S) Actions of Vitamin D
a) intestinal absorption of calcium
b) mobilises calcium and phosphorus at bone interface with PTH
c) renal tubular resorption

Factors involved in deficiency

1) Vitamin D3 lack
a) dietary insufficiency
b) insufficiency of UV light
c) malabsorption - various causes

2) Chronic renal failure

a) failure of la hydroxylation
b) acidosis
200 Advanced Histopathology

3) H)1JQPhosphataemia
a) renal tubular acidosis
b) Fanconi syndrome

4) Hereditary disease
a) Vitamin D dependent rickets

5) DruB induced
a) anticonvulsants

Assessment of osteomalacia
1) Bone biopsy
a) undecalcified sections - surface osteoid estimation
i) percentage of surface of osteoid seams (n<30%)
ii) thickness of polarised seams (n<3 'bright lines')
iii) total bone mass
b) decalcified sections
i) mineralisation fronts (Toluidine blue)
ii) mineralisation rate (double tetracycline labelling)
iii) osteoclast concentration
iv) osteoblast activity
(April 1982, Paper 1, Question 4)

References

1) Ellis, H.A. Metabolic bone disease. In: Recent Advances in Histopathology 11.
P.P. Anthony, RN.M. MacSween (eds.) pl85-202. Churchill Livingstone,
Edinburgh (1981).
2) Eastwood, J.B. Quantitative bone histology in 38 patients with advanced renal
failure. J. Clin. Pathol. (1982) 35: 125-134.

Describe the effects of Vitamin D deficiency on the skeletal

system

This should include an outline of Vitamin D metabolism and osteomalacia as

outlined in the previous question, together with a substantial section on rickets.
(May 1973, Paper 2, Question 2)

Describe the methods available for measurement of the relative

amount of osteoid in a bone biopsy. Discuss the value of such
quantititation in the diagnosis of metabolic bone disease

(October 1980, Paper 2, Question 5)

9. Osteoarticular Pathology 201

Discuss the uses and limitations of biopsy in the diagnosis of

metabolic disease of bone, and give an account of the histological
techniques you would employ to obtain as much information as
possible from a sample

The latter question involves expanding the outline of the morphometric and
dynamic measurements, and relating this to the findings in the major forms of
metabolic bone disease; osteomalacia, osteoporosis, chronic renal failure and
hyperparathyroidism.

The 1978 essay pre-<iates the widespread use of double-labelling techniques for
dynamic measurements, and thus some of the limitations are overcome. Others
include sampling error, complex situations such as renal failure with its multi-
factorial effects, and the possibility of misleading results from fracture sites, etc.
Otherwise the outline is very similar to the previous plan (April 1982, Paper 1,
Question 4). (Odober 1978, Paper 2, Question 2)

Give an account of the causes of hyperparathyroidism. What

corresponding bone changes may be presenH

The causes of hyperparathyroidism should include a discussion of primary

(adenoma, hyperplasia, carcinoma), secondary (chronic renal failure, malabsorp-
tion, hyperca1citoninaemia) and tertiary forms.

The bone changes need to be clearly discussed with respect to the increase in
number of both osteoclasts and osteoblasts in hyperparathyroidism. Abundant
osteoclasts result in numerous resorption lacunae, (erosion of phalangeal tufts)
and formation of brown tumours (diaphysis, ribs, jaw). A mention of the early
sensitive and specific sign of paratrabecular fibrosis is required. Hyperosteoidosis
is a feature of hyperparathyroidism and needs to be differentiated from osteo-
malacia using tetracycline labelling (include a comment on the relevant aspects of
bone morphometry, as discussed in the previous examples).
(April 1988, Paper 2, Question 2)

Reference

1) Revell, P.A. Metabolic bone disease. In: Pathology of Bone. pl13-146.

Springer-Verlag, Berlin (1985).

An elderly woman with backache is found to have a collapsed

lumbar vertebra and diffuse decrease in bone density of the spine.
List the possible underlying causes, indicating their relative
probability and explain how laboratory investigations could help
in reaching a diagnosis

Essentially a question about osteomalacia and osteoporosis in another form, the

underlying causes are wide ranging. The laboratory investigations not only
202 Advanced Histopathology

include the biochemical and histological evaluation of metabolic bone disease, but
in the investigation of the underlying causes such as malabsorption syndrome,
renal disease, Cushing's syndrome, etc. It is important to understand that the
underlying causes relate more to the metabolic bone disease than other factors
which may lead to collapsed vertebrae e.g. myeloma or secondary
carcinoma - these would be unlikely to produce a picture of diffuse decrease in
spinal bone density. (April 1976, Paper 1, Question 5)

Describe the structural changes in the bones in osteoporosis, and

discuss its causation
There is relatively little information which can be provided on the exact aetiology
of osteoporosis, but some of the metabolic alteration and associations could be
discussed. The structural alterations are relatively straightforward, but this type
of essay might prove quite difficult to answer in the examination situation because
of the relatively restricted amount of information which could be provided,
certainly by the average pathologist. (November 1971, Paper 2, Question 1)

Describe briefly the normal mechanism of bone formation and

destruction. How may the processes be altered in diseasel
The answer involves a discussion of normal bone metabolism and turnover as
already outlined, but the second part of the answer could essentially involve all
forms of metabolic bone disease, perhaps with the effects of secondary carcinoma
or even primary bone tumours as well. However, the wording of the question is
quite subtle, in that it is the alteration of the processes, and not the pathological
consequences that requires description. It could either be approached by
describing the altered mechanism in each disease state, or taking each individual
component (e.g. osteoclast, osteoblast, fibroblast, etc.) and illustrate how their
function may alter in response to such disease. This would require considerable
thought to be given in advance of the examination; it would be difficult to
organise an approach like this during it. (November 1977, Paper 1, Question 2)

Discuss the differential diagnosis of cysts in bone

Introduction
Meaning of 'cyst'
Radiological versus pathological cysts

1) Simple cyst
a) sites
b) clinical and radiographic features
c) gross pathology
d) histopathological appearances
9. Osteoarticular Pathology 203

2) Ganglion cyst
a) sites
b) radiological appearance
c) histological appearance

3) Epidermoid cysts
a) sites
b) radiological features
c) histological appearance (middle ear infection)

4) Joint disease
a) osteoarthritis
i) macroscopic
ii) microscopic
b) rheumatoid disease
i) inflammatory
ii) degenerative
c) villonodular synovitis
i) microscopic

5) Aneurl!.smaJ bone cyst

a) sites
b) clinical features
c) radiological changes
d) gross pathology
e) microscopic

6) Hl!.datid disease
a) sites
b) radiological features

7) Jaw cysts
a) radicular cyst
b) follicular cyst
c) fissural cysts
d) odontogenic cysts
(October 1985, Paper 1, Question 2)

Reference
1) Dahlin,D.C. Unni, K.K. Conditions that simulate primary neoplasms of bone,
and odontogenic and related tumours. In: Bone Tumours. 4th edition,
p356-440. Charles C. Thomas, Illinois (1986).
204 Advanced Histopathology

Write an essay on benign tumours of bone

It would clearly be impossible to cover all of the benign bone tumours with any
depth, unless emphasis was given to the commoner ones and those which require
particularly careful evaluation (e.g. giant cell tumour). Headings and discussion
of each entity could be made separately, but it might be preferable to use a formal
essay style, perhaps to compare aspects of the differential diagnosis of benign
bone tumours. Entities to consider are chondroma, chondroblastoma, chondro-
myxoid fibroma, osteoma, osteoid osteoma, osteoblastoma, giant cell tumour,
non-ossifying fibroma, with brief mention of others such as haemangioma,
neurofibroma, etc. (October 1978, Paper 1, Question 5)

Reference

1) Dahlin, D.C., Unni, K.K. Chapters 2-13. In: Bone Tumours. 4th edition,
pl8-192. Charles C. Thomas, Illinois (1986).

Discuss the application of synovial biopsy to diagnosis

This question may have been prompted by the appearance of the cited reference.
Some candidates may require a broader range of knowledge in order to make a
comprehensive, balanced answer, as the article in question only seeks to cover
certain selected aspects in detail. The commoner diagnostic problems, especially
acute and chronic synovitis, are mentioned briefly but would require considerable
elaboration for an adequate review. An alternative approach would be to use
some introductory paragraphs to explain the non-specific features in many
inflammatory processes, and concentrate on the more characteristic features
which would enable a specific diagnosis to be made, as outlined in Table 6.1 of the
reference. It is important for candidates to recognise that answers to questions
using wording such as 'Discuss' allow considerable flexibility, providing the
omission of certain topics is acknowledged and briefly justified.
(November 1988, Paper 1, Question 2)

Reference

1) Revell, P.A. The synovial biopsy. In: Recent Advances in Histopathology 13,
Chapter 6, p79-93. Churchill Livingstone (1987).

Discuss the pathogenesis of rheumatoid disease

(October 1986, Paper 2, Question 1)

Discuss the aetiology of rheumatoid disease

These two questions illustrate the necessity of understanding the distinction
between aetiology and pathogenesis, although there is a tendency for the two to
become confused when the aetiology, i.e. cause, is not certain. The pathogenesis
9. Osteoarticular Pathology 205

deals with the mechanisms which lead to the tissue damage, and in this sort of
disease, the aetiology, although to be considered, would playa relatively minor
part in the overall answer. (Odober 1984, Paper 1, Question 4)

Reference

1) Robbins, S.L., Cotran, R.S., Kumar, V. Joints and related structures. In:
Pathologic Basis of Disease, 4th edition. p1349-1354, W.B. Saunders,
Philadelphia (1989).

Describe the post-mortem findings in a woman who died of

rheumatoid arthritis. Indicate the significance of the lesions to
the disease as a whole
This answer should be fairly straightforward, with both articular lesions and
systemic associations requiring description, concentrating on the macroscopic
appearances. The extra-articular complications are more likely to account for the
demise of the patient, and should be assessed accordingly.
(April 1970, Paper 2, Question 4)

Discuss the non-articular lesions associated with rheumatoid

arthritis
Since the type of rheumatoid arthritis is not stated, both juvenile and adult forms
could be considered. The approach should be on a systematic basis, discussing
lymphoreticular changes, rheumatoid nodules, cardiac, pulmonary and vascular
changes, including immunopathology when appropriate. It is suggested that the
more tenuous associations (e.g. complications of therapy) are avoided as far as
possible. (April 1972, Paper 2, Question 5)
10. Reproductive System
208 Advanced Histopathology

Discuss the impact that the widespread use of synthetic

oestrogens and progesterone has had on the practice of
gynaecological pathology

At first glance this is not an easy question, but with a little reflection most surgical
histopathologists would have encountered many examples of tissue changes
connected with these agents. There are two ways to approach this answer, either
by describing the general category of usage (e.g. contraception, dysfunctional
uterine bleeding, management of carcinoma, etc.) or the changes induced by each
particular agent (or combination) and its effect on normal and pathological states.
It is important to firstly describe in detail the effect on normal tissues (endomet-
rium and cervix predominantly), and their effects on pathological conditions, (e.g.
endometrial hyperplasia, endometrial carcinoma) together with some conse-
quences of such therapy, in particular the diethylstilboestrol syndrome, and
potential effects on other tissues such as breast and liver (which could justifiably
be included). In order to answer this question adequately, it is important to relate
the difference that not only the effect of these agents has had on the pathology of
submitted specimens, but what changes there have been in nature and numbers of
material sent for examination in order to monitor the effects of treatment,
requiring somewhat broader scope than mere descriptive pathology.
(November 1974, Paper 1, Question 4)

References
1) Buckley, C.H. Pathology of contraception and of hormonal therapy. In:
Obstetrical and Gynaecological Pathology. H. Fox (ed.) Volume 2. Chapter 20,
p839-873. Churchill Livingstone, Edinburgh (1987).
2) Campbell, 1.S. et al. Iatrogenic disease of the female genital tract. ibid
p882-888.

Describe the tissue changes that have been attributed to oral

contraceptive therapy
(May 1973, Paper 2, Question 4)

What adverse effects may result from orally administered

oestrogensl

These two questions share much common ground, but it should be noted that the
second does not restrict itself to contraception since it includes oestrogens taken
orally in later life for the purpose of hormone replacement and also for the
treatment of prostatic carcinoma. The term 'tissue changes' in the first question
strictly includes the desired action of oral contraceptives (both combined and
progestagen-only types) on the reproductive system, as well as possible systemic
effects (e.g. venous thrombosis or atherosclerosis) while the second question does
not require a discussion of the primary action. The reference given contains a
good discussion of effects on the endometrium, cervix, vagina, ovary,
cardiovascular system, breast and liver. (April 1978, Paper 2, Question 3)
10. Reproductive System 209

Reference

1) Buckley, C.H. The pathology of contraception. In: Obstetrical and

Gynaecological Pathology. H. Fox (ed.) 3rd edition. p847-889. Churchill
Livingstone, Edinburgh (1987).

Write an essay on neoplasia of the uterine cervix

Introduction

Spectrum of diseases
Incidence of ca cervix vs. other tumours
Clinical features and diagnosis

1) Squamous
a) classification and nomenclature
b) pathological features
c) cytological diagnosis
d) pathogenesis
i) epidemiology and incidence
ii) viral infection
-HPV
-HSV
e) management
i) role of pathologist
ii) role of cytologist
2) Glandular
a) pathological features
b) cytology
c) relationship to squamous CIN

Invasive carcinoma
1) Squamous
a) relationship to CIN
b) microinvasive disease
i) definition
ii) diagnosis
iii) prognosis
c) larger tumours
i) classification
ii) spread
iii) prognosis
210 Advanced Histopathology

2) Adenocarcinoma
a) classification and pathology
b) behaviour
c) spread
d) rare variants
i) ciliated (serous)
ii) mucinous
iii) carcinoid
iv) oat cell carcinoma
e) Peutz-Jeghers' disease (adenoma malignum)
f) management

Mesenchymal tumours

Beni~n

7) Leiomyoma
a) pathological features

Ma1i~nant

7) Sarcoma botryoid
a) pathological features
2) Mixed Miillerian tumours

3) MUllerian adenosarcoma

4) Lymphoma

5) Leiomyosarcoma
(October 1986, Paper 2, Question 4)

References

1) Anderson, M.C. Premalignant and malignant disease of the cervix. In:

Obstetrical and Gynaecological Pathology. H. Fox (ed.) 3rd edition. p255-301.
Churchill Livingstone, Edinburgh (1987).
2) Brescia, R.J. et al. The role of human papilloma viruses in the pathogenesis
and histologic classification of precancerous lesions of the cervix. Human
Pathol. (1986) 17: 552-558.

'Carcinoma of the cervix is a disease that is eradicable from the

community'. Discuss this statement
This essay requires a structured plan more than most, as with questions which
have a scope as broad as this one there is a danger of producing an imbalanced
10. Reproductive System 211

and partly irrelevant discourse, a concentration on quantity rather than quality.

The answer should be divided into two parts, the first considering the premise
that the pre-invasive and early stages of carcinoma of the cervix are detectable by
exfoliative cytology, and treatable by various means. In addition, the significance
of minor degrees of cervical dysplasia should be considered. The second part of
the answer should consider the reasons for the present inability to eradicate the
disease, including social and logistical factors (e.g. efficiency of recall systems)
and technical aspects (e.g. screening failures). The subject is topical at present and
highly likely to be set again. There are frequent reviews in pathology and general
medical journals (e.g. British Medical Journal and The Lancet) on aspects of this
subject which are usually worth reading, and assessments of the efficiency of the
national computer recall system will emerge in the next few years.
(November 1976, Paper 2, Question 2)

References
1) Reid, B.L. Causation of cervical carcinoma. In: Clinics in Obstetrics and
Gynaecology. A. Singer (ed.) Chapter 1, pI-I8. W.B. Saunders, Philadelphia
(1985).
2) Hudson, E.A. The place of the cytological smear test. ibid. p33-52.

Discuss the role of viruses in the aetiology of disorders of the

cervix uteri
The previous essay included some reference to the role of viruses, but there is now
so much information in the literature, with abundant review articles, that most
modem pathologists would be able to write a detailed essay on this subject. The
issue is still contentious, however, and a balanced view should be taken to
encompass the role of herpes viruses as well as human papillomavirus. The
epidemiological evidence together with oncogenic properties of these viruses
should be discussed, along with the pathological evidence (e.g. morphological,
immunocytochemical, in situ hybridisation), for their associations. It is relevant
that Koch's postulates have still not been fulfilled in respect of virus-associated
carcinomas, but the theoretical basis for this is complicated, to say the least.
(April 1987, Paper 1, Question 3)

Reference
1) Anderson, M.C. Premalignant and malignant diseases of the cervix-
viruses. In: Obstetrical and Gynaecological Pathology. H. Fox (ed.) 3rd
edition. p261-265. Churchill Livingstone, Edinburgh (1987).

Write an account of trophoblastic tumours

A question which is somewhat difficult to answer because of the vagueness of the
term 'tumour'; is a partial or even complete hydatidiform mole to be regarded as
a tumour in the neoplastic sense, or within a broader context? This is one situation
where an introductory paragraph would be used to clearly define the
212 Advanced Histopathology

understanding of the term and justify the inclusion of these entities. It is fairly
obvious that atypical and typical choriocarcinomas should be described in detail,
together with the differential diagnosis from a normal placental implanted site
('syncytial endometritis'). It would probably not be justifiable to include chorio-
carcinomatous differentiation in teratomas of the testis, but this might be
mentioned in passing, or in desparation. (April 1979, Paper 2, Question 1)

Reference

1) Elston, C.W. Gestational trophoblastic disease. In: Obstetrical and

Gynaecological Pathology. H. Fox (ed.) 3rd edition. p1045-1078. Churchill
Livingstone, Edinburgh (1987).

Give an account of the pathology, including the pathogenesis of

hydatidiform mole

A more circumscribed question which is relatively straightforward to answer. A

more detailed account of the pathogenesis is required, and a comprehensive
account may be found in the previous references.
(November 1975, Paper 2, Question 2)

How would you differentiate between the various types of

endometrial hyperplasiaJ

It is probably best to approach this answer by describing the various forms into
hyperplasia with or without cytological and architectural atypia, defining the
point at which frank carcinoma can be diagnosed. This should be an easy question
for any working histopathologist providing a structured framework is used.
(April 1974, Paper 1, Question 2)

Reference

1) Hendrickson, M.R., Kempson, R.L. Endometrial hyperplasia, metaplasia and

carcinoma. In: Obstetrical and Gynaecological Pathology. H. Fox (ed.) 3rd
edition. p354-361. Churchill Livingstone, Edinburgh (1987).

Give an account of malignant neoplasms of the uterus other than

carcinomas

This question lends itself very well to being answered in small sections concerning
each entity, and is best divided into tumours of proposed endometrial origin, and
those from the myometrium and uterine wall. The former group include the
mixed Mullerian tumours, such as malignant mixed Mullerian tumour, of which a
detailed account should be made with mention of the rarer variants such as
adenosarcoma. Endometrial stromal sarcoma, low grade and high grade require
10. Reproductive System 213

consideration. Choriocarcinoma, both typical and 'atypical' (placental site

trophoblastic tumour), although not strictly of uterine origin, should be included
in your account, and could be easily overlooked.

Sarcoma botryoides of the cervix could be covered briefly, but the major emphasis
in non-endometrial malignancies should be given to leiomyosarcomas and the
various criteria for diagnosis in the well differentiated forms. Brief descriptions
could be made of tumours such as haemangiopericytoma or other sarcomas which
rarely affect the uterus, and possibly lymphoma although it is probably not a
primary site. (October 1979, Paper 2, Question 5)

References

1) Kempson, R.L., Hendrickson, M.R. Pure mesenchymal neoplasms of the

uterine corpus. In: Obstetrical and Gynaecological Pathology. H. Fox (ed.)
3rd edition. p 411-456. Churchill Livingstone, Edinburgh (1987).
2) Honore, L.H. Mixed Miillerian tumours of the uterus. ibid p457-478.

Discuss the primary malignant tumours of the uterus

There are so many entities involved in answering this question that there would
be little time for anything other than a brief discussion. One device might be to
exclude tumours of the uterine cervix, explaining the reasons in an introductory
paragraph. Discussion could then be confined to endometrial carcinoma and other
entities considered in the answer to October 1979, Paper 2, Question 5, or
problems such as the distinction between epithelial hyperplasia and neoplasia in
the endometrium, or on the criteria for diagnosis of malignancy in smooth muscle
tumours. This would have to be a selective essay which could be adapted to suit
each individual's areas of greatest interest or knowledge.
(November 1970, Paper 2, Question 2)

Give an account of the histopathology of ovarian carcinoma and

relate this to its biological behaviour

A very straightforward essay which includes a consideration of serous, mucinous,

endometrial, clear cell and undifferentiated carcinomas. Germ cell tumours such
as yolk sac tumour and choriocarcinoma could reasonably be included, together
with metastatic carcinoma and a brief reference to carcinomas in cystic teratomas.
A reasonable proportion of the essay should be devoted to a consideration of
'borderline' tumours including criteria for diagnosis, and behaviour.
(April 1975, Paper 1, Question 5)

References

1) Russell, P. Common epithelial tumours of the ovary. In: Obstetrical and

Gynaecological Pathology. H. Fox (ed.) 3rd edition. p556-622. Churchill
Livingstone, Edinburgh (1987).
2) Nogales, F. Germ cell tumours of the ovary. ibid p637-675.
214 Advanced Histopathology

Describe the pathology of fibrocystic disease of the breast

<excluding sclerosing adenosis) and discuss its aetiology and
significance

The most authoritative discussion of this subject is to be found in this reference,

but adequate though less comprehensive coverage can be found in general texts of
pathology. The subject is bedevilled by an excess of terminology, and further
confused by transatlantic differences (e.g. papillomatosis vs. epitheliosis). Fibro-
cystic disease (or better, cystic disease) should be strictly defined according to the
guidelines provided in the reference. (April 1986, Paper 1, Question 5)

Reference

1) Azzopardi, J.C. Terminology, plus cystic disease and duct ectasia. In:
Problems in Breast Pathology. p23-38; 57-91. W.B. Saunders, Philadelphia
(1979).

Discuss the pathological appearances which may be seen in

testicular swellings

Introduction
Testis and epididymis
Clinical features
Pre-operative investigations
Role of biopsy

Acquired diseases

Inflammation
1) Generalised infection
a) viral
i) mumps
- pathological features
ii) coxsackie
iii) other
b) bacterial
i) TB
- pathological features
ii) syphilis
- pathological features
iii) others
1o. Reproductive System 215

2) Localised infection
a) bacterial
i) gonorrhoea
- pathological features
- non-specific
- usually epididymitis
- chlamydial
ii) actinomyces
- pathological features
3) Non-infective/unknown
a) granulomatous orchitis
i) pathological features
ii) malakoplakia

Trauma
1) Haematoma

2) Torsion

Neo.plasia
1) Germ cell tumours
a) seminoma
i) clinical features
ii) gross pathology
iii) microscopic appearances
iv) (+ spermatocytic variant)
b) embryonal carcinoma
i) microscopic features
c) yolk sac tumour
i) microscopic features
ii) immunohistochemistry (AFP)
d) choriocarcinoma
i) microscopic features
ii) immunohistochemistry (HCG)
e) teratomas
i) mature
ii) immature
iii) malignant
o combined tumours
2) Sex cord - stromal
a) Leydig cell tumours
i) gross features
ii) microscopic
b) Seroli cell tumours
i) microscopic
c) granulosa cell tumours
216 Advanced Histopathology

3) Lymphomas
a) primary
i) 'mucosa associated'
ii) B cell
iii) large cell NHL
iv) ? Hodgkin's disease
b) disseminated
i) leukaemia/lymphoma

4) Secondary carcinoma
(April 1984, Paper 2, Question 3)

Reference

1) Robbins, S.L., Cotran, R.S., Kumar, V. Male genital system. In: Pathologic
Basis of Disease. 4th edition, pll04-1116. W.B. Saunders, Philadelphia (1989).

Discuss the cytological and histopathological aspects of the

investigation of infertility in the male
A fairly straightforward question, but which might pose some problems for those
candidates who have not had experience in semen analysis. The only way to really
understand this technique is to become involved at some stage during training.
The histopathological aspects do not only involve the use of testicular biopsy, as
extragonadal causes of infertility require some consideration (e.g. pituitary
disease, haemochromatosis, etc.). (May 1973, Paper 1, Question 5)

Reference

1) Lennox, B. The infertile testis. In: Recent Advances in Histopathology 11. P.P.
Anthony, R.N.M. MacSween (eds.) pI35-148. Churchill Livingstone,
Edinburgh (1981).
11. Dermatopathology
218 Advanced Histopathology

Discuss the pathology and differential diagnosis of bullous

diseases of the skin
A sensible approach to this group of disorders is provided in the first reference,
where the distinction between vesicle and bulla is avoided by the use of the term
'blister'. Within this term there are seven groups, a mixture of anatomical and
aetiological blisters; a) subepidermal b) blister following intracellular degenerat-
ion c) spongiosis d) acantholytic e) viral 0 basal cell degeneration and g)
basement membrane degeneration. Several conditions fall within each group, but
the main features of the most important condition should be included. Details of
the role of immunofluorescent techniques in the diagnosis should be included in
such an answer. (October 1983, Paper 2, Question 1)

References
1) Mackie, RM., Young, H. Use of the immunofluorescence technique in
diagnostic dermatopathology. ACP Broadsheet no. 110. (April 1984).
2) Meyrick-Thomas, RH. et al. The value of immunofluorescent techniques in
the diagnosis of skin diseases. In: Recent Advances in Histopathology 12. P.P.
Anthony, RN.M. MacSween (eds.) p69-81. Churchill Livingstone, Edinburgh
(1984).

Give an account of the histopathology of the skin in disorders

whose cutaneous lesions are manifestations of systemic disease
Systemic diseases could include conditions as wide-ranging as infections (e.g.
leprosy, tuberculosis, streptococcal sore throat, bacterial endocarditis), connective
tissue disorders (e.g. SLE, rheumatoid disease), various malignancies or indicators
of internal malignancy such as Cowdens, Leser-Trelat syndromes or acanthosis
nigricans, and immunosuppressed states (although it could be argued that
localised tumours do not constitute a systemic disease, whereas lympho-
proliferative disorders could be). Other systemic diseases could be discussed such
as sarcoidosis, drug eruptions, metabolic diseases (e.g. amyloidosis) as well as
rare conditions like glucagonoma syndrome or acrodermatitis enteropathica for
instance. There is enough potential information in the suggested categories to
supply material for several essays, therefore each candidate could select these
areas with which they are most familiar, while still providing a balance.
(November 1974, Paper 1, Question 5)

References
1) Lever, W.F., Schaumburg-Lever, G. Systemic diseases with cutaneous
manifestations. In: Histopathology of the Skin. 6th edition, p190-197 (and
other sections in addition). J.B. Lippincott Co, Philadelphia (1983).
2) Staughton, RC.D. Cutaneous manifestations of malignancy. Br. J. Hosp. Med.
(1978) 20: 38-47.
11. Dermatopathology 219

Discuss the interpretation of lymphocytic infiltrates in the skin

This question has been tailor-made for a candidate familiar with the article in
reference 1). It should include a description of the features of malignant cutaneous
lympho-proliferative conditions, including immunohistochemical features,
together with the spectrum of benign infiltrates. A consideration of differentiation
of benign from malignant lesions is best included after the descriptive sections.
Immunohistochemical features must be mentioned but need not be expanded at
the cost of an adequate discussion of benign entities. The answer should recognise
that at the present time, even with immunohistochemical marking techniques,
there are some cases that it will not be possible to characterise with certainty and
an equivocal report will be indicated. As with all dermatopathological work, the
value of clinicopathological exchange should be emphasised.
(April 1988, Paper 1, Question 5)

Reference

1) Slater, D.N. Lymphoproliferative conditions of the skin. In: Recent Advances

in Histopathology 12. P.P. Anthony, R.N.M. MacSween (eds.) p83-110.
Churchill Livingstone, Edinburgh (1984).

Give an account of pigmented tumours of the skin and discuss

their histological diagnosis

This includes an overview of benign and malignant tumours, and would necessar-
ily be very brief on each entity. Emphasis should be made on diagnostically
difficult benign tumours (e.g. Spitz naevus, dysplastic naevus) and malignant
melanoma. (April 1976, Paper 2, Question 4)

Describe the histopathological features which correlate with

prognosis in melanotic lesions of the skin
(April 1983, Paper 1, Question 3)

Discuss the difficulties in the diagnosis and assessment of

prognosis of melanin-containing tumours of the epidermis and
upper dermis

These answers all require concentration on malignant melanoma, but in addition

lesions which cause diagnostic difficulty should be described such as shave
naevus, benign epithelioid cell naevus (benign juvenile melanoma), spindle cell
naevus (Reed's tumour) and dysplastic naevus. There would be a large amount of
factual information to cover in the time available, and liberal use of side headings
and note form would almost certainly be required for a comprehensive answer.
(April 1975, Paper 2, Question 3)
220 Advanced Histopathology

Outline a classification of malignant melanoma and discuss

possible prognostic indices

Introduction
Classification
Radial and vertical growth phases - general features
General criteria of malignancy
Histologist's role in management - overview

Macroscopic examination

1) Description and measurement

2) Block selection

Lentigo maligna melanoma

1) Radial growth phase

2) Epidermal atrophy
3) Melanocyte nests

4) Vertical growth phase

a) spindle/epithelioid cells
b) desmoplasia
c) neurotropism

Acral lentiginous melanoma

1) Radial growth phase

a) large dendritic melanocytes
b) small nests
c) lichenoid lymphocytic infiltrate

2) Vertical phase
a) spindle cells
b) neurotropic

Superficial spreading melanoma

1) Radial
a) epithelioid cells
b) fine pigment
c) nests and single cells
d) intra-epidermal patterns
11. Dermatopathology 221

2) Vertical
a) epithelioid
b) rare desmoplasia and neutropism
c) little inflammation

Nodular melanoma
1) No radial phase
a) ? early nodular development
2) Vertical Browth phase
a) often nodular

Evaluation of risk

1) Thickness ranBe
a) < 0.76 mm
b) 0.76-1.5mm
c) > 1.5 mm

2) ProBnosis
a) 88% 5 year survival
b) 61% 5 year survival
c) 32% 5 year survival

3) Level of invasion
(Clark's classification I-V - detail)
Combined data of level and thickness - low, moderate and high risk groups.

4) Site (BANS)

5) Mitotic index

6) Host lymphocytic response

7J ReBional lymph node status

(April 1979, Paper 1, Question 4)

References

1) Clark, W.H. et al. The biologic forms of malignant melanoma. Human Pathol.
(1986) 17: 443-450.
2) Lever, W.F., Schaumberg-Lever, G. Melanocytic naevi and malignant
melanoma. In: Histopathology of the Skin. 6th edition, p702-723. }.B.
Lippincott Co, Philadelphia (1983).
222 Advanced Histopathology

Discuss the histological evaluation of malignant melanoma of the

skin
(October 1985, Paper 1, Question 1)

What is the role of the histopathologist in the diagnosis and

management of melanocytic lesions of the skinl
(April 1986, Paper 2, Question 5)
12. Miscellaneous
224 Advanced Histopathology

There has been a worldwide decrease in the hospital post

mortem rate in recent years. Discuss the reasons for the decrease
and suggest ways by which it could be reversed

Introduction
Post mortem rate ratios
Hospital and coroners' PMs
Aims of PM-Medical Audit

Reasons for decline

1) Clinical demand
a) more accurate ante mortem diagnosis
b) aesthetic objections
c) infectious hazards
d) fear of contradiction - legal considerations
e) lack of prompt, relevant information
f) lack of relevance to patient management
g) cost effectiveness
h) reduced demand for tissue material e.g. pituitaries

2) Lack of pathological demand

a) concentration on surgical pathology
b) alterations in teaching practice
c) lack of clinical interest and 'prestige'
d) infection hazards
e) labour intensiveness
f) demands from coroner's PMs

3) Insufficient demand for epidemiological data

a) education and interaction
b) critical assessment of data

4) Succestions for reversal

a) clinicopathological conferences
b) improved 'aesthetics' in necropsy suite
c) increased teaching role
d) higher medical audit status
e) research involvement
f) adequate level of funding
g) academic prestige
h) training and refresher courses
i) high level investigation into role of autopsy
j) college symposia
, 2. Miscellaneous 225

Conclusion

1) Personal outlook

2) General attitudes

3) Future trends
(October 1986, Page 1, Question 5)

References

1) Robinson, M.J. The autopsy, 1983; can it be revived? Human Pathol. (1983) 14:
566-568.
2) Smith, C. The autopsy diagnosis. Human Pathol. (1986) 17: 645-647.
3) Peacock, S.J. et al. The autopsy: a useful tool or an old relic? J. Pathol. (1988)
156: 9-14.
4) Reid, W.A. Cost effectiveness of routine postmortem histology. J. Clin. Pathol.
(1987) 40: 459-461.

Discuss the value of the routine hospital autopsy

(October 1988, Paper 2, Question 1)

Give a critical account of the laboratory procedures in all

pathology disciplines other than routine histological studies that
may be of use in an autopsy performed within four hours of
death

There are clearly many procedures which can be described in this answer. The
important point to remember is that a mention of many is better than an in depth
comment on only a few, and will reflect a 'rounded' education. Procedures to be
covered include biochemical analysis of ocular fluid (electrolytes, glucose),
microbiological examination, serological examination of blood, histochemical
examination of tumours, cytogenetic examination and drug screens (gastric
contents, liver, urine, blood, bile). Extraction of DNA is useful in looking for
genetic defects in which the gene locus can be identified, and chromosomal
analysis can be performed for karyotypic disorders. Rapid removal of tissue for
isolation of RNA is also useful by southern blotting or in situ hybridisation,
especially in determining the presence of gene expression for enzymes.
Fibroblastic cells may also be cultured from tissues after death to investigate gene
expression disorders. (November 1977, Paper 2, Question 5)

Discuss quality control in histopathological and cytological

diagnosis

This is a most important area, and it is perhaps surprising it has been so neglected
in the examination. There is a danger that such an essay could lend itself to an
226 Advanced Histopathology

overlong and rather anecdotal discourse, so that it would be advisable to discuss

the reasons for quality control in technical and clerical aspects, and suitable inter-
nal procedures, and which can be justified since these inevitably have a bearing
on diagnostic reporting. The bulk of the essay is concerned with the accuracy of
diagnosis, which is best assessed using external quality control schemes.
(April 1975, Paper 1, Question 1)

References
1) Underwood, J.C.E. Quality assessment and control. In: Introduction to
Biopsy Interpretation and Surgical Pathology. 2nd edition, Chapter 12.
Springer-Verlag. Berlin (1987).
2) Lee, F.D., Burnett, R.A. Quality assurance in histopathology. J. Pathol. (1987)
152: 247-251.
3) Cooke, R.A. Quality control in anatomic pathology: experience in Australia
and New Zealand. S.c. Sommers (ed.) Pathology Annual Part 1, p221-248.
W.B. Saunders, Philadelphia (1984).

