General Pathology:

Slide 2:
Liquefactive Necrosis of the Brain
Macroscopic:
Pale, purple chunk with Medium and large Gaps between them.
In the brain
Due to excitotoxicity, hypoxic death of cells within the central nervous system can result
in Liquefactive necrosis. This is a process in which lysosomes turn tissues into pus as a result
of lysosomal release of digestive enzymes. Loss of tissue architecture means that the tissue
can be liquefied.

Pathology
The patient could have suffered a stroke, fungal infection or degradation of tissues via
hydrolytic enzymes-
Loss of blood supply to the portion of cerebrum- leading to an infarction, necrosis with
marked loss of neurons and neuroglia cells.
A space is created and the liquefied space becomes a cyst (pseudocyst). Liquefactive
necrosis of the brain demonstrates many macrophages.
The cyst is formed by proliferating capillaries, inflammatory cells and gliosis.

For unclear reasons, hypoxic death of cells within the central nervous system also results in
Liquefactive Necrosis. (Brain Infarction => Emollition) This is a process in which lysosomes
turn tissues into soup as a result of lysosomal release of digestive enzymes in the face of
bacterial onslaught.

Citrobacter species, Serratia marcescens, Proteus, Pseudomonas, Enterobacter species.

These bacteria have a particular propensity to cause severe cerebral necrosis, usually
haemorrhagic One consequence of this tissue necrosis, in the presence of bacteraemia, is
the occurrence of brain abscess.

The cystic space contains necrotic cell debris and macrophages filled with phagocytized
material. e cyst wall is formed by proliferating capillaries, inflammatory cells, and gliosis
(proliferating glial cells) in the case of brain and proliferating fibroblasts in the case of
abscess cavity
 Slide 3
Fat Necrosis of the pancreas

Macroscopic:
Slide image would appear as: Purple and lobulated at several parts

Cellular injury to the pancreatic Acini leads to release of powerful enzymes which damage
fat by the production of soaps, and these appear grossly as the soft, chalky white areas seen
here on the cut surfaces.
At an autopsy, the peritoneum was studded with yellowish opaque plaques of fat necrosis

Fat necrosis is a special form of cell death occurring at mainly fat-rich anatomic locations in
the body. e examples are: traumatic fat necrosis of the breast, especially in heavy and
pendulous breasts, and mesenteric fat necrosis due to acute pancreatitis.

The necrosed fat cells have cloudy appearance and are surrounded by an inflammatory
reaction. Formation of calcium soaps is identified in the tissue sections as amorphous,
granular and basophilic material

Pathology:
There are some remaining Steatocyte at the left which are not necrotic. The fat necrosis
consists of Steatocyte (adipocytes) that have lost their nuclei and whose cytoplasm has a
granular pink appearance.
Each Steatocyte has a large amount of cytoplasm that is devoted to the storage of lipids.
The nucleus is pushed to one side.
Small sections are to be seen that are fat filled, stained light Pink, dense and dark
inflammatory cells.
The fatty acids then complex with calcium to form soaps.
In the areas of necrosis, and in the areolar tissue surrounding the pancreas, there is usually
a heavy, acute, inflammatory cell response. In some areas, fat necrosis is present. Some
vessels may show eosinophilic necrosis of their walls.

The way calcium is affected by pancreatitis is that insoluble calcium salts are present in the
pancreas, and the free fatty acids avidly chelate the salts, resulting in calcium deposition in
the retro-peritoneum
 Slide 5- Coagulative Necrosis of the Heart

Macroscopic:
Dark pink square-ish chunk, may have gaps at edge.
In the early stage is pale, firm, and slightly swollen and is called infarct. With progression,
the affected area becomes more yellowish, softer, and shrunken.

To note may be that: the walls of the left and right ventricle are slightly thicker than normal.

Pathology:
The Coagulative necrosis is a type of accidental cell death typically caused by ischemia
(Ischemic necrosis) or infarction. These types of Coagulative necrosis occur primarily in the
Kidneys, Heart, Spleen and Adrenal glands.

The hallmark of Coagulative necrosis is the conversion of normal cells into their
‘tombstones’ i.e. outlines of the cells are retained and the cell type can still be recognised
but their cytoplasmic and nuclear details are lost. e necrosed cells are swollen and have
more eosinophilic cytoplasm than the normal. These cells show nuclear changes of pyknosis,
karyorrhexis and karyolysis. However, cell digestion and liquefaction fail to occur (c.f.
liquefaction necrosis). Eventually, the necrosed focus is in infiltrated by inflammatory cells
and the dead cells are phagocytosed leaving granular debris and fragments of cells.

The outlines of cells remain, but cytoplasmic and nuclear details are lost. Necrosed cells are
swollen and eosinophilic. Eventually necrosis is infiltrated by inflammatory cells, dead cells
are phagocytosed, leaving granular debris. Neutrophilic infiltrate extends into interstitium in
1st week. By end of 2nd week, they are replaced by collagen fibres (scar) and less
vascularity.
 Slide 8- Brown induration of the Lung (CVC Lung)

Macroscopic:
Appearance of cells are: pink chunk, alveoli visible to naked eye.
The lungs are heavy.
The lungs appear brown = Brown Induration of Lungs

CVC= Chronic Venous Congestion is the long standing accumulation of deoxygenated blood
& hence it results to damaging the tissue.
They all have a link to the Heart Failure mechanism, depending on whether it is the left or
the right side.
LEFT= Pressure into the Pulmonary Vein = CVC Lungs
RIGHT= Pressure into the venous system= CVC Liver, Spleen or Kidney

Brown induration of the lungs as a result of small haemorrhages occurring in mitral stenosis
and left ventricular failure. Microscopy reveals the presence of ‘heart failure cells’ in the
alveoli which are Hemosiderin-laden alveolar macrophages.

Pathology:
 Rupture of congested vessel results in oedema& haemorrhage
 The alveolar septa appear thickened and fibrotic
 The alveolar septa are widened due to interstitial oedema
 Dilated/ congested capillaries with mild fibrosis
 Alveolar spaces and are broken down resulting in release of haemoglobin
 The alveoli are dilated and contain oedema fluid and RBC’s and macrophages in the
alveoli
 Heart failure cells are alveolar macrophages with hemosiderin pigment

Hemosiderin is most commonly found in macrophages and is especially abundant in

situations following hemorrhage, suggesting that its formation may be related to
phagocytosis of red blood cells and hemoglobin

Hemosiderin often forms after bleeding (hemorrhage). When blood leaves a ruptured blood
vessel, the red blood cell dies, and the hemoglobin of the cell is released into the
extracellular space.
The hemosiderin accumulates in the form of golden brown pigment as more and more RBC’s
are lysed.
Phagocytic cells (of the mononuclear phagocyte system) called macrophages engulf
(phagocytose) the hemoglobin to degrade it, producing hemosiderin and Biliverdin.
Biliverdin results from the breakdown of the heme moiety of hemoglobin in erythrocytes via
enzyme “Heme Oxygenase”. Heme Oxygenase is an enzyme that catalyzes the degradation
of heme to produce Biliverdin, Ferrous iron, and Carbon monoxide.
 Slide 18 +18a (Congo red)- Amyloidosis of glomeruli of the kidney

Macroscopic:
There is a pink chunk with a few small holes

Amyloidosis is the term used for a group of diseases characterized by extracellular

deposition of fibrillar insoluble proteinaceous substance called amyloid.
Based on analysis amyloid is composed of 2 main types of complex proteins:
- Fibril proteins, which comprise about 95% of amyloid
- Non- Fibrillar components, which include P- component predominantly, and other
types that make up 5%

Pathology:
There are several different types of Amyloidosis that are in relation to Renal diseases. They
are divided into:
- Systemic amyloidosis:
1. Primary (AL)
2. Secondary (AA)
3. Hemodialysis- associated (A-Beta-2M)
4. Heredofamilial (ATTR)

- Localized amyloidosis
1. Senile Cardiac (ATTR)
2. Senile Cerebral (A-beta, APrP)
3. Endocrine (Hormone Precursors)
4. Tumor- forming (AL)

- AL=
Also known as Primary amyloidosis. Due to plasma cell dyscrasias with systemic deposition
of amyloid and mild increase in bone marrow plasma cells that are monoclonal. 20% have
myeloma or other lympho-proliferative disorders. Deposits are more likely lambda (75%)
light chains or fragments than kappa type, often from amino-terminal fragment of variable
region of light chain.

- AA=
Also called Secondary amyloidosis. Associated with chronic inflammatory conditions, such as
osteomyelitis, decubitus ulcers, Rheuma and Crohn’s disease. The main amyloid component
is Protein A, that is derived from proteolytic cleavage of serum amyloid A protein, an acute
phase reactant.

Amyloid deposition occurs primarily in glomeruli, can also involve interstitial tissue and
arterioles. Glomeruli - start on basement membrane and extend to narrow and distort the
lumen. Tubules - deposits extend into connective tissue, degenerating tubular epithelial cells
and leaving amyloid casts. Vascular Lumina are also narrowed.
 Slide 21- Icterus of the Liver
Macroscopic:
Appear dark, purple with an elongated gap.
This disease is also known as ‘Jaundice’ where the patient visibly has Yellowish Skin. Hepatic
Jaundice is also referred to as Toxic Icterus. Liver cells damage may lead to jaundice by two
main mechanisms:
- In acute hepatic necrosis and hepatic lipidosis, damaged cells swell to such a degree
that flow of bile in the canaliculi is obstructed. There is intrahepatic obstruction and
conjugated bilirubin accumulates in the blood.
- In chronic liver failure, so much hepatic function is lost that the bilirubin produced
by the constant turnover of RBC cannot be taken up and conjugated, leading to an
accumulation of unconjugated bilirubin in the blood.

Bilirubin pigment has high a affinity for elastic tissue and hence jaundice is particularly
noticeable in tissues rich in elastin content.

Pathology:
Identification for brown pigment among hepatocytes. There are excessive bilirubin pigments
in the hepatocytes and bile sinusoids, exclude nutmeg liver. After the formation of the
bilirubin and into secretion in the blood stream, it becomes bound to albumin, and
facilitates the transport to the liver. It is conjugated with glucuronic acid-

Based on pathophysiology, jaundice may result from one or more of the following
mechanisms:
1. Increased bilirubin production
2. Decreased hepatic uptake
3. Decreased hepatic conjugation
4. Decreased excretion of bilirubin into bile

Infants born with G6PD deficiency may continue to have unconjugated hyperbilirubinaemia
and may even develop kernicterus.
Pyruvate kinase (PK) deficiency is the only significant enzymopathy of the Embden-
Meyerhof glycolytic pathway. The disorder is inherited as an autosomal recessive pattern.
Heterozygote state is entirely asymptomatic, while the homozygous individual presents
during early childhood with anemia, jaundice and splenomegaly.

Intrahepatic cholestasis is characterized by elongated bile plugs in the canaliculi of

hepatocytes at the periphery of the lobule. Extra hepatic cholestasis shows characteristic
bile lakes due to rupture of canaliculi in the hepatocytes in the centrilobular area.
 22- Intradermal Pigmented Nevus

Macroscopic:
There are several pink shaped structures that have edges of dark epithelium.

irrespective of the histologic types, all naevocellular naevi are composed of ‘naevus cells’
which are actually identical to melanocytes but differ from melanocytes in being arranged in
clusters or nests. Naevus cells are cuboidal or oval in shape with homogeneous cytoplasm
and contain large round or oval nucleus. Melanin pigment is abundant in the naevus cells
present in the lower epidermis and upper dermis, but the cells in the mid-dermis and lower
dermis hardly contain any melanin.

Intradermal naevus showing nests of naevus cells which are typically uniform and present in
the dermis. Melanin pigment in naevus cells is coarse and irregular.

Pathology:
- Small nests of melanocytes in upper dermis, often around pilosebaceous units, with
variable pigmentation and cellularity.

- May have multinucleated melanocytes; deeper portion is usually less pigmented and
less cellular and may have Wagner-Meissner corpuscles (representing neural portion
of nevus).

- Mucin in 3% of stroma and within nests of nevus cells.

- Can also be classified as Unna’s pattern (purely adventitial lesion confined to

expanded papillary dermis and often to perifollicular dermis, usually neck, trunk or
limbs) or Miescher’s pattern (melanocytes diffusely infiltrate adventitial and reticular
dermis in wedge shaped pattern, usually on face.

- Slit-like "pseudo-vascular" spaces may be seen through artifact of processing.

Intradermal naevus shows slight or no junctional activity. The lesion is mainly located in the
upper dermis as nests and cords of naevus cells. Multinucleate naevus cells are common.

Pigment found in dermis under squamous epithelium. Also find hair follicles and sebaceous
gland. There are clusters of benign pigment-producing nevus cells in dermis which contain
the coarse granular, brown-black melanin pigment.
 Slide 23- Anthracosis of Lungs

Macroscopic:
The alveoli are clearly visible in a pink chunk. Focal black pigmentation scattered through
the lung fields, most numerous in the upper zones of the upper and lower lobes.
Anthracosis is is defined in Bioline as, “the asymptomatic, milder type of pneumoconiosis as
caused by the accumulation of carbon in the lungs due to repeated exposure to air pollution
or inhalation of smoke or coal dust particle
The most commonly inhaled substances are carbon or coal dust; others are silica or stone
dust, iron or iron oxide, asbestos and various other organic substances.

The pigment particles after inhalation are taken up by alveolar macrophages. Some of the
pigment-laden macro- phages are coughed out via bronchi, while some settle in the
interstitial tissue of the lung and in the respiratory bronchioles and pass into lymphatic’s to
be deposited in the hilar lymph nodes. Anthracosis (i.e. deposition of carbon particles) is
seen in almost every adult lung and generally provokes no reaction of tissue injury.

Pathology:
There is presence of abundant coarse black carbon pigment in the septal walls and around
the bronchiole.
To be seen are, several to many black dots in septal wall, otherwise lung is normal. Coal
macules - aggregates of dust-laden macrophages - present in alveoli and bronchioles.
Increased network of collagen in the coal macules. Some distension, but no indication
towards a destruction.
Coal dust-filled macrophages located interstitially adjacent to bronchioles, pulmonary
arteries, sub-pleurally and within hilar lymph nodes.
The aggregation of black carbon particles, originating from inhaled smoke, contained in
macrophages which are obscured by the pigment, is typical.

Anthracosis, simple coal-workers’ pneumoconiosis and progressive massive fibrosis are

different stages
In the evolution of fully-developed coal-workers’ pneumoconiosis. However, progressive
massive fibrosis develops in a small proportion of cases (2-8%) of simple coal-workers’
pneumoconiosis. A number of predisposing factors have been implicated in this
transformation as follows:

1. Older age of the miners.

2. Severity of coal dust burden engulfed by macrophages.
3. Prolonged exposure (20 to 30 years) to coal dust.
4. Concomitant tuberculosis.
5. Additional role of silica dust.

Activation of alveolar macrophages plays a significant role releasing the following mediators:
Free Radicals, Chemotactic Factors for leukocytes (Leukotrienes, TNF, IL-8 and IL- 6 and
fibrogenic cytokines such as IL-1 and TNF.
 24- Steatosis of the Liver
Macroscopic:
On the slide, the image will appear with dark purple chunks, they may have clear lines
visible.
Steatosis (fatty liver) Steatosis is the build up of fat within the liver. This sometimes triggers
inflammation of the liver. It is also known as 'fatty liver'.
Fatty change represents the intra-cytoplasmic accumulation of triglycerides (neutral fats). At
the beginning, the hepatocytes present small fat vacuoles (liposomes) around the nucleus
(microvesicular fatty change). In this stage, liver cells are filled with multiple fat droplets that
do not displace the centrally located nucleus. In the late stages, the size of the vacuoles
increases, pushing the nucleus to the periphery of the cell, giving characteristic signet ring
appearance (macrovesicular fatty change).

Pathology:
In fatty liver, intracellular accumulation of triglycerides occurs due to defect at one or more
of the following 6 steps in the normal fat metabolism
1. Increased entry of free fatty acids into the liver.
2. Increased synthesis of fatty acids by the liver.
3. Decreased conversion of fatty acids into ketone bodies
1. resulting in increased esterification of fatty acids to triglycerides.
4. Increased alpha-glycerophosphate causing increased esterification of fatty acids to
triglycerides.
5. Decreased synthesis of ‘lipid acceptor protein’ resulting in decreased formation of
lipoprotein from triglycerides.
6. Block in the excretion of lipoprotein from the liver into plasma.

In most cases of fatty liver, one of the above mechanisms is operating. But liver cell injury
from chronic alcoholism is multifactorial as follows:
 Increased lipolysis
 Increased free fatty acid synthesis
 Decreased triglyceride utilization
 Decreased fatty acid oxidation to ketone bodies
 Block in lipoprotein excretion

- The vacuoles are initially small and are present around the nucleus (microvesicular).

- With progression of the process, the vacuoles become larger pushing the nucleus to
the periphery of the cells (macrovesicular).

- At times, the hepatocytes laden with large lipid vacuoles may rupture and lipid
vacuoles coalesce to form fatty cysts. iv) Infrequently, lipogranulomas may appear as
a reaction to extravagated fat and consist of collections of lymphocytes,
macrophages, and some multinucleated giant cells.

- Fat can be demonstrated in fresh un fixed tissue by frozen section by fat stains e.g.
Sudan dyes (Sudan III, IV, Sudan black) and oil red O. Alternatively, osmic acid which
is a fixative as well as a stain can be used to demonstrate fat in the tissue.
 47- Hypertrophy of the Heart

Macroscopic:
Bright- purple pink in appearance, containing a lot of square like chunks.
Hypertrophy is the increased size of the muscle cells, and for the heart, it is the cardiac
muscle cells called Cardiocytes. For humans to maintain the normal cardiac output, things
like compensatory mechanisms in the form of cardiac hypertrophy, cardiac dilation need to
be in place.
Cardiac hypertrophy is the abnormal enlargement, or thickening, of the heart muscle,
resulting from increases in cardiomyocyte size and changes in other heart muscle
components, such as extracellular matrix.

Increased activity of the heart (tachycardia) due to the stimulation of neurohumoral system
(norepinephrine and atrial natriuretic peptide activation of RAAS system are in place.
The weight of the heart is increased above normal, often over 500g. But excessive epicardial
fat is not indicative of true hypertrophy

Pathology:
Hypertrophy of the heart is de ned as an increase in size and weight of the myocardium. It
generally results from increased pressure load while increased volume load (e.g. valvular
incompetence) results in hypertrophy with dilatation of the affected chamber due to
regurgitation of the blood through incompetent valve. e atria may also undergo
compensatory changes due to increased workload.
The basic factors that stimulate the hypertrophy of the myocardial fibers are not known. It
appears that stretching of myocardial fibers in response to stress induces the cells to
increase in length. The elongated fibers receive better nutrition and thus increase in size.
Other factors which may stimulate increase in size of myocardial fibers are anoxia (e.g. in
coronary atherosclerosis) and influence of certain hormones (e.g. catecholamine, pituitary
growth hormone).

There is increase in size of individual muscle fibers. There may be multiple minute foci of
degenerative changes and necrosis in the hypertrophied myocardium. These changes
appear to arise as a result of relative hypoxia of the hypertrophied muscle as the blood
supply is inadequate to meet the demands of the increased fiber size. Ventricular
hypertrophy renders the inner part of the myocardium more liable to ischemia.

Electron microscopy reveals increase in the number of myofilaments comprising myofibrils,

mitochondrial changes and multiple intercalated discs which are active sites for the
formation of new sarcomeres. Besides, the nucleic acid content determinations have shown
increase in total RNA and increased ratio of RNA to DNA content of the hypertrophied
myocardial fibers.
 15 - Hyaline changes in corpus Albicans of ovary

Macroscopic:
Dark in appearance, thick periphery. Clearly visible is a large light center.
Corpus Albicans is a scar on the surface of the ovary which is remnant of ovulation.
If someone has been diagnosed with Corpus Luteum Cyst (CLC), even during pregnancy, it is
reassuring to know that they are rarely harmful to the fetus. CLC may disappear in a few
weeks or can take up to three menstrual cycles to vanish altogether. Before degeneration
into scar tissue, the Corpus Albicans was once a thriving endocrine organ (Corpus Luteum),
which functioned to maintain the fetus.

The difference between is that, whilst Corpus Luteum is yellow, Corpus Albicans is white.
Corpus Albicans also remains on the ovary for a few months until it eventually breaks down.
The Corpus Albicans does not appear to serve a specific purpose.

Pathology:
Luteal cysts are commonly lined by luteinized granulose cells. Lining by predominantly
luteinized theca cells may also be seen in cystic ovaries in association with hydatidiform
mole and choriocarcinoma, and rarely, in normal pregnancy. Corpus Albicans cyst is a
variant of corpus luteum cyst in which there is hyalinization in the wall and distension of the
cavity with fluid.
 48- Hyperplasia of Endometrial Mucosa

Macroscopic:
There are several structures of them to be seen, and they appear either round or long in
purple color.

Endometrial hyperplasia is a condition of the female reproductive system. The lining of the
uterus (endometrium) becomes unusually thick because of having too many cells
(hyperplasia). It's not cancer, but in certain women, it raises the risk of developing
endometrial cancer, a type of uterine cancer. In many cases it can be treated with
progestin. Progestin prevent pregnancy by inhibiting ovulation and reducing the amount
and stretchiness of cervical mucus, making it unfriendly to sperm that are trying to enter the
uterus.

Pathology:
- Proliferation of endometrial glands with a resulting increase in gland to stroma ratio
- Hyperplasia without Atypia
- Atypical hyperplasia/ endometrioid intraepithelial neoplasia (AH/ EIN)
- There is a risk of both types of progressions and simultaneous endometrial
endometrioid adenocarcinoma

The following classification of endometrial hyperplasia is widely employed by most

gynecologic pathologists:
1. Simple hyperplasia without atypia (Cystic glandular hyperplasia).
2. Complex hyperplasia without atypia (Complex non- atypical hyperplasia).
3. Complex hyperplasia with atypia (Complex atypical hyperplasia).

Endometrial hyperplasia is characterized by exaggerated proliferation of glandular and

stromal tissues. It is commonly associated with prolonged, profuse and irregular uterine
bleeding in a menopausal or postmenopausal woman.
It may be emphasised here that the syndrome of DUB (Dysfunctional Uterine Bleeding)
with which endometrial hyperplasia is commonly associated is a clinical entity, while
hyperplasia is a pathologic term.
Prolonged administration of estrogen to laboratory animals can produce endometrial
hyperplasia

Causes:
- Chronic unopposed estrogen Excess
- Obesity
- Diabetes
- Hypertension
- Nulliparous state
- Heredity
 77- Fibrinoid necrosis in peptic ulcer of stomach
Macroscopic:
In appearance, it is amorphous shape with slightly darkened mucosa. Generally, ulcers are
defined as a punch-out holes of the alimentary tract mucosa, that can extend through the
m. mucosae into the deeper layers in comparison to erosions which are confined up to m.
mucosae. Pus are usually solitary lesions, less than 2 cm in diameter, round to oval, sharply
punched-out defects with relatively straight walls. The mucosal margin may overhang the
base slightly, but heaping up of these margins is rare in the benign ulcers.
Mucosal injury due to Helicobacter pylori infection, NSAID use, Zollinger-Ellison syndrome
(multiple peptic ulcerations in stomach, duodenum and jejunum due to excess gastrin
secretion by a tumor), ischemia, bile / pancreatic juice reflux

Pathology:
There is no principal difference between gastric and duodenal ulcers.
Four main layers are present in chronic PUs:
1. Superficial Exudation
2. Fibrinoid Necrosis
Intensively eosinophilic and homogenous. It appears only in cases of exacerbation and is the
most important later that gives the ulcer ability to grow in depth
3. Granulation Tissue
4. Mature Fibrous Tissue (scar)

Complications of Peptic Ulcer: Hemorrhage, Perforation, Penetration, Pyloric Stenosis,

Malignant Transformation

 Generally associated with H. pylori gastritis, may see reactive gastropathy if history
of NSAID use
 Ulcer may be trans mural or limited to mucosa and submucosa
 Muscle wall replaced by fibrous tissue
 Serosal fibrosis
 Hyperplasia of adjacent lymph nodes
 Proximal mucosa may be overhanging
 Distal mucosa may have ladder-like configuration
 Accompanied by active and chronic inflammation, unless NSAID related

 Active ulcers have 4 prototypical zones:

o Surface neutrophils, bacteria, necrotic debris and possibly Candida
o Fibrinoid necrosis at base and margins
o Granulation tissue with chronic inflammatory cells
o Fibrous or collagenous scars in muscularis propria with thickened blood
vessels showing endarteritis obliterans

 Healing ulcers:
o Have regenerating epithelium over the surface
o May have intestinal metaplasia, marked reactive changes
 o Rarely exhibits hyalinization (severe thickening, usually of submucosa,

4- Ischemic Renal Infarction

Macroscopic:
Ischemic Renal infarction results from interruption of the normal blood supply to part of, or
to the whole kidney. Blood vessels shrink and undergo apoptosis which results in poor
blood flow in the kidneys. The main imaging differential diagnosis includes pyelonephritis
and renal tumors.
Majority of them are caused by thromboembolism, most commonly originating from the
heart such as in mural thrombi in the left atrium, myocardial infarction, vegetative
endocarditis and from aortic aneurysm. Less commonly, renal infarcts may occur due to
advanced renal artery atherosclerosis, arteritis and sickle cell anemia.

Biomarkers are a way for diagnosing Renal Infarction:

 Clusterin, Cystatin C, EGF, KIM-1, IL-6, Endothelin, NGAL, IMA, TIM-2 and IGFBP7

Pathology;
Renal infarct. Renal tubules and glomeruli show typical Coagulative necrosis i.e. intact
outlines of necrosed cells. There is acute in inflammatory infiltrate at the periphery of the
infarct.
Microscopically, the affected area shows characteristic Coagulative necrosis of renal
parenchyma i.e. there are ghosts of renal tubules and glomeruli without intact nuclei and
cytoplasmic content. e margin of the infarct shows inflammatory reaction initially acute but
later macrophages and fibrous tissue predominate
The subsequent changes are:
- Red Cells become sludge and lose hemoglobin
- Tubular epithelial cell nuclei condense
- Neutrophils accumulate
- Tubular epithelial and meningeal cell nuclei lyse but basement membranes remain
intact
- Fibrous tissue replaces infarcted area.

4 histological zones:
- Necrotic Zone - floor of ulcer, fibrinous exudate with necrotic debris and few
leukocytes.
- Superficial Exudative Zone - under necrotic zone, Coagulative necrosis with
eosinophilic, smudgy appearance, nuclear debris.
- Granulation Tissue Zone - nonspecific inflammatory infiltrate, proliferating
capillaries.
- Zone of Cicatrisation - dense fibro collagenous scar tissue under granulation tissue.

Clinical Features:
Unless large most are asymptomatic. If large there is a sudden onset of loin pain followed by
hematuria and proteinuria. If both renal arteries are occluded there is acute renal failure.
 7 - Chronic congestion of the liver
Macroscopic:
In appearance purple quadrilateral, somewhat wavy.
It results from obstruction of flow to venous blood. Usually die to thrombosis or external
pressure occlusion the vein from outside- it could be a tumor.
The effects depend on the speed of onset of the obstruction and the presence of collateral
draining veins. If the onset is acute then the presence of collateral draining veins. If the
onset is acute then the presence of collateral veins is vital to avoid local edema and
hemorrhage. In the brain collateral vessels are absent and venous occlusion not
uncommonly results in hemorrhages. When venous obstruction is chronic the collateral
system, if present will become distended and may themselves end up rupturing (e.g.
bleeding esophageal veins in portal hypertension)

Pathology:
Characteristic histological changes reflective of congestive hepatopathy, including sinusoidal
dilatation, congestion, hepatic cord atrophy, and extravasation of red blood cells into the
hepatocyte
Histologically, passive congestion of the liver is reflected by sinusoidal dilation, congestion,
and hepatocyte atrophy most prominent in zone 3. Elevated hepatic venous pressures may
precipitate extravasation of red blood cells into the ‘Space of Disse’.
If the passive congestion is pronounced, then there can be centrilobular necrosis, because
the oxygenation in zone 3 of the hepatic lobule is not great. The light brown pigment seen
here in the necrotic hepatocytes around the central vein is lipochrome.

The extent of necrosis, inflammation, and dilation has been correlated with right atrial and
hepatic pressures, although ischemia may lead to findings of necrosis as well.

Greatest change in centrilobular zone, central veins and sinusoids are distended and filled
with blood. Hepatocytes degenerate, eventually there is centrilobular hemorrhagic necrosis.
Peripheral zone shows fatty change. Prolonged cases regenerate and result in cardiac
cirrhosis

If chronic hepatic passive congestion continues for a long time, a condition called "cardiac
cirrhosis" may develop in which there is fibrosis bridging between central zonal regions, as
shown below, so that the portal tracts appear to be in the center of the reorganized lobule.
This process is best termed "cardiac sclerosis" because, unlike a true cirrhosis, there is
minimal nodular regeneration.
 9 - Pulmonary edema
Macroscopic:
On first appearance, it looks - pale purple chunk with small and large bubble-like gaps.
Pulmonary edema is often caused by congestive heart failure. When the heart is not able to
pump efficiently, blood can back up into the veins that take blood through the lungs. As the
pressure in these blood vessels increases, fluid is pushed into the air spaces (alveoli) in the
lungs.
Acute pulmonary edema is the most important form of local edema as it causes serious
functional impairment. However, it has special features and differs from edema elsewhere
in that the fluid accumulation is not only in the tissue space but also in the pulmonary
alveoli.
There are two types of Pulmonary Edema:
Cardiogenic and Non- Cardiogenic-
The first is from an elevated pulmonary capillary pressure from left-sided heart failure; The
second occurs from (increased permeability) pulmonary edema from injury to the
endothelial and (usually) epithelial barriers.

Pathology:
At a normal lung microscopically. The alveolar walls are thin and delicate. The alveoli are
well-aerated and contain only an occasional pulmonary macrophage (type II
pneumonocyte).
pale purple net with some breakage, some purple filling in (eosinophilic matter), and
occasional red fillings. The alveolar capillaries are congested, alveolar spaces/interstitium
contain eosinophilic, granular proteinaceous edema with some RBCs and inflammatory cells.
Prolonged cases prone to infection - hypostatic pneumonia.

 Injury causes leakage of fluids and proteins into interstitial space, eventually into
alveoli
 When diffuse, contributes to acute respiratory distress syndrome

At high magnification, the alveoli in this lung are filled with a smooth to slightly floccular
pink material characteristic for pulmonary edema. Note also that the capillaries in the
alveolar walls are congested with many red blood cells. Congestion and edema of the lungs
is common in patients with heart failure and in areas of inflammation of the lung.
 10 Micro-hemorrhages of the brain

Macroscopic:
In appearance it looks pink oblong, small and red peppering.
Cerebral microbleeds (MBs) are small chronic brain hemorrhages which are likely caused by
structural abnormalities of the small vessels of the brain.

Pathology:
In the grossly and microscopically image, the hemorrhage consists of dark mass of clotted
blood replacing brain parenchyma.
The central core of clotted blood, border shows anoxic neuronal and glial changes + edema.
Hyaline arteriosclerosis in vascular wall of a small ruptured vessel.

 Central core of clotted blood surrounded by a rim of brain tissue showing anoxic
neuronal and glial changes and edema.
 Hyaline arteriolosclerosis (pink amorphous matter) in the vascular wall of a ruptured
small vessel (arrow)
 Probably caused by hypertension

Micro hemorrhages around vascular structures of the brain. Micro hemorrhages occur more
frequently in the deep structures (thalamus, brain stem, basal ganglia, cerebellum)
compared with the lobar hemispheres.
In contrast with the other studies, lesions in the cerebral hemispheres were more common
than lesions in the basal ganglia or deep structures.
 11 Mixed Thrombus
Macroscopic:
It is a combination of white and red (layered thrombus) – consists of attached to the vessel
wall head (white thrombus), body (mixed thrombus) and tail (red thrombus) – usually in
veins and aneurysms
 Mixed (laminated) thrombi consist of alternative white and red layers.
 Light-staining aggregated platelets admixed with fibrin meshwork’s
 Dark-staining layer of red cells (erythrocytes) and leucocytes

Pathology:
Thick pale purple walls, red inside, alternating pale/red (Lines of Zahn) – Laminated
thrombus with white and red layers. Lines of Zahn. Light-staining platelets mixed with fibrin
meshwork. Dark staining layer of erythrocytes and leukocytes.