In a hospital laboratory service, it is essential that there should

be no errors in relating each specimen and report to the right
patient. Describe how such errors may arise in a surgical
histopathology service for a general hospital, and state the steps
you would take to avoid them
This question is clearly aimed to those candidates with experience in a busy
service laboratory, rather than the 'academic' pathologist who would be at a dis-
advantage. The wording clearly indicates that a very practical and simple answer
is required, detailing the passage of a specimen from theatre to pathological filing
and issue of the report, and could well be approached on this chronological basis,
discussing each step along the way. It is important to consider responsibilities of
the pathologist as head of department in the routine laboratory where the tissue is
processed, cut and stained, and not merely at the dissection and reporting stages.
Quality control is a rather peripheral issue to this question, but may merit some
consideration. (April 1974, Paper 2, Question 1)

Describe the office systems, quality controls, library facilities and

continuing training required by a hospital histopathologist
Another question which is directed at the service histopathologist rather than an
academic. Much of the essay would be based on a candidate's own experience
within a service laboratory, concerning the specimen reception systems in labora-
tory and secretarial office, together with reporting and filing systems, including
advantages or otherwise of computer storage and recall with pathological coding
systems. Quality control is discussed in the previous essay and the library facilities
and continuing training are matters of compromise between the ideal and the
practicalities of a service post. Consideration of the merits of mandatory accredit-
ation may be a suitable topic, but there is abundant scope for discussion in this
question. (October 1980, Paper 1, Question 5)
12. Miscellaneous 227

Reference

1) Morrow, J.S. Information systems in surgical pathology. In: Ackerman's

Surgical Pathology. J. Rosai (ed.) Volume 2. 7th edition, appendix B,
pI955-1978. C.V. Mosby Co, St. Louis (1989).

Discuss the role of the electron microscope in routine diagnostic

morbid anatomy
(April 1969, Paper 1, Question 4)

Discuss the role of electron microscopy in diagnostic

histopathology
Both of these questions are essentially similar and cover several groups of diseases
in which ultrastructural features may provide a diagnostic role. At least some of
these functions have been usurped by immunohistochemistry in recent years, and
facilities such as scanning electron microscopy have a very limited function in
diagnostic work. Transmission EM is probably of most value in the investigation
of renal disease, and this may form a substantial part of the answer. Other
applications include cellular pathology (e.g. detection of virus particles, or in
storage disorders), and tumour pathology, where the range of applications can be
very wide. Small cell tumours of childhood might provide some illustrative
examples. In a comprehensive review, it would be justifiable to include a brief
mention of energy dispersive X-ray analysis ('EDAX') in detection of non-organic
material, and immunolocalisation at the EM level. In the future, a more critical
approach to the value of electron microscopic examination may well be required,
calling on the candidate to justify the use of this expensive facility.
(November 1975, Paper 2, Question 4)

Reference

1) Mclay, A.L.C., Toner, P.G. Diagnostic electron microscopy. In: Recent

Advances in Histopathology 11. P.P. Anthony, R.N.M. MacSween (eds.)
Churchill Livingstone, Edinburgh (1981).

What methods are available to demonstrate mucosubstances

(mucins) in histological materian Discuss their value in diagnosis
and research. Details of technical methods are not required
This question requires a considerable amount of organisation to avoid repetition
in a potentially confusing area. The first part of the answer should describe the
basic composition of mucins and their distribution in tissues. A small table may·
suffice with different sorts of mucin (neutral, acid, sulphated and non-sulphated,
etc.), the tissue/cell distribution and methods of demonstration. It is important
not to forget about connective tissue mucins, and the enzymic digestion
techniques used in the assessment of some mucins must also be considered (e.g.
228 Advanced Histopathology

hyaluronidase, diastase). Diagnostic uses cover the recognition of mucin in poorly

differentiated adenocarcinoma, highlighting otherwise inconspicuous malignant
cells (e.g. signet ring cells in gastric carcinoma biopsy), demonstration of connect-
ive tissue type mucin in malignant mesothelioma, or in benign conditions such as
myxoedema and mucoid degeneration of the aorta. Research applications require
more thought, but one of the major topical issues is the claim that certain
metaplastic alterations of epithelia in the gut indicate pre-neoplastic potential.
Other components of mucins have recently been identified, such as epithelial
membrane antigen (EMA) and its use in research and diagnosis could be
evaluated, along with the emergence of lectin-binding studies which bind to
specific sugars in mucin side chains, and the variation in different disease states.
Wide-ranging questions such as this are particularly difficult to answer in a
satisfactory manner. (October 1986, Paper 1, Question 4)

References

1) Cook, H.C. Carbohydrates. In: Theory and Practice of Histological

Techniques. J.D. Bancroft, A. Stevens (eds.) 2nd edition, p180-216. Churchill
Livingstone, Edinburgh (1982).
2) Ramesar K.C.R.F., et al. Limited value of type III intestinal metaplasia in
predicting risk of gastric carcinoma. J. Clin. Pathol. (1987) 40: 1287-1290.
3) Gevers, W. Review article. Mucus and mucins. South Afr. J. Med. (1987) 72:
39-42.

Describe the techniques available to pathologists for the

demonstration of immunoglobulins in tissue sections. How may
these be of value in diagnostic histopathologyl

The skilled eye can suspect the presence of immunoglobulins, particularly in

glomeruli, in sections stained with H&E, PAS and toluidine blue. However, the
question clearly requires a discussion of immunochemical methods. In 1977 only
immunofluorescence was readily available, but now peroxidase and alkaline
phosphatase methods are available, along with enhancement techniques such as
immunogold-silver. The methodologies of the three techniques could be outlined,
mentioning their strengths and drawbacks and then discussion of their applicat-
ions, which presently are mainly in renal, dermatological and lymphoreticular
pathology. This question is considerably easier to answer with the benefit of
practical experience. (April 1977, Paper 1, Question 4)

References

1) Gatter, K.c., Falini, B., Mason, D.Y. The use of monoclonal antibodies in
histopathological diagnosis. In: Recent Advances in Histopathology 12. P.P.
Anthony, R.N.M. MacSween (eds.) p35-67. Churchill Livingstone, Edinburgh
(1984).
2) Meyrick-Thomas, R.H., Black, M.M., Bhogal, B. The value of
immunofluorescence techniques in the diagnosis of skin disorders. In: Recent
Advances in Histopathology 12. P.P. Anthony, R.N.M. MacSween (eds.)
p69-81. Churchill Livingstone, Edinburgh (1984).
12. Miscellaneous 229

Discuss the value of special staining techniques as an aid to

diagnosis in a routine histopathology laboratory.

This is a question put just when the potential of immunohistochemical staining by

light microscopy was beginning to be observed, but clearly more conventional
special stains would need to be discussed, a point which might have been over-
looked by a candidate who had in mind the last question (April 1979, Paper 2,
Question 3) which had been set in the previous examination. The following
question illustrates how a different aspect of staining was included in the second
paper. (October 1979, Paper 1, Question 5)

Describe the principles of immunohistochemical localisation of

antigens in routine paraffin sections. How has this technique
advanced accuracy of diagnosis in routine surgical pathology
practicel
(October 1980, Paper 1, Question 3)

Discuss the value of immunofluorescence in the histopathological

diagnosis and assessment of human disease

The question is directed towards the advantages of this technique in diagnosis

rather than the limitations, and appropriate weight should be given to uses in
renal, skin, tumour pathology and others. The assessment of human disease is a
broad term but presumably relates to the applications in immunological disease
or dermatopathology, for example. (October 1979, Paper 2, Question 3)

Discuss the role of immunofluorescent techniques in diagnostic

histopathology
The answer should be broadly the same as the preceding question, but with
expansion of the section on diagnosis. Nevertheless, inclusion of disease assess-
ment could probably be justified with an appropriate introductory sentence.
(November 1976, Paper 2, Question 1)

'If all staining methods other than haematoxylin and eosin were
abandoned, routine diagnostic histopathology would be quite
unaffected'. Discuss this assertion

This question antedates the expansion of immunohistochemical techniques, but

would naturally encompass all special stains and limited immunofluorescence
and the suggested method is to assess which techniques are required in each
particular system, with appropriate emphasis on their relative worth e.g.
methenamine silver in renal biopsy, reticulin stain in the liver, elastic stain in
cardiovascular pathology, etc. Also note that use of routine excludes research and
educational usage. (November 1969, Paper 1, Question 5)
230 Advanced Histopathology

What are the advantages and limitations of immunocytochemistry

in tumour pathologyl
(April 1987, Paper 1, Question 4)

Give a general account of the uses and limitations of

immunohistochemistry in histopathological diagnosis

The answer should include the uses of both fluorescent and light microscopic
techniques, and contrast the limitations and advantages of each.
(April 1979, Paper 2, Question 3)

'The use of monoclonal antibodies as laboratory reagents will

revolutionise diagnostic histopathology'. Give your views on this
statement, mentioning the principle of the production of such
reagents and giving examples of their possible uses

This question is very open-ended, and can be assessed more easily now with
retrospective information. Broadly speaking the statement is true, but the crux of
the matter is the relative ability of these techniques to improve diagnostic ability.
The emphasis should be laid on the essential advantages of monoclonal over
polyclonal antibodies. The principles of production of monoclonal antibodies
should not be overstated, occupying one or two paragraphs, or preferably
expressed by simple diagrams. (April 1982, Paper 2, Question 4)

Outline the present and possible future applications of

immunohistochemistry
(October 1983, Paper 1, Question 2)

Discuss the desirable contents of a code of safe practice

appropriate to a histopathology department, including the post
mortem suite
(October 1981, Paper 1, Question 2)

What are the safety hazards in performing a routine necropsy

and how may they be reducedl
(October 1979, Paper 1, Question 4)

Discuss health and safety in departments of histopathology. Refer

particularly to the handling of fresh tissues for frozen sections
and post mortems in cases of viral hepatitis and tuberculosis
(April 1980, Paper 2, Question 4)
12. Miscellaneous 231

What advice and instructions would you give to a newly

recruited mortuary technician concerning hazards from infection
in the post mortem suite

These questions obviously require more concentration on specific hazards in the

post mortem room. The recommended approach is to discuss general aspects of
dress and hygiene, post mortem room design and maintenance, technique of post
mortem examination and avoidance of infective risk from trauma, aerosol, etc.
and then to approach specific types of infection according to the classification
outlined in the Howie Report. (October 1983, Paper 1, Question 3)

Discuss the safety measures you would require to be observed

within a histopathology laboratory

These questions are clearly intended to provide an overview of the whole issue,
and it is very easy to be drawn into specific issues. One example should be used
fFom each category discussed, if at all. The use of the word 'including' means that
the discussion on the post mortem suite must be maintained in proportion and not
as the major aspect. (April 1984, Page 2, Question 2)

Reference

1) Department of Health and Social Security. Code of Practice for the Prevention
of Infection in Clinical Laboratories and Post-mortem rooms. HMSO, London
(1980).

Discuss the present and prospective value of quantitative

techniques in histopathology

Introducti on

Meaning of term 'quantitation'

General areas of application
Role of modern technology in quantitation

1) Applicability
a) detection of disease showing subtle deviation from normal values
b) improvement of objectivity in documentation
c) comparison of therapeutic response
d) facilitation of statistical analysis
232 Advanced Hi stopathology

2) Techniques
a) area/volume proportion
i) point counting
b) surface area
i) intercept measurement
c) complex measurements
i) numbers of objects/unit volume (computer assisted)
ii) size of included features
d) counts/unit area e.g. intestinal intraepitheliallymphocytes

Specific application

1) Metabolic bone disease - osteomalacia and osteoporosis

a) measurements
i) percentage trabecular surface osteoid
ii) percentage trabecular volume osteoid
iii) extent of mineralisation front
iv) mineralisation rate (double tetracycline labelling)
v) osteoblast/ osteoclast surface concentration
b) value
i) borderline/early disease otherwise missed
ii) monitoring of response to therapy

2) lejunal biopsy
a) measurements
i) villous status
ii) intraepithelial lymphocyte count
b) value
i) use in borderline villous atrophy and response to therapy
ii) coeliac disease contains increased epithelial lymphocytes

3) Pulmonary disease - emphysema and chronic bronchitis

a) measurements
i) alveolar air spaces (emphysema)
ii) Reid index (chronic bronchitis)
b) value
i) assessment of emphysema and clinicopathologic correlation

4) Muscle biopsy - congenital myopathy and polymyositis

a) measurements
i) fibre size
ii) fibre type proportions
b) value
i) diagnosis of myopathy vs myositis may depend on quantitation
ii) type of myopathy dependent in quantitation
12. Miscellaneous 233

5) Nerve biopsy - demyelinating disease

a) fibres/unit area
b) internodal lengths on teased fibres

6) Testicular biopsy - investigation of fertility

a) tubule diameter
b) spermatogenesis - Johnsen count

Prospective uses in neoplasia

1) Tumourlstroma ratio

2) Cell size in hyperplasia vs. carcinoma

3) Nucleolar organiser regions

4) Mitotic indices (e.g. in sarcomas)

(April 1981, Paper 2, Question 4)

References

1) Beck, J.S., Anderson, J.M. Quantitative methods as an aid to diagnosis in

histopathology. In: Recent Advances in Histopathology 13. P.P. Anthony,
R.N.M. MacSween, (eds.) p255-269. Churchill Livingstone, Edinburgh (1987).
2) Underwood, J.C.E. Introduction to Biopsy Interpretation and Surgical
Pathology. p121-130. Springer-Verlag, Berlin (1987).
3) Marchevsky, A.M., Gil, J., Jeanty, H. Computerised interactive morphometry
in pathology. Human Pathol. (1987) 18: 320-331.

Discuss the need for measurement in pathology

A broad question, with a danger that the candidate may be tempted to just write
as examples come to mind, thus illustrating the value of an essay plan. It should
be noted that this question is concerned with measurement in general and is not
restricted to morphometry and stereology. One approach is to divide the answer
into value of measurement in routine surgical pathology, autopsy pathology,
special uses of more specialised quantitative techniques in diagnostic work and
finally mention of research applications. In surgical pathology there are many
situations in which macroscopic specimens require weighing, measuring for
maximum dimension or assessment of volume, e.g. hyperplastic endometrial
curettings. Equally, microscopic measurement can be vital e.g. determination of
microinvasion in cervical squamous carcinoma, and depth of maximum invasion
of melanoma. Examples in autopsy work include assessment of organ atrophy,
hypertrophy, valve circumference in the heart, body measurements in neonates,
etc.

More specialised quantitative techniques are required for accurate assessment of

severity of pulmonary emphysema. The use of more specialised quantitative
techniques is discussed in the last essay plan (April 1981, Paper 2, Question 4),
where references are listed. (November 1975, Paper 2, Question 1)
234 Advanced Histopathology

In recent years increasing attention has been paid to quantitative

methods in morbid anatomy and histopathology for assessing the
severity of disease. Describe some of these methods and their
application to specific problems

This answer has a somewhat narrower scope which is a consequence of the

relatively restricted range of applications at the time it was set. As can be seen
from the length of the previous essay plan, which was of necessity rather overlong
and yet is by no means comprehensive, the best approach may be to select a
number of examples to illustrate aspects of the technique. Bone biopsies and
pulmonary emphysema would probably be the most popular choices. Future
questions on this theme may well restrict the scope by virtue of the wording.
(April 1972, Paper 1, Question 2)

Describe how you would measure the dimensions and area of an

irregularly shaped pathological lesion in a histological section~
How would you determine the proportion of an organ replaced
by discrete areas of disease visible to the naked eye~

Dimensions are easily measured using a calibrated eye piece graticule,

standardised by a known dimension that can be placed on the microscope stage
e.g. commercially available calibrated histological slides. This process should be
described from the basis of experience which all candidates should have had in
measuring dimensions e.g. depth of invasion of a melanoma or micro-invasive
squamous carcinoma of cervix. The assessment of surface area is more complicat-
ed but can be done by photographing the lesion at known magnification, and
using a planimeter. These days it is easier to use a digitising tablet and get a
computer to do the hard work!

Secondly, determination of the proportion of an organ replaced by discrete areas

of disease visible to the naked eye is best achieved using the Delesse principle.
This states that volume is proportional to surface area in random planes of the
object, and can be readily measured by a point-counting procedure. This principle
and methods of its practical application are well described in the second reference.
(October 1979, Paper 2, Question 1)

References
1) Beck, }.S., Anderson, }.M. Quantitative methods as an aid to diagnosis in
histopathology. In: Recent Advances in Histopathology 13. P.P. Anthony,
R.N.M. MacSween (eds.) p255-269. Churchill Livingstone, Edinburgh (1987).
2) Underwood, }.CE. Introduction to Biopsy Interpretation and Surgical
Pathology. 2nd edition, pI21-130. Springer-Verlag, Berlin (1987).
3) Ellis, M.A. Metabolic bone disease. In: Recent Advances in Histopathology 11.
pI85-202. P.P. Anthony, R.N.M. MacSween (eds.) Churchill Livingstone,
Edinburgh (1981).
12. Miscellaneous 235

Describe how you make a quantitative assessment of a) the

amount of emphysema in a lung and b) the amount of osteoid in
a bone biopsy

This question allows a concentration on two of the best known applications of

morphometric analysis which most candidates should have had practical
experience of. The necessary information is given in the previous references.
(April 1980, Paper I, Question 3)

Describe the techniques you would use in the interpretation of a

muscle biopsy. How would the results of these techniques assist
in the classification of muscular disordersl

Muscle biopsy technique

7) Procedure
a) site
b) transport
c) orientation
d) fixation and sectioning

2) Staining
a) H&E
b) PAS
c) reticulin

3) Fibre typing
a) Gomori
b) myosin ATPase pH 9.4
pH 4.6
pH 4.2
c) NADH-TR
d) myophosphorylase

4) Fibre type composition

5) Fibre diameter

Classification of disease
236 Advanced Histopathology

1) Neurogenic

a) H&E
i) atrophy
b) NADHTR
i) atrophy
ii) target fibres
c) fibre typing
i) type 1 and 2 atrophy
ii) renervation

2) Disorders of neuromuscular transmission

a) H&E
i) lymphocytes
b) fibre type
i) focal type 2 atrophy

3) Myopathies

Polymyositis
a) H&E
i) necrosis
ii) regeneration
b) NADHTR
i) 'moth eaten' change
c) fibre type
i) preserved

4) Dystrophies
a) H&E
i) muscle fibre size variation
ii) regeneration
iii) fibrosis (reticulin)
iv) fibre splitting

5) Type 2 fibre atrophy

a) H&E
i)variable
myotubular degeneration
ii)
b) NADHTR
i) minicore and central core disease
c) Gomori
i) nemaline myopathy
ii) mitochondrial myopathy
(April 1984, Paper 2, Question 4)
12. Miscellaneous 237

Describe the methods available for diagnostic interpretation of a

skeletal muscle biopsy specimen
This question is somewhat more difficult to answer, involving greater attention to
the management of the tissue and technical aspects. However, each stain or group
of stains could be taken individually, and which abnormalities it may demon-
strate, and so several diseases would be mentioned more than once, but this is
unavoidable. There should be more emphasis on the commoner conditions rather
than the obscure, rare myopathies. (October 1984, Paper 2, Question 2)

References
1} Weller, R.D. Muscle biopsy and the diagnosis of muscle disease. In: Recent
Advances in Histopathology 12. P.P. Anthony and R.N.M. MacSween (eds.)
p259-288 Churchill Livingstone, Edinburgh (1984).
2} Anderson, J.R. Muscle biopsy. Parts 1 and 2. Hospital Update (1985) 11:
199-207 and 11: 285-291.

Describe the morphological criteria and techniques which assist

in the diagnosis of malignancy in serous effusions
A question clearly designed for those candidates who have had a reasonable
amount of cytological training. It is quite difficult to prepare an adequate answer
to this question without practical experience of the problems in these specimens,
and which is difficult to glean from most texts. Several aspects could be discussed,
but the major problem is the distinction of reactive mesothelial cells from
adenocarcinoma and to a lesser extent mesothelioma. Other techniques could
include immunocytochemistry and electron microscopy.
(April 1987, Paper 1, Question 2)

Reference
1) Butler, E.B., Stanbridge, C.M. Cytology of Body Cavity Fluids: A Colour Atlas.
Chapman and Hall, London (1986).

Write a critical discussion of the role of exfoliative cytology in

the prevention of cervical carcinoma
A question which is just as relevant today, as the initial hopes for cytological
screening during this era were not fulfilled, partly because of organisational and
technical problems. An answer should cover the factors making screening feasible
(i.e. accessibility of the cervix, simplicity of the procedure), the proposed evolution
of cervical cancer, complementary clinical correlation from colposcopy and biopsy
and the factors which reduce sensitivity (poor technique, poor screening, etc.) and
selectivity (e.g. inflammation and wart virus infection). A critical discussion
should always include positive suggestions for improving the situation, which is
the main purpose of setting such a question. (April 1970, Paper 1, Question 2)
238 Advanced Histopathology

Discuss, critically, the relative value and limitations of fine

needle aspiration, percutaneous needle biopsy, and rapid frozen
section of tissue removed by open biopsy, of a lump in the breast

Introduction

Role of pathologist in diagnosis and management

Clinicopathological correlations
Treatment regimes available - changes in practice

Fine needle aspiration

Advanta~es

1) Patient
a) atraumatic
b) rapid answer
c) outpatient procedure at primary visit

2) Clinician
a) simple, clinic procedure
b) inexpensive
c) rapid report
d} planned management at primary consultation

3) Pathologist
a} cost
b} interest
c} higher profile in patient management
d) clinical contrast
e} accuracy of diagnosis

Disadvanta~es

1) Patient
a} higher rate of false negative reports
b} repeat procedure common

2) Clinician
a} false negative reports (up to 30%)
b) ? less confidence than histological report
c} increased formal biopsy rate
12. Miscellaneous 239

3) Pathologist
a) inadequate sampling
b) lack of familiarity with rare tumours
c) danger of false positive reports
d) lack of material for special staining, referrals, etc
e) difficulties in classification e.g. lymphomas

Percutaneous needle biopsy

Advanta~es

1) Patient
a) few false positives
b) fewer false negatives

2) Clinician
a) pre-operative tissue diagnosis
b) planned procedure
c) confidence in histological analysis

3) Pathologist
a) familiarity with tissue diagnosis and architecture
b) allows special staining
c) referral for second opinions
d) assessment of differentiation
e) complex pathologies

Disadvanta~es

1) Patient
a) traumatic
b) requires second visit
c) failed biopsy
d) delay in receiving report

2) Clinician
a) time-consuming
b) delays in diagnosis
c) cost

3) Pathologist
a) cost
b) failures in technique e.g. crush
240 Advanced Histopathology

Frozen section biopsy

Advanta~es

1) Patient
a) very few false negatives
b) very few false positives
c) avoids separate biopsy

2) Clinician
a) convenience
b) rapid procedure

3) Pathologist
a) rapid report
b) larger tissue diagnosis
c) macroscopic information

Disadvanta~es

a) pre-operative uncertainty
b) failure to discuss management strategies
c) equivocal reports - delayed procedures
d) traumatic

2) Clinician
a) equivocal reports
b) poor cost effectiveness - lack of pre-operative planning
c) delays in report

3) Pathologist
a) time-consuming
b) cost
c) stress
(April 1982, Paper 2, Question 1)

Reference

1) Melcher, D.H. et al. Fine needle aspiration cytology. In: Recent Advances in
Histopathology 11. P.P. Anthony, R.N.M. MacSween (eds.) Churchill
Livingstone, Edinburgh (1984).
12. Miscellaneous 241

Discuss the application of fine needle aspiration cytology as a

diagnostic aid
The role of cytology in diagnosis and screening will certainly be taking a much
greater proportion of the workload in general pathological training, and this will
be reflected in the questions set for the examination. As the applications and
expertise in this field expand rapidly, some familiarity with more specialised
aspects will be expected, and the questions more limited in scope than this one
(e.g. discuss the role in breast disease, etc), with consideration given to technique
for improving cell yield. In addition, candidates may well be expected to express
views on the effectiveness of various screening programmes, and how they might
be improved. Several reviews on the broader aspects of fine needle aspiration
cytology have been produced (see previous question).
(April 1985, Paper 2, Question 1)

Discuss the causes and effects of hypoxia in a full-term, new-born

baby
The major causes of hypoxia are atelectasis neonatorum, congenital heart disease,
pneumonia, and respiratory distress induced by maternal sedation, brain injury or
aspiration. Respiratory distress syndrome (hyaline membrane disease) is some-
what less likely in a full-term than premature infant, but some cases occur (e.g. in
diabetes). It is important to realise this in order that the answer is not dominated
by a discussion of this problem. (November 1974, Paper 2, Question 5)

Reference
1) Robbins, S.L., Cotran, R.S., Kumar, V. Diseases of infancy and childhood. In:
Pathologic Basis of Disease, 4th edition. p515-542. W.B. Saunders,
Philadelphia (1989).

What are the major causes of mortality in the neonatel Describe

and discuss the pathology, including pathogenesis, of one of these
The first half of the answer should comprise an overview of the causes of death as
outlined in the reference. It is important to choose the subject for the second half
of the answer carefully, as in all questions phrased in this manner. Thus it would
be sensible to outline a well described entity which provides abundant scope for
discussion of pathogenesis, such as respiratory distress syndrome, rather than an
equally important but somewhat more mundane topic such as cerebral birth
trauma, or pneumonia. (April 1977, Paper 2, Question 4)

What are the hazards and possible serious sequelae of premature

birtM
(November 1972, Paper 1, Question 4)
242 Advanced Histopathology

Discuss the value of the perinatal autopsy

(October 1981, Paper 2, Question 5)

Discuss the value of the autopsy in the investigation of neonatal

death
The last two of these questions relate closely to the reference below, which
contains sufficient detail to enable a comprehensive answer to be compiled. The
wording of the question clearly indicates that details of technique are not required,
but is more an appraisal of the clinicopathological correlation and value in
uncovering pathological changes not diagnosed ante mortem, or defining the
exact cause of death which may be of value for genetic counselling, or in clinical
management and investigation. (April 1985, Paper 2, Question 3)

Reference

1) Pryse-Davis, J. The perinatal autopsy. In: Recent Advances in Histopathology

11. P.P. Anthony, R.N.M. MacSween (eds.) p65-82. Churchill Livingstone,
Edinburgh (1981).
13. Short Notes Questions
244 Advanced Histopathology

Short notes questions used to be popular. Examples are:

Give short accounts of

a) i The lesions of disseminated (multiple) sclerosis
b) i The renal lesions of systemic lupus erythematosus
c) i The lesions of lichen planus
(April 1969, Paper 2, Question 5)

Write short notes on the nature and significance of any four of

the following
a) The arteriolar changes in chronic systemic hypertension
b) The 'Philadelphia chromosome'
c) Alcoholic hyaline
d) 'Sex chromatin' in the male
e) Fibrinoid necrosis
(November 1971, Paper 1, Question 5)

Give a brief account of

a) Familial amyloidosis
b) Macroglobulinaemia
c) Favism
(November 1972, Paper 2, Question 3)

Write short notes on

a) Alcoholic hyalin
b) Senile cardiac amyloid
c) Sertoli cell tumours
(November 1973, Paper 2, Question 5)

Write brief notes on three of the following

a) Quantitation in histology
b) Scanning electron microscopy in pathology
c) Histochemistry as an aid to diagnosis
d) 'Keeping up with the literature'
(May 1973, Paper 1, Question 2)
13. Short Notes Questions 245

Write short notes on the followi ng

a) Cytology of intracranial tumours
b) Clear cell adenocarcinoma of the vagina
c) Acanthosis nigricans
d) Lymphoid tumours of the rectum
(April 1974, Paper 1, Question 5)

Write short notes on

a) Medullary carcinoma of the thyroid
b) The skin lesion of pemphigus vulgaris
c) Pneumonia due to pneumocystis carinii
(November 1974, Paper 2, Question 2)

Write short notes on

a) Aschoff bodies
b) Zollinger-Ellison syndrome
c) Pleural mesothelioma
(November 1975, Paper 1, Question 2)

Describe how you would seek evidence of each of the following

conditions after death
a) Air embolus
b) Immune complex disease
c) Acute alcoholic poisoning
d) Drowning
(you are not required to give the techniques of any biochemical assays)
(April 1976, Paper 1, Question 3)

Write short notes on the pathology of the following

a) Pulmonary barotrauma
b) Paraquat poisoning
c) Fibrous dysplasia of bone
d) Rabies
(April 1977, Paper 2, Question 5)
246 Advanced Histopathology

Write short notes on each of the following

a) Pseudomembranous colitis
b) Extrinsic allergic alveolitis
c) The effects of paracetamol on the liver
d) The skin in smallpox
(April 1978, Paper 1, Question 5)

Write short notes on

a) Lymphoid infiltrations of the skin
b) Aneurysmal bone cyst
c) Argentaffin neoplasms
(April 1978, Paper 2, Question 2)

Write short notes on

a) Subacute (giant cell) thyroiditis
b) Verrucous carcinoma
c) Takayashu's disease
d) Synovial sarcoma
(October 1978, Paper 1, Question 3)

Write short notes on

a) Oestrogen receptors
b) Small cell tumours of the thyroid
c) Psoriasis
d) Colonic polyps
(April 1979, Paper 1, Question 5)

Write short notes on

a) Fibrous lesions of bone
b) Infantile respiratory distress syndrome
c) Myocarditis
(April 1979, Paper 2, Question 2)
13. Short Notes Questions 247

Write short notes on

a) Sclerosing cholangitis
b) Subepidermal bulIae
c) Seminoma
d) Bone infarcts
(April 1980, Paper I, Question 2)

Write short notes on

a) Polyarteritis nodosa
b) Scleroderma
c) Analgesic abuse
d) Renal artery stenosis
(April 1980, Paper 2, Question 1)

Write short notes on

a) Pseudolymphoma
b) Nasal angiofibroma
c) CerebelIar haemangioblastoma
d) Inflammatory fibrous polyp
(April 1981, Paper 2, Question 3)

These questions are listed as in the previous sections, but there are no outlines or
references given because most of the entities mentioned are reasonably welI
defined, and it would be relatively easy to look them up in the texts given in
Appendix 1 or from recent journal articles.
The short notes style is very similar to an essay plan, more 'fleshed out' perhaps
but using recognised abbreviations and brief phrases or sentences in place of
formalIy constructed paragraphs, so that there is a concentration of relevant facts
on any subject rather than description/discussion.
No questions have been set in this format since 1981 and one reason for this
may be that they merely require 'regurgitation' of facts while there is increasing
emphasis these days on a candidate's ability to interpret pathological data and
criticalIy discuss disease pathogenesis, something which is difficult to achieve in
notation. Moreover this type of question tends to limit the choice of subject which
can be set in the remaining nine, especialIy if it relates to something of major
topical interest which might form the basis of an essay instead. Having said alI
this, there is no reason to suppose that they may not be set in the future. There is,
unfortunately, no way to prepare specificalIy for this sort of question, as any
subject may be asked.
However, these questions do provide a very useful revision exercise. For each
of the sections, the most effective method is to write down everything one knows
on the subject and then review the answer with an appropriate article. This is a
248 Advanced Histopathology

fairly painless way of accumulating information on a wide range of diseases.

While this may not help in as much as these questions are unlikely to reappear in
the written examination in this form, the acquired knowledge would at least be
useful in many aspects of the practical examination.
 249

The Written Examination: Practical Aspects

This is held in London, Birmingham, Glasgow and Belfast in the UK. Candidates
are informed about one month in advance of the address and date for the
examination which is usually held on a Tuesday. Overseas candidates may attend
centres in Baghdad, Chicago, Dublin, Hong Kong, Johannesburg, Toronto and
Singapore, details of which are obtained from the College as the exact location
varies from year to year. In addition these applicants usually have to sit the
practical examination in the UK and because of the delays in communicating
results, cannot attend for the practical in that half year and have to wait six
months for the next one. As the majority of candidates sit the examination in
London, most of the following general points are derived from experience at that
centre. The College is at present considering the possibility of arranging practical
examinations overseas, and candidates should enquire about this prior to
application.
There are two papers of three hours' duration each, commencing at 9.30am and
2pm. Candidates who do not live in the city should beware of leaving insufficient
travelling time to the city centre, especially if staying in unfamiliar suburbs. It is
far better to stay in a hotel near the centre for the evening prior to the examination
and the address of suitable hotels could be obtained from the Tourist Information
Service or ask any colleagues who may live there for advice. If the examination
centre is not within convenient walking distance of the hotel it is best to take a
taxicab there to avoid the rush hour on public transport, and avoid unnecessary
further stress.
At this stage, most candidates will be aware of the instruments required for an
examination, but it is worthwhile duplicating pens, etc. or carrying refills, as they
always seem to cause problems during an examination. In addition, it is advisable
to check that the letter from the College which has the examination number on it
is in your possession, as you will need this to gain entrance to the hall, where the
seats are given corresponding numbers. It is prudent to make a copy of the letter
upon receipt so that there is less chance of it being mislaid.
After admission to the hall verbal instructions are given on how to fill in the
front pages of the manuscript booklets, and the first task is to write in the
examination number and full name. Separate slips requiring name, examination
number and signature are also completed.
During the examination it is necessary to add in the sequence of the
examination numbers attempted in the order in which they were answered, on the
front page of the booklet, since the examination papers are divided to be sent to
different examiners. In addition, each question should be commenced on a fresh
right hand page, again to allow this division and put the number of the
corresponding question on the top of each answer page. Rough work should be
crossed out, and supplementary pages are fastened inside the booklet if needed.
If there are any particular questions about the examination arrangements or
some clarification is required of the terms used in any of the questions, a senior
member of the College usually attends the first 30 minutes of the examination to
deal with such points, so it is best to read through all of the questions to check
right at the beginning.
During the course of the examination it is essential to be very careful of the
timing of the answers. It is often useful to have a digital watch or timer for this
purpose which can be reset for each 40-45 minutes (but it must not have a
distracting alarm). As previously outlined, the time allocated for completing the
essay 'plan' (4-5 minutes) should be strictly adhered to, and it is essential to stop
250 Advanced Histopathology

writing at the end of the allotted period for the question, whether finished or not.
Some other questions may be finished slightly ahead of time allowing more time
on the incomplete answer.
One reason for ensuring equal attention to each of the questions results from
the marking system. Each question receives one quarter of the marks, 25. An
overall 50% is the minimum pass-mark, and an average of 50% between the two
papers is required; 46% would be regarded as an overall fail in anyone paper (Le.
46 out of a total 100), but a deficiency of marks in the range 47-49% in one paper
could potentially be compensated by a corresponding surplus of marks in the
other.
A very good pass would be marked as 15 out of a total of 25, and a decisive fail
10 or less, but if only a nominal paragraph on anyone question is written, very
few marks (5) would be awarded. Given the exponential difficulty in achieving
marks over 15/25 (and indeed examiners are not encouraged to award higher
marks), it is unlikely such a candidate would pass even with three excellent
essays. However, it is relatively easier to score marks in the mid range (10-15) in
relation to the effort expended, hence the emphasis on achieving a balanced set of
essays.
Even in the event that an answer cannot be finished completely, strict
observance of the time allocated to each question is recommended. An examiner is
likely to be more favourable to one or two essays which are incomplete on account
of the abundance of relevant information provided (rather than 'padding'), than
to three complete answers and one which is rushed and half finished. They may
refer to the essay plan to see how the answer would have been completed.
As an emergency measure, (and it should be regarded as an exception), an
essay could be completed in short note form, to include as many key words as
possible. It is still important to ensure legibility however.
Note that the essay plans should be written into the answer book, as candidates
are not allowed to remove any written material from the examination hall. The
plan or outline should be clearly labelled at the beginning of the question, and can
be neatly crossed out with a line through it, as 'rough work', or left for
consideration with the rest of your answer if it is neat enough, which is the ideal
solution.
It is very important to ensure that 5-7 minutes at the end of the examination
are left for completing questions and double checking the numbering, etc.
Allocating exactly 43 minutes for each answer should give this leeway at the end.
If more than one of the answers is unfinished it is best to return to the one which
is least complete, and to which can be added useful, concentrated information.
It is important not to become over-anxious at the end as there is a grave danger
of spoiling otherwise good essays by untidy scribbling, or worse still making
major alterations to the main part of the essay. It is too late to significantly adjust
what has already been written, and it is quite likely that a mistaken impression
would be formed by a hurried 'reassessment' of an essay - critical judgement
becomes very unreliable at this stage in an examination.
After completing the writing, the sequence of the questions answered should
be confirmed to correspond to the order on the front of the booklet, and extra
pages need to be sorted accordingly.
Candidates are notified by post of the results in approximately three weeks,
although results are displayed for the nerveless at the College at 2 Carlton House
Terrace, usually on a Friday afternoon. Results are never given over the telephone
by the College.
 251

The Practical Examination

Introduction

It is difficult to give advice to potential candidates on whether they should

attempt to take both parts of the examination during the same half-year, or
exercise the option to sit the written examination at three years, and the practical
examination at five years or more. It largely depends on the breadth and quality
of training received and having confidence in one's abilities, as well as constraints
imposed by the demands of posts currently held. It might prove impractical to
obtain the necessary study leave to allow adequate preparation for instance. It
may help to take advice from colleagues who have attempted the examination
recently, and from supervisors who may be more able to assess whether an indivi-
dual has reached an adequate standard to have a reasonable chance of passing
both. The examination can prove quite stressful, which would be prolonged over
a period of two months by attempting both parts at once. Remember that after the
written examination most candidates will probably not want to work for a few
days, and being uncertain about the outcome of the written examination is not a
very good stimulus for preparation for the practical session. This factor should be
taken into account when planning a revision programme.
Assuming the written paper has been successfully completed previously or
during the current session, candidates will then receive a written letter giving
information about the examination centre, which is usually (but not necessarily) a
university teaching hospital, about two or three weeks in advance. It is usually
accompanied by some basic maps and information about the centre and who to
contact. At present, the allocation appears to be completely random, and
candidates could be required to travel anywhere within the UK. Most candidates
will not be asked to attend a centre in which they have worked for any significant
part of their training, but this is not unknown. There has been a tendency for the
College to encourage non-teaching, i.e. district general hospitals, to hold the
examination. Several of these centres have attracted a reputation for a difficult
and punitive examination. While this is by no means true for all such centres,
there appears to be a trend towards overinvestment in the practical examination
as a major event. With the increasing numbers of examinations required by the
new regulations, this policy may expand.
If there are any substantial objections to the centre allocated (e.g. previous
differences with the head of department, or domestic difficulties), it would be best
to contact the College immediately and explain the problem, (ensuring this is with
the support of your head of department, who might be required to make
representations). In these exceptional circumstances, alternative arrangements
might be made.
After receipt of the letter, the first task is to establish how to reach the
examination centre rapidly, and the departmental secretary may be able to give
some guidance on this. It is important to make sure they are given sufficient
details to enable them to pass on messages swiftly, as it is now usual practice to
ask candidates to attend for a post mortem in advance of the main examination,
and often at only one days' notice, if they are in reasonable commuting distance.
Where candidates have a long way to travel, the post mortem is often performed
at the time of the rest of the practical, but again, this is not always the case.
If it is necessary to stay in a hotel for the examination, arrangements should be
made as soon as possible, in addition to establishing what travelling is necessary
252 Advanced Histopathology

between the hotel and hospital. Some candidates have left the hotel booking until
very late, travelling to London with nowhere to stay, and encountered
considerable difficulty in obtaining suitable accommodation: a needless cause of
stress. It is also a mistake to economise when making hotel arrangements. It is
always better to stay at one which is recommended by trusted colleagues or
reputable organisations, as it is not conducive to a good performance to stay in a
noisy, uncomfortable environment.

Presentation

Candidates should bear in mind that they are attending an examination for a
professional qualification at the level of consultant, and will be expected to look
the part. It is essential to present a tidy, well dressed appearance, in order not to
be 'upstaged' by fellow candidates who will also be trying .their utmost to impress.
Certain individuals may feel 'thick-skinned' enough to withstand this, but it is
surprising how much of a 'negative' impression a scruffy candidate can make on
the more conservative examiners, who may even feel somewhat insulted that the
candidate does not view this as an occasion to be approached with some formality.
It is a situation in which to ask a spouse or best friend for advice!

The Necropsy: Preparation to Examination Standard

It is probably true to say that most pathologists in the UK ultimately have to rely
on using their own initiative in respect of necropsy training in order to perfect
their technique, usually by persuading senior colleagues and their peers to help
them, since there is no formal education in this skill, at least on a national level.
The resulting standard achieved is a direct result of the ability of a trainee to
communicate with colleagues and learn by example, fundamental qualities in a
good pathologist.
Each candidate is expected to perform a competent post mortem examination
using a conventional method, which would reasonably be expected to ensure the
detection of most disease processes. While interpretation of the findings during
the Final examination necropsy is one aspect, it is as well to note that a candidate's
technical skill is also under assessment.
In the earliest stages, pathologists are usually taught a technique from senior
colleagues or slightly more advanced trainees, and while learning by example is
the best method initially, it is unlikely that optimal methods of dissection have
been adopted in every centre and candidates who have a narrow range of
experience may well become aware of deficiences only when they are pointed out
by an examiner.
There are books which cover aspects of necropsy procedure, one of the best is
Post Mortem Procedures written by Gresham and Turner (Appendix 1), which
covers the layout of the necropsy suite, health and safety considerations and the
role of the post mortem technician. In addition, there is a well illustrated guide to
practical aspects of the dissection which would be of value for all candidates to
consult prior to the examination, whatever their level of ability.
There is one specialist 3-day course designed to cover some aspects of routine
and specialist necropsy procedures, and post mortem pathology, which may well
be of value (Appendix 2). It might be better to attend such a course with some
elementary experience, so that the recommended procedures can be established
The Practical Examination 253

prior to the acquisition of too many bad habits. The optimal time may be soon
after completing the Primary examination, but the course organiser would be able
to give more detailed advice. In addition, such a course may cover the aspects of
some necropsies with which some candidates have had limited experience (e.g.
neonatal, paediatric and Coroner's post mortems) which they might well be
confronted with as an examination case.
Even when the demands of routine work necessitate the performance of several
post mortem examinations per day, it is a good policy to dissect one to a high
technical standard in a relatively unhurried manner or if not take the time to
examine one organ system per case according to a standard anatomical method
outlined in a manual such as Cunningham's Manual of Practical Anatomy or an
anatomical or specialised textbook which includes dissection technique (e.g.
cardiac dissection as outlined in Olsen, E.G.J. Pathology of the Heart (Appendix 1)
This requires considerable self-discipline, but the consequence of not doing so is
that an individual's technique will become less than adequate, and bad habits will
become ingrained and difficult to eradicate when more advanced skills are
required in a particular case and in the examination. Therefore, the advice is to
aspire to perfection in at least one aspect of every necropsy!
One stimulus to improvement is to become involved in the tuition of junior
colleagues, and this supervision involves a considerable degree of responsibility
to ensure they learn the correct methods. Questions on technique should be
encouraged, and it is most important to demonstrate normal anatomical relation-
ships as well as pathology. In order to get the maximum from this, it is often a
good idea to choose one particular organ to demonstrate in detail, having revised
the protocol for dissection prior to starting.
If there are no junior colleagues, demonstrations for medical students or trainee
mortuary technicians are equally beneficial, in that they enable the development
of an ability to comment while continuing a dissection which is an essential skill
to acquire, and impressive to colleagues and examiners alike, but one which
requires considerable practice.
It is essential that a consultant is responsible for supervision of the dissection
and is available to give advice in the earliest stages, but at registrar level and
above, they may only wish to see the major findings at the end. However, it is
often possible to encourage them to actively criticise and demonstrate their
expertise in dissection, especially if they have a particular specialist interest in an
organ or system. Some pathologists are rather inhibited about criticising junior
colleagues who have had a few years experience, afraid of this being
misinterpreted as an insult. It is important to reassure them on this point, and
afterwards accept any comments made with good grace. Those who put up a
defensive 'shield' to avoid criticism and prefer to work in isolation severely
disadvantage themselves, as there is potential for improvement in every
pathologist's performance.
Communication with the clinical staff is of utmost importance, since the major
reason for performing a necropsy is to assess the course of an illness, the clinical
diagnosis and the effect of treatment, as the ultimate form of medical audit. It
should be second nature to ensure the clinical staff attend the necropsy itself, or
the presentation, and candidates would certainly be expected to request or
arrange this in the examination. Always contact them prior to starting the
dissection to check what might be a convenient time to hold the presentation and
discussion, to fit in with their clinical commitments.
It is expected that candidates will recognise that aesthetic objections to post
mortems are one of the main reasons why clinical staff may be reluctant to attend.
Therefore candidates should make every effort to finish the dissection, clean up
254 Advanced Histopathology

the area and arrange the organs so the findings can be demonstrated in a brisk,
professional style. There is no greater deterrent to clinical colleagues than a
rambling discourse from a pathologist attempting to finish a dissection, with
poorly prepared organs largely obscured by blood.
As well as the clinical staff, opportunities to present post mortem
demonstrations to medical students, which should be part of the teaching
programme in most University hospitals, should be taken. This can be a very
rewarding exercise which will quickly expose limitations in demonstration and
communication, and requires an alert mind especially relating to aspects of
normal anatomy, to avoid being 'upstaged' by medical students who would
recently have completed an intensive preclinical course in the subject. In more
formal presentations, arrangements can be made with the clinical staff to present
the history prior to death and ask questions from the students on what
pathological changes are to be expected. While this may be standard practice in
University Departments, there is no reason why similar arrangements could not
be instituted at a District General Hospital with an attachment of students.
As to more practical aspects of the necropsy, candidates should observe the
recommendations of the Howie Report (Code of Practice for the Prevention of
Infection in Clinical Laboratories and Post-mortem Rooms (Appendix 1) at all
times (and may well be asked about them during the examination). Safety is a
most important consideration but is surprisingly often neglected by trainee
pathologists. Examiners take particular note of the steps taken in preventing
injury from carelessly placed instruments, sharp bone edges, blood splashes and
minimisation of aerosols.
The correct choice and use of instruments may affect the ability to dissect quite
markedly. It is surprising how many trainees restrict themselves to the use of a
PM40 knife and one or two pairs of scissors. However the minimum requirements
are a large knife and scalpel, at least four pairs of scissors (including bowel and
artery scissors), probes, bone forceps, bowel clamps and a rule. Furthermore, the
correct technique for manipulating these instruments should be observed, which
is again a matter for practice. In particular, producing organ slices with a single
stroke of the large knife is a considerable improvement over a 'sawing' action. Use
of the necropsy saw is also neglected by many pathologists, but it is not unknown
for some centres to ask candidates to remove the cranial vault themselves.
The following section is intended to be a complementary rather than compre-
hensive guide to performing a necropsy, with comments on some often neglected
aspects of the general conduct of a post mortem, together with an idea of the
details of anatomy and technique which candidates might be required to know.
There is an attempt to highlight those areas which are sometimes a source of
particular difficulty. Some more difficult 'special' procedures are outlined and
illustrated, which examinees might be expected to perform or at least be asked to
explain.
Although it would clearly be impossible to follow to the letter all of the
protocols outlined here in every necropsy because it would take too long, they can
be adapted to suit the demands of each case as required.

The Necropsy: Procedures

One of the most important aspects of any post mortem examination is to review
the clinical notes on the patient. The first task is to ensure that the permission
form is in order and whether it is a hospital or Coroner's autopsy. (In the
The Practical Examination 255

examination this would usually have been checked beforehand.) Prior to starting,
the notes should be carefully read and adequate time should be given for this, but
candidates should not be inhibited from asking for more if the case is particularly
complicated.
During this time it is a good idea to obtain some paper and make a short
summary, including age of the patient, date and time of death, and a paragraph or
two on the clinical history, including relevant investigations. Trainees develop
their own methods of extracting information from notes rapidly, but in a complex
case, discharge and referral letters often give comprehensive, easily digestible
summaries.
During or at the end of the necropsy, candidates are expected to give an
accurate, brisk precis of the clinical history which is included in the written report,
so it is a good idea to take advantage of this time to assemble a coherent report
which can be easily transcribed. It is most important to identify the clinical
diagnoses, which would indicate the site of potential pathological lesions and
which would answer any specific questions raised by the clinical team.
The supervisor will conduct candidates to the post mortem changing rooms,
and in most circumstances they will be shown what to wear. If unsure, specific
questions can be asked about the protective clothing required, and appropriate
precautions must always be taken in any necropsy in cases of serious transmissible
disease. Remember that at this stage, a candidate is under the examiners' scrutiny,
(either consciously or unconsciously) and it is important to convey an air of
professionalism. Any opportunity the examiner may provide to discuss the
clinical aspects of the case should be taken, and any special requirements which
are anticipated (e.g. taking specimens for microbiology in an infective case,
radiographs in neonates or traumatic fractures, special fixatives for certain
tumours, etc.) should be raised and discussed, as the examiner may be kind
enough to make arrangements.
The supervisor will usually make an introduction to the mortuary technician
assigned to the case. It is very important to be polite and use his assistance to the
greatest benefit. Many candidates are so preoccupied that their behaviour may
seem offhand or even frankly rude to the mortuary staff, so it is important to
make the effort to converse. It would help if the case is briefly discussed with
them and the assistance which might be required outlined. Mortuary technicians
are usually experienced in looking after examination candidates, and will have
been briefed beforehand as to what help they can offer. However, there is nothing
to lose by asking, and the response may be more favourable if a rapport has been
established. Moreover, the technician is present throughout the dissection, and
will closely observe the technique. Some examiners will take the opinion of the
mortuary technician into account when assessing a candidate, especially if they
are experienced. Thus you will not 'get away' with any bad habits while the
examiners are away.
Instruments are provided, but if other types are required or preferred there is
no harm in requesting if they could be made available.
However, criticism of the standard of the equipment which has been provided
should be avoided at all costs. The mortuary staff will have made a special effort
for the examination, and it will be unnecessary criticism and may well be taken as
an insult.
Prior to commencing the dissection, the usual checks on the body should be
made, and a careful external examination conducted. Visible abnormalities should
be noted down at this stage for inclusion in your final report.
It is vitally important to ensure that the dissection is as tidy as possible. There
is probably nothing which counts against a candidate as much as making an
256 Advanced Histopathology

unpleasant mess during the dissection, especially on the floor and excessively
over the working surface. Many candidates do not even take the simplest of
precautions to avoid this. Expert prosectors will create remarkably little spillage
of blood, but this is a skill which has to be practised. Examiners recognise that if
this can be controlled, it is usually a reflection of a good pathologist. Moreover, if
the appearances are obscured then there is a potential for misinterpreting the
pathology, and we have already made the pOint that an unaesthetically presented
post mortem is one of the major reasons why clinicians are reluctant to attend.
Thus it is most important that steps are taken to avoid these problems. A
running water supply with a hose attachment should be provided, to wash down
the body after removal of the organs, and to clean the surrounding table. The
abdominal cavities should be rinsed out with water, and then a clean sponge used
to allow inspection of the surfaces - a pool of blood should not be left within
them. The thoracic and abdominal organs should be rinsed in cold water in a sink,
transporting them in a bowl to avoid blood spillage on the table or floor. The
dissection surface is kept clean by wiping down after each organ dissection with a
freshly rinsed sponge. Dissection instruments should be kept to one side in a neat
array when not in use (for safety reasons as much as appearances).
It is suggested that all organs are weighed as they are dissected clear,
requesting the technician to note the figures down. The organs are best kept
'orientated' preferably on a large tray or board, which is used to display them for
the summary presentation. In practice, it is very easy to forget which side the
kidneys or adrenals have come from, and even the lungs may be very difficult to
identify after dissection.
As already implied, technique in dissection will be noted by the examiner and
post mortem technician. For safety reasons it is important to always cut away
from one's body with scissors or a knife. The tissue should be continually
inspected while being divided to avoid destroying any unexpected pathology
which may be encountered. Sharp instruments should not be flourished, and care
taken to minimise the risks from sharp edges of bone, especially rib ends, by
covering them with cloth. Finally, aerosols and splashes should be kept to an
absolute minimum by careful handling of the organs.
The following sections relate to some of the more common problems which
trainees encounter but which they are expected to have mastered by the
examination. It includes selected practical, technical and anatomical aspects,
rather than purely pathological descriptions and it is stressed that this is not
intended to be a comprehensive methodology.

Removal of Organs
The body can be opened by a conventional midline incision, or 'Y' shaped cut
passing from the sternal-notch, behind the sternocleidomastoid muscles to the
mastoid bone.
The skin should be reflected off the chest, including muscle, down to the level
of the ribs and intercostal muscles. Removal of the sternal plate is easier if there is
no muscle or soft tissue over the anterior surface of the ribs. The abdominal wall
should be incised down to the peritoneum between the rectus muscles. The
abdominal organs should be protected from damage by lifting the peritoneum
with forceps and making an opening with scissors, the fascia being divided
towards the symphysis pubis, avoiding the bowel. Ascitic fluid, if any, should be
removed with a mechanical aspirator or ladles, and the quantity noted. With
The Practical Examination 257

intra-abdominal sepsis, samples should be taken for culture. It is often best to

remove the bowel at this stage and several points are often forgotten by
candidates. Firstly, both ends of the small bowel should be tied off or clamped at
the start of the jejunum to avoid spillage of contents. The bowel should be
removed from the mesentery by holding one end at slight tension and running a
PM40 knife along the junction, down to the terminal ileum. The large bowel is
then dissected out in continuity. While most of the colon is easy to remove with a
medium-sized pair of scissors from caecum to sigmoid colon, trainees are often
not aware that the rectum, which is often left in situ, is reasonably easy to remove,
and is often a site of 'missed' lesions. The rectosigmoid junction should be put on
slight tension, and using scissors the peritoneal reflections are cut around the
circumference of the rectum, including the rectovesical or rectouterine pouch. The
incisions are extended posteromedially in the vertical plane, avoiding the ureters,
and blunt dissection is used to push the soft tissues away from the wall of the
rectum down to the level of the levator ani, all the time keeping a tension on the
rectosigmoid colon with the other hand. When the anal sphincter can be palpated,
a cut is made just above this level with a PM40, through the anal canal. The
bladder (with prostate in the male) can be removed intact with a similar
combination of peritoneal incision, blunt dissection and incision across the upper
urethra. Significant pathology can be missed if bladder and rectum are left inside
the body and it is far more impressive when correctly removed and dissected.
The intact intestines should be placed immediately after removal into a bowl or
in a sink, and after opening longitudinally the contents washed away with cold
running water, to allow inspection of the mucosal surface. The colon is best
opened along the anterior taenia coli. Make sure the intestinal contents are not
allowed to contaminate the working surfaces or dissection table, either by seepage
when left in an untidy pile or by careless spillage during opening.
Removal of the remaining organs is rather dependent on an individual's
preferred approach but it is as well to have attempted both the Letulle and
Virchow techniques before making a final choice (see Gresham and Turner,
Appendix 1). Many pathologists use Virchow's method, taking out the liver and
biliary system followed by the remaining intraperitoneal and retroperitoneal
organs prior to opening the thorax, Using this approach, it is important to dissect
carefully around the gastro-oesophageal junction to avoid penetrating the
diaphragm. Care should be taken to remove the ureters as intact as possible. In the
event of potential disease in the genitourinary system, remove the bladder, ureters
and kidney intact. This should be possible if a careful approach has been taken
during the rectal dissection.
Opening the chest can be fairly straightforward, but elementary mistakes are
usually a consequence of rushing. A brief check for pneumothorax is advisable,
(and is a commonly asked question in examinations), usually by opening 'under
water' in a pouch formed by the reflected skin and the lateral chest wall. After the
incision of intercostal muscles over the 9-11 rib spaces anteriorly, a careful
inspection for pleural adhesions needs to be made before removing the ribs, to
avoid cutting into the surface of the lungs if they are adherent, in which case they
may be severely distorted. The line of the separation is best just medial to the
costochondral junction up to the first rib. This might be easiest with a knife
(unless there is heavy calcification, in which case bone forceps should be used).
Clean incisions through the cartilage avoid the danger of jagged rib edges which
are often left after cutting the bone. Care needs to be taken when removing the
sternum, which should be carefully lifted and dissected off the underlying lungs,
pericardium and anterior mediastinum. If the lungs and pleura are adherent it is
usually possible to use blunt dissection to find a plane between pleura and chest
258 Advanced Histopathology

wall, pushing the lung away from the chest wall if this plane is not completely
separated (laterally and rosteriorly as well). Removal of the lungs causes severe
tearing and distortion 0 the parenchyma, providing artefacts and masking the
pathology.
The thoracic pluck is best removed 'en bloc', starting from the tongue. Using
the 'Y' incision, the skin of the neck is reflected up over the face, and then a cut
made around the inner border of the mandible to include the submandibular
salivary glands, and vertically to include the posterior border of the sternomastoid
muscle down to the level of the cervical vertebrae, dividing the muscle at the level
of the mastoid bone. By this method, the internal and external carotid arteries are
included in the dissection, and the detection of parathyroid glands is considerably
easier (see page 281). When removing the thoracic pluck a releasing incision along
the inner border of the first rib needs to be made, posteriorly extending down-
wards through the parietal pleura parallel to the aorta. It is important to remove
the diaphragms intact, by cutting the muscle flush with the thoracic wall.
In removing thoracic organs with or without the abdominal contents, it is not
an excuse to exhibit 'brute' force by 'tearing' the tissues away using traction on
the tongue and neck contents. Not only will this disrupt delicate anatomical
relations, it inevitably leads to unnecessary aerosols and blood splashing. Instead
a knife or scissors should be used to release fascia and soft tissues (wherever
possible under direct vision), holding the tissues under slight tension to facilitate
this.
The abdominal organs can be removed attached to the thoracic block if
required, according to the method of Letulle (Gresham and Turner, Appendix 1)
but care should be taken to dissect around the lateral and posterior aspects of the
kidneys, extending the vertical incisions down to the level of the thoracic
vertebrae behind the psoas muscles. The latter can either be transected lateral to
the ureters, followed by medial extension of the incision across the lower edge of
the pelvic brim, or if the ureters and bladder are to remain intact the incision is
brought anteriorly, dissecting out the anterior and inferior aspects of the bladder,
which is then reflected upwards, and with gentle traction on the base of bladder,
the ureters can be teased away from the connective tissue with a scalpel up to the
level of the pelvic brim. The organs can then be removed en bloc as above, with a
releasing incision through the psoas muscle and fascia over the anterior sacral
promontory.
Immediately on removal, the organ block(s} must be transferred to a sink to be
rinsed in cold water, ensuring they are placed into a bowl during this transfer to
avoid the spillage of blood over the body dissection area and floor which would
inevitably occur otherwise, again creating a very bad impression.
At this stage, the outside and inside of the body should be cleaned using
sponges. Then the iliofemoral vessels should be dissected out, especially where
there is a history suggesting deep vein thrombosis or pulmonary thrombo-
embolism. In all cases the femoral vein should be opened, which involves cutting
across the inguinal ligament, at least to the origin of the great saphenous vein. At
this stage, in males the testes should be everted into the inguinal canal and
removed together with the spermatic cord. It is common for candidates to forget
this part of the dissection. The external genitalia should always be examined in
addition.
Having sponged out the thoracic and abdominal cavities, the peritoneal
surfaces should be closely inspected and the spine assessed for gross
abnormalities. A strip of bone should be removed from the anterior vertebral
bodies, after which the cut surface needs to be washed and sponged to assess for
collapse of vertebral bodies, or metastases in malignant disease. Some bone should
The Practical Examination 259

be taken for fixation at this point (otherwise, this is frequently forgotten). At some
centres it is routine practice to dissect around each rib to check for fractures. This
mayor may not be part of each individual's usual approach, but it is prudent to
establish whether this is routinely done· at that centre, and the post mortem
technician would be aware of this. Others prefer a close examination of the inner
aspect of the ribs to look for haemorrhage (which invariably accompanies
significant fractures) combined with palpation and subsequent dissection if
fractures are suspected.
The breasts are often overlooked. It is recommended that several neat, parallel
vertical incisions from the chest wall aspect are made, and which do not breach
the skin. One of these should be level with the nipple, and at least two
equidistantly spaced either side, following which the cut surfaces should be
palpated as well as inspected. At this stage it is convenient to check for axillary
lymphadenopathy.

Systematic Dissection
Cardiovascular System
Heart
The dissection technique outlined by Olsen (Pathology of the Heart Appendix 1) is
well illustrated and sufficiently comprehensive for nearly all situations. The heart
is such an important organ to examine and yet is paradoxically very badly
dissected by many candidates, usually due to bad habits which have developed to
save time. Some of the more practical points related to the dissection are
highlighted below.

a) Removal of the Heart

The protocol laid down in the above reference should be closely followed. It is
very easy to leave parts of the atria behind when cutting the pulmonary veins and
venae cavae, which can be lessened by putting slight tension in the heart prior to
cutting these structures with scissors. Examiners often check for this by asking to
be shown the location of the sinoatrial node. The pulmonary trunk should be
incised before removal of the heart (and preferably while still in the body) to
check for massive pulmonary thromboembolism. The pericardium should also be
included in any demonstration and commented upon in the report.

b) External Examination

The epicardial surface should be inspected very closely, with the heart orientated
as if in the body (after recognition of the acute right border and oblique left
border). As well as gaining an idea of the heart size, evidence of early infarction
may be apparent, where the more flaccid myocardium is depressed, and may
show some very fine epicardial vascular congestion. These changes can be
obscured on sectioning.

c) Coronary Arteries

All candidates should be familiar with the normal anatomy (and variations) as
260 Advanced Histopathology

ignorance about the location of the main branches will count heavily against
them. It may be quite difficult to find the arteries after dissection of the heart, but
useful landmarks are the tips of the auricular appendages and the great vessels.
The right coronary artery emerges between the right auricle and pulmonary trunk,
the left between the aorta and left auricle. It is an essential skill to identify these
structures swiftly, and with some 'panache', for demonstration of vessels to
clinicians and examiners alike. In the event that the vessels are still difficult to
identify on external examination, a look inside the sinuses of Valsalva from the
top will identify the orifices, (which should be demonstrated in any case). There is
nothing more irritating or depressing than a mumbling pathologist trying to find
the coronary arteries and failing to act with any degree of confidence.
The arteries may be sectioned longitudinally with artery scissors, or by
transverse sectioning. In the latter technique, regular cuts at 0.5 cm intervals
should be made (closer in the more proximal segments), and care taken that they
are transverse to the direction of the vessels. Heavily calcified arteries could be
removed for decalcification and subsequent sectioning in appropriate cases, as
there is a risk to attempted section of such vessels with a knife, but in the
examination advice could be sought from the supervisor on this point.

d) Valves

An attempt should be made to inspect all of the valves before they are divided, to
look for distortion or vegetations. As a general rule the incision is made through
the centre of valve cusps, or through the commissures of the mitral and tricuspid
valves. The valve diameters are measured (and candidates are expected to know
the normal values). Vegetations should be carefully searched for, as they can
easily be overlooked. It should be remembered that papillary muscles and chordae
tendinae are also part of the valve structure and often receive scant attention.
e) Atria

The usual structures are identified and a check made for small atrioseptal defects,
(apart from 'probe' potency of the foramen ovale). In atrial fibrillation the
auricular appendages may be thrombosed, and need to be fully opened. The
annulus of the mitral valve should be inspected after division of mitral valve and
ventricular wall. It can be calcified and predispose to incompetence of the valve.

n Myocardium

It is difficult to advise whether the ventricles should be removed from the

remainder of the heart when there is a pathological abnormality present. In
general, in macroscopically normal hearts, they are best removed and weighed
separately. When there is an abnormality, it is often better to keep the atria and
ventricles intact for demonstration purposes, after opening the heart as for the
standard protocol (it is often advantageous to make a transverse slice first of all
about 1 cm above the apex to inspect the chambers and examine the myocardium).
With valvular disease, the ventricles should be relatively intact, the chambers
being opened according to the direction of blood flow. In myocardial disease, the
ventricles are opened and the myocardium sliced transversely at 0.5-1 cm
intervals, keeping the epicardium intact so it can be 'reconstituted' as a structure
for demonstration - this is virtually impossible if the slices are completely severed.
In doing this the coronary arteries should be disturbed as little as possible,
otherwise further cuts are made in them and can ruin your neat dissection when
The Practical Examination 261

the outer surface of the heart is demonstrated. The myocardium should also be
washed after sectioning, as subtle changes such as fatty heart, papillary muscle
disease or early myocardial infarction are very easily obscured by even a small
amount of blood.

Conducting System

No candidate would really be expected to perform a detailed study of the

conducting system, but they may be asked to give an outline of how it might be
approached. It is relatively easy to find the major structures with a little practice
which could be pointed out if asked. The sinoatrial node is located at the junction
of the superior vena cava and a line extending from the superior border of the
right auricular appendage. The atrioventricular node can be located at the
intersection of a line passing through the papillary muscle of the conus with one
passing horizontally through the opening of the coronary sinus. This point is
variable when the myocardium is flabby, so a block of muscle needs to be removed
from the general area and divided into two or three small blocks. With practice, it
is possible to see both nodes macroscopically. Candidates should have some
knowledge of the general course of the bundle of His, the right branch passing
into the intraventricular septum, and the left travelling above the membranous
portion of the intraventricular septum before passing inferiorly.

Anatomical Structures

Candidates may be expected to demonstrate the following if asked, so it is useful

to have the ability to point them out rapidly and clearly, explaining the orient-
ation and outlining any anatomical variations which may occur.

1) Orifices of right and left pulmonary veins and venae cavae

2) Auricular appendages
3) Left coronary artery, main named branches, orifice in sinus of Val salva
4) Right coronary artery, branches and orifice
5) Posterior descending coronary artery (the main branch leading to this is
called 'dominant')
6) Range of total (defatted) heart weight, weights of right ventricle, left
ventricle and septum, and ratio LV+S: RV; relationship between LV&S
and RV; relationship between hypertrophy and weight
7) Valve circumference and diameters
8) Right atrium - foramen ovale, crista terminale, coronary sinus opening
9) Left atrium - fossa ovalis
10) Right ventricle - myocardial thickness, papillary muscle of conus, crista
su praventricularis
11) Left ventricle - myocardial thickness, membranous part of
interventricular septum
12) Sinoatrial node, atroventricular node, bundles of His (approximate
location)
13) Location of ductus arteriosus
262 Advanced Histopathology

Common General Questions in Examination

If there is a pathological abnormality in the heart, candidates would be asked to
demonstrate it and discuss aspects of the diagnosis. More general points that may
be asked by an examiner include:
a) Anatomical Features

Most important is the weight of the heart and ventricles. If asked, it is best not to
give one weight, or even an approximate range, but preface the answer with 'In a
male/female of this height and build (which should have already been established
from the clinical notes), I would expect the heart weight to range between X and Y
grams'. After this the case in question should be compared to the expected result
and assessed accordingly. If there is hypertrophy affecting the left and/or right
ventricle, weight ratios should again be quoted in support of the assessment.
Examiners will expect a fluent discourse from a candidate, so the explanation
should continue until interrupted. However, the aim is to include as many facts
per sentence as possible, avoiding the temptation to ramble. It is common for
examiners to go on to ask the causes of ventricular hypertrophy, isolated and
combined, which should also elicit a rapid, full answer.

b) Further Macroscopic Techniques

Some procedures may be performed on the gross specimen to demonstrate

specific pathology, such as the nitro-blue tetrazolium (NBT) test for myocardial
infarction. Candidates should be aware how to perform this test, (although it is
unlikely they will be asked to perform it), and of its limitations. Amyloid can be
demonstrated with Lugol's iodine/dilute sulphuric acid, and may be very useful
since cardiac amyloid is very common in the aged. It is important to know how to
take bacteriological samples in cases of suspected infective endocarditis, prior to
opening the heart.