When there is a thrombus in an artery, the thrombus is adherent to the arterial wall and is
seen occluding most of the lumen. It shows Lines of Zahn composed of granular-looking
platelets and fibrin meshwork with entangled red cells and leucocytes.

Lines of Zahn are a characteristic of thrombi that appear particularly when formed in
the heart or aorta. These lines represent layers of red cells, platelets, and fibrin which are
laid down in the vessel as the thrombus forms.

They have visible and microscopic alternating layers (laminations) of platelets mixed
with fibrin which appear lighter, and darker layers of red blood cells. Their presence implies
thrombosis at a site of rapid blood flow that happened before death. In veins or smaller
arteries, where flow is not as constant, they are less apparent.

Lines of Zahn are only seen when thrombi are formed in flowing blood as it is a
distinguishing marker between ante-mortem and postmortem thrombi formation.
 12 Recanalization thrombus
Macroscopic:
It appears to look like a ball that contains an outer capsule.
Recanalization is a complex process that initially involves adhesion of the thrombus to the
vein wall and an inflammatory response in the vessel wall, leading to organization and
subsequent contraction of the thrombus, and to neovascularization and spontaneous lysis
of areas inside the thrombus.

 Fibrin and cell debris of thrombus are substituted by formation of fibro vascular
granulation tissue
 Subsequently thrombus becomes dense and less vascular, covered over by
endothelial cells.
 Secondary endothelial clefts may appear
 It contains a pale area with heavy peppering
 There is a thrombus which is dense and less vascular, covered with endothelial cells.
Lines of Zahn.
 Composed of small head attached to the vascular wall with structure of white
agglutinative thrombus; usually long floating in the vascular wall with red.
 Coagulative thrombus and middle portion called body with lamellate structure.
 Light stain - aggregates of platelets mixed with fibrin meshwork
 Dark stain - erythrocytes and leukocytes.

Organization and recanalization involves the ingrowth of smooth muscle cells, fibroblasts
and endothelium into the fibrin- rich thrombus. If recanalization proceeds, it provides
capillary- sized channels through the thrombus for continuity of blood flow through the
entire thrombus but may not restore sufficient blood flow for the metabolic needs of the
downstream tissue.
 13 Hemorrhagic Pulmonary Infarction
Macroscopic:
It appears to look like a purple chunk with large darker purple chunk inside.
Obstruction of relatively small sized pulmonary arterial branches may result in pulmonary
infarction. The clinical features include chest pain due to fibrinous pleuritic, hemoptysis and
dyspnea due to reduced functioning pulmonary parenchyma.

These blood clots most commonly come from the deep veins of your legs, a condition
known as Deep Vein Thrombosis (DVT). In many cases, multiple clots are involved in
pulmonary embolism. The portions of lung served by each blocked artery are robbed of
blood and may die. This is known as Pulmonary Infarction.

Whatever the cause, very large pulmonary infarctions are relatively uncommon,
because lung tissue has three potential sources for oxygen: the pulmonary artery, the
bronchial artery (arteries that supply the bronchial tree), and the alveoli themselves.

Pathology:
 Coagulative necrosis of the alveolar walls
 Intense alveolar capillary congestion
 Infiltration by neutrophils
 At a later stage (hemosiderin; phagocytes; granulation tissue)
 Necrosis of alveolar walls - loss of nuclei.
 Alveolar hemorrhage.

Pulmonary infarct (hemorrhagic infarct of the lung) is an area of ischemic necrosis

produced by venous thrombosis on a background of passive congestion of lung. In infarct
area, alveolar walls, vascular walls and bronchioles are necrotic. They appear eosinophilic
(pink), homogenous, lacking the nuclei, but keep their shapes - "structured necrosis".
Alveolar lumens from infarcted area are invaded by red blood cells - hemorrhagic
infarct (red).
 27- Focal Serous Pneumonia
Macroscopic:
In appearance it is purple quadrilateral, bubble-like holes.
Depending on which lung lobe is affected, the pneumonia is referred to as upper, middle or
lower lobe pneumonia. If there are several multi-lobe focal inflammations in the lungs, the
term focal pneumonia is used. Some people use the term bronchopneumonia if
the focal inflammations started in inflamed airways (bronchi).
They are firm, friable, and grey in appearance- yellow foci can be up to 3 cm. Partially
confluent and slightly raised above the surface of the lung.

Depending on the extent of lesions, pneumonia can be :

 lobular (a lobe segment is affected)
 lobar (an entire lobe is affected)
 bronchopneumonia (affects bronchioles and adjacent alveoli)
 interstitial (inflammation affects the interstitial tissue, mainly the alveolar walls)

Pathologically:
The alveoli are filled with an exudate, that contains polymorphonuclear leukocytes,
desquamated epithelial cells, fibrin and pink stained serous fluid. The Alveolar walls are
hyperemic. The bronchi contain a purulent surface and desquamated ciliated epithelia.
The filled-in alveoli have many dark PMNs + pink-stained serous fluid. The bronchioles and
adjacent alveoli filled with exudate (mainly neutrophils). Thickened alveolar septa due to
congested capillaries. Less involved alveoli contain edema fluid.

Every alveolus is filled with granular pink exudate in this case pf Pneumocystis carinii
(jirovecii) pneumonia (PCP). This reduces oxygen exchange and leads to the dyspnea and
cough characteristic for PCP.

 In the first stage, congestion (day 1 - 2), the affected lung parenchyma is partially
consolidated, and red-purple, partially aerated. Microscopy: alveolar lumen contains
serous exudate, bacteria and rare leucocytes.
 In the second stage, red hepatization (day 3 - 4), the pulmonary lobe appears
consolidate, red-brown, dry, firm, with a liver-like consistency (Hepar, gr. - liver). The
cut surface is dry, rough. Microscopy: the characteristic aspect of this stage is
determined by the accumulation in the alveolar spaces of an exudate rich in fibrin
(mainly), with bacteria, leucocytes, and erythrocytes. Alveolar walls are thickened
due to capillary congestion and edema.
 The third stage, gray hepatization (day 5 - 7), the affected lobe has a liver-like
consistency, with uniform gray color (Figure 1). On the cut surface, a grayish
purulent liquid drains. It is because alveolar lumens are filled with leukocytic
(suppurative) exudate (neutrophils and macrophages, in order to remove the fibrin)
(leukos, gr. - white). Capillary congestion and edema are still present; therefore,
alveolar walls are thick. (Figures 2 and 3)
 The resolution stage begins on day 8 and continues for 3 weeks (uncomplicated
cases), while the exudate within the alveolar spaces will be drained through
 lymphatic’s and airways ("productive" cough) with gradually aeration of the affected
segment

28- Lobar Fibrinous Pneumonia

Macroscopic:
The walls have a zig-zag appearance, and the level of pale is seen across the levels:
Lobar pneumonia, also known as non-segmental pneumonia or focal non-
segmental pneumonia 7, is a radiological pattern associated with homogeneous and fibrino
suppurative consolidation of one or more lobes of a lung in response to
bacterial pneumonia.

Pathology:
The disease has Lobar pneumonia usually has an acute progression. Classically, the disease
has four stages:
 Congestion in the first 24 hours: This stage is characterized histologically by vascular
engorgement, intra-alveolar fluid, small numbers of neutrophils, often
numerous bacteria. Grossly, the lung is heavy and hyperemic.
 Red hepatization or consolidation: Vascular congestion persists, with extravasation
of red cells into alveolar spaces, along with increased numbers
of neutrophils and fibrin. The filling of airspaces by the exudate leads to a gross
appearance of solidification, or consolidation, of the alveolar parenchyma. This
appearance has been likened to that of the liver, hence the term "hepatization".
 Grey hepatization: Red cells disintegrate, with persistence of the neutrophils and
fibrin. The alveoli still appear consolidated, but grossly the color is paler and the cut
surface is drier. This is when death typically occurs in severe cases.
 Resolution (complete recovery): The exudate is digested by enzymatic activity, and
cleared by macrophages or by cough mechanism. Enzymes produced by neutrophils
will liquefy exudates, and this will either be coughed up in sputum or be drained via
lymph.

Lung parenchyma is the substance of the lung outside of the circulatory system that is
involved with gas exchange and includes the pulmonary alveoli and respiratory bronchioles,
although sometimes it includes alveoli.

The most common organisms which lead to lobar pneumonia are Streptococcus
pneumoniae, also called pneumococcus, Haemophillus influenza and Moraxella catarrhalis.
Mycobacterium tuberculosis, the tubercle bacillus, may also cause lobar pneumonia if
pulmonary tuberculosis is not treated promptly. Other organisms that lead to lobar
pneumonia are Legionella pneumophila and Klebsiella pneumoniae.
 29- Fibrinous Pericarditis
Macroscopic:
There are thin strands of fibrinous exudate that extend from the epicardial surface to the
pericardial sac.
This is typical for a fibrinous pericarditis.
The Pericarditis is the inflammation of the pericardial layers and is generally secondary to
diseases in the heart or caused by systemic diseases. Primary or idiopathic pericarditis is
quite rare. Based on the morphologic appearance, pericarditis is classified into acute and
chronic types, each of which may have several etiologies. Acute and chronic pericarditis has
further subtypes based on the character of the exudate

Pathology:
The response of the pericardium by fibrinous exudate is the most common type of
pericarditis. Quite often, there is admixture of fibrinous exudate with serous fluid. e various
causes of this type of pericarditis are as follows:
. i) Uremia
. ii) Myocardial infarction
. iii) Rheumatic fever
. iv) Trauma such as in cardiac surgery
. v) Acute bacterial infections.
The amount of fluid accumulation is variable. e cardiac
surface is characteristically covered by dry or moist, shaggy, fibrinous exudate which gives
‘bread and butter’ appearance. Clinically, these cases manifest by friction rub. In less
extensive cases of fibrinous or serous fibrinous pericarditis, there is complete resorption of
the exudate. In cases with advanced fibrinous exudate, pericarditis heals by organisation
and develops fibrous adhesions resulting in adhesive pericarditis.
 31- Purulent Nephritis
Macroscopic:
Purple quadrilateral, some geometric gaps.
This Pyelonephritis is inflammation of the kidney, typically due to a bacterial infection.
Symptoms most often include fever and flank tenderness. Other symptoms may include
nausea, burning with urination, and frequent urination. Complications may include pus
around the kidney, sepsis, or kidney failure.

 Focal abscesses or wedge shaped areas of suppuration.

 In emphysematous pyelonephritis, the kidney is smaller than usual with hemorrhage,
necrosis and crepitus on palpation; gas filled cysts are present in renal cortex and
renal papillae; renal capsule is detached and filled with sub capsular blood / blood
clots.

Pathology:
It Is characterized by production of large amount of pus or purulent exudate, consisting of
neutrophils, necrotic cells and edema fluid.
Extensive inflammation causing tubule destruction, glomeruli generally spared. Numerous
PMNs fill renal tubules across center and right of picture. Casts may form within tubule.
Vessels may exhibit hyaline arteriosclerosis.

 Papillary necrosis: more common with diabetes and urinary tract obstruction; usually
bilateral; variable number of pyramids involved; Coagulative necrosis of tubules;
usually limited white blood cell response
 Perinephric abscess: extension of pus through renal capsule into adjacent tissue
 Pyonephrosis: total or almost complete obstruction prevents drainage of pus
 Emphysematous pyelonephritis: gas in renal papillae, renal cortex, pararenal space
and inferior vena cava; it is a medical emergency

Most cases of acute pyelonephritis follow infection of the lower urinary tract. e most
common pathogenic organism in urinary tract infection (UTI) is Escherichia coli (in 90% of
cases), followed in decreasing frequency, by Enterobacter, Klebsiella, Pseudomonas and
Proteus.
The bacteria gain entry into the urinary tract, and then into the kidney by one of the two
routes: ascending infection and Haematogenous infection.
 32- Granulation tissue
Macroscopic:
Several small purple worms.
Proliferating blood vessels (small blood vessels without pericytes, endothelial cells of the
blood capillaries are with plump nuclei with condensed chromatin.

Do not make the following mistake – interpret tumor stroma as granulation tissue They are
identical in morphology. Be sure there is no tumor on your slide. Observe the whole slide
first.
Main bulk of secondary healing is by granulations. Granulation tissue is formed by
proliferation of fibroblasts and neovascularization from the adjoining viable elements. e
newly-formed granulation tissue is deep red, granular and very fragile. With time, the scar
on maturation becomes pale and white due to increase in collagen and decrease in
vascularity. Specialized structures of the skin like hair follicles and sweat glands are not
replaced unless their viable residues remain which may regenerate.

Healing (repair) by connective tissue has the granulation tissue as a hallmark. It consists of
new capillaries (result of proliferation of endothelial cells - angiogenesis or
neovascularization) in an edematous atmosphere of fibroblasts (spindle shaped),
myofibroblasts, mononuclear inflammatory cells, macrophages, neutrophils, cellular debris.
 33 “Foreign Body”- Granuloma
Macroscopic:
A foreign body granuloma forms when the host immune system is unable to digest
the foreign body, resulting in the accumulation of macrophages and histiocytes. As
macrophages surround and isolate the foreign body, some of them will fuse to form
multinucleated giant cells.

Foreign body granuloma has a non-immune mechanism. Foreign body granuloma is a

reaction to exogenous materials (talc, suture material, parasites, oil droplets, wood, metals,
silica, silicon) or endogenous (hail shafts, keratin, cholesterol, urates/goutous tophi), which
are immunologically inert.

Pathology:
From Microscopically, foreign body granuloma to suture material (nylon, silk) contains
multinucleated giant cells, with haphazardly arranged nuclei. These giant cells are fused
macrophages. The foreign body is birefringent, and sometimes may be visible by polarized
light in the middle of the granuloma or inside the giant cells. These granulomas are non-
necrotic.

I:
Foreign-body granulomas may develop around exogenous foreign bodies that are usually
introduced into the eye at the time of a penetrating ocular wound, or they may develop
around endogenous products such as cholesterol or blood in the vitreous.
An unusual cause of inflammatory granuloma of the conjunctiva is the synthetic fiber found
in teddy bears, called a “teddy-bear” granuloma.
II:
Rarely, blood in the vitreous incites a marked foreign-body inflammatory response. When
this occurs, the intravitreal hemorrhage almost is invariably traumatic in origin rather than
spontaneous.
III:
Histologically, a zonal type of granulomatous inflammatory reaction surrounds the foreign
body.
 34+35 Myocardial Scar HE+ VGN
Macroscopic:
Myocardial scar tissue consists mainly of fibrillar collagen, arranged mainly but not only in
circumferential, concentric layers but in a variety of fiber orientations, collagen cross-linking
but also surviving cardiomyocyte, which are widely separated by the fibrillar collagen fibers
and cells termed.
Myocardial scarring is the accumulation of fibrosis tissue resulting after some form of
trauma to the cardiac tissue. Fibrosis is the formation of excess tissue in replacement of
necrotic or extensively damaged tissue. Fibrosis in the heart is often hard to detect because
fibromas are often formed.

Pathology:
During first 2 weeks there is progressive Coagulative necrosis, inflammation, and collagen
formation. By third week (pic) necrosed muscle fibers are removed and replaced by new
collagen fibers. Pigmented macrophages, lymphocytes, and plasma cells are prominent.

Most often in left ventricle. Atherosclerosis of coronary arteries plays a role in 90% of cases.
Myocardial Ischemia due to diminished blood flow and/or increased demand. Platelet
aggregation and plaque rupture can cause coronary thrombosis. Other 10% caused by
vasospasm, arteritis, embolism, and trauma.