Aorta and Arteries

If the patient had severe arteriosclerosis producing major ischaemic effects on
other organs besides the heart, it may be useful to keep the aorta and major
branches as an intact dissection, which can be accomplished relatively easily,
especially in the Letulle method.
The subclavian, common carotid arteries, internal and external carotids should
always be opened (or at least the first 1-2 cm where much of the major pathology
lies), and the major branches of the abdominal aorta. The distal iliofemoral arteries
are best demonstrated in the body. In cases of ischaemic renal disease or
hypertension, remove the abdominal aorta with both kidneys (cutting across the
inferior vena cava), to open them as an intact dissection - remember to look for
accessory renal arteries. With intestinal ischaemia or embolism, identify the
superior mesenteric artery and cut down it with the aid of a probe. This will be
facilitated if you have left the mesentery intact when removing the bowel. You are
usually only expected to dissect down the first two or three branches however.
Abdominal aortic aneurysms are best opened from the posterior aspect. A
transverse cut may help to demonstrate the structure of the wall. It is best to check
the extension of any thrombus down the iliac vessels and for potency before
attempts are made to open them. It is very difficult to demonstrate any residual
The Practical Examination 263

lumen in a calcified, atherosclerotic iliac artery once it has been opened unless
great care is taken.
Dissecting aneurysms require particular care, and in suspected cases the
removal of organs needs handling with care. Transverse sections of the aorta may
help to demonstrate the pathology, and careful inspection may be required to
identify internal breaches.

Anatomical Structures
It is necessary to be familiar with the following arteries and their variation.
1) Subclavian and carotid arteries (including branches of the external carotid
arteries)
2) Vertebral artery origin (see 'Special Procedures', page 283)
3) Coeliac axis and major branches
4) Superior mesenteric artery
5) Renal arteries
6) Inferior mesenteric artery (may be a very inconspicuous branch in some
cases)
7) Iliofemoral vessels
More distal parts of the arteries are often covered under specific organ systems
e.g. internal carotid and vertebrobasilar arteries in CNS, hepatic and splenic
arteries in alimentary system, etc).

Common Questions
1) Anatomical relations
2) Clinico-pathological consequences of atherosclerosis
Venous System

It is most important to check the iliofemoral veins in all post mortems by opening
them at least to the origin of the great saphenous vein. In cases of significant
pulmonary thromboembolism, thrombus will be found up to this point in almost
all cases even if some has detached. In addition, a careful search for leg oedema
should be combined with measurement of the leg circumference around calves
and ankles.
The inferior vena cava should be opened from the posterior aspect, but the
renal artery should not be sacrificed if there is any significant pathology to
demonstrate. The orifice of the hepatic vein should be inspected for thrombosis or
tumour when the liver is diseased.
When the thoracic duct is to be examined (see 'Special Procedures'), it is better
to leave the venae cavae in situ to act as landmarks.

Alimentary System
Mouth and Oesopha~us

The mouth is often neglected, but should always be quickly inspected for obvious
dental abnormalities and mucosal disease such as thrush. The submandibular
salivary glands and tongue are dissected when examining the thoracic pluck, but
are often neglected. The parotid gland must be examined with great care because
264 Advanced Histopathology

of the risk of damaging the face, and is best left alone unless there is a gross lesion.
The tonsils should be inspected in cases of lymphoreticular disease.
The oesophagus can be removed after locating the parathyroid glands, by
dividing it 1 cm below the larynx, holding the upper border with forceps, and
freeing the fascial attachments to trachea, oesophagus and diaphragm with
scissors. It is very easy to remove it in continuity with the stomach if required, by
dividing the diaphragmatic attachments, when the organs have been removed by
the Letulle technique. This is desirable when there is suspected gastro-
oesophageal disease such as hiatus hernia, carcinoma or varices. Hiatus hernia
can only be convincingly demonstrated with an intact diaphragm, and division of
the crus will make it very difficult.
The oesophagus is opened from the posterior aspect after mobilisation of the
stomach, but the demonstration of varices requires particular care as they become
collapsed and inconspicuous on conventional dissection. The unopened oeso-
phagus, freed from its attachments, is tied at the upper end with string, and
mobilised along with the stomach (see beloW). The latter is opened midway along
the greater curve, to within 10 cm of the cardia. After removal of gastric contents,
a long Spencer-Wells forceps can be inserted through the cardia to grasp the
mucosa at the upper end. Withdrawing the forceps evaginates the oesophagus
and the dilated veins are well demonstrated.

Stomach
It is necessary to clamp or tie off gently (avoiding crushing) the gastro-
oesophageal junction and duodenum prior to removing the stomach. The stomach
is best opened along the greater curvature, putting the contents into a clean bowl
<extending it to open the oesophagus if required). In forensic cases the gastric
contents may need to be kept for analysis. Candidates who allow gastric contents
to spill over the organs or over the dissecting table will create an unfavourable
impression.
After removing the stomach, with or without the oesophagus, the mucosal
surface should be gently washed in clean water. Even when the mucosa appears
'autolysed', significant abnormalities such as chronic ulcers and neoplasms are
usually discovered because of their fibrous tissue base. The first part of the
duodenum should be closely inspected as it is a frequent mistake to miss chronic
ulceration at this site.

Small and Lar~e Intestines

The removal and inspection of the intestines were covered earlier. It is important
to wash the surface well and inspect the bowel thoroughly - it is often a neglected
part of a necropsy. The duodenum should be opened along the lateral border, and
examined with the pancreas and common bile duct. Opened small bowel can be
arranged fairly compactly on a board (if required), as a series of folds resembling
a ploughed field.

Liver and Biliary System

The liver is often removed from the surrounding tissues with scant attention paid
to the surrounding structures. Before this stage the biliary system should be
dissected, starting by opening the lateral border of the duodenum, exposing the
Ampulla of Vater. Patency of the common bile duct can be demonstrated by
gentle compression of the gall bladder.
The Practical Examination 265

The unopened gall bladder is mobilised from the liver attachments, and the
cystic duct identified with judicious incisions with a small scalpel in the surround-
ing connective tissues. It can then be opened with small scissors, and followed
into the common bile duct which is opened with artery scissors up to right and left
hepatic ducts, and downwards, into the duodenum via the ampulla. If there is no
ductal disease, the gall bladder, still containing its bile, can be freed by dividing
the cystic· duct; bile should not be allowed to contaminate the dissection, but is
discharged into a small container, and the gall bladder opened along its length.
The portal vein should be opened in all cases, and a comprehensive dissection
of the branches included in any case of portal venous hypertension, where it is
better to leave the splenic and gastric veins intact with the pancreas, stomach and
oesophagus for demonstration purposes.
The liver is often poorly sectioned with apparently random strokes, by many
candidates. In cases where no liver pathology is suspected, or where there may be
focal disease (such as metastases), the organ should be placed on its inferior
surface, and vertical antero-posterior incisions made from the superior border
almost to the level of the inferior capsular surface (to enable the slices to remain in
relationship to each other). As in all solid organs, a large knife is used to make a
single clean stroke, rather than a sawing action which produces an unsatisfactory,
ragged cut surface.
Another elegant but little known method can be used in cases of biliary or
venous disorders. The liver is rested on its superior capsular surface and probes
placed into the right and left main hepatic ducts to serve as guides for bisection of
the organ in the plane, thus giving a good view of the biliary tree. Section of the
lobe demonstrates the hepatic venous system. Slices can be either side of these
cuts as before to inspect the remaining parenchyma.

Pancreas
This seems to present problems for many candidates, and is often very badly
dissected. Palpation of the firm gland parenchyma around the borders will allow
for swift removal of the softer retroperitoneal fat with a pair of medium scissors.
The head of the organ should be excised from the duodenal loop except when
there is ampullary or biliary disease, and then the isolated organ is sectioned
transversely at 1 cm intervals, leaving the anterior capsular surface intact. In rare
cases with suspected pancreatic duct disease, a single transverse slice at the
junction of head and body will reveal the main duct, which can be opened through
to the duodenum with the aid of a probe. A well-dissected pancreas enhances the
final presentation and will impress examiners.

Anatomical Relations
1) Arterial supply to stomach, liver and pancreas
2) Arterial supply to small and large bowel
3} Portal venous system
4} Surface anatomy of the liver
5} Distinction between anatomical and functional liver lobes
6} Intra and extrahepatic bile ducts
7) Structure of the porta hepatis
8} Normal liver and pancreas weight ranges
9} Length of normal small bowel and colon
266 Advanced Histopathology

Common Questions
1) Structural effects of portal hypertension
2) Causes of biliary obstruction
3) Cholelithiasis - frequency and pathogenesis
4) Mesenteric ischaemia - venous and arterial
5) Classification of cirrhosis
6) Recognition of true cirrhosis vs. hepatic fibrosis
7) Aspects of gastrointestinal neoplasia
8) Malabsorption syndrome - causes and effects

Respiratory System
It is best to decide whether you wish to inflate one or both of the lungs with
formalin prior to starting the dissection, so that the post mortem technician can
make preparations. However, it is quite a time-consuming procedure in an
examination situation, and with recent guidelines restricting the use of formalin to
a suitably ventilated area, it is not always practicable. However, candidates should
be familiar with the technique of formalin liquid and vapour inflation (Dunnill,
M.S. Pulmonary Pathology Chapter 6, Emphysema p81-82. Churchill Livingstone,
Edinburgh, 1982). If in doubt it is best to ask if facilities are available. It is a
desirable procedure in a number of cases where primary pulmonary disease is a
major factor in the patient's demise, in particular in a case of pneumoconiosis or
emphysema. The usual compromise is to inflate one lung for later examination
(which a candidate may well be asked to perform subsequently!) and to dissect
the other at the time. It is important to be aware of potential artefacts produced by
lung inflation (usually by too high an inflating pressure), and enough main
bronchus needs to be left to enable it to be tied off.

Dissection Procedure
a) Chest Wall

Since the rib cage and parietal pleurae also form part of the respiratory system,
they should have been inspected for rib fractures, pleural plaques, metastatic
deposits, etc. earlier, when the organs were first removed.

b) Larynx and Major Airways

The larynx is usually opened from behind in the midline, cracking the thyroid
cartilage. In cases where patients have died suddenly in hospital or those which
give rise to suspicion of inhalation of food, it is important to visualise the larynx
before removing the organs, as material is often dislodged during manipulation.
The material in the airways should be examined closely (e.g. mucopus, viscid mu-
cus, food), and note whether there are associated mucosal inflammatory changes.

It is important to keep both lungs orientated both during and after the dissection.
It can be surprisingly difficult to identify right and left lungs, especially if they are
The Practical Examination 267

diseased, and is an embarassing mistake to make in front of an examiner or

clinician. Lungs should be displayed in the antero-posterior direction, and the
surface topographic features identified.
The pleural surface of the hemidiaphragm should be included in the
assessment, and attempts made to correlate any pathology (e.g. adhesions,
plaques, etc.) with corresponding abnormalities on the visceral pleura. In cases
of rib fracture, a close inspection should be made for damage to the underlying
lung.
Before starting to dissect the lungs, they are weighed and then placed in cold
water to assess the density. While a poor discriminator of inflation during life, a
disproportionate heaviness in one lobe might indicate some localised
consolidation.
It is important to strike a balance when searching for pulmonary
thromboembolism. Some candidates seem to forget to do it entirely, while others
follow the pulmonary arterial vasculature almost to the periphery. A compromise
is to open to the 4th or 5th branch of each artery which should locate significant
pulmonary thromboemboli. Smaller ones are better detected on the cut surface of
the lung (see below).
Similarly, the airways are opened to the level of the segmental bronchi. There is
little point in going further however, unless grossly diseased.
Sectioning of the lung always seems to cause problems for pathologists in
training. Many compress the lung with a sponge, and try to bisect the lungs by
sawing their way through the parenchyma with a large knife. This invariably
produces a flabby, poorly orientated mess, which is impossible to demonstrate
adequately.
It is better to take a slightly more refined approach, taking each lobe in turn
and making a single lateral to medial incision from the parietal surface towards
the hilus, holding the lung firmly on a flat surface without heavy compression. It
should be possible to make more than one cut, especially in the lower lobes, one in
the anterior half and one in the posterior. The right middle lobe is best displayed
by a horizontal incision.
The cut surfaces require close inspection, with sponging or washing where
necessary, and the lungs palpated (without squeezing), which is equally effective
in locating abnormalities, but is often neglected. Bronchopneumonia and small
thromboemboli are often palpable rather than visible. Parenchymal disease is
often missed, especially the more subtle forms of emphysema or fibrosis.
Examining the lungs under water may improve the architecture, but squeezing
the parenchyma should be avoided as it draws water in. When demonstrating the
lungs, an explanatory statement to the examiner to the effect that pathology is best
seen in inflated lungs should be made and that immediate dissection is a
compromise.
Specimens should be taken for bacteriological or virological examination in
suspected infections, but this should ideally be performed before removal of the
lungs from the body to lessen the risk of contamination.

Anatomical Relationships

1) Pulmonary lobes
2) Segmental bronchial nomenclature
3) Pulmonary lobular architecture
4) Vasculature (pulmonary and bronchial arterial, venous)
268 Advanced Histopathology

Common Questions
1) Weight of normal lungs
2) Pulmonary thromboembolism. Frequency and predisposing features
3) Methods of pulmonary inflation
4) Classification of emphysema
5) Macroscopic appearance of carcinomas
6) Spread of bronchial carcinoma
7) Appearances of pulmonary tuberculosis
8) Function and requirements of Pneumoconiosis Medical Panel.

Urinary System
KidneJIs
The renal dissection should be tailored to the abnormalities anticipated from the
clinical history or inspection in situ. In hypertension or renal arterial disease the
aorta and renal arteries should be kept intact with both kidneys. When there is
lower urinary tract disease, keep both kidneys, ureters and bladder (+/- prostate)
as an intact dissection as described on page 257.
When there is no obvious renal disease, it may suffice to 'enucleate' each
kidney from the perirenal fat, (after dissection of the adrenal glands), with the
renal vein and artery transected (which should also have already been opened
and inspected). The ureter is divided at the pelvic brim or bladder wall. One
disadvantage of using the Letulle method is that the bladder is usually left behind
in the body (and often forgotten by candidates).
The kidney itself should be examined by removing the renal capsule, by
making a nick and separating the plane between cortex and capsule with a finger.
The kidney is often then bisected without inspecting the subcapsular surface
closely, and it is advantageous to make the cut through any lesions on the convex
border (e.g. scars, abscesses, haemorrhages) angled towards the hilus. The aim
should be to bisect the kidney with a single cut, so that the surface is smooth. The
two halves can 'hinge' on the renal pelvis, which should remain intact medially.
Close inspection should be made of the parenchyma for other lesions, and
transverse or vertical incisions made as required, but in a systematic fashion so
that the kidney can be reconstituted.
The ureters should be opened longitudinally, preferably following them into
the bladder. The latter is best opened from the urethra up the anterior wall to
display the trigone. The prostate requires examination by making two or three
transverse cuts - this is often neglected.

Anatomical Relationships
1) Weight of kidneys
2) Thickness of cortex
3) Topography of cut surface
4) Number of calyces
5) Diameter of ureters
The Practical Examination 269

Common Questions
1) Causes of subcapsular scarring
2) Effects of renal artery stenosis
3) Effects of hypertension
4) Pyelonephritis vs. glomerulonephritis - macroscopic appearances

Female Reproductive System

The ovaries and uterus are inspected in situ, and can be removed separately from
both rectum and bladder. It is easier once the rectum is removed, to cut across the
upper vagina, and using scissors to remove the broad ligaments flush with the
pelvic wall, avoiding the ureters. The organs may then be displayed in the
anatomical orientation, with incisions in both ovaries, Fallopian tubes, and the
uterus and cervix opened either with multiple transverse incisions or a single
vertical incision on the anterior wall, exposing the endometrium. If pathological
lesions are present these should be dissected as for a specimen received in a
routine surgical dissection.

Central Nervous System

Removal of the brain is often performed ,by post mortem technicians during most
of the routine post mortems performed by a trainee, and examiners are well aware
of this. Removal of spinal cord is described under 'Special Procedures' (p 282).
However, the examinee may well be asked to remove the brain, under the scrutiny
of the examiner, and if this procedure has not been practised it is relatively easy to
damage and disrupt the delicate tissue. It is not unknown for candidates to be
asked to remove the cranial vault in addition. On the other hand, in a routine case,
the supervisor will let it be known if the post mortem technician may remove the
skull and brain. In cases of suspected meningitis or abscess, CSF should be taken
from the fourth or third ventricles area by syringe puncture for microbiological
studies.
In cases where intracranial pathology is suspected, the brain should be
removed by the candidate. During this the brain needs to be well supported (ask
for assistance). The first task is to reflect the meninges to inspect the subdural
space. The vault is inspected for signs of extradural haematoma, and other
conditions such as Paget's disease or hyperostosis frontalis interna, etc. In
removing the brain, special care must be taken to cut the delicate cranial nerves at
their foramina, rather than letting them tear if the brain is allowed to fall
backwards under its own weight. If the spinal cord is not to be removed, a deep
cut with a scalpel is made well into the foramen magnum to transect the upper
spinal cord, and care taken to include the vertebrobasilar arteries which are often
left behind.
Detailed dissection of the brain is described in Gresham and Turner (Appendix
1) and you should follow the general guidelines for a routine dissection. The first
thing to establish is whether it is the usual practice at that centre to dissect the
brain at the time, or to suspend it in fixative for later examination (which will
therefore not be by the examinee!). An opportunity to point out that this is always
preferable with suspected intracerebral pathology should be taken.
270 Advanced Histopathology

The carotid sinus, pituitary fossa and meninges need to be inspected and
commented upon. The eyes should not be removed except with express
permission or suspected intra-ocular pathology. The pituitary gland should
always be removed at this stage, by incising the diaphragm of the sella, displacing
the posterior clinoid process.
The outer surface of the brain should be closely inspected. In suspected
cerebrovascular disease, all of the vessels on the base of the brain should be
identified and displayed, including the vertebral artery, but also the internal
carotid artery within the carotid sinus should be inspected by removing the lateral
bony wall of the sinus. It is unlikely that a candidate would be asked to expose the
vertebral arteries, but the origins should be inspected along with the intracranial
segment.
Sectioning of the brain will not be covered in detail here, but in a soft, unfixed
brain, compression should be avoided, using a single stroke to make each slice.
The cut surface should be wiped with the knife blade held at an angle, to remove
blood before inspection of the white matter and if there is vascular disease the
major vessels should not be divided before they have been demonstrated to the
examiner. The medulla and cerebellum should be removed and dissected
separately usually with horizontal slices.
After sectioning, the slices are best displayed in a neat, orderly array,
preferably on a board. This may be difficult at times with unfixed brain, but is still
no excuse for presenting a rather jumbled mound of brain slices which have
received only a perfunctory inspection.
Candidates would not normally be expected to remove the spinal cord for a
routine post mortem, but if there was a specific clinical indication to do so (e.g.
muscle wasting, paralysis, sensory deficit, motor neurone disease, etc.) which was
directly connected with the cause of death, it should be performed without
prompting. On occasion, candidates have been asked to remove the spinal cord as
a special procedure (see page 282), but only usually with an otherwise straight-
forward examination (e.g. probable myocardial infarction, etc.)

Anatomical Relationships

1) Weight range of brain

2) Cranial nerves - origin and identification in skull
3) Cerebral arterial supply
4) Vertebral and carotid arterial supply
5) Surface anatomy of the brain
6) Main anatomical regions of brain
7) Major deep nuclei in midbrain and thalamus
8) Ventricular system
9) Hippocampus
10) Internal capsule
11) Pineal gland (candidates should ensure they are able to locate this
structure, which is often left behind in the cranial fossae if the brain is not
carefully removed).
The Practical Examination 271

Common Questions
1) Morphological sequelae of coning phenomenon
2) Appearances in senile dementia
3) Types of cerebral haemorrhage
4) Cerebral infarction. Sites and appearances
5) Demyelinating diseases

Endocri ne System
The pituitary gland is commonly neglected, but should always be carefully
removed and bisected, usually transversely. It is important to be familiar with the
normal macroscopic appearance.
The parathyroid gland dissection is described more fully in 'Special
Procedures' (page 281), and should ideally be performed at the start of the
dissection of the thoracic pluck prior to removing the oesophagus.
The thyroid gland should be carefully removed from around the trachea, and
from surrounding muscles, in one piece. Both lobes and the isthmus should be
vertically sectioned, leaving the capsule intact on the anterior surface of the gland
to allow it to be orientated afterwards.
Both adrenal glands should be dissected out prior to removing the kidneys, as
afterwards they may be difficult to find, and are often damaged. They are best
located by palpation, and separated from the surrounding fat using small dissec-
ting scissors, so that the gland is not disrupted. Glands removed cleanly from the
fat are impressive to examiners, and are another sign of the expert prosector. After
removal, several parallel cuts made into the gland allow inspection, but one
border should be left intact to allow reconstruction.
Although not strictly endocrine, it is as well to be familiar with the location of
the carotid bodies and other paraganglia, which is sometimes raised in discussion.

Anatomica I Relationships
1) Normal gland weights - especially adrenal glands and differences
between autopsy and operative gland weights.
2) Vascular supply of pituitary gland
3) Surface anatomy of adrenal glands
4) Aberrant locations of thyroid/parathyroid glands

Common subiects for discussion

1) Atrophy of thyroid gland - recognition and effects
2) Adrenal cortical hyperplasia in hypertension
3) Significance and frequency of adrenal cortical nodules
4) Effects of hypo/hyper function of glands
5) Methods of assessing ante mortem gland function from necropsy material
(blood, vitreous humour analysis, etc.)
6) Parathyroid and adrenal gland weights
272 Advanced Histopathology

Lymphoreticular System

This is often disregarded as a system unless there is a specific disease such as

leukaemia or lymphoma, and frequently no specific comment made in the final
report. It is necessary to examine certain node groups as a matter of routine,
including axillary, cervical, mediastinal, para-aortic, mesenteric and inguinal,
keeping them to one side, or in a small dish, in a specific order, as the dissection
proceeds. Otherwise it becomes all too easy to forget and overlook more subtle
forms of nodal pathology. Such attention to detail will always create a favourable
impression with the examiner.
The spleen is fairly straightforward to dissect. (The splenic artery and vein
should be examined before removing the pancreas.) The capsular surface is
inspected carefully, and the parenchyma is examined either by a single horizontal
cut from the anterior border, or as a series of vertical transverse cuts along the
length of the organ on the inferior surface, leaving the superior capsule intact. The
choice of approach is largely dictated by the consistency of the spleen, and when
'autolysed' a single horizontal cut may be all that is possible. The cut surface
needs to be carefully washed in order to examine and display the parenchyma,
otherwise some features may be obscured by blood.
The thoracic duct dissection is described in detail under 'Special Procedures'
(page 283).

Anatomical Relationships
1) Drainage areas of the major nodal groups
2) Normal splenic weight range
3) Anatomy of thoracic duct

Common Questions
1) Causes of splenomegaly
2} Causes of local and generalised lymphadenopathy
3) Spleen in portal hypertension
4) Location of accessory spleens
5) Spleen in Hodgkin's disease/NHL

Musculoskeletal system
Much of this should be covered by the external examination of the body. All
deformities should be carefully noted, and the corresponding joints examined.
Lesser degrees of rheumatoid disease may be easily overlooked and the hands
require particularly careful assessment. A check should be made for alignment of
the legs, especially for true leg shortening, as a fractured neck of femur is easily
missed otherwise.
The rib cage should be examined as previously described. The cranial vault is
inspected when the brain is removed, and it is worthwhile measuring the
thickness of the skull if there is any suspicion of Paget's disease. The spine must
be assessed for deformity, and a careful examination of the atlanto-axial joint and
other cervical vertebrae should be made in Coroner's cases, especially where there
has been trauma. In the thoracic and lumbar spine, collapsed vertebrae are easily
The Practical Examination 273

overlooked. This may be facilitated by removing a strip of bone from the vertebral
column. Blood and bone dust should be removed from the cut surface, preferably
with a sponge, as the finer detail is usually obscured otherwise.
In cases of bone disease diagnosed ante mortem, the clinical history and
radiological studies may well dictate the bones and joints to be examined, and this
should have emerged during assessment of the clinical notes. It is often useful to
make a note of any bones requiring particular examination, writing a reminder on
the board in the post mortem room, as it is something that is easily forgotten,
since it is customary to perform detailed examination near the end of the
dissection.
Removal of the femur is described under 'Special Procedures'. However, it is
regarded as an essential part of the procedure in some centres, a point which
should be established with the post mortem technician, who must also have the
materials available for reconstruction. Dissection of the temporal bone (middle
ear) is also described under 'Special Procedures' (page 281).
It is worthwhile examining any joint that has had an operative procedure
performed on it, especially in the case of prosthetic replacements such as an
artificial hip. The orthopaedic surgeons may well find it of value to have a careful
assessment of the state of the prosthesis, and its integration with the surrounding
tissues.
The muscles are rarely examined in detail at post mortem, but any wasting
should be carefully noted, and the cause for this established if possible, in
conjunction with examination of the nervous system.
274 Advanced Histopathology

Presentation of the Post Mortem

Candidates may find that they are unable to make a formal presentation of the
findings at the end of the examination, but should always prepare just the same. It
is a mistake to attempt to 'sort out' the organs at the end of the dissection, as the
examiner may return at any time to inspect the findings, and may wish to make
several visits. Therefore each organ should be laid out on a separate board or dish
as it is finished, ensuring it is washed and dried to avoid too much seepage of
blood. It is often useful to rest the tissues on paper towelling, which can be later
removed.
It is important to keep in control of the presentation, and anticipate the
questions that are likely to be asked. In certain cases, a skilful presenter will be
able to suggest an interpretation, prompting the examiner to discuss the different-
ial diagnosis. In this situation, the best candidates have prepared good reasons for
supporting their interpretation in the light of the clinical information, and indicate
that they considered alternatives, discussing the reasons for their decisions. This
requires careful advance 'planning' during the course of the dissection.
The manner of the presentation is most important. It is best to commence with
a concise clinical history (if it has not been discussed with the examiner
previously). After this, attention should be turned to the major pathology, stating
initially the opinion as to the cause of death as it would be phrased for death
certification. The evidence to support this should be presented in a logical order.
In pulmonary thromboembolism for example, the starting point is the pulmonary
arteries and on to the lung parenchyma, moving then to the inferior vena cava and
leg veins. After this the factors considered to have predisposed to this pathology
are discussed (e.g. recumbency due to fractured neck of femur), which are in effect
underlying causes of death, rather than the acute event. In appropriate cases it is
useful to comment on the clinical course and effects of therapy on the disease. If
the clinical staff responsible for the patient attend they should be engaged in the
discussion, and the presentation aimed as much to them as the examiner. They
may provide some observations which will aid in the interpretation of the case,
and the examiner will always be impressed by a pathologist who clearly
demonstrates an ability to establish a rapport with clinical colleagues.
After discussion on the cause of death and major associated pathology, then
other findings should be considered, starting with the most important, leaving the
trivial abnormalities until last. If a long time has been spent on the major
pathology these findings may not be required by the examiner. Many candidates
approach the presentation in the opposite way, starting with minor, irrelevant or
peripheral abnormalities, as if to impress the examiner with the thoroughness of
their dissection. Unfortunately this has the opposite effect, merely providing
distractions and using up valuable time which could be better spent on the main
pathology, and runs the risk of irritating the examiner, who may interrupt and
take the initiative away. Trainees should enquire from senior pathologists about
their presentation style, and whether they achieve the right balance and emphasiS.
As well as verbal presentation, every effort should be made to be specific when
illustrating the pathological changes. Rather than vaguely pointing things out, a
probe or similar blunt instrument should be used but not a knife. The organ or
tissue must be displayed to the best advantage, orientating it towards the
examiner and held steadily. The skill of communicating while manipulating the
tissues should be developed by constant practice in order to maximise the
information which is to be conveyed in a most succinct manner. Avoid giving lists
of negative findings.
The Practical Examination 275

After the presentation, candidates are given time to finish the examination.
Tissues are taken for histological examination and it is important to take special
care over this, as examination of these may comprise part of the examination
subsequently. It is always best to take uniform blocks during training, and if
possible regular slices no greater than 5 mm in depth which will fit into a standard
cassette. These will fix well, unlike larger, poorly orientated lumps of tissue. It is
up to personal preference whether tissue is taken for histology as each organ
dissection is finished, or at the end of the necropsy. The advantage of the former
method is that it is possible to 'picture' where the blocks have been taken from
when the sections are examined, and candidates are less likely to forget to include
tissues from any site, a distinct risk if things are rather rushed at the end of the
necropsy. Extra pots can be labelled separately for particular lesions or sites, in
order to make the subsequent histological assessment easier. A record of the
blocks taken should be kept and put in the post mortem report. It is common for
examiners to enquire what tissues are required for histological examination and
what constitutes an adequate or optimal number to examine.
When satisfied that the dissection is complete, the area should be tidied and all
instruments located for safety reasons. Then a note of the organ Weights and other
abnormalities identified on external examination written on the post mortem
room board, should be made.

Writing the Report

In many centres candidates are asked to write up the report on blank A4 paper, as
this will constitute part of the submitted examination data. Therefore they must
be able to set out a report in this fashion, which may be a problem if they are used
to standardised sheets with pre-typed headings and sections. Conversely, in some
centres they may be given these sheets to complete for the report which, while this
will avert any errors of omission, may be in a different format to a form which a
candidate is used to so needs to be read through carefully prior to starting.
The following is an example post mortem report which is considered perfectly
adequate for examination purposes. It is not intended to be a counsel of excellence.
The same principles as for essay writing should be followed in the actual written
report on examination with attention paid to legibility, subheadings, etc. It is
always better to submit a neat handwritten report (some centres may allow you to
send the completed report the next day, especially if the dissection was in the
afternoon, but it should not be typewritten). In general, it is best to complete the
report at the centre the same day, otherwise there is a temptation to embellish and
modify findings after discussion with colleagues.
276 Advanced Histopathology

POST MORTEM EXAMINATION

Hospital:
Name of Patient:
Date of Birth: 13.6.20 Age: 69
Nationality: British Ward: X Consultant: Dr ......... .
Date of latest admission: 13 July 1989 13.40 hours
Date and time of death: 23 July 1989 04.10 hours
Date and time of necropsy: 24 July 1989 0900 hours
Weight of patient: 74.5 Kg Height: 5'9"
Coroner's report submitted: No
Prosector: Dr ......... .

Cause of death
I a) massive pulmonary thromboembolism
due to
b) thrombosis of the iliofemoral veins
due to
c) recumbency following acute myocardial infarction
II Ischaemic heart disease and essential hypertension
Maturity onset diabetes mellitus

Summary of pathological findings

1) Thrombus in main pulmonary arteries
2) Bilateral thrombosis iliofemoral veins and major branches of legs
3) Acute myocardial infarction (10-14 days)
4) Myocardial scarring and left ventricular hypertrophy
5) Coronary artery atheroma with thrombotic occlusion of the left anterior
descending branch
6) Systematic atherosclerosis
7) Bilateral renal cortical scarring
8) Nodular hyperplasia of adrenal cortex
9) Small oesophageal nodule (? leiomyoma)
10) Splenic mesothelial cyst
11) Seborrhoeic keratoses chest waIl
12) Previous appendicectomy

Clinical history
The patient had been treated for mild hypertension for 7 years, and maturity
onset diabetes was diagnosed 2 years later (controIled by diet). His only health
problem prior to this was an appendicectomy in 1955. Three years ago he was
admitted to this hospital for suspected anterior myocardial infarction, and had
been followed up since that time in the outpatient clinic, during which he was
requiring increasing levels of therapy to control his hypertension. He had also
noted increasing angina of effort in the past year.
On 13 July 1989 he was admitted via the accident and emergency
department with a 4-hour history of breathlessness and severe anginal pain
The Practical Examination 277

resistant to sublingual glyceryl trinitrate. Acute myocardial infarction was

confirmed by ECG examination. Over the next few hours he developed signs
of acute left ventricular failure, managed by diuretic therapy.
The patient made slow progress over the next 6 days, but was generally
weak: with poor mobilisation. On 19 July, 7 days after admission, he was noted
to have swelling of the right lower leg, and ultrasound examination confrrmed
the suspicion of deep venous thrombosis. Anticoagulant therapy had been
commenced 2 days previously, and mobilisation was encouraged. Despite this
he developed thrombosis in the left leg.
At 03.35 hours on 23 July he suffered a cardiac arrest. Resuscitation
attempts, including injection of streptokinase via a central venous line and
intracardiac injection of calcium and adrenaline, were unsuccessful, and the
patient was declared dead at 04.10 hours.

External examination
The body is of a mildly obese, elderly white male. Recent needle puncture
wounds are noted in the right and left antecubital fossae, left neck and
subclavian region, and over the fifth and sixth intercostal spaces on the
anterior chest wall. A 7 cm appendicectomy scar is present. There is marked
pitting oedema of both lower limbs (mid calf circumference 22 cm right, 21
cm left), with pitting oedema over the sacrum. A few seborrhoeic keratoses
are noted over the anterior chest wall.

INTERNAL EXAMINATION
Cardiovascular System
a) Veins
Thrombus occludes both femoral veins, to the origin of the giant saphenous
vein on the left, and the origin of the internal iliac vein on the right. A
fragment of thrombus 2.0 cm by 1.5 cm is found in the inferior vena cava.
The superior vena cava, subclavian and jugular veins are normal.
b) Heart
The pericardium has an area of fine fibrous adhesions over the anterior surface
of the heart, and there is a small amount of fibrinous exudate mainly over the
lateral and posterior wall of the left ventricle, with 80 ml of yellow, slightly
turbid pericardial fluid.
The heart weighs 510 g. The orifices of the venae cavae and pUlmonary
veins are normal. The atria are normal, and the auricular appendages are free
from thrombus.
The tricuspid valve is normal (circumference 12.5 cm). The right ventricle
is of normal size (defatted weight 60 g) and the pulmonary valve is normal
(circumference 7.5 cm). The pulmonary arteries contain pieces of cylindrical
thrombus (see Respiratory System). The left ventricle and septum are diffusely
hypertrophied (combined weight 215 g), and there is a transmural fibrotic scar
1.5 x 1.0 cm in the anterior wall consistent with an old healed infarct. The
myocardium over the anterolateral border is softened over a 3 cm diameter
area, and is pale, with a distinct hyperaemic margin. Areas of yellow/grey
mottled appearance are seen on the cut surface, and there is a small amount of
adherent thrombus on the endocardial surface. The appearances are consistent
with acute myocardial infarction of 10-14 days duration.
278 Advanced Histopathology

The mitral valve shows slight mucoid nodularity of the leaflets but is
otherwise normal (circumference 11.0 em). The aortic valve is normal
(circumference 7.0 em).
The right coronary artery shows two foci of severe (75%) atherosclerotic
narrowing, 2 cm and 3.5 em from its origin. The left coronary artery shows
marked narrowing of the main branch and the anterior descending branch is
occluded over a 1.0 cm length by recent thrombus. There is severe narrowing
over the rust 3 cm of the circumflex branch, but no occlusion is present. The
posterior descending artery is formed from the right coronary artery and is
patent. The coronary ostia are patent.

c) Arteries
Atherosclerotic plaques are present in the aortic arch and in the common
carotid arteries near the bifurcation, the left having surface thrombus.
Increasingly severe complicated atherosclerosis is encountered in the distal
thoracic and abdominal segments of the aorta, the latter showing confluent
ulcerated plaques with heavy calcification of the wall. There is severe
atherosclerosis of the iliac and femoral arteries. The renal arterial orifices are
surrounded by atherosclerosis but are not occluded.

Respiratory System
a) Airways
The larynx, trachea and major bronchi appear normal.

b) Vascular Supply
The pulmonary trunk and both the right and left main arteries are occluded by
fragmented and coiled cores of thrombus.
c) Parenchyma
The lungs are mildly oedematous (right 530 g, left 470 g). A few
emphysematous bullae are noted in both upper lobe apices, but there is no
gross emphysema elsewhere. There is some fibrotic scarring at the left apex in
addition, possibly a result of old healed tuberculosis. The parenchyma
elsewhere is slightly congested. Some of the medium-sized branches of the
pulmonary arteries contain thrombus visible on the cut surface. There is no
evidence of infarction or bronchopneumonia.

d) Pleural Cavities
The left and right pleural cavities each contain 100 ml of serous fluid.

Alimentary System
a) Alimentary Tract
The mouth is edentulous. The tongue oral cavity and pharynx are normal.
There is a 0.9 cm, light grey, ovoid, firm nodule in the wall of the lower third
of the oesophagus, probably a leiomyoma. The gastric mucosa is partly
autolysed but appears normal. The duodenum, jejunum and ileum all appear
normal. The large intestine is normal apart from occasional diverticula in the
sigmoid colon. The anus appears normal.
The Practical Examination 279

b) Liver and Biliary System

The liver is of normal weight (1470 g), but has a mildly congested appearance
on cut surface. The hepatic and portal veins are normal. The gall bladder is
distended with bile but no calculi are found. The common bile duct is normal,
and bile could be expressed from the ampulla prior to dissection.

c) Pancreas
Normal appearance (weight 145 g).

Genitourinary System
a) Kidneys
Both kidneys are generally atrophic (right 120 g, left 115 g), with adherent
capsules and a finely granular subcapsular surface, with focal small scars up to
0.5 cm across. The cortical width is reduced averaging 0.4 cm, but the
corticomedullary distinction is maintained. The medulla and renal pyramids
are normal. The renal pelvis and calyces are normal. Both renal arteries show
atherosclerosis, but this is considerably less than in the adjacent aorta and no
occlusion is demonstrated. The renal veins are normal.
Both ureters are of normal size. The bladder appears normal. The prostate is
nodular but not significantly hypertrophied. The penis and testes are normal.

Central Nervous System

The meninges are normal. The brain is of normal size (weight 1390 g). There
is mild atheroma of the internal carotid and vertebrobasilar arteries and
atheromatous plaques are visible on the arteries of the circle of Willis. No
occlusion is demonstrated. The cut surface of the brain parenchyma is normal
to inspection. The cerebellum, mid-brain and brains tern are all normal. There
is no visible abnormality of the cranial nerves within the skull. The eyes
appear normal. The middle ears were not examined. The spinal cord was not
removed.

Endocrine System
a) Pituitary Gland
Normal appearances.
b) Thyroid Gland
Normal appearances Weight 28 g.

c) Parathyroid
Three glands were identified and all appeared normal.

d) Adrenal Glands
Both adrenal glands were enlarged (left 11 g, right 10 g). This was due to
nodular hyperplasia of the cortex, with the fine nodules ranging from 1 - 4
mm across. The medulla appeared normal.
280 Advanced Histopathology

Lymphoreticular System

There was no significant lymphadenopathy. The splenic artery was rather

tortuous and calcified but no occlusion was demonstrated. The spleen was of
normal size (weight 190 g), with normal appearances on cut surface.

Musculoskeletal System
The skull and vertebrae appear normal. The left 6th and 7th ribs are fractured
anteriorly near the costochondral junction, but the lack of associated
haemorrhage indicates this was almost certainly a result of resuscitation
attempts. The consistency of the bones generally appeared normal.

Comments
The post mortem findings are in keeping with those expected from the clinical
history. The renal and cardiovascular abnormalities present are consistent with
long standing hypertension, complicated by atherosclerosis and ischaemic
heart disease. Diabetes mellitus may well have accelerated the development of
atherosclerosis. Nodular hyperplasia of the adrenal glands is considered to be a
frequent finding in long-standing hypertension, but its exact functional
significance is obscure.
The patient died from pulmonary thromboembolism due to venous
thrombosis of the legs. The latter was predisposed to by the patient's poor
mobility, myocardial infarction with an element of left ventricular failure and
severe atherosclerosis of the lower aorta and major arteries of the legs.
Blocks taken for histological examination:
1) Heart x 4
2) Coronary artery x 2
3) Lung x 6
4) Brain x 2
5) Kidneys x 4
6) Liver xl
7) Pancreas x 3
8) Spleen xl
9) Pituitary x 1
10) Thyroid x 1
11) Adrenal x 2
12) Lymph node x 1 Signature ............................................. .

This is a conveniently straightforward case, but which is designed to illustrate the

general layout of a report. The 'Comments' section is a particularly useful device
to interpret the pathological findings, emphasising the most important and
providing clinicopathological interpretation usually appreciated by clinical
COlleagues who can otherwise be somewhat unsure of the possible sequence of
events and the relevance of certain abnormalities to the overall picture. It is best to
limit this section to one or two fairly succinct paragraphs.
It is even more important to provide this information for the Coroner in
complex cases. However, if in the examination you are asked to perform a
The Practical Examination 281

Coroner's necropsy then a senior member of staff or your examiner will usually
take an interest and assume responsibility for completing the official report and
notifying the Coroner's office of the findings. You should conduct the necropsy as
for a detailed hospital case, and not as an exercise to determine the immediate
cause of death.

Special Techniques

1) Parathyroid gland dissection

2) Middle ear dissection
3) Removal of brain and spinal cord
4) Removal of femur
5) Identification of thoracic duct
6) Vertebral artery dissection

Parathyroid Glands

It is a favourite examination task to be asked to identify one or more parathyroid

glands. Some candidates often find this difficult and possibly because they
attempt to find them too late in the dissection, when many of the crucial
landmarks have been distorted. It is not unreasonable, however, to expect
pathologists to identify the glands in every post mortem.
The suggested method starts with examination of the neck viscera after
removal from the body. It is facilitated if the carotid arteries are removed as
previously suggested (page 258). From the posterior aspect, the oesophagus and
both carotid arteries are identified. Then gentle dissection between the two using
vertical strokes with a scalpel will eventually reveal the lateral margin of the
thyroid gland and trachea. The fine fascial tissues between the posterior border of
the thyroid gland and the lateral border of the oesophagus are teased away using
a scalpel which is facilitated by putting the tissues under slight tension. The
posterior and medial aspect of the thyroid lobes are then revealed, and the
parathyroid glands should become visible, attached to the thyroid gland capsule.
The upper glands are found midway down the posterior border, the lower pair at
the inferior margin or just underneath the thyroid lobe, although these can be very
variable. Examined under a strong light, they are quite distinct from lymph nodes
or nodular thyroid, with which they may be confused on superficial inspection.
The parathyroid glands have a distinctive tan coloration, with a very delicate
vascular network under the capsular surface. At least two glands should be
identified. However, with practice it is possible to identify all four glands as a
routine very swiftly.

Middle Ear Dissection

It could be argued that the proper way to examine the middle ear is to remove the
temporal bone intact, decalcify it and section it in a large microtome, but few
pathologists have the expertise or patience to accomplish this. However,
alternatives such as cracking off the roof of the temporal bone with bone forceps
or chisel are equally unsatisfactory, often destroying much of the detail. The
282 Advanced Histopathology

following method is relatively quick, but does require practice to get the optimal
alignment of the saw cuts.
The first task is to remove the dura mater over the petrous temporal bone with
forceps and a scalpel (or as much as possible). A 'I' blade is put into the necropsy
saw, and the first antero-posterior cut is made vertically 1 cm in from the squam-
ous portion of the temporal bone, and passes into the external auditory meatus.
This cut should be 2 cm deep. The second antero-posterior cut is 1 cm in from the
edge of the sella turcica, again 2 cm deep. Cut three runs in between these two,
parallel to and 1.5 cm anterior to the superior border of the petrous temporal bone.
The fourth cut is the most difficult. This should be made parallel to the edge of
the petrous temporal bone, 3-4 mm below the superior border. It will require
assistance to support the head and hold it forwards to effect this. It is important
not to cut in too deeply, 3-4 mm at most. Then a bone chisel with a 'T' bar is
inserted, and with a rocking motion the plate of bone between the cuts is levered
off. It may need a few sharp taps with a hammer to loosen it. The bone plate
usually comes off intact but occasionally loose fragments are left. However, the
structure of the middle ear is clearly revealed, after bone dust is gently washed
away. With practice, the procedure can be accomplished in 2-3 minutes.

Removal of Spinal Cord

Candidates are unlikely to be asked to remove the spinal cord unless there is a
specific indication in the history, of if the necropsy is otherwise very simple (e.g.
myocardial infarction with no other pathology present), to provide some more
stringent assessment of the capability of the candidate. However it is not
uncommon for the candidate to be asked to remove the cranial vault, since it is
recognised that this task is frequently neglected by delegating it to the mortuary
technician. The following method includes the removal of brain and spinal cord
intact. The cord is best removed from the posterior aspect, as it is very hard to
remove the anterior spinal bodies to gain access, although it is perhaps less time-
consuming for the technical staff.
A longitudinal incision is made over the whole length of the spine, and the
erector spinae reflected over the medial aspects of the ribs, so that the 'field' is
clear. It is most important to scrape away the muscles over the vertebral arches so
that a clean cut can be made with the saw. This may take 10 minutes to perform,
but it is reasonable to ask the mortuary technician to assist.
Having done this, transverse processes are transected using a circular or T-
shaped blade on the necropsy saw, angling the cut at about 30° to the vertical, 2.5
cm from the midline. It is best to start on the mid-thoracic vertebrae where the
arches are thinnest. It is important not to penetrate too deeply or the cord may be
damaged. If the penetration of the spinal canal cannot be felt (there should be a
sudden 'give' when cutting the arch), the cut is either too lateral or the blade is
held in too vertical a plane.
These cuts are continued either side, leaving a gap of at least 3 cm between the
two. When completed the cervical vertebral region is transected between C2-3 or
C3-4, severing the interspinous and posterior ligaments (but not the cord), the
vertebral arches can be peeled back by holding them with large Spencer-wells
forceps, progressively dividing ligaments with a scalpel.
If the saw cuts have been made at the correct angle, the dura mater will still be
intact, but it requires some practice to get this exactly right.
The arches are removed down to the level of the sacrum. Then the dura mater
is gripped in the lumbar region border with toothed forceps, gently elevated and
nerve roots progressively divided near their exit from the canal with a sharp
The Practical Examination 283

scalpel, up to the level of the cervical spine. Keep the dura on slight tension while
doing this, and avoid any flexion or kinking.
If the brain has already been removed, the whole cord from the Cl-2 level
downwards should be excised from the canal still within the dura. If not, the
spinal cord is usually transected at this level and removed separately. In particular
cases, both are to be removed in continuity. To do this an incision needs to be
made in the dura around the foramen magnum from inside the skull, to release
the dura mater. The brain is mobilised in the conventional fashion, but it is still
quite a difficult exercise to cut the dura around the foramen magnum with the
brain in place, to enable the cord to be delivered via the foramen. This is quite
time-consuming, and hence not really appropriate for examination purposes, but
may be of value when there is suspected pathology in the medulla/upper cervical
cord.

Removal of Femur

This procedure is not very complicated technically, but requires some thought to
minimise the effort involved, and to avoid the possible hazards in deep dissection.
One method is well illustrated by Gresham and Turner (Appendix 1).
A lateral longitudinal incision is recommended, from the iliac crest to below
the knee. It is easiest to incise deeply and remove all the muscles and ligaments
around the knee, cutting into the joint to mobilise the lower end of the femur. The
femur is manipulated to allow muscles up to the hip joint to be dissected off.
Assistance may be needed to hold the femur out laterally to gain access.
Having freed the muscle attachments lower down the bone enables it to be
manipulated to remove the gluteal hamstring muscle insertions, and the joint
capsule around the acetabulum is incised. If there is a fracture of the femoral neck,
great care is required as the bone splinters are a considerable hazard.
After removal, the femur is immobilised with a clamp and longitudinally
sectioned with a tenon saw, bisecting the head and neck. The cut surface is washed
as bone dust obscures much of the detail.

Thoracic Duct

This structure is largely ignored by most pathologists but it is useful to be able to

find it if required, perhaps for demonstration to medical students. Candidates
have been asked to demonstrate it on occasion, particularly in malignant
necropsies.
The duct is a thin-walled, pale cord which can be observed on the posterior
aspect of the thoracic viscera, at its lower end (cisterna chyli) by the right side of
the aorta and right crus of the diaphragm, ascending between the right side of the
aorta and main azygous vein, where it lies adjacent to the left side of the aorta.

Vertebral Arteries

While it should be a matter of routine to inspect the origins of the vertebral

arteries as they enter the cervical vertebral transverse process, and the intracranial
segments proximal to the vertebrobasilar artery after removal of the brain, the
intracervical segments of the vessels are more of a problem. It is certainly not an
easy process to remove and inspect these but there may be a specific clinical
indication to do so, and the candidate may be asked to perform it in an otherwise
straightforward necropsy, or at least asked how it could be performed.
284 Advanced Histopathology

One elegant methodology is described in detail in the reference below and is

very useful in that the cervical spine does not have to be removed. The
instruments required are two particular types of scalpel and a pair of curved,
wire-cutting scissors. It is unlikely that a candidate would be faulted for not being
capable of performing this dissection but, as already pointed out, it is expected
they would be able to point out the origin of the vessels.

Reference
Bromilow, A., Bums, J. J. Clin. Pathol. (1985) 38: 1400-1402.

Paediatric and Neonatal Necropsies

Although most of the technique of post mortem examination of foetuses, neonates

and children is similar to that in adults, there are a few critical differences, which
candidates are often unfamiliar with because they have had access to far fewer
paediatric than adult necropsies. Examination candidates should appreciate that
they may well be required to conduct such an examination. Failure to do so has
resulted in several candidates being surprised when faced with such a task, with
consequent very poor performances. The frequency with which candidates are
required to undertake neonatal and paediatric necropsies may well rise in the
future, as the numbers of suitable adult necropsies decline, which is often the case
at many of the examination centres. Nor will the argument be accepted that the
request to perform a neonatal/paediatric necropsy is unfair, as it is as much a
function of a consultant pathologist as a routine adult case.
Each candidate should take the necessary steps to obtain experience in these
examinations during the course of their training, and preferably not just before
the practical examination. Specialist paediatric pathologists, or consultant pathol-
ogists with an interest in this field, could be approached with a view to arranging
some supervision in these necropsies, which could be made on an informal basis
or as a formal part of a training rotation, with the approval of the departmental
chief. (The ACP might be able to arrange a secondment in certain cases).
The necropsy itself differs in many respects from the adult, and it is worthwhile
reiterating the major alterations in emphasis and technique which may provide
problems for trainees. Examiners usually recognise that examination candidates
have particular difficulty in performing such necropsies, because for the majority
an opportunity to perform them is restricted to some degree, and will thus make
some allowances. This does not extend to awarding a pass standard for hopelessly
incompetent performances, even with the advantage of a 'sympathy vote'.
In the external examination, it is extremely important to accurately weigh the
body and make certain measurements, especially foot length, head circumference,
crown-rump and crown-heel lengths. The last three are prone to inaccuracies,
especially as a result of intrauterine death, where widening of the sutures and
joint laxity may occur. Weights and measurements should be assessed against
appropriate gestation or age-related normal values in tabular form, which should
be available in the mortuary. (It is not expected that candidates should learn such
values). It might be prudent to take copies of such tables to the examination
centre, however, just in case.
Radiographic examination of the body should be suggested in all cases of
suspected congenital abnormalities, sudden infant death syndrome, growth
disorders or deformities, among others. Arrangements would probably have been
The Practical Examination 285

made in advance by the mortuary technical staff to perform this in the hospital
radiology department but a well-equipped mortuary usually has a self-contained
x-ray unit such as a Faxitron for this purpose. Having requested radiographs, it
would be as well to have some knowledge of bone development and appearance
of the major ossification centres, and be aware of a reference source for more
detailed appraisal.
If there are clinical reasons to suspect congenital abnormality or if dysmorphic
features are apparent then medical photography should be requested. This again
is something to be discussed with the supervisor or mortuary technician who will
advise of the usual procedure in that department.
In addition to the pathological assessment of the body, the position and
appearance of any drains, catheters or vascular lines should be noted, and
preparation made for taking bacteriological samples from these during the
dissection.
In neonates and infants an inverted Y incision is usually adopted to allow
reflection of the bladder and umbilical vessels. In the older child a conventional Y
incision is usually made. In cases from intensive treatment units or where
ventilation has been given, testing for pneumothorax should be made. Use of a
small manometer attached to a hypodermic needle may be useful in this
assessment.
One of the major problems with the assessment of a paediatric post mortem is
a familiarity with the relative size of organs, and this is difficult to assess from
theoretical knowledge rather than practical experience. Tables are available of
organ weights compared to the gestational age and should be consulted.
The conventional removal of organs is well described in the reference at the
end of this section, but there are three main blocks: neck structures, thoracic and
upper abdominal viscera, and intestines, urogenital tract and related vessels. The
liver should always be removed in continuity with the thoracic viscera in cases of
congenital heart disease. In intrauterine death, congenital heart disease is a major
unsuspected discovery and this is therefore the recommended technique in this
situation.
From a practical point of view, organs must be dissected resting on a sponge to
maintain them in a static position, essential for accurate and safe sectioning. The
detailed examination of organs is comprehensively described and illustrated in
the given reference texts, and are generally modifications of the adult dissection.
Examination of the cranial contents is always a problem for the inexperienced.
It is tempting to incise along suture lines once the scalp is reflected, but this
destroys the venous sinuses and dural folds, structures which are much more
important in neonatal and infant pathology than in adults. Bony 'flaps' should be
made and folded back to expose the brain, but the latter's removal is often a
problem to candidates because of its delicate, easily disrupted tissue. Assistance
from the post mortem technician in supporting the brain is invaluable. Some
authorities have advocated removing the foetal brain under water to provide this
support, but this can be awkward and is a matter for personal preference.

Reference

1. Berry, c.L. Examination of the Foetus and Neonate. In: Paediatric Pathology,
pl-39. Springer-Verlag, Berlin (1989).
 287

Surgical Pathology Slides

These are the most important part of the examination and a poor performance in
this section is unlikely to be retrieved by anything other than exceptional
performances in the others, and usually not even then. Candidates are expected to
demonstrate a sound and thorough approach to examining histological material.
However, no one is expecting perfect answers to all of the slides, as this would be
highly unusual in the examination situation. It is therefore very difficult to convey
any consensus opinion on the standards required, so the following discussion
attempts to provide some guidelines on the way to approach the answers, which
may reflect the attitude of a competent histopathologist.
In most centres, candidates are asked to examine about 20 slides, ranging from
18 to 26. It is always better to use a familiar type of microscope, preferably the one
used in routine daily work. It can be very difficult to adapt to one provided by the
examination centre, and leaves a candidate at some disadvantage. If this is
unavoidable, it would be reasonable to ask if the instrument could be made
available to enable some familiarisation with it prior to the examination itself.
The examination is conducted in a quiet room, usually with one supervisor
present. Candidates are instructed about the nature of the examination and in
general terms what is required. A typewritten sheet with brief clinical histories
relating to each of the slides is distributed.
The first thing to do is work out how many slides there are, and what is the
average time allowed to answer each of them. This calculation is most important.
With 20 slides, there are about 8.5 minutes for each one, allowing 10 minutes at
the end of the period. It is absolutely vital to be aware of how long it takes to
examine a section of the appropriate degree of difficulty, and write a report on it,
during revision preparations. Misjudgement of the time available is one of the
major reasons for candidates running into problems with this part of the examina-
tion. It is therefore of great importance to be very strict with the timekeeping. This
really requires a small clock or watch, if possible with a timer (but not an alarm!),
and sufficient self-discipline to adhere to the allocated time for each section. It is
usually possible to return to some of the cases at the end of the period.

Recommended Approach to Examination of Sections

It is difficult to dictate to pathologists who are considering applying for the Final
examination on how to examine a tissue section, which is after all the main skill
which they have developed. However, it is surprising how often deficient
technique is responsible for misinterpretation, as all pathologists have to admit (if
they are honest). It is a useful exercise to ask senior colleagues to admit to mis-
diagnoses they have made, and describe the factors that led to these problems.
More than that, however, are the unconscious lapses in technique which the
examination may well uncover. These are either a result of inadequate training
and supervision, or a mistaken belief that a diagnosis is usually reached by
examining sections under high power magnification.

Assessment of the Clinical Information

This was mentioned in the introduction but its importance cannot be over-
emphasised. All of the information provided must be taken into account, as it is
288 Advanced Histopathology

there for a purpose. Although exceptions can occur, it is unlikely that a section of
something which is inconsistent with the usual age and sex incidence of a
particular entity will be introduced, unless it is a very distinctive lesion.
Conversely, great consideration should be given before suggesting a diagnosis
which would be distinctly unusual in that setting (e.g. a liposarcoma in a 5 year
old child, Gaucher's disease in a bone marrow biopsy of a 70 year old woman).
The site, size and duration of the lesion, plus any other clinical information,
must be taken into account. The amount given in the examination is variable, but
is usually no more than one or two sentences, or even just a few words. It is vital
that each lesion is assessed in the light of this information and the answer directed
accordingly. The differential diagnosis of any particular problem may also vary
considerably, and candidates will be marked down if they are incapable of
adapting to this in order to make a rational assessment. In cases where the clinical
information is particularly scanty or vague, then it usually means either that the
diagnosis would be very straightforward if the exact location is given, or that the
lesion is difficult to define and only a differential diagnosis is required (with
indications as to how to resolve the problem). The former situation is much more
common.
The macroscopic description of a lesion may also be given. If so, there is
usually a very good reason, probably that this may help in the differential
diagnosis between two similar lesions.
On the other hand, having read and digested the clinical information, it is
important not to form an opinion on a preconceived notion of the likely diagnosis
prior to examining the slide, as then the risk of 'seeing what you wish to to see'
occurs. Some people find it better to look at the section 'blind' to form an
impression and then read the clinical information. Whatever the individual
preference, it must be stressed that the clinical information is taken into account
before forming a final opinion.

Naked Eye Examination

It is remarkable how often some experienced pathologists, as well as trainees, fail
to look at the slide with the naked eye or even low magnification, merely
examining it under medium to high power to make the diagnosis. While this may
be effective with a number of cases, dangers lie in missing focal lesions or
architectural clues.
The recommended approach is to examine sections against a sheet of blank
white paper in a good light. Holding it up to the window is not really adequate as
features may be obscured. (An old x-ray viewing box or transparency viewing box
is ideal but not really practicable for examination purposes.)
The first thing to assess is the distribution of the material on the section.
(Candidates in the habit of circumscribing the limits of the area to be examined
with a felt pen, should ensure that a washable one is used and the slide wiped
clean afterwards.) A mental note of the number of tissue fragments is made to
ensure all of them are examined under the microscope. It is a favourite manoeuvre
of examiners to include cases where only one of a number of biopsy fragments
includes the diagnostic features.
Secondly, the architecture of the section is assessed. It is important to try to
identify any normal tissue landmarks, especially at the margins. If there is an
obvious lesion present, the circumscription or otherwise is noted, together with
variations in staining, and any patterns which may be visible. A magnifying glass
or loupe may help reveal these features. There may be a single focus or multifocal
Surgical Pathology Slides 289

lesions. A wealth of information can be gleaned from examining sections in this

way, and its real value can only be appreciated by constantly examining sections.
Sadly this appears to be neglected by many trainees (who have possibly followed
the example set by senior colleagues) and is responsible for many errors.
The section should then be examined under the microscope in the usual
fashion, but again the low magnifications often reveal more information. Good
diagnostic pathologists will make great use of all of the magnification powers
available. Oil immersion is often valuable for looking at subcellular features
which are difficult to resolve with the higher power lenses. Confirming or
excluding the presence of cross-striations in primitive sarcomas is one example.
However, it can be somewhat time-consuming to do this and should only be used
in selected cases.
As with naked eye examination, discipline is required to inspect all of the
material with a low power magnification, which following practice becomes a
habit with good histopathologists. Inexperienced ones often wish to use the high
power lens at first sight of a potentially diagnostic field, and this is sometimes the
reason for misinterpretation.

Writing the Report

It might seem obvious, but the main function of the report is to convey a diagnosis
or interpretation to the examiners in the shortest and most unequivocal manner
possible. About a paragraph of writing is adequate for most of the cases, using
concise descriptive language as for a report to be issued to a clinician. The format
will vary from case to case and according to personal preference, but it is often a
good idea to write a few words or one sentence giving the major diagnosis (or
diagnoses) at the beginning, followed by a few lines to a paragraph describing the
major features, other conditions considered in the differential diagnosis (and the
evidence against them), and a sentence outlining which special stains or other
procedures (e.g. electron microscopy) might be performed to support the diag-
nosis. An alternative format is to place the diagnosis at the end. The most
important point is not to 'lose' the main diagnosis in amongst the description, as
examiners recognise this is an important cause of misunderstanding in the
interpretation of reports.
Another general point is that ambiguity must be avoided at all times. In some
of the cases, there may well be uncertainty about the diagnosis, in which event a
clear differential diagnosis should be stated, followed by an outline of the
procedures necessary to resolve this problem. There is a great temptation to word
the report in order to disguise the inability to reach a definitive diagnosis, the
most crass examples being to avoid stating whether a particular tumour is benign
or malignant and leaving it as a 'neoplasm' hoping this will be a good 'each way'
bet. There are numerous other examples which all candidates will be only too
aware of, as of course are the examiners.

Types of Cases Used in the Examination

It is not unusual for senior colleagues and contemporaries to declare that a
particular section or case is of 'MRC Path standard'. Usually this means that it is
particularly hard and that they have reached a diagnosis after much deliberation
and consultation of the literature! In reality such cases actually form a minority in
the examination, and are more likely to be a device for keeping an up and coming
290 Advanced Histopathology

trainee in their place. Most centres aim to achieve a balance of material from
reasonably straightforward to impossible, and naturally this is highly variable. In
general terms, about half of the cases could well be encountered fairly often
during routine practice and have a fairly distinctive histological appearance
(examples are given at the end of this section). It is very reassuring to identify
these cases, but the relative proportions do vary widely among centres (so it is not
a cause for undue concern if an individual finds relatively few in their particular
examination!) Candidates would be expected to identify most or all of these,
giving a reasonable description and a confident diagnosis, or a limited differential
diagnosis. As far as can be ascertained, no centres have 'automatic fail' slides, but
any candidate making more than one or perhaps two serious errors in this lower
category will be marked down very heavily, (unless some mitigation of the
mistake can be made in the viva voce - see later).
Around one third or more will be more difficult problems. These fall into
several groups (anecdotal examples given for illustrative purposes).
1) Good examples of rare diseases e.g. epithelioid sarcoma
2) A reasonably common lesion in an unusual location e.g. non Hodgkin's
lymphoma in the uterus
3) Rare entities which may simulate commoner diseases e.g. progressive
multifocalleucoencephalopathy resembling astrocytoma
4) Common diseases with an uncommon or potentially misleading
histological appearance e.g. lymphadenitis due to EB virus, healing
fracture simulating osteosarcoma
'5) Subtle changes in tissues (the history is often a major help in such cases)
e.g. amyloidosis in the gut or heart
6) Sections containing a small area having the diagnostic features, which
gives some idea of the ability of a candidate to comprehensively examine
sections e.g. focus of CLIS in otherwise benign breast disease
7) Dual pathology. Either two related entities e.g. villous atrophy with small
intestinal lymphoma, hepatocellular carcinoma in cirrhosis, or two
unrelated diseases which are identifiable in a single tissue section (often a
local lesion and a systemic disease) e.g. adrenal myelolipoma with
metastatic carcinoma in residual adrenal parenchyma.
Many candidates worry unduly about the incidence of groups 5) and 6) in
examinations, suspecting every slide may hold a potential trap. While it may be a
useful discipline to make a check for other pathology in every section, it is most
important not to become too obsessed with this. If the right approach to examining
sections has been adopted, the main diagnosis will usually be identified. In the
case of 'coincidental' dual pathology, both conditions should be readily
identifiable in a properly examined section; candidates would not be expected to
make a 'spectacular' diagnosis if there were only a small group of cells at the
periphery of the tissue for example.
Some of the sections, usually (but not always) less than a quarter, will be
particularly difficult. There are several aims to putting such examples into an
examination. It is not always expected that a definitive diagnosis should be made
but rather that a reasonable differential can be proffered. The examiners take note
of a candidate's method of approaching such problems and follow the method of
reasoning. If they can see that the assessment is sound, and suggested further
investigations would probably lead to a correct diagnosis, then this is all that is
expected. These cases should not cause too much despair if they cannot be sorted
Surgical Pathology Slides 291

out immediately. It is far better to move to the next case and return at a later stage,
when the problem may even have resolved itself by subconscious processes! The
problems seem to arise when candidates panic, and write disjointed, ill-thought-
out answers which either suggest rare, unlikely diagnoses (which if they bear no
resemblance to the lesion in question, further compound the error) or, worse,
come to a certain diagnosis because the candidate thinks it is an appropriate lesion
to be in an examination and interprets the appearances in order to make them fit
this diagnosis. This is one of the major pitfalls of any diagnostic histopathologist
and is a habit into which any pathologist must gain some insight. This is
considered further in the next section.

Preparation for the Surgical Histopathology

General Principles

Candidates have different ideas on how to prepare, but there appears to be a

prevalent belief that wading through masses of sections from various sources in
the few weeks leading up to the examination will somehow enhance their
diagnostic ability, resulting from the rather restricted attitude that to have seen a
certain entity will ensure its future recognition. It is unlikely to yield significant
improvements in proportion to the effort expended. It is necessary to adopt other
tactics to enable the information to be usefully retained, otherwise it is merely an
exercise in 'wallpaper matching'. The following sections suggest methods of
improving the retention of information during revision exercises, and for
enhancing interpretation as opposed to merely recognition.
Instead of examining random collections of slides, examples should be
arranged in systematically organised groups. The advantage of this is that
comparisons can be made between different pathological changes within the same
tissue, which are a potential source of confusion. It is a great deal easier to identify
the more subtle differences when concentrating on a particular tissue, and can
recall the appearances of other conditions which have been examined in conjunc-
tion. When many slides are examined on a random basis, it is far more difficult to
retain the mental 'image' of the section when it is a condition with which you are
not familiar.
One reason for this phenomenon may be the selective nature of recall necessary
to make a differential diagnosis, where the major differences are the crucial
elements, while insignificant or common features require less active interpret-
ation. When other completely different sections are interposed between two
conditions which may be confused, it is more difficult to get a perspective on the
most and least important differences between them. Collaborative exercises
involving active interpretation rather than passive recognition are the key to
committing the information to long-term memory.
It is always advisable to further reinforce the effective yield from any revision
session by writing a report as for the examination, and it will help to organise the
interpretation of the condition. It is a mistake to make a particular diagnosis and
assume that the report will be easy to write. If a conscious effort is made to justify
the reasons for reaching a particular conclusion in descriptive terms, and how it
may be confirmed further, the interpretative element of the answer will not be
lost. Recognition alone is not sufficient. The ability to compile reports in concise,
accurate and relevant detail is a skill to be acqUired as much as examining the
292 Advanced Histopathology

section, and unfortunately requires constant practice. (It is probably unnecessary

to write longhand reports in the later stages of revision; note-form will suffice and
will actual highlight the key words in each sentence of a report, and indicate the
overall structure.)
It should be obvious that maximum benefit would be gained by examining
sections with the help of clinical information only, prior to being given or looking
up the correct diagnosis, otherwise opinion will be biased and will not accurately
reflect the level of ability. It may be necessary to take steps to remove t~e
diagnoses from vision or preferably from easy reach during the session. After· or
during each microscopic session, it is absolutely essential to read up on the
conditions examined, using either comprehensive textbooks (e.g. AckermJln's
Surgical Pathology) or specialist books. This is another reason for examining one
system at a time, to avoid searching for different subjects in a multitude of books
at each session, which is time<onsuming and generally discouraging.
The relevant section of each text can be quickly scanned in cases where the
diagnosis is certain, and the key words in the report serve as a guide. Those items
found to be incorrect or were omitted from the written report can be revised,
which is a very efficient way of revealing deficiencies and for remember-ing them.
If the reports are used as a basis for a revision session following the microscopy,
perhaps later in the evening, it may also provide an opportunity to read up on
related subjects.
It is perhaps even more vital to write reports for sections where the diagnosis is
not straightforward and only a differential diagnosis can be made, or where
further investigations are required. These are the sorts of cases which provide
practical difficulties in the examination, and are most revealing about a
candidate's ability to deal with a particular problem. Writing down the
interpretation of a slide as a report during revision can reveal whether incorrect
emphasis is given or assumptions made when the subject is reviewed with the aid
of a textbook. It is important to be honest about one's own capacity and the only
way to do this is to have it written down. Otherwise a degree of self-deception
will inevitably be acquired, as no one likes to admit they are wrong!
If there are a large number of slides to be examined which are relatively
straightforward, or the time of the examination is very near, then in order to save
time it might be helpful to mentally compose a report rather than note it down.
However, it is most important to know exactly what would be written word for
word as a report. If circumstances permit, it may be an advantage to dictate the
report aloud. The danger lies in reverting to only having a vague idea about what
to say, and it would still be better to avoid this as far as possible.
Adopting a different theme every few days will help to maintain interest in the
material, which is most important to gain maximum benefit. On the other hand,
there can be too much of a good thing, as attempts to examine large numbers of
cases only result in a superficial coverage of each subject. This is often the case
with senior colleagues' personal slide collections, compiled from randomly
selected 'interesting cases'. While these certainly have a role to play (see later),
they are often the staple diet of the examination 'crammer' and one which is often
too rich for examination purposes. Very often, these are not filed on a systematic
basis, and it would be inadvisable to disrupt the order unless the owner is in full
agreement. However, it is an idea to work through the key to select out cases
pertaining to the system currently under review. If such collections are the only or
major source of revision material, it is most important to take this extra effort.
While it may be initially discouraging to learn from boastful colleagues that they
have examined in excess of 100 slides in a day, it is important to remain confident
that a more circumspect inspection of even a quarter or less of that total coupled
Surgical Pathology Slides 293

with a written report and brief reading will be far more productive in the long
run, with more detailed information being retained and understood, whereas it
would have largely evaporated from the mind of the former. If confidence in the
approach is still lacking, it is suggested that some simple trials are conducted
(well in advance of the examination) to test this hypothesis!
As already explained, personal collections can form the bulk of many
candidates' revision, but the following sections deal with the use of alternative
sources of material which could form the basis of a more structured and
comprehensive approach. Of these, there is no doubt that routine surgical
reporting is the best method of achieving proficiency, and every effort should be
made to gain experience at this, even at the expense of formal revision sessions.