VVG is used to identify the presence or absence of elastic fibers in tissues. For instance,
pathologists may use it to demonstrate loss of elastic tissue in the lung in patients with
emphysema, and thinning and loss of elastic fibers in blood vessels of patients with
arteriosclerosis.
 38- Tuberculous Granuloma
Macroscopic:
Tuberculosis is the formation of an organized structure called granuloma. It consists mainly
in the recruitment at the infectious stage of macrophages, highly differentiated cells such as
multinucleated giant cells, epithelioid cells and Foamy cells, all these cells being surrounded
by a rim of lymphocytes.
The granulomas of tuberculosis tend to contain necrosis ("caseating tubercules"), but non-
necrotizing granulomas may also be present. Multinucleated giant cells with nuclei arranged
like a horseshoe (Langhans giant cell) and foreign body giant cells are often present, but are
not specific for tuberculosis. A definitive diagnosis of tuberculosis requires identification of
the causative organism by microbiologic cultures.

The tubercle contains a central area of amorphous necrotic debris (caseous necrosis) which
is surrounded by a zone of activated macrophages. Some of the macrophages that are
activated fuse in order to form large macrophage polykaryons- which contain many nuclei
arranged around the periphery and a large central cytoplasmic mass (Langhans Cells).

Pathology:
The etiology of granulomatous inflammation is broad and expands many etiologies including
infectious, autoimmune, toxic, allergic, and neoplastic entities.

In the macrophage layer can be seen a typical Langhans’ giant cell. Outside the layer of
activated macrophages is a ring of lymphocytes. An early stages of the disease the
fibroblasts are not in huge numbers and insignificant. The nuclei in some cases can be seen
arranged peripherally and the amorphous nature of the caseous necrosis/

Due to the fact the Mycobacterium is so resistant to destruction, the infections/ or those
infected tend to be chronic or persistent, making it difficult to eradicate the bacteria by a
natural immune or humeral defense mechanism.
 40- Actinomycosis
Macroscopic:
Actinomyces are common commensals in the mouth, particularly in the crypts of the tonsils
and around the necks of the teeth. It can happen that the organism becomes Pathogenic-
with spreads in to the soft tissues of the neck to produce a lumpy swelling, which can
discharge onto the surface through numerous sinuses. The discharge is a thin, watery fluid,
within which can be seen small yellow fragments (sulfur granules).

Sulfur granules are aggregates of microorganisms admixed with inflammatory debris

characteristically but not exclusively found in Actinomycosis. Granules vary in color (white to
yellow) and size (0.25 to 2 mm in diameter). Sulfur granules may be absent or poorly
organized in an occasional case of Actinomycosis. Caution should be exercised in
interpretation of granules from sputum, since they may be produced by saprophytic
organisms in the tonsillar crypts.

The colony of Actinomyces israelii in a jaw abscess is made up of colonies that are
surrounded by neutrophils. These colonies from the sulfur granules are extruded when the
abscess discharges.

It is caused by Actinomyces israelii in humans and Actinomyces bovis in animals.

 Firm, swollen region on the skin with multiple draining abscesses and fistula tracts
 Pus draining yellow sulphur granules

Pathology:
 Characteristic clumps of basophilic filamentous bacteria in a vaguely rosette-like
configuration surrounded by acute inflammatory cells are characteristic
 Acute inflammation is accompanied by dense fibrosis described as "woody"
 Eosinophilic clubs may be found at periphery (Splendore-Hoeppli phenomena)
 Granulomatous inflammation may be present
 41- Sarcoidosis of Lymph Nodes
Macroscopic:
Sarcoidosis may affect regional notes or be part of a generalized lymphadenopathy.
Sarcoidosis is a multisystem disease that involves the lungs in 90% of cases. It has a
predilection for the upper lobes of the lung and bronchovascular bundles more than other
lung compartments, although it can affect any area Granulomatous inflammation in lymph
nodes can present with generalized or localized lymphadenopathy; lymph node biopsy is
performed to establish the cause.
The main function of lymph nodes is to allow the interaction of antigen, antigen-presenting
cells and lymphoid cells.
The most common reason for patients to develop enlargement of lymph nodes is as a
reaction to antigenic stimuli (reactive lymphadenopathy).
There are 5 main pattern of reactive response, but in most diseases a mixed pattern
of responses is seen:
- Follicular hyperplasia
- Paracortical hyperplasia
- Sinus Hyperplasia
- Granulomatous inflammation
- Acute Lymphadenitis

The main causes include:

Sarcoidosis, TB, Cat- Scratch Disease, Crohn’s Disease and Toxoplasmosis

Pathology:
Histologically, Sarcoidosis is characterized by the presence of noncaseating granulomas.
Within involved lymph nodes, the usual architecture is effaced by multiple well-defined,
“tight”, and discrete granulomas which in some instances may coalesce.
Characteristically, there are non-caseating epithelioid cell granulomas which have paucity of
lymphocytes. A giant cell with inclusions is also seen in the photomicrograph.
 1. The diagnostic feature in Sarcoidosis of any organ or tissue is the non-caseating
Sarcoid granuloma, composed of epithelioid cells, Langhans’ and foreign body giant
cells and surrounded peripherally by fibroblasts.
2. Typically, granulomas of Sarcoidosis are ‘naked’ i.e. either devoid of peripheral rim of
lymphocytes or there is paucity of lymphocytes.
3. In late stage, the granuloma is either enclosed by hyalinised fibrous tissue or is
replaced by hyalinised fibrous mass.

123- Allergic Nasal polyp

Macroscopic:
Nasal polyps are soft, painless, noncancerous growths on the lining of your nasal passages
or sinuses. They hang down like teardrops or grapes. They result from chronic inflammation
and are associated with asthma, recurring infection, allergies, drug sensitivity or certain
immune disorders.

Nasal polyps are common and are pedunculated grape-like masses of tissue. They are the
end result of prolonged chronic inflammation causing polypoid thickening of the mucosa.
They may be allergic or inflammatory. They are frequently bilateral and the middle turbinate
is the common site. Antrochoanal polyps originate from the mucosa of the maxillary sinus
and appear in the nasal cavity. Morphologically, nasal and Antrochoanal polyps are identical.
In Gross appearance- Grossly, they are gelatinous masses with smooth and shining surface.

Pathology:
Microscopically, they are composed of loose edematous connective tissue containing some
mucous glands and varying number of inflammatory cells like lymphocytes, plasma cells and
eosinophil. Allergic polyps have plenty of eosinophil and hyperplasia of mucous glands. Both
inflammatory and allergic polyps are covered by respiratory epithelium which may show
squamous metaplasia. Nasal polyps may have superimposed fungal infection.
The overlying mucosa is covered partly by respiratory and partly by squamous metaplastic
epithelium. The underlying stromal is edematous and contains inflammatory cells with
prominence of eosinophil.

78- Acute Phlegmonous Appendicitis

Macroscopic:
Appendicitis, grossly, the appearance depends upon the stage at which the acutely-
inflamed appendix is examined. In early acute appendicitis, the organ is swollen and serosa
shows hyperemia. In well-developed acute inflammation called acute suppurative
appendicitis, the serosa is coated with fibrin purulent exudate and engorged vessels on the
surface. In further advanced cases called acute gangrenous appendicitis, there is necrosis
and ulcerations of mucosa which extend through the wall so that the appendix becomes soft
and friable and the surface is coated with greenish-black gangrenous necrosis.
Acute Appendicitis is the most common acute abdominal condition.

Appearance varies from grossly normal to hemorrhagic and necrotic with a fibrinopurulent
coating
 Serosa often congested
 Rupture may be evident
 Mucosa shows ulceration and hyperemia
 Lumen may contain pus and blood
 Fecalith may be present

A.
Obstructive: 1, Faecolith 2. Calculi 3. Foreign body 4. Tumor, 5. Worms (especially
Enterobius vermicularis) 6. Diffuse lymphoid hyperplasia, especially in children.
B.
Non-obstructive: 1. Haematogenous spread of generalized infection 2. Vascular occlusion 3.
Inappropriate diet lacking roughage

Pathology:
Microscopically, the most important diagnostic histological criterion is the neutrophilic
infiltration of the muscularis. In early stage, the other changes besides acute inflammatory
changes are congestion and edema of the appendiceal wall. In later stages, the mucosa is
sloughed off, the wall becomes necrotic, the blood vessels may get thrombosis and there
may be neutrophilic abscesses in the wall. In either case, an impacted foreign body,
faecolith, or concretion may be seen in the lumen.
Thus, there is good correlation between macroscopic and microscopic findings in acute
appendicitis.

 Hallmark of acute appendicitis is neutrophilic infiltrates of the wall of the appendix

o Acute mucosal inflammation is usually present
o Often neutrophilic infiltrates within the lumen
o Histologic findings alone are not sufficient to diagnose acute appendicitis
o Depending on the severity of the inflammation, variable necrosis of the
appendiceal wall is present with mucosal sloughing
 Process may be divided into
o Acute focal
o Acute suppurative
o Gangrenous
o Perforative
Tumor Pathoanatomy
50- Fibro-adenoma of the breast
Macroscopic:
Most often it is a solitary small sized (3 - 4 cm.) nodule, well circumscribed, firm, mobile (it
doesn’t infiltrate the teguments or the deep structures fat tissue or skeletal muscle). On cut
surface, the tumor is white-greyish, lobulated or cauliflower-like resemblance, with a whorl-
like pattern and irregularly slit-like spaces.
It looks like - pink chunk - varying shapes.
Fibroadenoma are common benign (non-cancerous) breast tumors made up of both
glandular tissue and stromal (connective) tissue. Fibroadenoma are most common in
women in their 20s and 30s, but they can be found in women of any age. They tend to
shrink after a woman goes through menopause.

Pathology:
 Delicate, cellular, fibroblastic stroma resembling interlobular stroma, enclosing
glandular and cystic spaces lined by epithelium.
 The epithelium may be surrounded by stroma (pericanalicular fibro adenoma) or
compressed and distorted by it (intracanalicular fibroadenoma).
 The border is sharply delimited from the surrounding tissue.
  Mostly fibrous tissue, 2 types of pattern: Intracanalicular - stroma compresses ducts
to slit-like clefts lined by ductal epithelium Pericanalicular - fibrous stroma around a
patent duct Fibrous stroma may be cellular or collagenous, sometimes there is little
fibrous material with closely-packed ducts (tubular adenoma). During pregnancy or
lactation, the Acini may have secretory activity.
 Fibroadenoma is nodular and encapsulated, included in breast. The epithelial
proliferation appears in a single terminal ductal unit and describes duct-like spaces
surrounded by a fibroblastic stroma. Depending on the proportion and the
relationship between these two components, there are two main histological
features intracanalicular and pericanalicular. Often, both types are found in the same
tumor.
 Intracanalicular fibroadenoma: stromal proliferation predominates and compresses
the ducts, which are irregular, reduced to slits. Pericanalicular fibroadenoma. Fibrous
stroma proliferates around the ductal spaces, so that they remain round or oval, on
cross section. The basement membrane is intact.
 Fibroadenoma of the breast is a benign tumor composed of a biplastic proliferation
of both stromal and epithelial components. This biplasia can be arranged in two
growth patterns: pericanalicular (stromal proliferation around epithelial structures)
and intracanalicular (stromal proliferation compressing the epithelial structures into
clefts).
 These tumors characteristically display hypo vascular stroma compared to
malignant neoplasms. Furthermore, the epithelial proliferation appears in a single
terminal ductal unit and describes duct-like spaces surrounded by a fibroblastic
stroma. The basement membrane is intact.
 Fibrous tissue comprises most of a fibroadenoma. The arrangements between
fibrous over growth and ducts may produce two types of patterns which may coexist
in the same tumor. These are intracanalicular and pericanalicular patterns

51a - Mucinous Cystadenoma of the Ovary

Macroscopic:
The lines appear wiggled, they are thin and overall appear as pink.
It is a type of Ovarian tumor, classified under ‘Tumor pf Surface epithelium’. This is further
divided as: Serous tumors, Mucinous tumors, Endometrial tumors, mesonephroid tumors
and Brenner tumors.
Mucinous tumors are somewhat less common than serous tumors and constitute about 30%
of all ovarian tumors. Over 80% are benign, 10-15% are borderline (atypical proliferating)
and 5% are malignant.

Pathology:
Mucinous Cystadenoma of the ovary. The cyst walls and the septa are lined by a single layer
of tall columnar mucin-secreting epithelium with basally-placed nuclei and large apical
mucinous vacuoles.

Mucinous Cystadenoma is lined by a single layer of these cells having basal nuclei and apical
mucinous vacuoles. ere is very little tendency to papillary proliferation of the epithelium.
Tumors with more abundant stroma are called mucinous Cystadenofibromas.
Histologically, the endometrioid adenocarcinoma is distinguished from serous and mucinous
carcinomas by typical glandular pattern that closely resembles that of uterine endometrioid
adenocarcinoma. There may be foci of squamous metaplasia justifying the diagnosis of
adenoacanthoma. Papillary pattern and foci of serous and mucinous carcinoma may also be
found. Benign variety closely resembles endometriosis with cystic change. ere are no clearly
de ned criteria for borderline endometrioid tumors.

Mucinous tumors are grossly, much larger than than serous tumors Their surface is smooth
with cysts and characteristic multiloculations that contain thick and viscid gelatinous fluid.
The benign tumors, their walls are thin and septa dividing the loculi are also think and often
translucent.

51 - Serous Papillary Cystadenoma of the ovary

Macroscopic:
It appears to contain many dark purple shapes, and are not in touching contact with the
ovary lumen.
It is also known as the ‘Wharthin’s Tumor’
A Cystadenoma is a type of benign tumor that develops from ovarian tissue. They may be
filled with a mucous-type fluid material. Cystadenoma can become very large and may
measure 12 inches or more in diameter
It is slightly more common in parous than in nulliparous women.
Serous tumors develop by invagination of the surface epithelium of ovary and they secrete
serous fluid. Serous tumors are generally benign; 5–10% have borderline malignant
potential, and 20–25% are malignant. Serous Cystadenoma usually are multilocular and
sometimes have papillary projections
Serous Cystadenoma, they have a smooth outer surface and contain one or more thin-
walled cysts filled with clear, watery fluid. Serous Cystadenoma are usually unilocular but
may be multilocular.

The tumor is encapsulated round or in oval shape with smooth surface.

Pathology:
The tumor is showing 2 components: Epithelial parenchyma and Lymphoid Stroma
 Epithelial parenchyma:
Composed of a glandular and cystic structure that contains papillary arrangement and is
lined by characteristic eosinophilic epithelium. The variants of epithelial pattern include:
mucous goblet cells and sebaceous differentiation
 Lymphoid Stroma:
This one is located under the epithelium in the form of prominent lymphoid tissue, often
with germinal centers.

Within ovary or solitary - papillary-shaped islands with pink stroma, dark thick border - lined
by low columnar epithelium, sometimes ciliated. If there is cellular atypia, Psammoma
bodies, and stromal invasion, then it may be malignant.
Psammoma bodies (PBs) are concentric lamellate calcified structures, observed most
commonly in papillary thyroid carcinoma (PTC), meningioma, and papillary serous cyst
adenocarcinoma of ovary but have rarely been reported in other neoplasms and non-
neoplastic lesions.
PBs are associated with the papillary (nipple-like) histomorphology and are thought to arise
from, Infarction and calcification of papillae tips. Calcification of intralymphatic tumor
thrombi.
They are suspected to be caused by thickening of the basal lamina, thrombosis, calcification,
and necrosis of the affected area in an attempt to halt the growth and spread of cancer
cells.

54- Squamous Cell Carcinoma of the Skin

Macroscopic:
In appearance it looks like amorphous purple chunk, find darker epithelium.
The Squamous cell carcinoma (SCC) is the second most common form of skin cancer. It's
usually found on areas of the body damaged by UV rays from the sun or tanning beds. SCC is
a fairly slow-growing skin cancer. Grossly, Squamous Carcinoma of the skin and squamous-
lined mucosa can have one of the following two patterns:
 More commonly, an ulcerated growth with elevated and indurated margin is seen.
 Less often, a raised fungating or polypoid verrucous lesion without ulceration is
found.