Material Sources and their Utilisation for Surgical Pathology

Revision
The key to a good revision programme is to arrange the material source in an
organised fashion, at least in the early stages, which involves some effort and not
a little ingenuity at times. We suggest that the following sources be tapped.

Routine Surgical Files

All hospitals have interesting and unusual pathological material in the files, but
there can be a problem in extracting it. The best way is to plan in advance, making
notes on selected cases or keeping a special file. Unfortunately, trainees are often
not in one department for long enough to establish anything substantial in the
way of numbers. There may be a departmental filing system in operation for such
cases.
Running through coded files to identify potentially interesting cases is often
unsatisfactory and disheartening. This is because the material is often of poor
quality, perhaps a small biopsy or not a typical example. Also, there may be many
sections to examine, which is time consuming. The sections may be misfiled or
frequently 'missing', a not uncommon experience with interesting cases. The
expenditure of effort is therefore quite large for a relatively small return, and the
place for examination of routine files is considered more in conjunction with
routine surgical reporting.

Post Mortem Files

Surprisingly, these often yield substantial amounts of pathology, which while not
strictly surgical pathology, may well be useful material to review. It is relatively
easy to leaf through post mortem reports, and select some which might yield
material. The advantage of post mortem sections are that they are often large and
relatively well orientated, although the preservation may not be optimal. Post
mortem files are more likely to be intact, and are useful because it enables material
to be extracted and grouped into systems. This is inadvisable with routine surgical
files because material may be removed which has some relevance to the current
specimens.
294 Advanced Histopathology

Teaching Collections

Some departments have teaching collections specifically compiled for trainees.

However, the quality can be variable and the material may not have been updated
for some years.

Course Material

Slides given out during a teaching course or symposium are an invaluable source
of revision material, as they are usually accompanied by an explanatory text. It is
often unclear which courses will provide sections to take away, but it is useful to
make enquiries of the organisers, or better still speak to previous applicants.
Courses designed specifically to meet the needs of trainees, covering a wide range
of subjects, are the most useful in this respect (see Appendix 2), as well as other
courses organised in some of the major teaching centres, in Britain, Australia, USA
or elsewhere.
Symposia or courses on more specialised fields of pathology are also organised
regularly, and may well provide a slide set, sometimes for an additional fee. It is
usually worth investing in one, and if finance is a problem it may be possible to
purchase a set with departmental funds to include as part of the teaching
collection, or the cost spread amongst several colleagues.
There are more compelling reasons for attending the courses other than the
acquisition of a teaching set however, which should not be a primary reasons for
deciding whether or not to attend. After all, the most important factor is to have
the opportunity to examine the material and be involved in a discussion and
review, so that the appearances would be sufficiently explained to enable a
recognition of the entity again, even in a slightly different form. Again, the best
way of doing this is to look at the sections with the clinical data, write a report,
and then see how the answer tallies with the correct diagnosis.
It is important to decide at what stage to attend such courses. All regional
teaching sessions should be attended throughout training. Comprehensive
courses are best attended around two years prior to the examination, so that there
is time to absorb and read around the course material, and perhaps identify any
areas of particular weakness that the course may uncover. In this event,
arrangements can be made to attend some more specialised teaching sessions or
symposia to redress this.
Some trainees prefer to attend some of the advanced histopathology sessions
just prior to the practical examination. While this may provide some advantage in
that the entities examined will be fresher in the memory, there may be little time
to correct any deficiencies. It may be better to go to such courses six or seven
months prior to the examination for this reason. On the other hand, certain
individuals find that they are better motivated close to the examination.
It is important to take full advantage of these courses, in particular to discuss
various problems with the supervisors. Many trainees appear inhibited, a problem
which appears to increase the nearer the examination is. However, course students
who fully participate in discussion during microscopy revisions and reviews
undoubtedly gain a great deal more, and it is important to make a determined
effort to ask questions, in order to gain maximum benefit.
While it is advisable to attend as many courses as possible in the year before
the examination, it is also just as important to be selective. Some courses may be
too narrow, being concerned with a subject more suited to post-MRCPath
specialisation, and it is best to take advice from your Head of Department or even
the course organisers to find out if you would benefit merely in terms of
Surgical Pathology Slides 295

examination revision. Further comments on this aspect are made in Appendix 2.

Persona I Slide Collections

All pathologists should compile a personal slide collection, as this will be useful in
future teaching of junior colleagues, presentations and in revision, where they are
able to pool resources with others in a similar position (see later). One of the major
failings of many pathologists is to forget to catalogue the slides with an adequate
clinical history. It is virtually impossible to do this just before the slides are
needed, if they are in a large disorganised pile when the relevant information has
been forgotten or is incomplete. Therefore each slide should be filed, preferably in
a purpose-made slide box, as soon as it is obtained. Over the course of a few years
several hundred examples will accumulate, and will be an invaluable collection if
properly documented. (One way of keeping the history and diagnosis intact is to
write it on the back of the slide with a permanent fibre pen marker.)

Slide Clubs

It is most important for every pathologist to join a slide club. This may be difficult
as a junior registrar because the post may be relatively transient, but is easier at a
senior registrar level. The purpose is to exchange slides of interesting cases and
have regular meetings to present and discuss the diagnoses. If properly organised,
it can be a great source of material, but there are many other advantages to such a
club. As well as the academic exchange, insight will be gained into the problems
colleagues are facing, as well as information about courses and teaching
opportunities.
In order to investigate this possibility, colleagues should be contacted at
various hospitals to enquire if they are members of a slide club, whether it is
possible to join. Otherwise it is necessary to initiate a group de novo. Optimal
numbers vary, but 10-12 contributors are probably about right, from different
hospitals to maximise the input of material. The benefits of a slide club far
outweigh the effort expended in organising and maintaining it.
Having obtained material from a personal slide collection, including that of the
slide club, it is useful not only for revision, but in order to pool resources with
other colleagues taking the examination, in the later stages of revision. The cases
can be used for practice examinations, and reciprocation made with personal
material. In order to do this, it is necessary to simulate examination conditions,
being in a quiet room, and remaining undisturbed for three hours - this can be
difficult to arrange but is most essential.
These exercises should be commenced three or four months prior to the
examination, increasing the frequency to one or two per week in the final month.
The number that can be performed is limited by the availability of material and
this in turn is dependent on the number of colleagues it is possible to exchange
slides with. This is why slide club contacts and organising revision with
colleagues is so important, maximising the exposure to this kind of revision. Even
a few such tests are of great value for organising timing and fluency of the report
writing.
As well as contemporaries, senior colleagues may be willing to set mock
examinations. They may be more keen to do this than lend their valuable slide
collections, since they are only on loan during the test session, and are hence less
likely to be lost or damaged. Moreover, they would have a better idea of the
examination standards required, and are able to criticise the technique of
answering.
296 Advanced Histopathology

These sessions are very important, as it is all t-oo easy to wade through a great
number of slides during private revision, but be deceived into believing that this
could be repeated under examination conditions.

Current Literature
Although it is not usually possible to have the opportunity of examining directly
sections of recently described entities, (unless encountered at certain symposia) it
is useful to keep a continued awareness of recent advances by reviewing the major
pathology journals up to the examination. Again, it is important to be selective,
and read only about lesions which appear to be of recurrent interest and
argument, or concern major or common lesions, or which attract editorials and
comments. Only a small proportion of published material is liable to achieve any
substantial or lasting influence. However, it is not unusual for 'topical' pathology
to appear in the examination, and while candidates would be unlikely to fail for
not being aware of it, an opportunity to impress may be lost.
Much of the current literature is concerned with the application of monoclonal
antibody technology in restricted fields of pathology, and while this is an exciting
area of research, it is vitally important not to draw too many conclusions relating
to their application in diagnostic pathology. There are innumerable instances
where an initially promising reagent has not proved to be of truly restricted
specificity which enables any reliance to be placed on the results. The range of
antibodies used for diagnostic purposes is relatively small and has been verified
in several laboratories over a period of time. The pathologist who displays a
rather naive over-enthusiasm to utilise the newly described antibodies might give
the impression that such results may heavily influence the diagnostic criteria for a
particular lesion, without taking proper account of the morphological details.
Therefore while it is all very well to be aware of the latest reports, the assessment
should be tempered with the appropriate degree of scepticism, especially in the
presence of more experienced and conservative examiners. Review articles by
respected pathologists experienced in the field of immunohistochemical
techniques in diagnostic surgical pathology are a better source of information, and
often give much more insight into the limitations.

Routine Surgical Reporting

This is by far the best method of improving technique, and it is a great advantage
to arrange a work rota which will include at least two months' reporting in the six
months prior to the examination. This may be difficult in a heavily staffed
University Department, but it may be possible to arrange a locum position in a
district general hospital with other senior registrars or consultants, if possible in a
department previously attended to avoid the need to become familiar with the
environment.
Since the examination aims to assess whether candidates are competent to
undertake the responSibilities of a consultant pathologist, routine experience is
very valuable and helps to develop the attitudes and qualities which the
examiners are looking for, whether the candidate is aware of them or not. It may
be a mistake to avoid routine duties as much as possible to concentrate on other
forms of revision, especially as it may not be viewed too favourably by one's
peers.
Surgical Pathology Slides 297

In addition to undertaking or assisting with reporting, at other times attempts

should be made to review interesting cases which have passed through the
Department each day. To do this effectively requires the cooperation of the report-
ing team who may be able to select cases. Each case should be evaluated with the
clinical information only, and appropriate further investigations chosen. If
possible these cases should be followed up (with the permission of the reporting
team), including the results of various special stains where indicated.

Specialised Pathology
If any particular areas of weakness can be identified in terms of specialised
material not available during training, attempts to remedy this by arranging to
visit pathology departments within the region or as secondments may help. In
some cases, such as neuropathology, this may be the sole concern of a particular
unit, in which case the concentrated experience would be invaluable.
Particular needs should be discussed with the head of the department, who
may be able to arrange this or else personally contact the consultant in charge of
the particular unit.
While it would be unduly optimistic to expect individual attention, there may
be teaching sets available; many specialist pathologists welcome the opportunity
to teach using routine material. However, arrangements should not be left too
late, so that it does not become an attempt to 'cram' all the information into a
couple of days, without displaying any real enthusiasm for the subject. This is not
only discourteous, but is often a waste of effort.
 299

Cytology
Cytopathology is assuming greater importance in diagnostic pathology and this is
being reflected in the emphasis given to proficiency in this discipline in the
examination. Part of the reason is the increasing number of specimens from fine
needle aspiration as advances in guided needle biopsy techniques enable access to
virtually all sites in the body, resulting in a very varied workload. As confidence
in the technique among clinicians rises, it may, in some instances, supplant the
need for surgical biopsy. Other reasons are that cytological preparations are also
obtained in increasing numbers to complement endoscopic biopsies (e.g. in the
respiratory and alimentary tracts), and are now routine practice in most centres.
Although diagnosis is still largely morphological, certainly in gynaecological
cytology, conventional histochemical and immunocytochemical methods can be
applied to cytological preparation to refine the diagnosis, and in many cases
prompt and optimal fixation techniques may allow a greater flexibility than with
surgical biopsy.
Thus the number and variety of cytological cases included in the examination
have increased markedly in the last decade, and greater importance is laid on the
ability to interpret cytological preparation than has hitherto been the case.
Most centres now allocate a separate session for cytology in the examination
timetable, lasting anything from 30-90 minutes, though the recommended
duration is one and a half hours. There is a minimum of six cases, and candidates
may be asked to examine up to 10 or 12, about a third to a half of which are
usually gynaecological.
This means that the time spent on each slide could be from 5-7 minutes, to
include a standard (fortunately brief!) report, but which is still less time than a
professional screener would take to review a case. Examiners appreciate this, and
almost invariably the cases are selected as 'classical' examples, or perhaps have a
focal but very obvious abnormality designed to assess the screening ability of a
candidate.

General Principles in Examination Preparation

Even more than in surgical pathology, 'hands on' experience in cytology is the
only route to proficiency. Expert guidance from a consultant cytologist(s) is
essential in assessing progress, and of far more value than any textbook. While
several excellent monographs and atlases are available, it is probable that
photographs are less useful than in surgical pathology, perhaps because it is
impossible to reflect the more subtle features of particular cells in a single field,
without relating them to the whole content of the preparation, something which
can only be achieved by direct examination.
'Wallpaper matching' can be a risky business in cytology, and one of the most
important principles is to identify the normal population(s) of cells in any
cytological preparation before starting to look for abnormalities. Not only will this
give you some idea of the size of normal cells, the scale of which can be easily
forgotten when examining abnormal cells only, but will provide a subconscious
wealth of experience with which to compare an abnormal cell population.
Teaching collections have a role in the recognition of straightforward entities,
but many trainees find it difficult to develop the skill necessary to interpret less
well defined conditions such as severe inflammatory change versus dyskaryosis
in a cervical smear. The sound knowledge of normal cell populations and their
300 Advanced Histopathology

variations, and modifications in disease states, can only really be acquired by

examination of routine material. The clinical relevance of current cases, which
have to be correctly examined, may provide the motivation which is absent in
archive material, and which otherwise could not sustain an interest for very long.
One other practical point is that some laboratories prefer air-dried to alcohol-
fixed preparations, and some centres may provide only one or the other in the
examination. Most laboratories prepare both types, and it is important to gain
experience using each of them as they are to some extent complementary.
At least two months of full-time cytological training is necessary in order to
reach a reasonable standard for the average candidate, but to be capable of
providing a good clinical service, this period would be considerably longer. Early
in their training many pathologists appear reluctant to become involved in
cytology, and posts still exist which do not involve cytology rotation. It is
important to gain this experience, so if this is the case representations should be
made to the Departmental Head to obtain an attachment to a busy laboratory.
Moreover the sponsor for the examination must also certify an applicant has
completed three months training in cytology as a condition of sitting the
Examination.
In order to maintain a level of competence in cytology, it would be an idea to
examine about ten mixed cases a week, which should not be too time-consuming.
It may be of value to examine them without a preliminary opinion, and it would
be ideal if the consultant cytologist could be persuaded to select soine cases, and
review written reports with the aid of a discussion microscope, demonstrating
any mistakes. It is most important not to imagine that it is possible to retain a
static level of ability in cytology without practice, as it is perhaps easier to lose
perspective in this discipline than in any other in pathology.
In addition,. the biopsy specimens which are taken concurrently or
subsequently following the cytological report should be followed up, with actual
examination of the histology rather than just reading the report. Not only does
this act as a quality control but it enables an appreciation of the differences in cell
morphology by these different techniques.
Having stated that texts in cytology are of limited value, nevertheless it is
important to have access to some books to reinforce the interpretation of certain
conditions. Diagnostic Cytology (Koss, L.) is a large, two volume book, which
although admirably comprehensive, is virtually impossible to digest prior to the
examination. It is of great use as a 'bench book' for reference to certain diagnostic
problems. There are copious illustrations, and it is useful just to examine these
rather than read the full text, which is an undemanding exercise which can be
accomplished relatively swiftly, helping to fill in some gaps in experience.
Similarly some cytology atlases (Cardozo, L) are useful (although the one quoted
only contains air-dried preparation). Review articles on fine needle aspiration
biopsy abound, but the following is suggested as initial reading (Lever, J.,
Melcher, D.H., Lineham, J.J., Smith, R.S. Fine Needle Aspiration Cytology. In:
Recent Advances in Histopathology 11. P.P. Anthony and R.N.M. MacSween
(eds.) Churchill Livingstone, Edinburgh 1981).

Approach to Cytology Specimens

In the examination, each case will have appended a brief clinical history, which
should be read carefully. Each interpretation must be placed in its clinical context,
as in the surgical histopathology. Even with information as brief as 'cervical
smear', the age of the patient mu!:t be taken into account. For example, in a 70 year
old female it is unlikely to be an example of mild dyskaryosis. Similarly, if other
Cytology 301

information is given in a case, such as 'vaginal discharge', it is almost certain there

is something present to account for this, but of course there may be a combined
pathology, (e.g. dyskaryosis plus infection). In non-gynaecological specimens the
histories are often more relevant. For instance, a cellular breast aspirate from a 65
year old is highly unlikely to be from a fibroadenoma.
Although not as important as in surgical pathology, the slide should be looked
at with the naked eye, before placing it under the microscope, to assess the
distribution of material, which may indicate the most rewarding areas. The
number of the slide should be double-checked at this stage.
In cytological practice, most of the slides have been pre-screened, but
candidates are expected to have developed sufficient skills to identify abnormal-
ities themselves, and so no preliminary opinion is provided in the examination.
Any dots that may remain on the slides may have been put there by a previous
candidate or screener and are potentially misleading, so while these should of
course be examined, it is not to be assumed that these indicate the major
abnormality on the slide. Furthermore, it is all too easy to become reliant upon
having a screening opinion in routine cytological practice. During preparation, it
is important to continually practise reaching an independent opinion rather than
being directed to abnormalities by a screener. This is the basis of good screening
technique, which might not be developed otherwise, and it is worthwhile to
consider this separately.

Screening Technique
This skill seems to receive insufficient attention in many centres so that candidates
often appear undisciplined in screening, randomly scanning the slide. It is a major
factor in poor cytological acumen.
The xlO objective should be used since the magnification given by x4 is not
sufficient for recognising most abnormalities. (It is often a good idea to remove
the x4 objective from the microscope during training for cytology!) The slide is
placed on the stage and moved to one corner, and the examination proceeds in a
vertical or horizontal direction in order to scan all the area under the coverslip. To
obtain a 'feel' for the movement required from one scanning line to the next, the
stage should be moved so that a cell at the right or left of the field crosses to the
opposite side. With a xlO objective, this distance is about 2 mm.
If this is difficult, it is a useful exercise to take a plain glass slide and make a
careful grid with several horizontal or vertical lines one xlO field apart, using a
ruler and fine permanent fibre tip marker pen. This can be used to follow the
edges of the lines to gain some idea of the necessary discipline and fine control of
the microscope. Later a grid could be superimposed on an old or duplicate
cytology slide to give some perspective to cell size and distribution. This exercise
needs repeating at regular intervals until an ability to scan accurately develops
and becomes 'second nature'. A random, undisciplined scanning pattern is the
cause of many errors in cytological interpretation.

Cytological Reports
These are usually brief and do not require much descriptive detail. It is usually
best to start with a firm, unequivocal diagnostic assessment in notation style if
necessary. Some qualification is usually given to refine any diagnosis and put it in
a clinically useful form, as for example in an ascitic fluid specimen in suspected
ovarian carcinoma 'Malignant cells present consistent with an origin in an ovarian
adenocarcinoma'. No further descriptive detail is required. In gynaecological
302 Advanced Histopathology

smears, it should be stated whether malignant cells are present or not. If

dyskaryosis is seen, an assessment should be made of the grade of CIN in which
the cells may have originated e.g. 'Dyskaryotic cells present consistent with an
origin in CIN II. Colposcopy and biopsy advised'. The significance and further
management of the case are also unequivocally stated. All reports are based on
similar principles. Even when the diagnosis is not established, there should be a
clear statement of the abnormalities present and of the steps which would be
necessary to identify the underlying pathology. In such cases, it might be
reasonable to compile a report such as in a surgical case: 'A few glandular cells
present showing nuclear enlargement and atypia in an inflammatory smear.
Endocervical biopsy advised'. Equivocation should be restricted as far as possible
to the few cases where it is genuinely not possible to make a diagnosis. Using such
devices to avoid coming to a conclusion in most instances will certainly detract
from a candidate's overall assessment, in cases where a firm diagnosis could
reasonably have been expected. Again, it comes down to experience, and it is
probably more difficult to recognise the cases which require caution to be
exercised than others which permit an unequivocal opinion.
If there are no identifiable malignant cells, this must be stated in the first
sentence, and then an outline given of whatever other diagnosis is made in concise
terms, e.g. 'No malignant cells seen. An inflammatory smear pattern with a
trichomonas infection. Repeat after treatment'.
Non-gynaecological specimens may occasionally require slightly more in the
way of description, but in general little more than two or three sentences are
required. The sequence should run 1) abnormality, 2) origin and 3) underlying
pathology.

Standards in Cytology
A list of the conditions which most often appear in the examination, with which
candidates would be expected to be familiar, is given at the end of this chapter,
but it is worthwhile making explanatory comments on some of these,
acknowledging that it is not attempting to be a comprehensive account.
The choice of examination material is somewhat restricted compared to
everyday practice as the cells need to be well preserved and present in such a
form or sufficient numbers to enable unequivocal interpretation. Furthermore, it
is highly unlikely a 'normal' specimen would be included in the examination. If
this is the assessment it is almost certainly mistaken and it is best to review the
case at the end rather than attempt to guess. Further ideas may come to mind
while concentrating on the other cases. If a case is left then it is important to
ensure enough time is left to try again.
Of the gynaecological specimens, it is usual to be given at least one or two
cervical smears, including examples of dyskaryosis which should be graded.
Adenocarcinomas of endocervical or endometrial origin crop up relatively often
but are suprisingly easy to overlook sometimes. In this respect candidates should
ensure they are fully familiar with the range of appearances in post-natal and
atrophic smears which can look very alarming to the inexperienced, due to the
immaturity of their cell populations, with relatively large nuclei.
Infections may be easily overlooked, especially Trichonomas and Candida.
Active herpetic infection is fairly characteristic but again may be mistaken for
dyskaryotic cells. Endometrial brush specimens are sometimes taken for
assessment of carcinoma, but in general the same criteria for adenocarcinoma
apply here as elsewhere, except that squamoid cells are common features as seen
in histological sections. Ovarian cyst fluids are usually very straightforward, but
Cytology 303

it is important to be familiar with granulosa cells from a follicular cyst, which can
look quite alarming, sometimes with mitotic figures.
Non-gynaecological cases are very varied. Sputum examination is included in
most examinations since it comprises such a large proportion of routine workload.
Candidates are expected to be able to distinguish between keratinising and non-
keratinising squamous cell carcinoma, adenocarcinoma, large cell undifferentiated
carcinoma and small cell carcinoma. The latter can be particularly difficult to
identify and requires some degree of expertise. Some clusters of reactive bronchial
epithelial cells can show a worrying appearance, but one of the best guides is to
see if any particular cluster contains ciliated cells at the periphery. If these are
present, they should never be called malignant!
Benign conditions in sputum are relatively limited but it is useful to identify
asbestos fibres which can be surprisingly variable in morphology, and be aware of
the appearance of various fungal organisms such as aspergillus.
Endoscopic brushings from the upper gastrointestinal tract are generally taken
to distinguish between benign and malignant ulcerative lesions. Squamous carcin-
oma of the oesophagus is relatively straightforward but reactive changes in
glandular cells can produce considerable pleomorphism. In malignant ulcers,
there is often a large number of fungal organisms, whose presence should prompt
a thorough search for malignant cells.
Fine needle aspirates can be from many sources as already pointed out. A lot of
the interpretation is purely common sense, applying principles which anyone
with a good working knowledge of surgical histopathology would easily under-
stand. The breast is an important site in which to have a very sound working
knowledge, and misdiagnosis of these aspirates would be viewed with concern.
Within the benign breast diseases, it is most important to recognise fibroadenoma
with its cellular clusters and 'naked' nuclei, apocrine cells which are pleomorphic
with a large nucleolus, reactive breast epithelial changes in duct ectasia, and
lactational changes in which the cells are very active-looking and vacuolated.
Malignant cells are often accompanied by cell debris and are often easier to assess
under oil immersion. Not all carcinomas are ductal in type but unless the features
are particularly striking candidates would probably not be expected to subtype
any breast carcinoma.
Other sites of fine needle aspiration are many and varied and general
principles are applied in diagnosis in most sites. However, the thyroid gland is a
particularly common and favoured site, mainly because of the superficial location
and the relative difficulty of obtaining a diagnostic surgical biopsy, so it is as well
to have a working knowledge of the appearances. Hashimoto's thyroiditis is an
important benign condition favoured in examinations because it can be easily
confused with malignancy.
Serous fluid specimens are also frequently set. The distinction between reactive
mesothelial cells and malignancy is an everyday problem in cytological practice
and one which examination candidates are expected to resolve. Malignant
mesothelioma can be a difficult diagnosis to make but, as a general rule, if there is
difficulty in making a decision in the examination situation (as opposed to real
life), then it is best to err on the conservative side. One point worth making is that
not all laboratories cytospin their fluids because there can be loss of cytological
detail, cell crowding and some nuclear aberrations due to this technique.
Therefore it is worthwhile to become familiar with these changes, so if the local
laboratory does not do it as a routine, they could be requested to perform it in
surplus fluid specimens.
Urinary cytology can be a minefield for the inexperienced as reactive changes
in urothelial cells can closely mimic malignancy. Post instrumentation, in urinary
304 Advanced Histopathology

tract infection or calculus disease, and even odd cells from the seminal vesicle or
prostate can lead to a potential misdiagnosis of malignancy. Transitional cell
carcinoma is generally obvious when poorly differentiated, but the diagnosis of
grade I transitional cell carcinoma is really for the experts. One benign condition,
but which is sufficiently distinctive to be included in the more difficult slides for
the examination, is polyomavirus infection in the immunosuppressed.
Cerebrospinal fluid specimens are generally for the diagnosis of a primary
brain tumour invading the meninges (e.g. medulloblastoma, which can look very
like lymphoma), leukaemic/lymphomatous infiltration or infection. There can be
a marked excess of lymphoid cells in conditions such as tuberculosis but the
important thing to note is that these cells are not morphologically atypical. Oil
immersion examination is particularly useful in CSF cytology.
Imprints are of somewhat less use in diagnostic cytology as the main diagnosis
will be based on histological examination in the majority of circumstances, but
may be a better source of material for immunostaining. More importantly, they
can provide experience of a wider range of appearances which can later be applied
to fine needle aspiration cytology and thus it is not merely an academic exercise.
This is particularly applied to lymph node pathology where the distinction
between reactive changes and lymphoma can be difficult to assess. Candidates
might be expected to recognise Reed-Sternberg cells in Hodgkin's disease or
granulomatous lymphadenitis on an impression or aspirate so it is wise to obtain
some familiarity with these conditions.
Smears of central nervous system tumours have been set in the examination.
While some are fairly easily recognisable the fact that such specimens are not
universally available is acknowledged by examiners, and these are probably only
included as an exercise for the more advanced candidate. However, a wild
diagnosis of malignancy when most of the cells are bland would indicate that the
candidate is unable to apply the general principles of cytological assessment. It is
far better to be circumspect, make a limited report and admit one's deficiencies in
these rarefied cases rather than guess.

Common Cytological Specimens in Examinations

Gynaecological

1) Dyskaryosis
2) Inflammatory changes
3) Infection - wart virus (HPV), candida, herpes simplex, trichomonas, ?
chlamydia
4) Endocervical cells - inflammatory and neoplastic
5) Post-natal and post-menopausal smears
6) Endometrial cells - normal and neoplastic
7) Radiation changes
8) Ovarian cyst aspirates
Cytology 305

Non-gynaecological
Sputum
1) Inflammatory changes and asthma
2) Asbestos bodies
3) Fungi (e.g. aspergillus)
4) Malignancy
Endoscopic Samples (brushings, washings, suckings)
1) Inflammatory changes
2) Squamous ceIl and adenocarcinomas
3) Specific infections (e.g. herpetic oesophagitis, fungal pneumonia)
Serous Fluids
1) Reactive mesothelial cells
2) Adenocarcinoma and mesothelioma
3) Lymphoma/leukaemia
Urine
1) Reactive changes (post instrumentation, calculus disease, urinary
infection)
2) Malignancy (transitional cell carcinoma, prostatic carcinoma, renal
carcinoma)
3) Specific infections (e.g. polyomavirus)

Fine Needle Aspiration

1) Breast (fibroadenoma, duct ectasia, lactation, apocrine cyst, papilloma,
ductal and lobular carcinoma, medullary carcinoma with lymphoid
infiltration)
2) Thyroid (colloid nodule; papillary, follicular and medullary carcinomas)
3) Liver (normal hepatocytes, secondary carcinoma and carcinoid tumour,
hepatocellular carcinoma)
4) Pancreas, testis, lung (commoner malignant tumours)
5) Lymph nodes (large cell NHL, Hodgkin's disease, granulomatous
lymphadenitis)
Cerebrospinal Fluid
1) Meningitis - pyogenic and viral/tuberculosis
2) Lymphoma/leukaemia
3) ? primary CNS tumour
Imprint
1) Lymph nodes
2) ?CNS tumour
 307

Surgical Dissection and Macroscopic Examination

One or two of the examiners usually conduct this part of the examination, the
main aim of which is to assess how a candidate would deal with specimens
received in a routine surgical laboratory, and for discussion of practical aspects of
macroscopic inspection, block selection, laboratory safety and procedures for
ensuring correct block labelling, etc.
In many centres, the specimens are selected from the routine material awaiting
dissection and require examination, description and block taking for processing.
In others the specimen may already have been dealt with, and a candidate would
just be expected to identify and describe tissue, illustrating which areas should be
sampled.
There are usually one or two larger specimens (such as a pneumonectomy,
colectomy or nephrectomy for example), and several smaller ones (e.g. thyroid
gland, breast lump or skin tumour). The specimens should be examined as for a
routine surgical 'cut up', including checks on the labelling of the specimen,
request form (and cassettes if blocks are to be taken). The clinical information
should also be taken into account.
During the inspection and dissection, the examiners will be looking for the
practical skill and awareness of the candidate as much or more than any
theoretical knowledge. It is therefore important to ensure the working surface is
kept clean, instruments are cleaned after each use, and selected blocks placed in
order away from the main specimen, measures which are necessary to minimise
'carry-over'. The tissues should be washed with a spray or hose attachment after
each phase of the dissection and comments made as appropriate.
A description should be given to the examiner or dictated to an assistant as for
a routine specimen, and not over-elaborated merely because it is the examination.
Only relevant information should be included, as well as measurements and
weight. Similarly, blocks should be selected according to standard protocols, and
only a reasonable number taken from standard sites and visible lesions.
It is important to pay attention to safety at the conclusion of the session, by
tidying the area, remOving scalpel blades and cleaning the work surface.

Preparation for Surgical Dissection

Surprisingly there are few sources which give advice on dissection of surgical
specimens, apart from the appendix in Ackerman's Surgical Pathology (AppendiX
1), which gives the most comprehensive recommendations. These guidelines are
very useful and candidates might be advised to review them prior to the
examination. Specialised texts sometimes give further information on the correct
dissection of some organs, and the Association of Clinical Pathologists have
Broadsheets, advising on the dissection of particular specimens (e.g. No 116, July
1987 - Examination of Breast Specimens). However, most trainees are expected
to learn by practical experience at the SHO or junior registrar level from more
qualified colleagues. The adequacy rather depends on the level and care of
supervision in this respect, which can be very variable. There is no guarantee that
the methods adopted for each specimen are detailed enough to satisfy an expert
within that particular field. Therefore it is important to take each type of specimen
individually and critically assess the method of dissection, seeking advice from
senior colleagues, especially if they have a specialist interest.
308 Advanced Histopathology

Many common surgical specimens show a surprising variation in the selection

of blocks and thoroughness of the dissection. Examples include mastectomy or
colectomy specimens for carcinoma, as a review of archive reports and sections in
many Departments would reveal. The optimal methods of dissection, which really
need to be viewed as a skill rather than a chore (as is the case in many busy
Departments) require constant motivation which is not always easy to achieve.
Many trainees do not seem to be aware that their diagnostic acumen in surgical
histopathology is limited by the effort expended on the macroscopic specimen,
with a critical and careful selection of blocks. Unfortunately, many trainees are
not encouraged to gain this insight, possibly because the necessary tuition is
extremely time-consuming for supervisors. It is largely up to the person concerned
to engender the necessary attention, and persistence usually pays off.

Special Stains
This is often a separate section from the surgical pathology, but is very variable in
format and may not be included in some centres. In other cases, candidates may
be provided with additional stains on request to supplement the surgical
histopathology section. One danger here lies in requesting too many, since it does
not impress examiners to request a plethora of unnecessary stains, which not only
would not be made available, but indicates a pathologist who adopts a
'blunderbuss' approach, rather than intelligent discrimination.
If this is a separate session, the slides are provided in a format similar to the
conventional surgical pathology, with brief clinical histories. H&E stained sections
mayor may not be provided. Candidates are normally expected to comment on
the presumptive diagnosis, and the architectural or cytological features which are
being demonstrated;
In some centres, several short questions may be asked on each stain, and the
citation of other instances where the stain may be of value in diagnostic pathology
is frequently required of candidates. Alternatively an H&E section may be
provided with a variety of stains, all of which should be relevant to the diagnosis
or which at least exclude some aspect of the differential diagnosis. The choice of
stains given will almost certainly aid in reaching the correct diagnosis but it is the
pattern of staining that is important. There is a great tendency to make apparently
contradictory staining patterns fit the diagnOSis, by 'seeing what one wants to
see'. This must be avoided at all costs as anomalous results can occur and there
are certain diseases which simulate others on conventional stains but have
different staining characteristics (e.g. systemic kappa light chain deposition
disease vs. amyloidosis in the kidney). It is therefore important to keep an open
mind until all of the material has been examined, and then review the findings in
total.