Pathology:
Microscopically, squamous cell carcinoma is an invasive carcinoma of the surface epidermis
characterized by the following features:
i) There is irregular downward proliferation of epidermal cells into the dermis.
ii) Depending upon the grade of malignancy, the masses of epidermal cells show
atypical features such as variation in cell size and shape, nuclear
hyperchromatism, absence of intercellular bridges, individual cell keratinization
and occurrence of atypical mitotic figures.
 iii) Better-differentiated squamous carcinomas have whorled arrangement of
malignant squamous cells forming horn pearls. The centers of these horn pearls
may contain laminated, keratin material.
iv) Higher grades of squamous carcinomas, however, have fewer or no horn pearls
and may instead have highly atypical cells.
v) An uncommon variant of squamous carcinoma may have spindle-shaped tumor
cells (spindle cell carcinoma). Vi) Adenoid changes may be seen in a portion of
squamous cell carcinoma (adenoid squamous cell carcinoma). Vii) Verrucous
carcinoma (Ackerman tumor) is a low- grade variant located most commonly in
oral cavity in which the superficial portion of the tumor resembles verruca
(hyperkeratosis, parakeratosis, acanthosis and papillomatosis) but differs from it
in having downward proliferation as broad masses of well-differentiate
squamous epithelium into deeper portion of the tumor. However, there is lack of
cellular atypia.
vi) All variants of squamous cell carcinoma show inflammatory reaction between
the collections of tumor cells, while in pseudocarcinomatous hyperplasia there is
permeation of the epithelial proliferations by inflammatory cells.

In skin, tumor cells destroy the basement membrane and form sheets or compact masses
which invade the subjacent connective tissue (dermis). In well differentiated carcinomas,
tumor cells are pleomorphic/atypical, but resembling normal keratinocytes from prickle
layer (large, polygonal, with abundant eosinophilic (pink) cytoplasm and central nucleus).
Their disposal tends to be similar to that of normal epidermis: immature/basal cells at the
periphery, becoming more mature to the center of the tumor masses. Tumor cells transform
into keratinized squames and form round nodules with concentric, laminated layers,
called “cell nests” or “epithelial/keratinous pearls”. The surrounding stroma is reduced and
contains inflammatory infiltrate (lymphocytes). Poorly differentiated squamous carcinomas
contain more pleomorphic cells and no keratinization.
55- Basal Cell Carcinoma
Macroscopic:
In appearance- it is amorphous purple chunk, find darker epithelium.
Basal cell carcinoma is a malignant epithelial tumor arising only in skin, from the basal layer
of the epidermis or of the pilosebaceous adnexa.
Tumor is represented by compact areas, well delineated and invading the dermis, apparent
with no connection with the epidermis. Tumor cells resemble normal basal cells (small,
mono- Morpheus) are disposed in palisade at the periphery of the tumor nests, but are
spindle-shaped and irregular in the middle. Tumor clusters are separated by a reduced
stroma with inflammatory infiltrate.
 Basal cell carcinoma (BCC) arises from the inter-follicular or follicular epithelium
 Most common malignant tumor type in humans
 Local aggressive course
 Low disease associated death rate; metastases to lung and bone exceptionally rare
 When multiple, associated with a number of genetic conditions, including basal cell
nevus (Gorlin), Bazex-Dupré-Christol, Rombo syndromes and xeroderma
pigmentosum
Pathology:
The cells forming the periphery of the tumor cell islands tend to be arranged radially with
their long axes in approximately parallel alignment (palisading). The stroma shrinks away
from the epithelial tumor nests, creating clefts or separation artifacts that assist in
differentiating basal cell carcinomas from certain appendage tumors also characterized by
proliferation of basaloid cells.

Basal-cell carcinoma can broadly be divided into three groups, based on the growth
patterns.
1. Superficial basal-cell carcinoma, formerly referred to in-situ basal-cell carcinoma, is
characterized by a superficial proliferation of neoplastic basal-cells. This tumor is
generally responsive to topic chemotherapy, such as imiquimod, or fluorouracil.

2. Infiltrative basal-cell carcinoma, which also encompasses morpheaform and micro

nodular basal-cell cancer, is more difficult to treat with conservative methods, given
its tendency to penetrate into deeper layers of the skin.

3. Nodular basal-cell carcinoma includes most of the remaining categories of basal-cell

cancer. It is not unusual to encounter heterogeneous morphologic features within
the same tumor.

Islands of tumor cells invade the dermis, note hair follicles and sebaceous glands. It can be
described as proliferation of basaloid cells. Various patterns - solid masses (with peripheral
palisade arrangement of the nuclei), strands, keratotic masses, sebaceous differentiation.

56- Adenocarcinoma of the Large Bowel

Macroscopic:
It clearly looks wiggled surface of mucosa.
Colorectal cancer comprises 98% of all malignant tumors of the large intestine. It is the
commonest form of visceral cancer accounting for deaths from cancer in the United States,
next only to lung cancer. e incidence of carcinoma of the large intestine rises with age;
average age of patients is about 60 years. Cancer in the rectum is more common in males
than females in the ratio of 2:1, while at other locations in the large bowel the overall
incidence is equal for both sexes.
Grossly, there are distinct differences between the growth on the right and left half of the
colon:
 Right-sided colonic growths tend to be large, cauliflower-like, soft and friable
masses projecting into the lumen (fungating polypoid carcinoma).
 Left-sided colonic growths, on the other hand, have napkin-ring configuration i.e.
they encircle the bowel wall circumferentially with increased fibrous tissue forming
annular ring, and have central ulceration on the surface with slightly elevated
margins (carcinomatous ulcers).
Pathology:
Microscopically, the appearance of right and left-sided growths is similar. About 95% of
colorectal carcinomas are adenocarcinomas of varying grades of differentiation, out of
which approximately 10% are mucin-secreting colloid carcinomas. The remaining 5% tumors
include uncommon microscopic patterns like undifferentiated carcinoma, signet-ring cell
carcinoma, and adeno squamous carcinomas seen in more distal colon near the anus. e
histologic grades indicating the degree of differentiation may range from well-differentiated,
to moderately-differentiated and poorly-differentiated.

The spreading of the Carcinoma in the Large Bowel/Intestine may spread via the following
routes:
 Direct Spread:
The tumor spreads most commonly by direct extension in both ways- circumferentially into
the bowel wall as well as directly into the depth of the bowel wall to the serosa, pericolic fat,
and sometimes into peritoneal cavity.
 Lymphatic Spread:
Spread via lymphatic occurs rather commonly and involves, firstly the regional lymph nodes
in the vicinity of the tumor, and then into other groups of lymph nodes like pre-aortic,
internal iliac and the sacral lymph nodes.
 Haematogenous Spread:
The blood spread of a large bowel cancer occurs relatively late and involves the liver, lungs,
brain, bones and ovary.

STAGING AND PROGNOSIS e prognosis of colorectal cancer depends upon a few variables:
. Extent of the bowel involvement
. Presence or absence of metastases
. Histologic grade of the tumor
. Location of the tumor

69- Teratoma of the Ovary

Macroscopic:
On the microscopic image, it appears irregular pink shape with gaps.
Teratomas are tumors composed of different types of tissues derived from the three germ
cell layers—ectoderm, mesoderm and mesoderm in various combinations.
Teratomas are divided into 3 types: mature (benign), immature (malignant), and
monodermal or highly specialized Teratomas. Ovarian Teratoma arises from a twisting
pressure on the ovary (ovarian torsion) caused by the growing mass. Sometimes ovarian
Teratoma can be accompanied by a rare condition known as NMDA encephalitis.

Pathology:
Mature:
The the most prominent feature is the lining of the cyst wall by stratified squamous
epithelium and its adnexal structures such as sebaceous glands, sweat glands and hair
follicles. Though ectodermal derivatives are most prominent features, tissues of
mesodermal and endodermal origin are also commonly present. Various other tissue
components frequently found in Teratomas are bronchus, intestinal epithelium, cartilage,
bone, tooth, smooth muscle, neural tissue, salivary gland, retina, pancreas and thyroid
tissue. us, viewing a benign cystic Teratoma in different microscopic fields reveals a variety
of mature differentiated tissue elements, producing kaleidoscopic patterns.

Immature:
parts of the tumor may show mature tissues, while most of it is composed of immature
tissues having an embryonic appearance. Immature tissue elements may differentiate
towards cartilage, bone, glandular structures, neural tissue etc. and are distributed in
spindle- shaped myxoid or undifferentiated sarcoma cells. An important factor in grading
and determining the prognosis of immature Teratoma is the relative amount of immature
neural tissue. Immature neural tissue can undergo maturation even at the site of
metastases over a period of years. Immature Teratoma may contain areas of other germ cell
tumors such as endodermal sinus tumor, embryonic carcinoma and choriocarcinoma.

Monodermal: Struma Ovarii and Carcinoid Tumor

 Struma Ovarii: It is a Teratoma composed exclusively of thyroid tissue, recognizable
grossly as well as microscopically. Most often, the tumor has the appearance of a
follicular adenoma of the thyroid. Rarely, Struma Ovarii may be hyper functioning
and produce hyperthyroidism
 Carcinoid tumor: This is an ovarian Teratoma arising from argentaffin n cells of
intestinal epithelium in the Teratoma. Ovarian carcinoid may also hyper function and
produce 5-HT and consequent carcinoid syndrome.
 Struma-carcinoid This is a rare combination of Struma Ovarii and ovarian carcinoid.

132- Seminoma of Testis

Macroscopic:
Appears semicircular chunk with pale curve.
A seminoma is a germ cell tumor of the testicle or, more rarely, the mediastinum or other
extra-gonadal locations. It is the most common type of ‘Germ Cell Tumor’. It is a malignant
neoplasm and is one of the most treatable and curable cancers, with a survival rate above
95% if discovered in early stages.
A seminoma arises from germ cells that grow uncontrollably. Germ cells are the cells that
form an embryo in a mother's womb. Later on in development, germ cells are supposed to
mature into sperm-producing cells within the male testicles.

 Well demarcated, homogeneous, solid cream or grey tumors; surface nodularity and
lobulation; may be multiple nodules
 Necrosis or hemorrhage usually minimal
 If regressed, only a scar may be visible
 Usually confined to testis (90%)

Pathology:
Seminomas are typically composed of uniform cells arranged in sheets or divided into
clusters or columns by fine fibrous trabeculae associated with a lymphocytic infiltrate, which
may be dense with follicle formation.
 Significantly greater atypia with lack of distinct cell borders
 Nuclei overlap and increased mitotic activity
 May have additional growth patterns present

 Sheets or lobular configuration of tumor with fibrous septae

 Cells are typically pale (glycogen) but may be eosinophilic
 Cell membranes are well defined with distinct cell boundaries
 Nuclei are polygonal and may have a flat edge giving a squared off appearance; they
contain one or more prominent central nucleoli; no nuclear overlap if well fixed
tissue
 A lymphocytic infiltrate is present (T lymphocytes) with plasma cells; germinal
centers may occur
 Granulomas noted in up to 50% of cases
 Intercellular edema with microcytic spaces and Coagulative type necrosis can be
present

In about 40%, there is a increase in plasma alkaline phosphatase. Occasionally the serum
levels of the Beta- sub unit may be raised too.
Sheets of primitive germ cells divided into lobules by fine connective tissues bands. In about
80% the connective tissue shows infiltration by lymphocytes and plasma cells and
occasionally granulomas some of which may contain giant cells of ‘Langhan’s Type’.
The tumor cells are large and have a lot of clear cytoplasm and well defined plasma
membranes. The nuclei contain 1 or 2 nucleoliand- clumped chromatin. Occasionally
multiply –nucleated tumor cells resembling syncytiotrophoblasts are seen and they secrete
Beta-sub-unit of human chronic gonadotropin.

59- Renal Carcinoma

Macroscopic:
On the microscope it appears purple chunk with some pale areas. Renal carcinoma is an
adenocarcinoma arising from tubular epithelium.
Renal cell carcinoma (RCC) is also called hypernephroma, renal adenocarcinoma,
or renal or kidney cancer. It's the most common kind of kidney cancer found in adults. The
kidneys are organs in your body that help get rid of waste while also regulating fluid
balance.

Pathology:
 Tumor cells have abundant cytoplasm that is vacuolated, fluffy or granular, usually
with indistinct cell borders (chromophobe renal cell carcinoma has distinct borders)
 Tumor nuclei have variable atypia, irregular contours, haphazard orientation with
abnormal chromatin, variably prominent nucleoli
 Renal tubular cells have well defined cell borders, homogenous cytoplasm, round,
regular and orderly nuclei
 Important features to distinguish from other neoplasms include heterogeneous cell
population, small cytoplasmic vacuoles and hemosiderin deposits.
Renal clear cell carcinoma (Grawitz tumor) is a malignant epithelial tumor resulted from
proliferation of tubule cells. Tumor cells form cords, papillae, tubules or nests, and are
atypical, polygonal and large. Because these cells accumulate glycogen and lipids, their
cytoplasm appears "clear", lipid-laden, the nuclei remain in the middle of the cells, and the
cellular membrane is evident. Some cells may be smaller, with eosinophilic cytoplasm,
resembling normal tubular cells. The stroma is reduced, but well vascularized. The tumor
grows in large front, compressing the surrounding parenchyma, producing a pseudocapsule.

Presented case - clear cell type (there are several types):

• The tumor cells are with clear cytoplasm (due to removal of glycogen and lipid from
cytoplasm during processing of tissues)
• Tumor cells are arranged in several different patterns- solid, trabecular and tubular,
separated by delicate vasculature

1. Clear cell type RCC (70%): is is the most common pattern. e clear cytoplasm of tumor
cells is due to removal of glycogen and lipid from the cytoplasm during processing of
tissues. The tumor cells have a variety of patterns: solid, trabecular and tubular,
separated by delicate vasculature. Majority of clear cell tumors are well
differentiated.
2. Papillary type RCC (15%): The tumor cells are arranged in papillary pattern over the
fibro vascular stalks. The tumor cells are cuboidal with small round nuclei.
Psammoma bodies may be seen.
3. Granular cell type RCC (8%): The tumor cells have abundant acidophilic cytoplasm.
These tumors have more marked nuclear pleomorphism, hyperchromatism and
cellular atypia.

115- Hepatocellular Carcinoma

Macroscopic:
It appears solid purple in square chunk.
Hepatocellular, Liver cell carcinoma or Hepatoma is the most common primary malignant
tumor of the liver.
 Well circumscribed mass that appears tan-yellow to green (color variation depends
on proportion of fat and bile content)
 Areas of hemorrhage and necrosis are common
 Solitary or dominant nodule with multiple satellite nodules or multiple discrete
nodules or multiple distinct nodules
 Contains pedunculated hepatocellular carcinoma

HCC may form one of the following 3 patterns of growth, in decreasing order of frequency:
i) Expanding type: Most frequently, it forms a single, yellow- brown, large mass,
most often in the right lobe of the liver with central necrosis, hemorrhage and
occasional bile- staining. It may be deceptively encapsulated.
 ii) Multifocal type: Less often, multifocal, multiple masses, 3-5 cm in diameter,
scattered throughout the liver are seen.
iii) Infiltrating (Spreading) type: Rarely, the HCC forms diffusely infiltrating tumor
mass.
Pathology:
Microscopically, the tumor cells in the typical HCC resemble hepatocytes but vary with the
degree of differentiation, ranging from well-differentiated to highly anaplastic lesions
Most of the HCC have trabecular growth pattern. The tumor cells have a tendency to invade
and grow along blood vessels. us important diagnostic features are the patterns of tumor
cells and their cytological features:
1. Histologic patterns: These include the following:
 Trabecular or sinusoidal pattern is the most common. e trabeculae are made up of 2-
8 cell wide layers of tumor cells separated by vascular spaces or sinusoids which are
endothelium-lined
 Pseudo glandular or acinar pattern is seen sometimes. The tumor cells are disposed
around central cystic space formed by degeneration and breakdown in solid
trabeculae.
 Compact pattern resembles trabecular pattern but the tumor cells form large solid
masses with inconspicuous sinusoids.
 Scirrhous pattern is characterized by more abundant fibrous stroma.

2. Cytological features:
The typical cytological features in the HCC consist of cells resembling hepatocytes having
vesicular nuclei with prominent nucleoli. e cytoplasm is granular and eosinophilic but
becomes increasingly basophilic with increasing malignancy. Aside from these features, a
few other cellular features are: pleomorphism, bizarre giant cell formation, spindle-shaped
cells, tumor cells with clear cytoplasm, presence of bile within dilated canaliculi, and intra
cytoplasmic Mallory’s hyaline.

Immunohistochemically, hepatocellular carcinoma cells stain positively with AFP, EMA,

keratin etc.
60b- Fibroma of the Ovary
Macroscopic:
On the microscope on observation it may look like it has 2 stains. An ovarian fibroma is a
rare, benign tumor of the ovary. Most commonly found in women in their 50s during peri-
menopause (transition to menopause) or post- menopause, ovarian fibromas account for
approximately four percent of all ovarian tumors. However, ovarian fibromas are benign
and can be treated completely by surgical removal, and laparoscopic surgery can be an
effective and safe alternative approach.

 Well circumscribed mass with smooth, lobulated surface

 Firm, chalky, solid, white to yellow-white to tan-yellow cut surface that may be
whorled
 Frequent edema resulting in softer consistency

Pathology:
The disease undergoes neoplastic transformation of ovarian stromal cells due to hereditary
or sporadic genetic abnormalities.

Conventional fibroma:
o Recapitulates ovarian cortex
o Usually well circumscribed but non encapsulated
o Variably cellular fascicular or less frequently, storiform growth of tumor cells within a
variably collagenous stroma, sometimes with hyaline plaques.
o Bland spindled to ovoid nuclei with pointy ends and scant eosinophilic cytoplasm
blending with surrounding stroma
o Occasional mitoses (usually up to 3 mitoses per 10 high power fields)
o With or without Verocay-like areas (slightly wavy, parallel arrays of spindled nuclei),
calcification, edema, hemorrhage, infarct type necrosis, rare groups of luteinized
cells
o Rarely intra cytoplasmic lipid (may be diagnosed as thecoma), eosinophilic hyaline
globules, melanin pigment or bizarre nuclei.

 Cellular fibroma (10% of cases):

o Resembles diffuse type of adult granulose cell tumor
o Densely cellular with little intercellular collagen
o Bland spindled nuclei with up to 3 mitoses per 10 high power fields
o "Mitotically active cellular fibroma" has been proposed for cellular fibromas
with ≥ 4 mitoses per 10 high power fields
 Fibroma with minor sex cord elements:
o Sex cord component accounting for < 10% of overall tumor volume
o No prognostic significance

Histologically, they are composed of spindle-shaped well-differentiated fibroblasts and

collagen. Sometimes, combination of fibroma and thecoma is present called fibrothecoma.

Clinical Pathoanatomy:
111- Lobular Pneumonia with Abscess formation
Macroscopic:
Aspiration pneumonia is an infection that develops after food or secretions from your
mouth, stomach, or sinuses are inhaled into your lungs instead of going into your
esophagus. It's a very common cause of primary abscesses.
Lobar pneumonia, also known as non-segmental pneumonia or focal non-segmental
pneumonia is a radiological pattern associated with homogeneous and fibrino-suppurative
consolidation of one or more lobes of a lung in response to bacterial pneumonia.
Lobar Pneumonia is characterized as an acute inflammation of all the lobes in the Lungs.`

Pathology:
Lobar pneumonia has 4 classical stages of inflammatory response if left untreated, namely:
 1. Congestion/consolidation in the first 24 hours in which the lungs are heavy, red,
and, boggy. Microscopically characterized by vascular engorgement and intra-
alveolar edema. Many bacteria and few neutrophils are present.
2. Red hepatization/early consolidation begins 2 to 3 days after consolidation and lasts
for 2 to 4 days and named because of firm liver-like consistency. The affected lung is
red-pink, dry, granular and, airless. Fibrin strands replace the edema fluid of the
previous phase. Microscopically marked cellular exudate of neutrophils with some
showing ingested bacteria, extravasation of erythrocytes, desquamated epithelial
cells, and fibrin within the alveoli are seen. The alveolar septa become less
prominent because of the exudate.
3. Grey hepatization/late consolidation occurs 2 to 3 days following red hepatization
and lasts for 4 to 8 days. The lung appears gray with liver-like consistency due to
fibrinopurulent exudate, progressive disintegration of red blood cells, and
hemosiderin. The macrophages begin to appear.
4. Resolution and restoration of the pulmonary architecture start by the eighth day.
The enzymatic action begins centrally and spreads peripherally which liquefies the
previous solid fibrinous content and eventually restores aeration. Macrophages are
the predominant cells which contain engulfed neutrophils and debris.

 Bronchopneumonia: A descending infection started around bronchi and bronchioles,

which then spreads locally into the lungs. Lower lobes are usually involved. Patchy
areas of consolidation which represents neutrophil collection in the alveoli and
bronchi.

 Lobar pneumonia: Acute exudative inflammation of the entire lobe. Uniform

consolidation with a complete or near complete consolidation of a lobe of a lung.
Majority of these cases are caused by Streptococcus pneumoniae.

85- Silicosis of the Lungs

Macroscopic:
Silicosis is a pneumoconiosis caused by the inhalation of silicon dioxide (silica), usually in
crystalline form as quartz. They are scattered throughout the lung parenchyma but are
initially more often located in the upper zones of the lungs. These nodular lesions frequently
have simultaneous deposition of coal-dust and may develop calcification. The pleura is
grossly thickened and adherent to the chest wall. There may be similar fibrotic nodules on
the pleura and within the regional lymph nodes. The nodular lesions are detectable as egg-
shell shadows in chest X-rays. The lesions may undergo ischemic necrosis and develop
cavitation, or be complicated by tuberculosis and rheumatoid pneumoconiosis.
Pathology:
 The silicotic nodules are located in the region of respiratory bronchioles, adjacent
alveoli, pulmonary arteries, in the pleura and the regional lymph nodes.
  The silicotic nodules consist of central hyalinised material with scanty cellularity and
some amount of dust. The hyalinised center is surrounded by concentric laminations
of collagen which is further enclosed by more cellular connective tissue, dust-filled
macrophages and a few lymphocytes and plasma cells. Some of these nodules may
have calcium deposits.

 The collagenous nodules have cleft-like spaces between the lamellae of collagen
which when examined polariscopically may demonstrate numerous birefringent
particles of silica.

 The severe and progressive form of the disease may result in coalescence of adjacent
nodules and cause complicated silicosis similar to progressive massive fibrosis of
coal-workers’ pneumoconiosis.

 The intervening lung parenchyma may show hyperinflation or emphysema.

 Cavitation when present may be due to ischemic necrosis in the nodules, or may
reveal changes of tuberculosis or rheumatoid pneumoconiosis (Caplan’s syndrome).

The Silicotic nodule consists of hyaline center surrounded by concentric layers of collagen
which are further enclosed by fibroblasts and dust-laden macrophages. Polarizing
microscopy in photomicrograph on right shows bright fibers of silica

45- Pulmonary Emphysema

Macroscopic:
The WHO has defined pulmonary emphysema as combination of permanent dilatation of air
spaces distal to the terminal bronchioles and the destruction of the walls of dilated air
spaces. Thus, emphysema is defined morphologically, while chronic bronchitis is defined
clinically. Since the two conditions coexist frequently and show considerable overlap in their
clinical features, it is usual to label patients as ‘predominant emphysema’ and ‘predominant
bronchitis’.
Pathology:
Microscopically, depending upon the type of emphysema, there is dilatation of air spaces
and destruction of septal walls of part of Acinus involved i.e. respiratory bronchioles,
alveolar ducts and alveolar sacs. Changes of bronchitis may be present. Bullae and blebs
when present show fibrosis and chronic inflammation of the walls.
There are two major types of emphysema:

 Centrilobular (centriacinar): primarily the upper lobes. Occurs with loss of the
respiratory bronchioles in the proximal portion of the acinus, with sparing of distal
alveoli. This pattern is most typical for smokers.
 Panlobular (panacinar): involves all lung fields, particularly the bases. Occurs with
loss of all portions of the acinus from the respiratory bronchiole to the alveoli. This
pattern is typical for alpha-1-antitrypsin deficiency.

General findings
o Airspace enlargement; the size of airspace in the background parenchyma will be a
good reference
o Fragmented alveolar walls
 If the acinar arrangement is well remained, it is representing pores of Kohn
 If not, it is representing acinar destruction
o The subtype is determined with histological landmarks:
 Bronchovascular bundle of terminal bronchiole and arteriole is in the center
of acinus
 Connective tissue septa ("secondary lobule of Millar") are the periphery of
acinus, which is often ambiguous in less inflamed lung
91-Subacute Glomerulonephritis
Macroscopic:
Glomerulonephritis (GN) or Bright’s disease is the term used for diseases that primarily
involve the renal glomeruli.
It is convenient to classify glomerular diseases into 2 broad groups:
I. Primary glomerulonephritis in which the glomeruli are the predominant site of
involvement.
II. Secondary glomerular diseases include certain systemic and hereditary diseases which
secondarily affect the glomeruli.

Pathology:
Diffuse proliferative GN with thickening of the glomerular capillary walls, and GBM splitting.
Diffuse coarsely granular C3 and IgG deposits along GBMs. Electron- dense sub endothelial
deposits.

92- Chronic Pyelonephritis

Macroscopic:
Kidneys (one or both) are small and contracted (< 100 g) showing unequal reduction; the
surface is irregularly scarred and granular. The capsule can be stripped off with difficulty due
to adherence to scars. Scars are different in size and show U-shaped depressions. Pelvis
is dilated. Parenchyma is atrophic and replaced by fat tissue.
Pathology:

- Chronic inflammation:
In the interstitium, presented by Ly, Pl, and Mph and pronounced interstitial fibrosis,

-Tubules show varying degree of atrophy and dilation. Pink-stained casts may be present in
their lumens giving them a thyroid-like appearance (thyroidisation).

- The walls of blood vessels show marked thickening, resulting from secondary
hypertension – fibro elastic hypertrophy of arteries and hyalinosis of arterioles.

- Although glomeruli are spared and intact, there is often per glomerular fibrosis
(concentric). In advanced cases hyalinization can take place in the glomerular tufts.

Chronic pyelonephritis: The scarred area shows atrophy of some tubules and dilatation of
others which contain colloid cast s (thyroidisation). The tubules are surrounded by abundant
fibrous tissue and chronic interstitial inflammatory reaction. The blood vessels included are
thick-walled and the glomeruli show Peri-glomerular fibrosis.

100 -Fibrocystic Disease of the breast

Macroscopic:
Fine fibro-fatty tissue with bluish cystic spaces different in shape and named “blue domed”
cysts. On Microscopic it will come up showing cystic dilatation of ducts and increase in
fibrous stroma. There is mild epithelial hyperplasia in terminal ducts.
In appearance very light pink with visible clear holes.
It is the most common benign breast disease, producing palpable tumor. Patients are
between the ages of 25 – 50 years. It is uncommon before adolescence and after
menopause.

Pathology:
As such, fibrocystic change of the female breast is a histologic entity characterized by
following features:
. I) Cystic dilatation of terminal ducts.
. II) Relative increase in inter and interlobular fibrous tissue.
. II) Variable degree of epithelial proliferation in the terminal ducts.

 Increase in the number of Acini per lobule

 Pregnancy- Normal Physiologic adenosis
 Non-Pregnant Women- adenosis- Focal change
 Acini- Enlarged not distorted (blunt- duct adenosis)
 Calcification- occasionally within the Lumen
 Acini- Lined by Columnar cells – benign/ atypical features (“flat epithelial atypia”-
Earliest recognizable precursor of epithelial neoplasia

It has large ducts have thick edges (apocrine metaplasia), stroma is fibrous and with strands
sometimes metaplasia breaks off into the duct. Clumps of glands (adenosis)
It looks like it has cystic dilation in terminal ducts with varied linings - can be flattened or
hyperplastic.
Apocrine metaplasia in lining of cyst may occur and produce irregular cysts. Increased
fibrous stroma surrounding cysts, variable degree of lymphocytic infiltrate

The changes in fibrocystic breast disease are characterized by the appearance of fibrous
tissue and a lumpy, cobblestone texture in the breasts.
These lumps are smooth with defined edges, and are usually free-moving in regard to
adjacent structures. The bumps can sometimes be obscured by irregularities in the breast
that are associated with the condition. The lumps are most often found in the upper, outer
sections of the breast (nearest to the armpit), but can be found throughout the breast.
Women with fibrocystic changes may experience a persistent or intermittent breast aching
or breast tenderness related to periodic swelling.
Breasts and nipples may be tender or itchy. Symptoms follow a periodic trend tied closely to
the menstrual cycle. Symptoms tend to peak in the days and, in severe cases, weeks before
each period and decrease afterwards. At peak, breasts may feel full, heavy, swollen, and
tender to the touch. No complications related to breastfeeding have been found.

103- Neonatal Respiratory Distress Syndrome- Hyaline Membrane Disease

Macroscopic:
Acute respiratory distress syndrome (ARDS) is a severe, at times life-threatening, forms of
progressive respiratory insufficiency which involves pulmonary tissues diffusely i.e.
involvement of the alveolar epithelium, alveolar Lumina and interstitial tissue. ARDS exists in
2 forms: neonatal and adult type. Both have the common morphological feature of
formation of hyaline membrane in the alveoli and hence is also called: Hyaline Membrane
Disease/.

Deficiency of pulmonary surfactant (S) that reduces surface tension within alveoli and hold
them open. It is synthesized by alveolar cells type 2 mostly after 35th week of gestation. RDS
is primary initiated by hypoxia.

• Preterm infants (born before 37th week) - the incidence of RDS is inversely
proportional to gestational age. It occurs in about 60% in infants born before
28thweek of gestation, 15 – 20% between 32 – 28th weeks and less than 5% after
37thweek.

• Infants born to diabetic mothers - S-synthesis can be suppressed by the

compensatory high blood levels of insulin in these infants.

• Delivery by Caesarian section

• Birth asphyxia at various causes

Pathology:
The lesions of RDS are never seen in stillborn infants or in infants who die within a few hours
of birth, because entry of air into alveoli is essential for formation of hyaline membranes.
• Lungs are normal in size, reddish – purple in color, solid and airless so they sink in water.

- Atelectasis – small alveolar spaces with thick alveolar septa lined by cuboidal or columnar
epithelial cells
- Hyperventilated alveoli (dilated) - Hyaline membranes
– eosinophilia, homogenous bands or ribbons, composed mainly of fibrin and lining the
respiratory bronchioles, alveolar ducts and proximal alveoli.- Congestion and
hemorrhages- Absence of inflammatory reaction

Neonatal ARDS occurring in newborn infants begins with dyspnea within a few hours after
birth with tachypnea, hypoxia and cyanosis; in severe cases death may occur within a few
hours.

1. There is presence of collapsed alveoli (atelectasis) alternating with dilated alveoli.

2. Necrosis of alveolar epithelial cells and formation of characteristic eosinophilia hyaline
membranes lining the respiratory bronchioles, alveolar ducts and the proximal alveoli. The
membrane is largely composed of fibrin admixed with cell debris derived from necrotic
alveolar cells.
3. Interstitial and intra-alveolar edema, congestion and intra-alveolar hemorrhages.

93- Grave’s Disease- Diffuse Toxic Goiter

Macroscopic:
Graves' disease is an immune system disorder that results in the overproduction of thyroid
hormones (Hyperthyroidism). Although a number of disorders may result in
hyperthyroidism, Graves' disease is a common cause. Thyroid hormones affect many body
systems, so signs and symptoms of Graves' disease can be wide ranging.

Graves’ disease, also known as Basedow’s disease, primary hyperplasia, exophthalmic

Goitre, and diffuse toxic goitre, is characterized by a triad of features:
 Hyperthyroidism (thyrotoxicosis)
 Diffuse thyroid enlargement
 Ophthalmopathy

Grossly, the thyroid is moderately, diffusely and symmetrically enlarged and may weigh up
to 70-90 gm. On cut section, the thyroid parenchyma is typically homogeneous, red-brown
and meaty and lacks the normal translucency.

Pathology:
Histologically, the following features are found:
 There is considerable epithelial hyperplasia and hypertrophy as seen by increased
height of the follicular lining cells and formation of papillary inholdings of piled up
epithelium into the Lumina of follicles which are small.

 The colloid is markedly diminished and is lightly staining, watery and finely
vacuolated.

 The stroma shows increased vascularity and accumulation of lymphoid cells

 The follicles are small and are lined by tall columnar epithelium, which is piled up at
places forming papillary inholdings. Colloid is nearly absent and appears lightly
staining, watery and finely vacuolated.