Selection of Material
There are a wide range of stains available to choose from, but in many centres
there is a tendency to try to concentrate on more established histochemical
techniques which are often neglected by trainees who have recently become more
obsessed with immunostaining. Among the former, stains for various mucins are
frequently included, as they can reveal a good deal of valuable diagnostic
information, and be confusing to the pathologist who only has a superficial
knowledge of these techniques. For example, Alcian Blue will stain acid muco-
polysaccharides at pH 2.5, sulphated acid mucopolysaccharides at pH 1.0,
Surgical Dissection and Macroscopic Examination 309

connective tissue mucin at pH 2.5 is removed by hyaluronidase digestion, etc. It

makes little sense to list all the various conditions which may be illuminated by
the use of special staining techniques, as this should come from application of
them during training, with a knowledge of recent advances in the literature. It is
also helpful to read some of the textbooks on histochemical and immunochemical
techniques and applications (Bancroft, J.D., Stevens, A. Theory and Practice of
Histological Techniques, 2nd edition, Churchill Livingstone, Edinburgh, 1982).
310 Advanced Histopathology

Necropsy Histology
This section is again variable, depending on the examination centre and may be
replaced by a clinicopathological conference. If included, it may take the form of
examination of the sections from the candidate's post mortem or a mixture of post
mortem sections from a variety of cases.
A candidate is unlikely to be asked to examine the sections from their own case
if performing the necropsy during or just before the major part of the examination
(although rapid processing of one or two selected blocks may be possible on
occasion). However, if the examination was one or two weeks beforehand, they
may well be given for evaluation and reporting.
This is where careful selection of the material for histology during the necropsy
can pay dividends. It is difficult to make generalisations on how many blocks
need to be taken from each necropsy since at the commencement of training each
pathologist should take a large number to obtain an idea of normal histological
appearances and of artefacts due to autolysis. By the time of the final examination,
a pathologist has usually acquired sufficient skill to recognise when a more
restricted number of blocks is required, usually as a routine from major organs,
the minimum being one or two from heart, lungs, brain, liver, spleen and
endocrine glands, when these are ostensibly normal, and obviously from any
macroscopic abnormality.
It is a useful habit to take blocks from standard sites as a routine so that the
recognition of any subtle abnormality is not obscured by difficulties in inter-
pretation of architecture (especially in the kidney or brain, for example). Selecting
too many blocks will not create a good impression with the examiners and will
not facilitate concentration on the more important aspects during subsequent
histological evaluation, especially during an examination.
If there is a suspected diffuse abnormality in an organ, it is useful to have a
policy of selecting several blocks from defined sites which are recognisable by
their outline on naked eye examination of the section (perhaps by including
adjacent distinctive structures) or by cutting the tissue to a distinctive shape. This
avoids wasting any time during histological examination. To ensure that the
trimmed tissue which is processed will represent the area of interest, it is very
important to select the area, a block of which would fit within a standard process-
ing container and which is about 0.5 cm in thickness (if it is thinner the tissue may
become distorted during fixation; it can easily be thinned later). Placing such
neatly prepared tissue into the container will dictate the appearance and
orientation of the subsequent section. It also enables a prompt fixation. On the
other hand, a somewhat randomly selected, large lump of tissue, which patho-
logists often take at autopsy, results in poor fixation and in less well chosen
blocks. By such selection, the number of blocks put through for processing is also
known. The reports can be formulated according to the scheme of block selection,
e.g. in cardiac cases; sinoatrial node, atrial wall, left and right ventricles, conduct-
ing system, valvular pathology, etc. or in the eNS, meninges, cerebral cortex,
hippocampus, internal capsule and basal ganglia, medulla, cerebellum, upper
spinal cord, etc. Clearly, the emphasis will depend on the pathology, both in the
examination and in routine practice. Where further histological examination may
be of value, larger samples of tissue can be stored in a separate container.
If there is a particularly difficult problem, there is no reason why tissues cannot
be labelled in individual pots. This is suggested as an exception rather than a
routine, and will not be viewed too favourably by the examination centre because
of the extra work this involves, unless there is good justification. In cases of
Necropsy Histology 311

pathological abnormality, a well orientated junction with normal tissue should be

included in cases of focal abnormality <e.g. in tumours or infection), or tissue
selected where the changes are likely to be maximal in cases of more diffuse
disease <e.g. hippocampus in Alzheimer's disease, lower lobe of lung in asbestosis,
etc.). The histology must also be viewed in the light of other results from bacterial
or viral culture, blood levels of hormones, etc. Naked eye examination of post
mortem sections is just as important as in the surgical cases, and is otherwise
evaluated in the same methodical fashion.
Post mortem reports should be as concise as possible, since many of the
conclusions will already have been drawn from macroscopic examination. The
report should be related to the visible abnormalities and the correlation comment-
ed on, being very brief if merely confirmatory. If the result is contradictory, a
more detailed appraisal is called for, the length varying according to the
importance of the abnormality. In other words, the temptation to make too much
of a minor insignificant change with little clinical relevance should be avoided.
The examiners will be looking for the ability to interpret the post mortem findings
for the benefit of the clinical staff in terms of their diagnosis and management,
which may be obscured by over-indulgence in pathological minutiae.
The report should start with the organs showing the major pathological
abnormalities, and leaving incidental findings and normal tissues until last. A
concluding paragraph may be helpful along the l~nes of that given at the end of
the initial report, indicating where further procedures such as EM or special
stains, may be of value. This final paragraph should put the major histological
abnormalities into context related to the clinical progress, mode of death and
findings at necropsy.
In the event that slides are not available from the examination necropsy,
material from other cases may be provided. Apart from gaining a wide experience
of tissue changes encountered in necropsy material during training, there is little
in the way of specific revision which can be performed. These cases overlap to a
large degree with a following section on clinicopathological conferences, which
contains further observations on the way to approach this material.

Mounted Museum Specimens ('Pots')

These are often used during the course of viva voce examinations, during the
clinicopathological conferences or to complement the post mortem histology
slides so that some correlation of macroscopic and microscopic appearances can
be made.
The technique for examination of mounted specimens can often be poorly
displayed by examination candidates and severely disadvantage them during the
course of a viva voce, and it is useful to consider the basic approach.
Firstly, the container should be placed upright on the table surface and rotated
as required. It should never be shaken or inverted. The specimen should be
examined from the front, sides and back and, if examiners are present, placed in
such a position that the specimen is clearly visible to both candidate and
examiners, and so the relevant features pointed out. The time taken to complete
this initial examination should be kept to a reasonable minimum and the initial
comments on the nature of the tissues or organ displayed should be made during
this time to avoid a prolonged silence, which might precipitate unwanted
questions or prompting by the examiners.
After determining the anatomical site of the specimen, comment should be
made on the way in which it is displayed or dissected, as bisected solid organ,
312 Advanced Histopathology

opened viscus or blood vessel for example. Note should be taken whether any
tissue has been removed during this process, e.g. in cardiac dissections, where
portions of the ventricular wall or valve leaflets are sometimes removed.
As a routine, the size, configuration, colour, architecture and anatomical
relationships are all assessed for any specimen, with any deviation from the
expected normal appearances commented on, as will be the case with most diffuse
pathological abnormalities, and which may be rather subtle (e.g. amyloidosis).
Methods of enhancing such changes on tissues can be commented on at this stage
(e.g. Lugol's iodine/dilute sulphuric acid in amyloidosis, NBT in myocardial
infarction) and may even have been performed in the mounted specimen.
If a focal lesion or lesions are present, they will usually be at the focal point of
the specimen, which in most cases is central. It is best to concentrate on this area
for the detailed description, gradually including the effects of any lesion which
may be produced on the surrounding tissue (e.g. indurated lungs in mitral
stenosis, hydrocephalus in ventricular obstruction), or possible predisposing
factors to any lesions (such as thrombotic occlusion of an artery in cases of
possible infarction). The potential existence of these secondary changes can often
be inferred from an understanding of the pathogenesis of any particular lesions
and searching carefully for this underlying cause.
After the appraisal of the specimen, which should occupy two or three concise
sentences, a likely diagnosis t~ account for the appearances should be suggested.
In appropriate cases, a differential diagnosis should be presented (in descending
order of likelihood) together with brief reasons for not regarding them as the
primary diagnosis. The aim is to produce a logical, fluent appraisal of each
specimen, where the candidate dictates the direction of the discussion, rather than
making rather tentative suggestions requiring frequent prompting by the
examiner. However, the reaction of the examiners to any suggestion should be
carefully assessed, and the approach taken modified accordingly until a satis-
factory response is obtained.
As well as the primary disease process present, there are sometimes subtle
changes of an associated but entirely distinct condition (e.g. scarring due to
asbestosis in a case of lung carcinoma, or hepatocellular carcinoma in cirrhosis) so
that it is as well to bear this in mind as these are often favoured specimens for
mounting. Occasionally specimens with two entirely unrelated pathologies are
included, but are fortunately uncommon.
The ability to describe a 'pot' in a fluent fashion is a matter of practice, which to
be effective should not merely entail a silent inspection of museum specimens,but
demands active demonstration. The best method is to demonstrate to or interro-
gate medical students with such specimens, usually during tutorial sessions.
Alternatively, arrangements could be made with a colleague to provide each other
with half a dozen or so specimens, each being assessed on a 'mock' examination
basis, with criticism centred on the style of assessment as much as the diagnosis.

Case Discussion or Clinico Pathological Correlations

This is a frequently used format for the introduction of post mortem material and
hence is more likely to be a part of the examination in centres where the necropsy
is not done a week or so in advance. It enables a more 'standardised' level of
material and allows for the introduction of various other items such as special
stains, electron micrographs, microbiological and biochemical investigations, etc.
as appropriate. There is no way to prepare for these cases, as the exercise is
designed to assess practical and interpretative skills acquired during training.
Necropsy Histology 313

However, there are ways of approaching these sessions which are helpful in
making a good presentation.
The clinical history given in these cases is often quite lengthy and must be read
carefully since if often contains many valuable clues to the primary disease
process present, and to the anticipated pathological changes.
The candidate will usually be asked to examine a set of slides, possibly in
conjunction with macroscopic photographs or other material as indicated above.
The point to remember is that the cases are usually selected because they illustrate
either the effects of and progression of a systemic disease throughout the body
(e.g. systemic lupus erythematosus, rheumatoid disease in a coal miner), or are
concerned with a primary disease and its complications (e.g. carcinoid syndrome
and heart disease, or parenchymal disease of the lung and pulmonary hyper-
tension). There may well be iatrogenic changes in addition, and this being the
Final Examination, the pathology may be slightly atypical as there may be
unrelated disease processes present.
The most important task is to identify the 'theme' or primary disease process
present and evaluate whether the remaining organs fit in with any predicted
patterns. Having said this, the temptation to make the features fit the anticipated
change must be avoided. The case may have been so constructed to lure
candidates into this trap, so it is vital to keep an open mind until certain. It is
helpful to imagine whether it could be demonstrated as a convincing example of
the pathology (an idea which could be adopted in other parts of the examination).
The answers, which may be written or verbal, should be concise and to the
point. In oral sessions, after answering the direct question, a reason for the
conclusion should be given with a short qualifying sentence or two. In some
instances, the sequence of events present has been identified, the next question
can be anticipated, in which case the next step in the predicted disease process can
be suggested, or what information might be required to confirm any suggested
diagnosis. The examiners may supply the material, e.g. EM plates, and ask for
comments. It is important to avoid interrupting examiners however and always
let them finish asking the question since they may give some guidance to the
required answer, consciously or otherwise.
'Viva technique' may be of great value in these sessions and is a factor many
candidates fail to take into account. It is important to look at the examiners both
when they are asking questions and when giving replies. The response to the
answers or comments given is very valuable in assessing how accurate it is, and
whether it is the required information. Guarded questions from the examiner <e.g.
'why would you think that?') often indicate a candidate has failed to justify their
statements or have deviated from the expected line of the discussion. Overlong
attempts to justify any conclusion are a mistake if it is clear from the responses
that the arguments have failed to convince the examiner. It is far better to concede
the issue and move to another subject than argue over a point which may be of
little consequence, risking antagonising the examiner.
Case conferences usually last 40 minutes to an hour. There are often two or
even three cases, one a longer, more complicated case, the other rather shorter,
which usually illustrates one or two specific diagnostic features or includes the
use of special techniques. In some cases, candidates may be expected to examine
fixed organs, which should be demonstrated as outlined in the necropsy or
macroscopic dissection sections.

Electron Micrographs
It is possible that ultrastructural pictures would be included in case conferences,
314 Advanced Histopathology

or perhaps during the viva voce examination. At some stage in training candidates
should have had access to EM facilities, and it is as well to develop at least a
rudimentary knowlege of various cellular features. The following list contains
many of these, together with an appropriate cell type in which it is found, and
suggested references where such a feature is well illustrated. Many of these may
be found in reference 2, a fairly comprehensive book which should be available in
most EM departments. However, Diagnostic Ultrastructural Pathology, by the
same author (reference 4), is an excellent, well-illustrated book containing 50
ultrastructural interpretation exercises, (hence the unpaginated references) and it
is ideal preparation for an examination candidate.
One word of caution is that it is vital to take account of the magnification in
ultrastructural pathology, especially when looking at subcellular particles: these
sometimes appear very different or inconspicuous at lower magnification.

Feature Cell type or location Reference

Glycogen e.g. renal tubular cell 1) p912 2) p181-183

Lipid e.g. liposarcoma 2) p370-373
Mucin e.g. adenocarcinoma 2) p88-91
Lipofuscin e.g. hepatocyte 1) p25
Dense bodies e.g. leiomyoma 3) p253
Intermediate filaments e.g. keratinocytes 2) p350-357
Mallory body e.g. hepatocellular carcinoma 2) p353
Short microvilli glandular cells 4) question 4
Long microvilli mesothelial cells 2) p101
True desmosomes epithelial cells 2) p65-84
Desmosome-like e.g. synovium, Schwannoma 2) p80
structures
Lamellated bodies alveolar cell carcinoma 2) p418-419
Muscle striations e.g. rhabdomyosarcoma 3) p369 2) p190-193
Melanosomes melanocytes and melanoma 2) p106-121
4) Question 13
Birbeck granules Langerhans cells 2) p427-429
4) Question 17
Luse bodies Schwannoma 2) p212
Crystalloid bodies alveolar soft part sarcoma 2) p395-398
Renin crystal juxtaglomerular cell 5) p796
Reinke crystalloids Leydig cells 2) p286
Weibel-Palade bodies endothelial cells 4) p413
Lysosomes granular cell myoblastoma 2) p166
Megamitochondria hepatocytes or oxyphil
adenoma 1) p29 2) p159
Sphingolipid (Tay-Sachs) ganglion cell 6) p247
Gaucher body macrophage 4) Question 8
Zebra body neurone 7) p107 4) Question 4
Adrenoleucodystrophy adrenal cortical cell 1) p1438
Necropsy Histology 315

Neurosecretory granules diffuse endocrine cells 2) p123-147

Alpha, beta, delta endocrine pancreas 1) p993
granules 4) Question 7
Plasma cell 2) p257-263
Myeloma plasma cell 6) p251
Dutcher body Waldenstrom's macro-
globulinaemia 5) p1287
Sezary cell blood/lymph node 7) p290
Podocytes glomerulus 1) p1013
Membranous GN Glomerular basement
membrane (GBM) 1) p1035
Mesangiocapillary GN GBM 1) p1040
(I and II) 4) Question 37
Amyloid mesangiioma 1) p217
4) Question 42
Hereditary nephritis GBM 1) p1026
4) Question 44
Minimal change GN podocytes 6) p243
Lupus nephritis GBM 6) p251
Virus-like particles (SLE) mesangium 5) p755 4) Question 47
Virus particles e.g. herpes virus, CMB 4) Question 25
6) p246
Bacilliform bodies macrophages 6) p249
(Whipple's disease)

References

1) Robbins, S.L., Cotran, R.S., Kumar, V. Pathologic Basis of Disease, 4th edition.
W.B. Saunders, Philadelphia (1989).
2) Ghadially, E.N. Diagnostic Electron Microscopy of Tumours, 2nd edition.
Butterworths, London (1985).
3) Enzinger, F.W., Weiss, S.W. Soft Tissue Tumors. 2nd edition. CV. Mosby Co,
St Louis (1988).
4) Ghadially, F.N. Diagnostic Ultrastructural Pathology - a self evaluation
manual. Butterworths, London (1984).
5) Rosai,]. Ackerman's Surgical Pathology, 7th edition. CV. Mosby Co, St Louis
(1989).
6) McLay, A.L.C, Toner, P.G. Diagnostic electron microscopy. In: Recent
Advances in Histopathology 11. Anthony, P.P., MacSween, RN.M. (eds.)
Churchill Livingstone, Edinburgh (1981).
7) Anthony, P.P., Woolf, N. (eds.) Recent Advances in Histopathology 10.
Churchill Livingstone, Edinburgh (1981).
 317

Cryostat Sections
It is advisable to make your own arrangements with the laboratory staff to cut
spare sections of selected cases, or else contact the Head of the Department to
institute a more formal policy to provide material for a teaching set.
Alternatively, it may be possible to arrange for frozen sections received in the
department to be collected within the laboratory after return for filing, and
reviewed on a weekly or monthly basis depending on numbers received, perhaps
in conjunction with a surgical meeting or on an informal basis with colleagues. In
addition, the paraffin sections should be obtained for comparison at the same
time, to get some idea of the differences in morphology that may be produced in
cryostat sections.
On this point, one of the major problems in interpreting cryostat sections is the
failure to appreciate that the cell and nuclear size is considerably greater than in
conventionally processed tissue, and minor differences may be greatly
exaggerated, which may give a misleading impression of nuclear pleomorphism.
Furthermore, the sections are much thicker, which makes any lesion appear more
cellular than in paraffin section. Another factor is that cellular and cytoplasmic
fine detail may be largely obscured, such as the nuclear membrane and chromatin
pattern, nucleolus and cytoplasmic staining properties. These differences are well
illustrated in examples such as sclerosing adenosis of the breast, or reactive lymph
nodes, both of which can look very alarming on frozen section but are easily
assessed on paraffin sections.
Some of the other difficulties encountered in frozen section diagnosis are in
part due to poor technique. In routine practice, there is always the macroscopic
inspection of the tissue and selection of material which provides valuable inform-
ation, but this is admittedly lacking in the examination. However, many trainees
fail to adopt the principles of examining a section outlined on page 288, and try to
make a diagnosis using medium and high power objectives. On cryostat sections,
as already explained, most of the detail at these magnifications is lost. Therefore it
is considerably more important to be able to make a diagnosis on the basis of
naked eye followed by low and medium power microscopic examination,
reserving the high power to confirm details such as mitotic figures.
Using the previously cited tissues as examples, compare cases of sclerosing
adenosis and invasive ductal carcinoma or reactive lymph nodes and lymphoma,
first with the naked eye/hand lens and then under high power objectives. The
amount of information gleaned from the former should be much greater in nearly
all circumstances, and it will demonstrate how pattern and architectural
considerations are of greater value than. cytological detail. This is not to say that
frozen sections should not be examined under high magnification, but that the
information it reveals must be placed in the context of the previous impressions
gained. If there is some contradiction in the two, the case, including clinical
information, must be critically reviewed, avoiding the temptation to make a
rushed decision.
The examination format is usually intended to provide an assessment of a
candidate's approach to frozen section diagnosis within the setting of a routine
surgical pathology laboratory, so that most (but not all) of the cases are relatively
straightforward. The usual number of slides is between six and eight and very
brief clinical information is given, apart from the patient's age.
The time allocated to each section is usually 4-5 minutes, and overall duration
of this part of the examination is 30-45 minutes. It is possible that other candidates
be in the room but more often each assessment is performed on an individual
318 Advanced Histopathology

basis. The examiner may interrupt and ask questions during this time, unlike the
surgical pathology section. Indeed, some candidates are asked to look at the
sections in a double headed microscope with the examiner, resembling a viva voce
examination. If this happens to you, you just have to grin and bear it, or take the
positive view that this is an ideal opportunity to explain the reasoning behind the
diagnosis, and impress the examiner with a careful technique. In addition, the
alert candidate will act on the verbal and non-verbal clues as to the accuracy of
any particular answer, and adjust their tack accordingly.
The form of the answers expected is somewhat different to those of the surgical
histopathology. Less description is required, as a surgeon merely wishes to have a
diagnosis on which to base a decision on the operative management. This is also
the form in which the report is expected in the examination and long descriptions
will definitely detract from the answer. The majority of cases are concerned with
tumours, and the first sentence should clearly include the words benign or
malignant, with an exact classification where possible.
Equivocal diagnoses, or avoidance of a decision (e.g. 'await paraffin sections')
where a decision ought to be made, are usually marked down heavily in the
examination, as it indicates a weakness and lack of experience in the candidate.
Equally well, there are situations where a distinction between benign and
malignant should not be made on frozen section. For instance, while a large
nodular malignant melanoma is usually not a problem, deciding whether a small
melanotic skin lesion in a young person is a malignant melanoma or Spitz naevus
is often impossible on cryostat sections. Similarly, small, well-differentiated
papillary lesions of the breast are difficult to assess, as are some endocrine
tumours, which may even be impossible to categorise as benign or malignant even
after multiple paraffin sections (e.g. phaeochromocytoma). There may be one or
two cases which fit into this category, but it would be manifestly unfair to have
the whole section composed of such examples, (although this is often the pre-
examination 'dread' of a candidate). It should be appreciated that they serve to
indicate a degree of maturity in a candidate who recognises his limitations and
will not take risks in overdiagnosis.
Benign and non-neoplastic lesions of all types may be included in the cases,
and one of the purposes is to ensure trainees do not become conditioned into
thinking that frozen section equals tumour. It is an attitude which may lead to a
misdiagnosis when an unexpected inflammatory, hamartomatous or degenerative
lesion is encountered which simulates a tumour.
Therefore the material selected for the examination may obviously be from a
very wide range of pathologies (and is often dependent on local surgical practice
including occasional 'idiosyncratic' or rare cases encountered), resulting in a
particular composition in each centre. The list given at the end of this chapter
includes a selection of entities which are either known to have been included in
the examination in some centres, or which a candidate may be expected to have
seen during training or recognise de novo on frozen section. It clearly cannot be a
comprehensive list, but it may be useful to work through any archive material of
cryostat sections to examine such entities, or make some special effort to perform
a cryostat section should fresh material become available. One way of doing this is
to review the operating lists for the following day when on a surgical pathology
rota and make arrangements with the surgical team.
Although it is a rather superficial generalisation, there are three broad
categories of case submitted for the cryostat sections in the examination:

A) Lesions which the candidates may commonly encounter in clinical practice, or

are particularly distinctive, and in which the surgical management is dependent
Cryostat Sections 319

on a correct, unequivocal diagnosis. Misdiagnosis in this category would be

regarded as a serious error.
B) Lesions which are encountered reasonably often but which might be confused
with other entities, or in which a diagnosis may not materially alter the
management. Misdiagnosis of malignancy in a benign condition (and vice versa)
may be viewed as a serious mistake in some of these, but the inability to make a
firm diagnosis would not result in failure, and some equivocation or differential
diagnosis might even be expected.
C) Rare but distinctive lesions, or commoner lesions in an unusual site, the
diagnosis of which (or failure to diagnose) would not be a matter of failure in an
examination. Nevertheless, a correct appraisal would obviously be impressive.

Clearly, each type of lesion in the examination would vary in the degree of
difficulty depending on the material available and some might fall into more than
one category (e.g. chronic pancreatitiS can be very difficult to diagnose on biopsy
and yet is of considerable importance in surgical management decisions). In such
cases, category A/B or B/C is given and there are several such examples quoted.
It is worthwhile to make specific points relating to some of the entities
mentioned in the following, but it should be appreciated these are selective. There
can be no adequate substitute for practical experience in first hand (supervised)
cryostat section diagnosis.

Breast Lesions
(A) Invasive carcinoma NOS
(A) Intraductal carcinoma
(B) Lobular carcinoma in situ
(A/B) Medullary carcinoma with lymphoid infiltration
(A) Mucoid carcinoma
(B/C) Ductal papilloma
(C) Papillary carcinoma
(A) Fibrocystic disease with epitheliosis
(A) Sclerosing adenosis
(A) Duct ectasia/lobular mastitis
(A) Fat necrosis
(A) Lactating breast/lactational adenoma
(B) Phyllodes tumour
It is extremely common for breast carcinomas to be included in the examination
for obvious reasons. Diagnosis of malignancy is the prime objective but some
cases are sufficiently typical to allow distinction between lobular and ductal
carcinoma, but it is by no means imperative to make this decision. In situ ductal
carcinoma can be difficult to recognise, but in in the examination a fairly obvious
example such as comedocarcinoma would be included. Lobular carcinoma in situ
is more of a problem, and since it may not materially alter the immediate surgical
management paraffin section assessment may be preferable. The less common
sorts of breast cancer should be sufficiently distinctive to be fairly easily
recognisable.
Of the benign conditions, epitheliosis and sclerosing adenosis can look
alarming with high power objectives on cryostat section, and the architecture is all
320 Advanced Histopathology

important. One of the classic 'traps' for an unwary pathologist is the lactational
adenoma, which can look very aggressive even in paraffin sections but in which
the history will be helpful. Similarly, all pathologists should be familiar with the
cellular changes of lactation in the normal breast. The other conditions mentioned
are straightforward matters of recognition.

Respiratoty System
(C) Nasal glioma
(C) Rhinoscleroma
(C) Foetal rhabdomyoma of larynx
(C) Sclerosing haemangioma
(B) Rheumatoid nodule
(A/B) Oat cell carcinoma of lung
(A) Squamous carcinoma
(A) Adenocarcinoma
(A) Large cell carcinoma
(A) Carcinoid tumour
(A/B) Secondary deposits (including chondrosarcoma (B),
choriocarcinoma (A/B), leiomyosarcoma (A/B), renal cell carcinoma
(A/B»
(A/B) Epithelioid malignant mesothelioma
(B) Spindle cell or mixed malignant mesothelioma

Rare lesions in the upper respiratory tract and nose at the top of this list have been
included at some centres but these are presumably to provide some scope for the
more advanced candidate. The importance of distinguishing between various
main types of bronchial carcinoma has been mentioned previously but the most
important distinction is oat cell from non-oat cell varieties. The more distinctive
types of secondary deposits are included as a measure of awareness since these
may occasionally pose a problem in practice and can easily be misdiagnosed.
Mesotheliomas are rarely biopsied but it has been known. The distinction from
adenocarcinoma or spindle cell carcinoma is often impossible on cryostat sections.

Lymphoreticular System
(A) Granulomatous lymphadenitis - sarcoidosis (B), toxoplasmosis (B),
tuberculosis (B)
(C) Silicone lymphadenopathy
(A) Reactive follicular hyperplasia
(A/B) Castleman's disease - hyaline vascular
(B) Castleman's disease - plasma cell
(A/B) Secondary carcinoma and melanoma
(A) Non-Hodgkin's lymphoma (follicular/diffuse)
(B) Hodgkin's disease
(C) Splenic kala-azar
(B) Splenunculus (laparotomy)
Cryostat Sections 321

It is important to be familiar with the range of appearances in lymph nodes on

cryostat sections and architectural changes are of far more value than cytological
features. A diagnosis of lymphoma can usually be made but subtyping is often
difficult, and large cell lymphomas may look like undifferentiated carcinoma or
melanoma. Splenic frozen sections are rarely performed and are often rather
difficult diagnoses, as in the quoted examples. Splenunculi are a not uncommon
clinical request, especially if enlarged by processes such as CML. They may be
misdiagnosed as lymph nodes or lymphoma by the unwary.

Endocrine Glands
(A) Follicular adenoma/colloid nodule of thyroid
(A/B) Follicular carcinoma of thyrOid gland
(A) Papillary carcinoma of thyrOid gland
(B) Medullary carcinoma of thyroid gland
(A) Grave's disease
(A/B) Hashimoto's disease
(C) Riedel's thyrOiditis
(A/B) Dyshormogenetic goitre
(A) Parathyroid adenoma/hyperplasia
(B) Phaeochromocytoma of adrenal
(B) Adrenal cortical adenoma/carcinoma
(B/C) Paraganglioma (e.g. carotid body)

Benign thyroid nodules are very common and in most cases pose little problem.
Follicular carcinoma should only be diagnosed on frozen section in the presence
of clear vascular invasion or other compelling evidence. The nuclear pleomorph-
ism of benign thyroid tumours can be grossly exaggerated on cryostat section and
very misleading. 'Orphan-Annie' nuclei in papillary carcinoma are also much less
obvious but for examination purposes other helpful features such as psammoma
bodies will usually be present. Medullary carcinomas can look very odd in
cryostat sections and the distinctive amyloid seen in paraffin section is often pale
and inconspicuous. It is often worthwhile to automatically ask 'could this be
medullary carcinoma?' in thyroid lumps, before considering the more common
possibilities.
Hashimoto's disease can be problematic as the oxyphilic cells are often large
and pleomorphic. Dyshormonogenetic goitre is a rare but recognised 'trap' but a
consideration of the patient's age and the lack of normal tissue are strong
indicators of this possibility.
An enlarged parathyroid gland is frequently included as the surgical manage-
ment of hyperparathyroidism is strongly influenced by the pathology and it
provides a convenient subject for discussion between examiner and candidate on
the practical aspects.

Alimentary System
(A) Pleomorphic salivary adenoma
(A) Adenoid cystic carcinoma
(A) Low grade mucoepidermoid tumour
(B) High grade mucoepidermoid tumour
322 Advanced Histopathology

(B) Granular cell myoblastoma of tongue

(A) Smooth muscle tumour ( 'bizarre leiomyoma') of gut
(B) Inflammatory fibroid polyp
(B) Gastric lymphoma - low grade
(A) Gastric lymphoma - high grade
(A) Pancreatic carcinoma - poorly differentiated
(A/B) Pancreatic carcinoma - well differentiated
(A) Chronic pancreatitis
(B) Islet cell tumour
(A/B) Adenoma or adenocarcinoma of ampulla/lower CBD
(A) Bile duct adenoma of liver
(C) Linguatula (tongue worm) cysts
(A) Von Meyenberg complex (bile duct hamartoma)
(A) Hepatocellular carcinoma - typical
(B) Hepatocellular carcinoma - variants
(A) Secondary carcinoma or leukaemic infiltration in liver
(C) Epithelioid haemangioendothelioma
(B) Secondary malignant melanoma in gut or liver
(A) Rectal biopsy for? Hirschprung's disease
(A) Peritoneal endometriosis/endosalpingiosis

Despite the length of this list, cryostat sections are relatively infrequently
requested presumably reflecting the use of endoscopic and needle biopsy. Salivary
gland tumours are usually fairly characteristic and it would not be expected for
candidates to recognise the rare variants. Adenoid cystic carcinomas can be
particularly difficult on frozen section. The distinction of chronic pancreati-tis
from scirrhous pancreatic carcinoma is a clinical and pathological problem, and is
one situation where higher power examination of the cytological features can be
of value in a particularly fibrotic biopsy. At least in the examination situation, a
distinction should be possible. One feature of pancreatic carcinomas is that they
tend to fragment, so it is important to check for material lying adjacent to the main
biopsy tissue on the section.
Bile duct adenomas are sometimes biopsied at laparotomy because of their
resemblance to secondary deposits, but their architecture is characteristic. Fibrotic
tongue worm nodules are more common than most pathologists imagine, and are
biopsied for similar reasons, but this would only be included as a difficult case.
Some of the variants of hepatocellular carcinoma can be confusing and simulate
other entities (e.g. secondary carcinoma). Bile pigment may be present to assist in
the diagnosis. Malignant melanoma has very occasionally been included, but is
more likely to appear in the surgical histopathology. Searching for ganglion cells
in a putative Hirschprung's disease can be tedious if they are not there and
ganglion cells can look rather unusual on frozen section so familiarisation with
these appearances is advised. Peritoneal endosalpingiosis or endometriosis may
be included to trap the inexperienced pathologist who might be tempted to
diagnose metastatic adenocarcinoma or even papillary mesothelioma.
Cryostat Sections 323

Female Reproductive System

(B) Ovarian fibrothecoma
(A) Serous, mucinous and endometrial carcinoma
(B) Borderline tumour
(A) Pregnancy luteoma
(A) Endometrioma
(B) Yolk sac tumour or dysgerminoma of ovary
(A) Endometrial adenocarcinoma
(B) Mixed Mullerian tumour
(A) Choriocarcinoma

The commoner malignant ovarian tumours do not provide many problems

although the fibrothecoma can look rather nondescript. It would be unusual for
lesions such as granulosa cell tumour to be included and this would certainly fall
into the difficult diagnosis category. Although pregnancy luteoma and endome-
triosis are mentioned, these rarely provide a clinical diagnostic problem. Tumours
such as choriocarcinoma are usually diagnosed preoperatively but cryostat section
may be requested for confirmation.

Male Reproductive System

(B/C) Sperm granuloma
(B) Adenomatoid tumour
(C) Mesothelial proliferation in hernial sac
(A) Seminoma
(A) Germ cell tumour - choriocarcinoma
(B) Germ cell tumour - embryonal carcinoma
(B/C) Germ cell tumour - yolk sac tumour
(C) Interstitial cell tumour
(B) Primary testicular lymphoma
(A) Prostatic nodular hyperplasia
(A) Prostatic carcinoma

The benign entities mentioned are sometimes included because they can be
misdiagnosed as malignant and candidates should be aware of this possibility.
The other entities mentioned are fairly straightforward diagnostic problems, but
seminomas rich in lymphocytes can be misinterpreted as lymphoma and vice
versa. Intratubular germ cell neoplasia may be recognisable on the section and
help in this respect.

Urinary Tract
(A) Renal adenoma I adenocarcinoma
(B/C) Angiomyolipoma
(C) Oncocytoma
(B/C) Rapidly progressive glomerulonephritis
(C) Nephrogenic adenoma of bladder
(A) Transitional cell carcinoma of bladder
324 Advanced Histopathology

Most of these lesions are relatively straightforward and of varying degrees of

difficulty. Rapidly progressive (crescentic) glomerulonephritis can be recognised
on frozen section, which is sometimes requested because of the urgency required
in instituting treatment. Nephrogenic adenoma is an example of an 'idiosyncratic'
slide which you would be unlikely to encounter.