In Graves’ disease, TSH-receptor auto antigen is the main antigen against which
autoantibodies are directed. These are as under:

i) Thyroid-stimulating immunoglobulin (TSI): It binds to TSH receptor and stimulates

increased release of thyroid hormone.
ii) Thyroid growth-stimulating immunoglobulin’s (TGI): It stimulates proliferation of
follicular epithelium.
iii) TSH-binding inhibitor immunoglobulin’s (TBII): It is inhibitory to binding of TSH to its
own receptor. Depending upon its action as inhibitory or stimulatory to follicular epithelium,
it may result in alternate episodes of hypo- and hyperthyroidism

46- Non Toxic Nodular Colloid Goiter

Macroscopic:
Diffuse, nontoxic simple or colloid goitre is the name given to diffuse enlargement of the
thyroid gland, unaccompanied by hyperthyroidism. Most cases are in a state of euthyroid
though they may have passed through preceding stage of hypothyroidism due to
inadequate supply of iodine. TSH levels are invariably elevated. In general, goitre is more
common in females. Simple goitre often appears at puberty or in adolescence, following
which it may either regress or may progress to nodular goitre.

Pathology:
Histologically, two stages are distinguished:
1. Hyperplastic stage is the early stage and is characterized by tall columnar follicular
epithelium showing papillary inholdings and formation of small new follicles.

2. Involution stage generally follows hyperplastic stage after variable period of time. This
stage is characterized by large follicles distended by colloid and lined by flattened follicular
epithelium

3. To note is that colloid nodules and cysts may contain tiny crystals resulting from the
desiccation of the gelatinous colloid material. They have a comet-tail artifact.

Histologically, the initial stage of colloid goitre is cellular hyperplasia of the thyroid Acini,
followed by a micro nodular and macro nodular formation, which is often indistinguishable
from normal thyroid parenchyma, even on histological examination. True thyroid epithelial
cysts are rare. Hyperplastic nodules are often subject to liquefying degeneration,
accumulating blood, serous fluids and colloidal substances. In this cystic-degenerative
process, calcification can occur, which is often coarse and Peri-nodular.

95- Diabetic Neuropathy- Nodular Glomerulosclerosis

Macroscopic:
Diabetic nephropathy (diabetic kidney disease) is kidney damage that results from having
diabetes. Having high blood glucose levels due to diabetes can damage the part of the
kidneys that filters your blood. The damaged filter becomes 'leaky' and lets protein into your
urine.
Renal involvement is an important complication of diabetes mellitus. End-stage kidney with
renal failure accounts for deaths in more than 10% of all diabetics. Renal complications are
more severe, develop early and more frequently in type 1 (earlier called insulin-dependent)
diabetes mellitus (30-40% cases) than in type 2 (earlier termed non-insulin-dependent)
diabetics (about 20% cases).

Diabetic nephropathy encompasses 4 types of renal lesions in diabetes mellitus: diabetic

Glomerulosclerosis, vascular lesions, diabetic pyelonephritis and tubular lesions (Armanni-
Ebstein lesions).

Pathology:
 Diffuse uniform thickening of glomerular basement membrane (GBM)
 Matrix expansion encroaching on the capillary lumina may be diffuse, nodular or
both
o Nodular lesions are also called Kimmelsteil-Wilson lesions
 Diffuse uniform thickening of glomerular basement membrane (GBM)
 Matrix expansion encroaching on the capillary lumina may be diffuse, nodular or
both
o Nodular lesions are also called Kimmelsteil-Wilson lesions

Biopsies diagnosed as diabetic nephropathy are classified as follows:

Class I: Glomerular basement membrane thickening: isolated glomerular basement

membrane thickening and only mild, nonspecific changes by light microscopy that do not
meet the criteria of classes II through IV.
Class II: Mesangial expansion, mild (IIa) or severe (IIb): glomeruli classified as mild or severe
Mesangial expansion but without nodular sclerosis (Kimmelstiel–Wilson lesions) or global
Glomerulosclerosis in more than 50% of glomeruli.
Class III: Nodular sclerosis (Kimmelstiel–Wilson lesions): at least one glomerulus with
nodular increase in Mesangial matrix (Kimmelstiel–Wilson) without changes described in
class IV.
Class IV: Advanced diabetic Glomerulosclerosis: more than 50% global Glomerulosclerosis
with other clinical or pathologic evidence that sclerosis is attributable to diabetic
nephropathy.
 1- Caseous Tuberculous Lymphadenitis
Macroscopic:
Tuberculous lymphadenitis is the result of lymph nodal infection by tuberculous
mycobacteria, such as Mycobacterium tuberculosis or Mycobacterium bovis.
M.tuberculosis is a serious global health problem, with approximately one third of the
world's population infected by this microorganism
Tuberculous lymphadenitis may present as a mediastinal mass. Fine-needle aspiration often
yields small loose aggregates of epithelioid histiocytes associated with scattered
multinucleated giant cells, necrotic debris, and caseous material in the background.
TB can spread in several different ways- Local, Haematogenous, Natural Passage and Lymph
spread.
2. Lymphatic spread. Tuberculosis is primarily an infection of lymphoid tissues. The bacilli
may pass into lymphoid follicles of pharynx, bronchi, intestines or regional lymph nodes
resulting in regional tuberculous lymphadenitis which is typical of childhood infections.
Primary complex is primary focus with Lymphangitis and lymphadenitis.

With the help of Ziehl- Neelsen stain, it would allow you to visualize having many different
Tubercle bacilli.

Pathology:
Caseating epithelioid cell granulomas with some Langhans’ giant cells in the cortex of lymph
node-
When the excised specimen was histopathologically examined, it showed lymph node with
thickened capsule, infiltrated by coalescent epithelioid histiocytic granuloma with areas of
central caseous necrosis.

Stages of tubercular lymphadenitis:

1. Lymphadenitis
2. Periadenitis
3. Cold abscess
4. 'Collar stud' abscess
5. Sinus
 76- Intestinal Metaplasia in the Stomach Mucosa
Macroscopic:
Gastric intestinal metaplasia (GIM) is an intermediate precancerous gastric lesion in the
gastric cancer cascade of chronic gastritis, atrophic gastritis, intestinal metaplasia (IM),
dysplasia, and adenocarcinoma. Although the risk of gastric cancer is increased in patients
with GIM, the absolute risk is modest. Cause of the chronic Inflammation is H. Pylori.
It is a type of columnar metaplasia.
Intestinal metaplasia is more common and involves antral mucosa more frequently.
Characteristic histologic feature is the presence of intestinal type mucus-goblet cells; Paneth
cells and endocrine cells may also be present. Parietal cells are very muscularis mucosae
may extend into the thickened folds. Epithelium-lined cysts are commonly seen in the
glandular layer. Inflammatory infiltrate is usually mild but lymphoid follicles may be present.
The condition is considered significant in view of the risk of developing cancer.

Pathology:
Intestinal metaplasia is characterized by the presence of well-formed goblet cells, which
may be present in the surface epithelium or the foveolar region (Fig. 5.19). Goblet cells are
large round vacuoles filled with acid mucin. The diagnosis of intestinal metaplasia depends
on the identification of at least one well-defined goblet cell in a routine hematoxylin and
eosin-stained section.

Complete metaplasia is currently diagnosed when the epithelium resembles the small
intestinal phenotype, with eosinophilic enterocytes displaying a well-defined brush border
(representing absorptive microvilli) and well-formed goblet cells. Paneth cells may also be
present. Incomplete metaplasia resembles a colonic epithelium phenotype with multiple,
irregular mucin droplets of variable size in the cytoplasm and absence of a brush border.

In an incomplete metaplasia, all metaplastic cells are irregular goblet cells without a brush
border. The Gastric Complete metaplasia, the glands and foveolar epithelium are replaced
by eosinophilic enterocytes with a brush border. At regular intervals, mucus filled goblet
cells are seen amongst the enterocytes.
 117- Hashimoto’s Thyroiditis
Macroscopic:
Hashimoto’s thyroiditis, also called diffuse lymphocytic thyroiditis, struma lymphomatosa or
goitrous autoimmune thyroiditis is characterized by 3 principal features:
1: Diffuse goitrous enlargement of the thyroid
2. Lymphocytic infiltration of the thyroid gland
3. Occurrence of thyroid autoantibodies

The classic form is characterized by diffuse, symmetric, firm and rubbery enlargement of the
thyroid which may weigh 100-300 gm. Sectioned surface of the thyroid is fleshly with
accentuation of normal lobulations but with retained normal shape of the gland. The
fibrosing variant has a firm, enlarged thyroid with compression of the surrounding tissues.

Pathology:
Histologically, the classic form shows the following features:
1: There is extensive infiltration of the gland by lymphocytes, plasma cells, immunoblasts
and macrophages, with formation of lymphoid follicles having germinal centres
2: There is decreased number of thyroid follicles which are generally atrophic and are often
devoid of colloid
3: The follicular epithelial cells are transformed into their degenerated state termed Hurthle
cells (also called Askanazy Cells, or Oxyphil cells, or Oncocytes). These cells have abundant
Oxyphilic or eosinophilic and granular cytoplasm due to large number of mitochondria and
contain large bizarre nuclei.
4: There is slight fibrous thickening of the septa separating the thyroid lobules. The less
common fibrosing variant of Hashimoto’s thyroiditis shows considerable fibrous
replacement of thyroid parenchyma and a less prominent lymphoid infiltrate.

Histologic features include: Lymphoid cell infiltration with formation of lymphoid follicles
having germinal centres; small, atrophic and colloid-deficient follicles; presence of Hurthle
cells which have granular Oxyphil cytoplasm and large irregular nuclei; and slight fibrous
thickening of lobular septa.
 130- Prostatic Hypoplasia

Macroscopic:
Appears round, with a thick wall and pale in color. In the center it is finely bubbled.
 Atrophic and hyperplastic glands
 Maintenance of lobular architecture but scanty cytoplasm
 Glands stand out at low power due to basophilic appearance
 Basal layer usually present
It is a common condition as men get older. An enlarged prostate gland can cause
uncomfortable urinary symptoms, such as blocking the flow of urine out of the bladder. It
can also cause bladder, urinary tract or kidney problems
As the prostate enlarges, it presses against the urethra. The bladder wall becomes thicker.
One day, the bladder may weaken and lose the ability to empty fully, leaving some urine in
the bladder. Narrowing of the urethra and urinary retention.

Pathology:
The prostatic stroma that surrounds the prostatic urethra extends dorsally and ventrally to
almost the limit of the prostate, whereas the lateral projections of the stroma are thinner.
These stromal projections subdivide the prostate into several lobules of glandular
epithelium. This epithelium is mostly columnar that modifies to cuboid within the ductal
structures of the prostate; meanwhile the epithelium of the prostatic urethra may be cuboid
or columnar, simple, or stratified

The prostatic urethra passes through the prostate gland, showing a urothelial (transitional)
epithelium, and the prostatic ducts have connection with the prostatic urethra. Then,
inflammatory cells infiltrating the prostatic stroma are common due to the constant
antigenic stimulus related with ascended bacteria contamination of the urinary system.
Thus, the prostatic stroma is composed by collagen fibers, fibroblast, smooth muscle (for
prostatic contraction), and few mononuclear inflammatory cells

In every case there is hyperplasia of all three tissue elements in varying proportions –
glandular, fibrous and muscular. Glandular component is made up of small and large Acini,
some showing papillary inholdings and projections containing central fibro vascular cores.
Some of the glands are cystically dilated. The stromal component often shows both fibrous
and smooth-muscle elements. A diffuse stromal infiltrate of lymphocytes and plasma cells in
a peri-glandular distribution is often found.

Complications – urethral obstruction ~> retention of urine ~> bladder hypertrophy and
cystitis ~> hydro ureter ~> hydronephrosis and pyelonephritis.

Both the glandular epithelial cells and the stromal cells (including muscular fibers) undergo
hyperplasia in BPH. Most sources agree that of the two tissues, stromal hyperplasia
predominates, but the exact ratio of the two is unclear.
 36+36a Cirrhosis of the Liver
Macroscopic:
Cirrhosis is a late stage of scarring (fibrosis) of the liver caused by many forms of liver
diseases and conditions, such as hepatitis and chronic alcoholism. Each time your liver is
injured — whether by disease, excessive alcohol consumption or another cause — it tries to
repair itself.

It is a chronic irreversible, progressive disease that ends with scarring of the entire organ
and its structural and functional rearrangement.

It represents the irreversible end-stage of several diffuse diseases causing hepatocellular

injury and is characterized by the following 4 features:
1. It involves the entire liver.
2. The normal lobular architecture of hepatic parenchyma is disorganized.
3. There is formation of nodules separated from one another by irregular bands of fibrosis.
4. It appears following hepatocellular necrosis of varying etiology so that there are alternate
areas of necrosis and regenerative nodules. However, regenerative nodules are not essential
for diagnosis of cirrhosis since biliary cirrhosis and cirrhosis in hemochromatosis have little
regeneration.

Pathology:
 Histologically: pseudolobuli of varying size delimited by septa, randomly located
central veins, connective tissue is infiltrated by inflammatory cells. Proliferation if
bile ducts.

 Gross morphology: loss of parenchyma, nodular regeneration by connective tissue, 3

morphological types of cirrhosis - micro nodular, macro nodular, and mixed. Small
liver.

 Inflammatory infiltration may be limited into the portal tracts without parenchymal
invasion or may be prominent with formation of lymphoid follicles, invading deeply
into parenchyma. It consists of Ly, Pl, Mph.
 Tumor Pathoanatomy
113- Endometrial Adenocarcinoma
Macroscopic:
To be seen are purple chunks with darkened mucosa.
Carcinomas are divided in 2 groups: Adenocarcinomas which develops in an organ or gland,
or Squamous Cell Carcinoma, which originates in the squamous epithelium.
Adenocarcinomas generally occur in mucus membranes and are first seen as a thickened
plaque-like white mucosa.

Pathology:
Characterized by increased number of glands which sometimes show back-to-back crowding
due to obliterated stroma. Poorly-differentiated adenocarcinoma my show solid sheets of
malignant cells.
he most common histologic pattern is well-differentiated adenocarcinoma showing closely
packed (back- to-back) glands with cytological atypia.
The tumor protrudes into the endometrial cavity as irregular, friable and grey-tan mass.
Extension of the growth into the myometrium may be identified by the presence of soft,
friable and granular tissue in cut section.
At an advanced stage- it may extend into the cervical canal, into the peritoneum, besides
lymphatic metastases to distant sites such as lungs, liver, bones and other organs.
Most endometrial carcinomas are ‘Adenocarcinomas’ due to their resemblance with normal
endometrium. Depending on their pattern of glands and individual cell changes, these may
be defined as:
1. Well Differentiated Adenocarcinoma (Predominantly Glandular)
2. Moderately- differentiated Adenocarcinoma (Glandular and partly solid areas)
3. Poorly- differentiated Adenocarcinoma (Predominantly solid)

- Papillary serous carcinoma of the endometrium resembling its ovarian counterpart

is distinct since it occurs in the background of atrophic endometrium and is more
aggressive.
- Uncommon histologic variants of endometrial carcinoma are: adenocarcinoma with
squamous metaplasia (adenoacanthoma), Adeno-squamous carcinoma (when both
components are frankly malignant), clear cell carcinoma, mucinous adenocarcinoma
and papillary serous carcinoma.

 Altered differentiation / metaplasia:

o Squamous, morular and mucinous differentiation are characteristically associated to
endometrioid type adenocarcinomas; generally, not observed in serous, clear cell or
other histotypes
o Squamous or "squamous" morular: usually banal but occasionally cytological malignant;
former can be glycogenated which imparts appearance of clear cytoplasm
o Secretory: sub / supra-nuclear vacuolization
o Ciliated / tubal: resembles fallopian tube lining; scattered cells with apical terminal bars
and ciliated
 Papillary type variants:
o Villoglandular
o Small non villous papillae and Micropapillae
62 - Leiomyoma of the Uterus
Macroscopic:
They are uniform and clustered in a big chunk
Leiomyoma or Fibromyomas as they are also known, are the most common uterine tumors
of the smooth muscle origin.
Symptomatic cases produce abnormal uterine bleeding, pain and symptoms due to
compression of surrounding structures and infertility. The cause is unknown, but probably
due to possible stimulus to their proliferation is estrogen.