Skin
(C) Juvenile xanthogranuloma
(C) Keratoacanthoma
(C) Spitz naevus
(A) Nodular malignant melanoma - Advanced
(B/C) Nodular malignant melanoma - Early
(B) Lentigo maligna
(B) Paget's disease of nipple

The problems in the diagnosis of melanocytic lesions of the skin have already
been discussed and unless the diagnosis is certain there is little to be lost by
prevaricating. Paget's disease of the nipple and lentigo maligna are distinctive
lesions but there is little clinical value in their recognition on frozen as opposed to
paraffin sections.

Nervous System
(A) Meningioma
(B) Acoustic Schwannoma
(B) Glioma
(B/C) Retinoblastoma
(C) Med ulloblastoma
(C) MyxopapiIlary ependymoma

Examiners recognise that not all candidates have had the opportunity to train in a
centre specialising in neuropathology but some of the more distinctive or
commoner entities are often included. Astrocytomas are the commonest glioma
and are usually fairly straightforward with prominent gemistocytes, or as the
'glioblastoma multi forme' type.
 325

The Viva Voce Examination

Introduction

Many candidates have a disproportionate dread of this part of the examination

but it helps to remember that in the great majority of cases the fate of the candidate
is already sealed by this stage. However, it is a natural tendency for most
individuals to believe that they may be just on or below the borderline and that a
good performance in the viva will tip the balance in their favour. While this is only
true in the occasional case, there is still an incentive for candidates who have
definitely failed overall, as on rare occasions the examiners might insist that a
candidate re-take the written papers; a satisfactory showing in the viva could help
avert this. For those who are confident they have performed adequately
beforehand, it may be an almost enjoyable experience and provides an opportun-
ity to impress examiners. It is not unknown for some pathologists who came to the
attention of certain examiners during the Final examination to end up working in
their Department!
It is still necessary to have a neat appearance and the bearing of a potential
consultant pathologist, as for the situation in general. It is perhaps even more
important to have a positive attitude and desire to project an impression of
knowledgeability, rather than adopt the attitude of some candidates who try to
extract a sympathetic response from the examiners who they hope will understand
that their poor showing is merely the result of the stress of the examination and
does not reflect their 'true' ability. Unfortunately, most of these candidates tend to
overcompensate and end up appearing rather more pathetic than impressive.
One important piece of 'homework' to be done is to try to establish who the
internal and external examiners might be. There is no obligation for the centre or
the College to give this information but it may be either volunteered by one of the
examiners and, if not, it is reasonable to ask discreetly. Obviously, the best time to
do this is during the first visit for the necropsy. Alternatively, more senior
colleagues who have visited the centre previously may be able to offer advice.
Once having found out who the examiners are to be, either prior to or during
the examination, their particular fields of interests should be established. This is
essential because some examiners cannot resist the temptation to concentrate on
their speciality and it is as well to anticipate this possibility. Moreover, it is
advisable to try to direct attention away from these areas and proffer any opinions
with some deference to their expertise; it is usually not advisable to argue with
examiners on their special subject or claim any particular interest in it unless there
is good justification, for the examiner would doubtless ask out of interest. Those
who are less than proficient in their reply would create a very bad impression.

The Examination Itself

Most centres allocate about 20-30 minutes to the viva, but this may be rather
longer for candidates on the borderline or who have performed very badly, and
for whom resitting of the written papers may be contemplated. Generally
speaking the chief internal and external examiners conduct the interview together.
Many of the recommendations on the approach to this session have already
been covered under clinicopathological conferences or mounted specimens and
326 Advanced Histopathology

there is no point in repeating them but certain aspects relating to this particular
stage merit consideration.
Firstly it is important not to take too much account of other candidates prior to
the viva, especially of their views on some aspects of the surgical histopathology.
Their comments are equally likely to be incorrect as correct and this should not
undermine confidence. Similarly, disregard the attitude of those individuals
emerging from the viva, as their attitude would undoubtedly be affected by the
relief at completing the examination. They are unlikely to provide any useful
information at this stage, and interrogating them would only serve to increase
anxiety.
At the start of the viva, the examiners would usually attempt some form of
'undemanding' general questions which might help to put the candidate at greater
ease. It is very common to be asked an opinion as to how an individual thinks
they have performed and where they thought errors may have occurred. It is
advisable to prepare for this eventuality because it is possible to anticipate what
answers to give. It is worth reflecting on the surgical histopathology during the
subsequent evening, checking on any uncertain cases, and reading up on the
differential diagnosis of selected examples. Comments made by other candidates
can be taken into account, but must be viewed with particular caution, unless they
clearly fit the diagnosis and reveal an obvious mistake. However, it should be
noted that the memory can often be deceptive and uncertainties placed in one's
own mind by others can overcome the product of a reasoned assessment made at
the time. It is worth remembering the idiom 'Empty vessels make the most noise'
when listening to fellow candidates! As a general rule, avoid 'post mortems' on
the component parts of the examination, particularly the surgical pathology. They
sap confidence and rarely do anything but harm. It is good advice to decline,
politely, to discuss your answers with fellow candidates. Remember, you are just
as likely as they are to be correct and expressed second thoughts about your
correct diagnosis will do you no good at all.
Thus, if the examiners ask, take one or two examples where a mistake could
definitely be identified and state openly what the assessment should have been
and why the error was made. It is possible to redeem a certain amount in this way.
It does not help to make generalisations about the whole of the surgical
histopathology having been difficult, without subsequently identifying specific
examples. The examiners may identify examples they are particularly concerned
about, and ask for comments. In this situation it is almost certain that an error has
been made and therefore the attitude of the candidate should be humble and
introspective, rather than defensive and somewhat arrogantly refusing to consider
alternatives.
Of course, there could be many other areas of the examination performance
which the examiners would seek to qualify and thus candidates should be
prepared to reconsider any aspect they have covered, and explain and discuss
their reasoning. If such questions are forthcoming, it should be uppermost in the
candidate's mind to try to ascertain what information the examiners are seeking to
extract. If in doubt, it is better to admit either that the question is not understood
or ask for guidance. It is not a good idea to try to bluff one's way out of answering,
or to digress into other subjects; examiners like to pursue candidates who try to
evade questions.
In the event that a candidate clearly does not know the answer, but has been
honest enough to recognise and admit this, examiners usually move to another
topic, as they appreciate that areas of ignorance are almost certain to be uncovered
in all but the exceptionally able pathologist. They are more interested in the
capacity to be flexible in interpretation and the ability to take a balanced view of
The Viva Voce Examination 327

certain problems, placing ideas in perspective, rather than in a candidate who is

technically bright but is arrogant and somewhat narrow-minded, which is often
the recipe leading to potentially dangerous diagnoses.
There are other comments which need to be made on the general attitude to be
adopted during the examination, especially in the viva. Another common question
is what you thought about the examination. Any temptation to criticise the centre,
staff or even examiners must be avoided at all costs. Very few candidates turn out
to have legitimate grounds for complaint and the mature individual always
accepts there are always inequalities in standards, and differences in procedures,
with which they might not entirely agree. Therefore it is important not to argue in
an aggressive fashion, even when the examiner may appear provocative (which is
unusual) or complain that the examination has been unfair, no matter how trivial
or serious this may be. Anyone who feels that there are legitimate grounds for a
formal complaint should discuss the matter with their Head of Department
afterwards. It is very rare for the matter to be taken further, and even when formal
complaints are made to the College about examination procedure, it appears to be
unusual for any action to be taken. For example, at a certain examination centre, it
was customary for the examiner to increase the level of anxiety during the frozen
sections by walking among the candidates, continually remarking in a loud voice
that surgeons were waiting and time was of the essence. Complaints made on
behalf of both successful and unsuccessful candidates were met by acknowledge-
ment of receipt, and the continuation of the same practice by the examination
centre. At other centres examiners persist in confronting candidates on a double
header in frozen sections, a practice heavily frowned on in the instructions to
examiners. So the fact remains: the College make the rules, and the examiners
interpret them. Arguing with the referee will not help. It is up to you to win in
spite of the referee.
The answers in the viva should be positive and clearly spoken, and special care
should be taken that an impression of enthusiasm and alertness should be
maintained throughout the period of the viva voce, as there is a tendency to relax
or even despair halfway through. The candidate who becomes gradually more
inaudible and reticent will end up being a source of irritation to the examiner.
At the end of the viva, it is common courtesy to thank the examiners for their
hospitality. In addition, candidates should not expect to be told outright how they
have fared. It would embarrass the examiners to be asked by the candidate
directly, as they are not permitted to divulge the information. Nevertheless, do
listen carefully to the last few remarks made to you: it is certainly not unknown
for examiners, particularly if they have partaken of liquid refreshment at lunch
time, to forget the College's injunction and drop a distinct hint; usually only if
you've passed however.

Notification of Results
The results are published within two weeks of the end of the practical
examinations and are available at the College in Carlton House Terrace (and
candidates will be informed of the exact time and should receive notification
through the post the following day). Results are never given over the telephone.
In the case of unsuccessful candidates, the examiners will send a report to the
Regional adviser. These reports are sometimes helpful but for the most part have
attracted criticism because of their brevity and vagueness. There are two things
you can do which may give more information. Discuss the surgical cases, etc.,
with successful fellow candidates after the examination, especially if they are
328 Advanced Histopathology

familiar colleagues. This may be a difficult business but it is valuable because it

may give more insight into the material. The second is to ask the Head of
Department to contact one of the examiners personally. This will often elicit a
helpful reply which will identify particular weaknesses and help in preparing for
another attempt.
At present, the regulations allow three sittings of the examination without
question but thereafter, entry is conditional upon the support of the Regional
adviser. This arrangement is partly to allow deficiencies in training to be identi-
fied as some candidates have, perhaps unknown to them, had very lop-sided
experience because of a poor rotation or other factors (as discussed earlier in this
book). The maximum number of attempts appears to be limited to six, however.

So here you are. You've read the books, spotted all the questions you can, polished
your autopsy technique, looked at many, many sections and are replete with facts,
from asteroid bodies to zoonoses. Tomorrow you sit the papers, and in three
weeks' time, if spared, you confront the examiners at the dreaded practical.
Are there any final words of advice? There is a deadly tendency, especially if
preparation for an examination has been intense, to feel anti-climactic at its
immediate prospect. Try to kick yourself out of this. Remember you've prepared
hard and well - 'Train hard, fight easy' has been your maxim. It's all too easy
with an examination directly in your sights to think only of those things you do
not know, or are unsure of, and forget the many facts of which you are certain.
Don't do this. Be confident. Be positive. And pass.
 329

Appendix 1

Reference List of Major Texts

1. Gresham, G.A., Turner, A.F. Post-Mortem Procedures (an illustrated

textbook). Wolfe Medical Publications, London (1979).
2. Robbins, S.L., Cotran, RS., Kumar, V. Pathologic Basis of Disease, 4th edition.
W.B. Saunders, Philadelphia (1989).
3. Anderson, J.R. (ed.) Muir's Textbook of Pathology, 12th edition. Edward
Arnold, London (1985).
4. Enzinger, F.M., Weiss, S.W. Soft Tissue Tumors. 2nd edition. C.V. Mosby Co,
St Louis (1988).
5. Taussig, M.J. Processes in Pathology and Microbiology, 2nd edition. Blackwell
Scientific Publications, Oxford (1984).
6. MacSween, R.N.M., Anthony, P.P., Scheuer, P.J. (eds.) Pathology of the Liver,
2nd edition. Churchill Livingstone, Edinburgh (1987).
7. Rosai, J. (ed.) Ackerman's Surgical Pathology, 7th edition. C.V. Mosby Co, St.
Louis (1989).
8. Anthony, P.P., Woolf, N. (eds.) Recent Advances in Histopathology 10.
Churchill Livingstone, Edinburgh (1978).
9. Anthony, P.P., MacSween, RN.M. (eds.) Recent Advances in Histopathology
11. Churchill Livingstone, Edinburgh (1981).
10. Anthony, P.P., MacSween, RN.M. (eds.) Recent Advances in Histopathology
12. Churchill Livingstone, Edinburgh (1984).
11. Anthony, P.P., MacSween, RN.M. (eds.) Recent Advances in Histopathology
13. Churchill Livingstone, Edinburgh (1987).
12. Fox, H. (ed.) Haines & Taylor. Obstetrical and Gynaecological Pathology, 1,2.
3rd edition. Churchill Livingstone, Edinburgh (1987).
13. Dunnill, M.S. Pulmonary Pathology. Churchill Livingstone, Edinburgh (1982).
14. Olsen, E.G.J. Pathology of the Heart. Intercontinental Medical Book
Corporation, New York (1973).
15. Davies, M.J., Pomerance, A. The Pathology of the Heart. Blackwell Scientific
Publications, Oxford (1975).
16. Morson, B.c. (ed.) Alimentary Tract. Systemic Pathology, Volume 3. (general
ed. W. St. C. Symmers ) Churchill Livingstone, Edinburgh (1987).
17. Department of Health and Social Security. Code of Practice for the Prevention
of Infection in Clinical Laboratory and Post-mortem Rooms. 6th Impression.
HMSO, London (1987) (NB Currently under review). Also see:
a) Health Services Advisory Committee. Safety in Health Service
Laboratories - Hepatitis B, HMSO London (1985).
b) Health Services Advisory Committee. The labelling, transport and
reception of specimens. HMSO, London (1986).
18. Underwood, J.C.E. Introduction to biopsy interpretation and surgical
pathology. 2nd edition. Springer-Verlag, Berlin (1987).
19. Berry, c.L. Paediatric Pathology, 2nd edition. Springer-Verlag, Berlin (1989).
330 Advanced Histopathology

Additional Reading/Reference List

1. Stansfeld, A.G. (ed.) Lymph Node Biopsy Interpretation. Churchill

Livingstone, Edinburgh (1985).
2. Lever, W.F., Schaumberg-Lever, G. Histopathology of the Skin, 6th edition.
J.B. Lippincott Co, Philadelphia (1983).
3. Wickramasinghe, S.N. (ed.) Blood and Bone Marrow. Systemic Pathology,
Volume 2. (general ed. Wt. St. C. Symmers) Churchill Livingstone, Edinburgh
(1987).
4. Dahlin, D.C., Unni, K.K. Bone Tumours, 4th edition. Charles C. Thomas,
Illinois (1986).
5. Azzopardi, J.G. Problems in Breast Pathology. W.B. Saunders Co Ltd, London
(1979).
6. Spencer, H. Pathology of the Lung, 4th edition. Pergamon Press, Oxford
(1985).
 331

Appendix 2

Teaching Courses in Histopathology and Morbid Anatomy

1. Royal Postgraduate Medical School

a) Advanced Histopathology
Biannual (September and February)

A well-established two week course which many candidates attend just prior to
the practical examination, comprising a morning practical examination of compre-
hensive slide collections on a particular topic (e.g. gastrointestinal tract,
dermatopathology, breast, etc.) which are discussed and illustrated by the course
teachers in the afternoon session. This course is often oversubscribed.

b) Diagnostic Liver and Gastrointestinal Pathology

Annual (November)

A five day set of practical sessions and illustrated discussion, together with guest
lectures, intended to provide an intensive coverage of most entities in practical
diagnostic pathology in this field. An explanatory course booklet is provided.
Maximum benefit would be gained by attending this course at least six months in
advance of the examination, but is perhaps of greater benefit for post MRCPath
senior registrars and consultants with a specialist interest.

c) Diagnostic Dermatopathology
Annual (November)

Another five day intensive course organised in a similar fashion to the above. The
standard of the course is high and may be too intensive for candidates just prior to
the examination, but candidates would benefit by attending well in advance to
allow time for reflection and assimilation of the information.

d) Diagnostic Haematopathology
Annual (January)

An advanced five day course for pathologists and clinicians perhaps best suited to
those with an interest in the areas or at post MRCPath standard. Practical sessions
and lectures are provided on a variety of topics including bone marrow, lymph
nodes and spleen.

e) Diagnostic Pathology of Soft Tissue Tumours

Annual (February)

A comprehensive five day course which would be of interest to pathologists at all

levels of training. Soft tissue tumours comprise a disproportionate number of the
more difficult sessions in surgical histopathology at many examination centres.
332 Advanced Histopathology

f) Diagnostic Histopathology and Cytopathology of Breast Disease

Annual (February)

A new course which clearly would be an attraction to most pathologists and is

very relevant to the examination. Details: Professor N.A. Wright, Department of
Histopathology, Royal Postgraduate Medical School, Du Cane Road, London W12
OHS. Telephone 01-743 2030.

2. The British Postgraduate Medical Federation, University of London

Histopathology Module

This was formerly organised on a day-release basis over a period of six months
every two years but is currently under review. It may be re-introduced at a later
stage and· is more likely to be as a concentrated two or three week course,
which aims at a fairly comprehensive coverage. Details: Dr J. Tinker, British
Postgraduate Medical Federation, 33 Millman Street, London WCIN 3EJ.
Telephone 01-831 6222.

3. London Hospital Histopathology Course

This formerly very popular course was organised on weekly evening sessions
with emphasis on diagnostic histopathological problems which were released for
participants to review in the week prior to the meeting. The course is presently
under review, and may be organised in conjunction with the British Postgraduate
Medical Federation. Announcements will be made in the major pathology journals
when a decision is taken.

4. The Autopsy
Annual (July)

A three day course providing a fairly comprehensive coverage of most topics

associated with autopsy pathology, predominantly on a lecture basis, with some
practical demonstrations. The course may well be of greatest value to pathologists
in the middle stages of their training to allow them to refine and practise their
techniques in accordance with the experience gained. We are not aware of any
other nationally available course which specifically deals with these topics.
Details: Dr Dennis Cotton, Department of Pathology, University of Sheffield
Medical School, Beech Hill Road, Sheffield S10 2RX.

5. Diagnostic Histopathology Course

Annual (July)

A two week residential course consisting of practical sessions followed by

discussion of the material, aiming to cover most aspects of general surgical path-
ology. Each three hour session covers one system, and there is particular emphasis
on practical diagnostic problems rather than esoteric entities. Accommodation,
meals and a social programme are provided. The course is popular and often
oversubscribed. Details: Dr A.J. Howat, Department of Pathology, University of
Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX.
Appendix 2 333

6. Cytopathology for Histopathologists

January /February and mid-September

A very popular five day course which includes both practical sessions and lectures
from a variety of specialist cytopathologists. Most candidates would gain
maximum benefit by having at least a few months experience in cytopathology
and many attend in the session prior to sitting the practical examination. Details:
Dr E.A. Hudson, Department of Histopathology, Northwick Park Hospital,
Watford Road, Harrow, Middlesex HAl 3UJ.
7. Diagnostic Dermatopathology
Annual (April)

An established course in this subject which covers many aspects of neoplasia and
inflammatory disorders of the skin. Details: Mrs W.E. Scott, Administrative
Assistant, West of Scotland Committee for Postgraduate Medicine, University of
Glasgow, Glasgow G12 8QQ.
8. Paediatric Pathology
Annual (April)

Courses which are sponsored by the Association of Clinical Pathologists which

are to take place in Sheffield and Birmingham on alternate years. Details: Dr F.
Raafat, Consultant Paediatric Pathologist, Department of Histopathology, The
Children's Hospital, Ladywood Middleway, Ladywood, Birmingham B16 8ET.
9. Management Course for Junior Pathologists
April and September
A three day residential course relevant to those intending to work within the
National Health Service. Topics covered by a series of lectures include manage-
ment quality control and funding as related to pathology disciplines, and would
be of value in preparation for certain questions in the written paper, but more
especially to prospective applicants for consultant posts. Details: Dr D.H. Orrell,
Department of Pathology, Lancaster Royal Infirmary, Lancaster LA1 4RP.
10. Regional Courses in Pathology
Most university centres within each Regional Health Authority provide training
courses in histopathology and/or morbid anatomy on a regular weekly or
monthly basis. Attendance at such courses should be de rigeur for candidates
within that Region, providing an opportunity to meet colleagues as well as gain-
ing experience. Details: Either from the Regional Adviser in Histopathology
(Royal College of Pathologists) or in the A.C.P. Programme of Postgraduate
Education, which is automatically sent to associates and members.
11. Secondment Schemes in Pathology
Formal arrangements to attend a wide range of general and specialist pathology
units can be made via the Education Secretary of the Association of Clinical
Pathologists rather than on an individual basis. These may be of great value to
those trainees who have a specific deficiency in their training. Details: Dr J.D.
Davies, University Department of Pathology, Bristol Royal Infirmary, Bristol BS2
8HW. Telephone 0272-23000 extension 2582.
334 Advanced Histopathology

12. Symposia organised by the Royal College of Pathologists, Association of

Clinical Pathologists and the International Academy of Pathologists

Symposia on subjects of topical interest are organised by these bodies and details
are circulated to members and associates, as well as advertised in the society
journals. Attendance at these symposia is highly recommended for trainees, and
many of the topics, especially those organised by the College are not infrequently
used as a basis for a question in the subsequent written examination. Attendance
at all of these symposia would be impossible for most trainees, but a well
organised group of trainees would send one representative to each and pool the
information.
 335

Appendix 3
Professional Societies and Associations

1. The Royal College of Pathologists

2 Carlton House Terrace, London SW1Y 5AF
Telephone: 01-930 5861

Society publication - Bulletin of Royal College of Pathologists

2. The Association of Clinical Pathologists

57 Lower Belgrave Street, London SW1 W OLR
Telephone: 01-730 0078

Society publication - Journal of Clinical Pathology

3. The Pathological Society of Great Britain and Ireland,

c/o Department of Pathology, Royal Infirmary, Glasgow G4 OSF
041-552 3535 ext. 4224

Society publication - Journal of Pathology

4. The British Medical Association

BMA House, Tavistock Square, London WC1H 9JP
Telephone: 01-387 4499

Society publication - British Medical Journal

5. The International Academy of Pathologists (British Division),

Dr M. Wells, Department of Histopathology,
Leeds University Medical School, Leeds LS2 9JT

Society publication - Histopathology

6. British Association of Clinical Cytology,

c/o Dr P.A. Trott, Dept of Cytopathology,
Royal Marsden Hospital, Fulham Road, London SW3 6JJ
336 Advanced Histopathology

Regulations Regarding the Examinations for

Membership (Medically-Qualified Candidates)

The Council of the College finalised the regulations for the Membership
examinations at its meeting on 24th November 1988. The detailed requirements
for the individual specialties will be published together later.

1. A candidate is admitted to the examinations, Part I and Part II, solely at

the discretion of Council.
2. The candidate must hold a qualification in medicine that is approved by
Council.
3. A candidate holding a medical qualification not registered by the General
Medical Council in the United Kingdom must furnish with his/her
application form the document or certificate whereby registration or
permission to practise is granted in the country or territory of domicile in
which the qualification is granted.
4. Entrance to any College examination can be effected only by completion of
the printed application form obtainable from the Registrar. The form and
entrance fee must be returned to the Registrar not later than the date
specified in the public announcement of the examination. Incomplete or
later applications cannot be accepted.
5. It can sometimes be arranged for a candidate for the Part I Examination to
take the written part of the examination overseas; a candidate who passes
the written papers overseas is usually asked to attend for his/her practical
and oral components in the United Kingdom at the next session of the
examination.
6. A candidate must have held suitable clinical appointments for not less
than one year; pre-registration appointments are accepted for this purpose.
7. A candidate shall not be admitted to an examination until he/ she has
fulfilled the training requirements set out in the appropriate sections of
these regulations.
Training in laboratories outside the United Kingdom will be considered on
an individual basis. An applicant who has worked in appropriate
laboratories or departments other than pathology laboratories may be
admitted to the examination at the discretion of Council.
8. The applicant is responsible for keeping the College office informed of
his/her address and telephone number during the time of the examination.
9. The applicant should be sponsored by a Fellow or Member of the College.
When sponsorship by a Fellow or Member is impracticable the signature
of the head of the department in which the candidate is working may be
accepted by Council.
10. Part I Examination
(a) Training requirements: A candidate entering for the Part I Examination is
required to have worked in departments recognised for training in the
relevant discipline for a total period of not less than three years, of which two
and a half years must have been in the subject in which the candidate elects to
be examined. A candidate who has held or hopes to hold part-time posts must
obtain the approval of the College for his/her training (overseas candidates see
Regulation 7).
Regulations 337

Up to one year in a relevant clinical or research appointment or in training

courses of certain MSc degrees and Diplomas approved by the College may be
accepted towards the training period. A full list of approved postgraduate
qualifications may be obtained from the Registrar.
(b) Entrance fee for the Part I examination is set by Council and details may be
obtained from the Registrar; withdrawal from the examination after
candidature has been accepted may involve the forfeiture of all or part of the
entrance fee.
(c) The candidate must state which one of the following branches of pathology
he/she has chosen for the examination: chemical pathology, clinical
cytogenetics and molecular genetics, haematology, histopathology,
immunology, medical microbiology, neuropathology, oral pathology, toxi-
cology, virology and any other subjects which Council may approve.
(d) Form of the examination: the Part I Examination comprises:
(i) two three hour written papers in the chosen branch of pathology which
may, at the discretion of the Examiners' Sub-committee, contain an MCQ
component;
(ii) a practical and oral examination in the branch of pathology the
candidate has chosen (with the exception of haematology). The candidate
will be notified of the time and place of the practical and oral examination
(see Regulation 8). In Haematology, the Part I examination will comprise
written papers only. Candidates selecting histopathology must provide
the College with a certificate indicating competence in cutting and staining
frozen sections.
(e) A candidate who fails to satisfy the examiners in the written papers will
not go forward to the practical and oral stage.
(f) A candidate who obtains an acceptable mark in the written papers and
who fails the practical and oral examination by only a small margin may, at the
discretion of Council, retain the pass in the written papers.
(g) A candidate will normally be allowed four attempts at the Part I
examination in whole or in part, after which he/she may re-enter only for a
specified number of attempts to be decided by Council.
11. Part II Examination
(a) Training requirements: A candidate may not enter for the Part II Examination
until he/she has successfully completed the Part I Examination.
(b) A candidate for the Part II examination is required to have completed the
equivalent of five years - full-time approved training of which two years must
have been in a post recognised for higher specialist training and four years in
the branch of pathology chosen for the examination (overseas candidates should
see Regulation 7).
The entrance fee for the Part II Examination is set by Council and details may
be obtained from the Registrar; withdrawal from the examination after
candidature has been accepted may involve the forfeiture of all or part of the
entrance fee.
(c) Candidates must state which branch of pathology they have chosen for the
examination. A candidate who wishes to sit the Part II examination in a subject
other than that passed in Part I must obtain the permission of the Council.
All candidates for the Part II examination in haematology are required to have
undertaken training in blood transfusion in an approved blood transfusion
centre. This should normally be for a period of at least six months of which
three months may be in a hospital centre which is recognised for this purpose.
338 Advanced Histopathology

Application forms are obtainable from the Registrar. Examinations are held
twice a year, except in clinical cytogenetics and molecular genetics and
toxicology, which are normally held once a year in the Spring.
(d) Form of the examination: the Part II examination and completion of the
training programme are designed to ensure that the candidate has advanced to
a stage of full professional competence in a branch of pathology. The
examination comprises:
1. an oral examination and
2. one or more of the following options agreed by Council for the discipline
concerned:
(i) a test of practical competence appropriate to the discipline or
subspecialty and agreed by Council;
(ii) a dissertation;
(iii) a suitable higher degree;
(iv) a collection of refereed, published papers with a critical commentary;
(v) a casebook with a critical commentary.
(e) A candidate who fails to pass the Part II examination in whole or in part
after two attempts will only be permitted to re-enter after a review of his/her
training programme and on the advice of the Regional Adviser in Postgraduate
Education in Pathology. Extenuating circumstances supporting the re-
admission of a candidate after four failed attempts to any part of the Part II
examination must be referred to Council.
12. These regulations may be varied from time to time by decision of Council.
13. Membership
(a) Every Member of the College shall be held to have agreed to be bound by
provisions of the Charter and the Ordinances as amended from time to time
and shall be bound to further to the best of his/her ability the objects and
interests of the College (Ordinance 2).
(b) Membership of the College may be followed after a twelve year period by
an offer, to those Members in good standing, of admission to the Fellowship.

Regulations Regarding the Examinations for Membership

(Candidates Without a Medical Qualification)

1. The candidate is admitted to the examinations, Part I and Part II, solely at
the discretion of Council.
2. The candidate must hold a qualification that is approved by Council. For
the purpose of this regulation Council recognises the qualifications in dental
surgery and veterinary medicine that are registrable in the United Kingdom
and 1st and 2nd class honours degrees or equivalent qualifications granted in
the United Kingdom and Republic of Ireland in appropriate science subjects.
Applications may also be considered on an individual basis from those holding
other science degrees granted in the United Kingdom and Republic of Ireland
and from those holding science degrees from overseas universities.
3. Entrance to any College examination can be effected only by completion of
the printed application form obtainable from the Registrar. The form and
entrance fee must be returned to the Registrar not later than the date specified
in the public announcement of the examination.
Regulations 339

Incomplete or late applications cannot be accepted.

4. It can sometimes be arranged for a candidate for the Part I Examination

to take the written part of the examination overseas; a candidate who passes
the written papers overseas is usually asked to attend for his/her practical
and oral components in the United Kingdom at the next session of the
examination.
5. A candidate shall not be admitted to an examination until he/she has
fulfilled the training requirements set out in the appropriate sections of these
regulations. Training in laboratories outside the United Kingdom will be
considered on an individual basis.
An applicant who has worked in appropriate laboratories or departments other
than pathology laboratories may be admitted to the examination at the
discretion of Council.
6. The applicant is responsible for keeping the College office informed of
his/her address and telephone number during the time of the examination.
7. The applicant should be sponsored by a Fellow or Member of the College.
When sponsorship by a Fellow or Member is impracticable the signature of the
head of the department in which the candidate is working may be accepted by
Council.
8. Part I Examination
(a) Training requirements: Veterinary and dental candidates cannot enter for
the Part I examination until four years after obtaining the qualification laid
down in Regulation 2. Non-medical candidates other than veterinary and
dental cannot enter for the Part I examination until six years after obtaining the
qualifications laid down in Regulation 2. Of these four and six years
respectively, three years must have been spent in approved appointments in
laboratories recognised for Part I training. A candidate who has held or hopes
to hold part-time posts must obtain the approval of the College for his/her
training (overseas candidates see Regulation 5).
Other laboratory experience up to one year may be accepted towards the
training requirements of the College's examinations but only posts held after
an acceptable degree (or degree equivalent) has been obtained will be accepted
towards the College's training requirements. For each applicant, the nature and
suitability of the post must be approved by the Council.
Up to one year in a relevant clinical or research appOintment or in training
courses of certain MSc degrees and Diplomas approved by the College may be
accepted towards the training period. A full list of approved postgraduate
qualifications may be obtained from the Registrar.
(b) The entrance fee for the Part I examination is set by Council and details may
be obtained from the Registrar; withdrawal from the examination after
candidature has been accepted may involve the forfeiture of all or part of the
entrance fee.
(c) The candidate must state which one of the following branches of pathology
he/she has chosen for the examination: chemical pathology, clinical
cytogenetics and molecular genetics, immunology, medical microbiology, oral
pathology, toxicology, virology.
(d) The examinations are held twice a year, except in clinical cytogenetics and
molecular genetics, veterinary pathology and toxicology, which are normally.
held once a year in the Spring.
340 Advanced Histopathology

(e) Form of the examination: The Part I examination comprises:

(i) two three hour written papers, which may, at the discretion of the
Examiners, contain an MCQ component.
Special papers for non-medical candidates will be set in certain disciplines.
(ii) a practical and oral examination in the branch of pathology that the
candidate has chosen. The candidate will be notified of the time and place
of the practical and oral examination (see Regulation 6).
(f) A candidate who fails to satisfy the examiners in the written papers will
not go forward to the practical and oral stage.
(g) A candidate who obtains an acceptable mark in the written papers and
who fails the practical and oral examination by only a small margin may, at the
discretion of the Council, retain the pass in the written papers.
(h) A candidate will normally be allowed four attempts at the Part I
examination in whole or part, after which he/she may re-enter only for a
specified number of attempts to be decided by Council.

9. Part II Examination
(a) Training requirements: A candidate may not enter for the Part II Examination
until he/she has successfully completed the Part I Examination.
(b) A dental and veterinary candidate may not enter for the Part II
examination until six years after obtaining his/her basic qualification (see
Regulation 2) and must have completed the equivalent of five years full-time
training in recognised appointments, of which two years must have been in
appointments recognised for higher specialist training in pathology.
(c) A science graduate may not enter for the Part II Examination practical and
oral examination until eight years after obtaining his/her basic qualification
(see Regulation 2) and must have completed the equivalent of five years full-
time training in approved appointments of which two years must have been in
appointments, approved for higher specialist training and four years in the
branch of pathology chosen for the examination.
The entrance fee for the Part II Examination is set by Council and details may be
obtained from the Registrar; withdrawal from the examination after
candidature has been accepted may involve the forfeiture of all or part of the
entrance fee.
(d) Candidates must state which branch of pathology they have chosen for the
examination. A candidate who wishes to sit the Part II examination in a subject
other than that passed in Part I must obtain the permission of Council.
(e) Examination are held twice a year, except in clinical cytogeneticS and
molecular genetics, veterinary pathology and toxicology, which are normally
held once a year in the Spring.
(f) Form of the examination: The Part II examination and completion of the
training programme are designed to ensure that the candidate has advanced to
a stage of full professional competence in a branch of pathology. The
examination comprises:
1. an oral examination and
2. one or more of the following options agreed by Council for the discipline
concerned:
(i) a test of practical competence appropriate to the discipline or
sub speciality and agreed by Council;
(ii) a dissertation;
(iii) a suitable higher degree;
Regulations 341

(iv) a collection of refereed, published papers with a critical commentary;

(v) a casebook with a critical commentary.
(g) A candidate who fails to pass the Part II examination in whole or in part
after two attempts will only be permitted to re-enter after a review of his/her
training programme and on the advice of the Regional Adviser in Postgraduate
Education in Pathology. Extenuating circumstances supporting the re-
admission of a candidate after four failed attempts to any part of the Part II
examination must be referred to Council.
10. These regulations may be varied from time to time by decision of Council.
11. Membership
(a) Every Member of the College shall be held to have agreed to be bound by
the provisions of the Charter and the Ordinances as amended from time to time
and shall be bound to further to the best of his/her ability the objects and
interests of the College (ordinance 2).
(b) Membership of the College may be followed after a twelve year period by
an offer, to those Members in good standing, of admission to the Fellowship.