Van Gienson’s stain may be used to distinguish between connective tissue and muscle
(Yellow and Red).

Uterine fibroids are noncancerous growths of the uterus that often appear during
childbearing years. Also called Leiomyomas or myomas, uterine fibroids aren't associated
with an increased risk of Uterine Cancer and almost never develop into cancer

Pathology:
Leiomyomas are most often located in the uterus, where they may occur in the
myometrium (intramural or interstitial), serosa, (subserosal) or just underneath the
endometrium (submucosa).
They are essentially composed of 2 tissue elements—whorled bundles of smooth muscle
cells admixed with variable amount of connective tissue. e smooth muscle cells are uniform
in size and shape with abundant cytoplasm and central oval nuclei.
Cellular leiomyoma has preponderance of smooth muscle elements and may superficially
resemble leiomyosarcoma but is distinguished from it by the absence of mitoses
The pathologic appearance may be altered by secondary changes in the Leiomyomas; these
include: hyaline degeneration, cystic degeneration, infarction, calcification, infection and
suppuration, necrosis, fatty change, and rarely, sarcomata’s change.

- Whorled (fascicular) pattern of smooth muscle bundles separated by well

vascularized connective tissue
- Smooth muscle cells are elongated with eosinophilic or occasional fibrillar cytoplasm
and distinct cell membranes
- May develop areas of degeneration if large including hyaline or mucoid change,
calcification, cystic change or fatty metamorphosis
- Usually no infiltrative, thick walled arteries throughout and cleft-like spaces
- May have extensive hyaline necrosis if protrudes into endometrial cavity
- Variable lymphocytes and mast cells
- Usually less than 5 mitotic figures per 10 high power fields in most mitotically active
area, no significant atypia
- Rarely has focal skeletal muscle differentiation
 99 - Invasive Cervical Squamous Cell Carcinoma
Macroscopic:
Appears light in purple in chunks with dark sections.
It is the most common type of pattern, at a rate of 70%. It is moderately differentiated with
non- keratinized large cell type and has a better prognosis.
What is Cervical Cancer (Squamous Cell Carcinoma of the Cervix) Cervix cancers may be of
the Squamous Cell Carcinoma type and usually arise from the epithelium lining the cervix.
90% of all carcinomas of the cervix are of the squamous cell type. The cervix is the
extension of the uterus into the top part of the vagina.
 Red, friable, indurated or ulcerated lesion or elevated granular area in early stage
tumors
 Exophytic, papillary, polypoid, nodular or ulcerated mass
 Deeply invasive mass with infiltration into surrounding structures
 Variable size

Pathology:
 It is an invasive epithelial tumor composed of neoplastic cells with varying degrees of
squamous differentiation
 Nearly all cases associated with it are at risk of the Human Papillomavirus (HPV) and
arise from a precursor lesion, high grade squamous intraepithelial lesion (HSIL)
 Tumor cells infiltrating as irregular anastomosing nests or single cells within
desmoplastic or inflammatory stroma
 Stromal loosening, desmoplasia or increased epithelial cell cytoplasmic eosinophilia
in tumors with superficial stromal invasion
 Lymph vascular invasion may be present
 Grading is based on nuclear pleomorphic, size of nucleoli, mitotic activity and
necrosis and does not correlate with prognosis
 Well differentiated: variably shaped and sized nests with abundant keratin
pearls, large cells with abundant eosinophilic cytoplasm and well developed
intercellular bridges, occasional mitoses, necrosis may be present
 Moderately differentiated: round to irregular and variably sized nests, cords and
sheets, focal keratinization, large to medium sized and relatively uniform cells
with indistinct cell borders, readily identifiable mitoses
 Poorly differentiated: small nests, cords and sheets and single cells, small cells
with scant cytoplasm, hyper-chromatic nuclei and brisk mitoses, absent or rare
keratinization
 Morphologic variants:
 Keratinizing, Irregular shaped keratinizing cells
 Keratin pearls, abundant keratohyaline granules and intercellular bridges
 Large, hyper-chromatic nuclei with coarse chromatin and inconspicuous
nucleoli
 Non-keratinizing
 Polygonal cells forming sheets or nests, large to medium sized non-
keratinizing cells
 Intercellular bridges but not keratin pearls
  Large, round and naked nuclei with unevenly distributed, coarsely granular
chromatin and one or multiple nucleoli
Kruckenberg’s Tumor

It is a bilateral tumor metastatic to the ovaries by transcoelomic spread. The tumor is

generally secondary to a gastric carcinoma, but other primary sites where signet ring
carcinomas occur (e.g. colon, appendix and breast) may also produce Kruckenberg’s tumor
in the ovary.
Kruckenberg’s tumor forms moderately large, rounded or kidney-shaped, firm, multilocular
masses in both ovaries. Cut section shows grey-white to yellow, firm, fleshy tumor and may
have areas of hemorrhage and necrosis.

Microscopically, it is characterized by the presence of mucin-filled signet ring cells which

may lie singly or in clusters. They lie in the tissues of the ovary; and when the primary tumor
is discovered, the same signet-ring cells are typically found. However, other microscopic
features can predominate. Kruckenberg’s tumors are most commonly metastases
from gastric cancer, particularly adenocarcinoma, or breast cancer particularly invasive
lobular breast carcinoma but they can arise in the appendix, colon, small intestine, rectum,
gallbladder, and urinary bladder or gallbladder, biliary tract, pancreas, ampulla of Vater
(opening of the duodenum from the Pancreas) or uterine cervix.

Brenner’s tumor

Brenner tumors are uncommon and comprise about 2% of all ovarian tumors. They are
characteristically solid ovarian tumors. Less than 10% of Brenner tumors are bilateral. Most
Brenner tumors are benign. Rarely, borderline form is encountered called proliferating
Brenner tumor while the one with carcinomatous change is termed malignant Brenner
tumor.
Histogenesis of the tumor is from coelomic epithelium by metaplastic transformation into
transitional epithelium (urothelium).

Grossly, Brenner tumor is typically solid, yellow-grey, firm mass of variable size.
Occasionally, a few scattered tiny cysts may be present on cut section.
Histologically, Brenner tumor consists of nests, masses and columns of epithelial cells,
scattered in fibrous stroma of the ovary. These epithelial cells resemble urothelial cells
which are ovoid in shape, having clear cytoplasm, vesicular nuclei with characteristic nuclear
groove called ‘coffee- bean’ nuclei.
 131- Prostatic Carcinoma
Macroscopic:
The prostate may be enlarged, normal in size and even smaller than normal. In 95% the
tumor is located mainly in the peripheral zone especially in the posterior lobe – it is firm,
homogenous yellowish. Large, pink, round shape - some paler parts.
The tumor is usually papillary, but may be flat or ulcerating. It is most commonly located on
the frenum or prepuce.
Prostate cancer is considered a malignant tumor because it can invade other areas of the
body. This invasion is called metastasis. Prostate cancer most commonly metastasizes to the
bones and lymph nodes, and may invade the rectum, bladder, and lower ureters after local
progression.

Pathology:
The most common morphologic type is “acinar type” where tumor is thought to arise from
or recapitulate prostatic Acini. Other uncommon variants exist including ductal,
neuroendocrine, and mucinous types among others. The acinar type (usual type) is
characterized by back-to-back proliferation of small to intermediate sized tumor Acini with
scant to moderate intervening stroma.

Hi – 4 histologic types are described:

 adenocarcinoma
 transitional cell carcinoma
 squamous cell carcinoma
 undifferentiated carcinoma.
Adenocarcinoma is the most common type and may be well - to poorly differentiated.
Glands are lined by single layer of clear, dark or eosinophilic cells. There is a pre-malignant
lesion – prostate intraepithelial neoplasia /PIN/.

There are also 4 types of Prostate Carcinoma:

1. Latent Carcinoma:
Is is found unexpectedly as a small focus of carcinoma in the prostate during autopsy studies
in men dying of other causes. Its incidence in autopsies has been variously reported as 25-
35%.

2. Incidental Carcinoma:
About 15-20% of prostatectomies done for BEP reveal incidental carcinoma of the prostate.

3. Occult Carcinoma:
Is is the type in which the patient has no symptoms of prostatic carcinoma but shows
evidence of metastases on clinical examination and investigations.

4. Clinical Carcinoma:
Clinical prostatic carcinoma is the type detected by rectal examination and other
investigations and confirmed by pathologic examination of biopsy of the prostate.
 133 -Granulomatous Orchitis
Macroscopically:
It appears as a solid, unilateral nodular enlargement of testis; resembles lymphoma. The
testes and epididymis are enlarged, tense and become very painful.

Etiology:
Many Bacteria, Viruses, fungi and parasites.
Orchitis is most often the result of a bacterial infection, such as a Sexually
Transmitted Infection (STI). In some cases, the mumps virus can cause Orchitis.
Most people with viral Orchitis start to feel better in three to 10 days, although it can take
several weeks for the scrotal tenderness to disappear.

Pathogenesis:
There can be an extension of the epididymitis both in non-sexually (e.g. E. Coli,
Pseudomonas, Brucellae) and Sexually (Gonorrhea and Chlamydia) transmitted conditions.

Microscopically:

 Lymphocytes and plasma cells infiltrate interstitium and surround seminiferous

tubules
 Giant cells and histiocytes that resemble (but are not) actual granulomas
 Granulomatous ischemic lesion:
o Zone of necrosis involving efferent ducts and interstitial connective tissue,
with adjacent lymphocytes and macrophages
o Macrophages form large clusters with cholesterol crystals and foreign body
type giant cells in duct lumen
o Also intra-tubular epithelial regeneration and proliferation of small ducts
showing epithelial regeneration and numerous spermatozoa in their lumen
o Associated with ceroid granuloma, spermatic granuloma and epidermoid
metaplasia of the efferent ducts

Acute non- specifically inflammatory reaction initially confined to the interstitium spreading
to involve tubules. Tissue breaking down with Pus formation may occur,
Edema leading to swelling and increased intra-testicular pressure which then leads to
ischemic damage. It can leave behind some scaring.
Ischemic Orchitis may result from damage to the blood vessels of the spermatic
cord during inguinal herniorrhaphy and may in the worst event lead to testicular atrophy.
 134 - Squamous cell carcinoma of the penis
Macroscopic:
Pink with much dark infiltration, look for dark line of epithelium
Squamous cell carcinoma may arise on any part of the skin and mucous membranes lined by
squamous epithelium.
Grossly, the tumor is located, in decreasing frequency, on frenum, prepuce, glans and
coronal sulcus. The tumor may be cauliflower-like and papillary, or at and ulcerating.
There is either a papillary mass (more common on glans) or ulcerating tumor (more
common on prepuce)

Etiology:
Risk is inversely related to circumcision particularly if carried out in early life. The presence
of phimosis (the inability to retract prepuce) is an additional risk factor. Also associated with
Human papilloma infection with type 16 found in 50% and type 18 in just under 10% of
cases.

Pathology:
Squamous cell carcinoma of both fungating and ulcerating type is generally well
differentiated to moderately-differentiated type which resembles in morphology to similar
cancer elsewhere in the body.
Papillary tumors tend to be well- differentiated keratinizing carcinomas while the ulcerated
lesions are poorly differentiated and highly invasive.

Squamous cell carcinoma consists of nests, sheets and strands of squamous epithelial cells
which arise from the epidermis and extend into the dermis for a
variable distance. The cells have abundant eosinophilic cytoplasm and a large, often
vesicular, nucleus similar to spinous layer of epidermis. There are prominent intercellular
bridges. There is variable central keratinization and horn pearl formation, depending on the
differentiation of the tumor. So well-differentiated are called keratinized squamous cell
carcinoma, and ‘moderately’ and ‘poorly’ differentiated are called non- keratinized
squamous cell carcinoma.
 101 Non- Invasive Intraductal Carcinoma
Macroscopic:
On small microscopic imaging, small or larger, poorly defined focus, firm with cheesy
necrotic material, /comedo type/ on cut section.
Ductal carcinoma is a common type of breast cancer that starts in cells that line the milk
ducts, which carry breast milk to the nipple. There are two types: Invasive ductal carcinoma
(IDC) Ductal carcinoma in situ (DCIS), also called Intraductal carcinoma.

DCIS is also called Intraductal carcinoma or stage 0 breast cancer. DCIS is a non-invasive or
pre-invasive breast cancer. This means the cells that line the ducts have changed to cancer
cells but they have not spread through the walls of the ducts into the nearby breast tissue.

Pathology:

 Papillary pattern
o Intraductal papillary projections, which
o lack the fibro vascular stalk
 Cribriform pattern -
o Papillary projections fuse each other into
o the duct lumen and form
o the cribriform pattern
 Solid pattern
o The ductal lumen is full and plugged of tumor cells
 Comedo pattern
o Small or larger necrotic areas appear
o through the solid mass of tumor
o cells. Higher recurrence rate

 It is called non-invasive because the cancer cells have not spread out of
the ducts and glands into the surrounding breast tissue.
 If left untreated, ductal carcinoma can lead to a more serious disease called invasive ductal
carcinoma.
 DCIS can be detected on mammograms by examining tiny specks of calcium known as micro
calcifications. Since suspicious groups of micro calcifications can appear even in the absence
of DCIS, a biopsy may be necessary for diagnosis.
 58 - Invasive Ductal Carcinoma
Macroscopic:
It appears dark purple with many round pale areas.
Grossly, the tumor is irregular, 15 cm in diameter, hard cartilage like mass that cuts with a
grating sound. e sectioned surface of the tumor is gray white to yellowish with chalky
streaks and often extends irregularly into the surrounding fat
At gross examination, the invasive carcinoma of the breast is a solid tumor, gray-whitish,
usually with irregular borders infiltrating the adjacent adipose tissue. The consistency is firm
to hard, due to the marked desmoplastic reaction sometimes with calcifications. Rarely, the
tumor can be well circumscribed and have a softer consistency. The dimensions of the
tumor range from 2 cm to 5 cm.

Pathology:
From Microscopically, this infiltrating ductal carcinoma of breast extends irregularly through
the stroma as cords and nests of neoplastic cells with intervening collagen. There is a
purplish micro-calcification at the lower center right. Neoplastic cells are not as robust or as
organized as normal cells and are more likely to undergo necrosis. Dystrophic calcification
can occur in these areas.

Histologically, as the name NOS suggests, the tumor is different from other special types in
lacking a regular and uniform pattern throughout the lesion. A variety of histologic features
commonly present:
 Anaplastic tumor cells forming solid nests, cords, poorly formed glandular structures
and some Intraductal foci.
 Infiltration by these patterns of tumor cells into di use fibrous stroma and fat.
 Invasion into perivascular and perineural spaces as well as lymphatic and vascular
invasion.

Anaplastic cells form solid nests, glandular structures, Intraductal foci. Invasion can involve
stroma, fat, perivascular & perineural spaces, lymph & blood vessels.

this infiltrating ductal carcinoma of breast has pleomorphic cells forming small nests
and irregular gland like structures. The carcinoma cells infiltrate through the collagenous
stroma. Note the abundant pink collagen bands from desmoplasia, which makes the tumor
feel firmer than normal surrounding breast tissue on palpation.
 57- Invasive Lobular Carcinoma
Macroscopic:
Classic invasive lobular carcinoma is seen diffusely infiltrating the whole specimen as single
cells and single files of cells.
Well to poorly defined firm area that may remain undetected.
Being more frequently bilateral; and within the same breast, it may have multi-centric
origin.
Invasive lobular carcinoma (ILC) is characterized by cells lacking cohesion, which arrange in a
linear fashion (single-file) within fibrous stroma. Over 90% of the tumor must be
morphologically lobular to be classified as such. There are also a number of histological
variants of ILC, including classic, alveolar, solid, pleomorphic, tubulolobular and those of
mixed phenotypes.

Pathology:
 Cells grow in single file, linear pattern and are loosely dispersed throughout fibrous
matrix
 Cells can often be seen encircling normal ducts (onion skin pattern)
 Variable dense fibrous stroma with periductal and perivenous elastosis
 Dense lymphoid infiltrate may accompany tumor at periphery
 Classic invasive lobular carcinomas will not show tubule formation and will
commonly be given a tubule score of 3 ( < 10% tubule formation)
 Tumor cells are usually small, uniform, round with minimal pleomorphic, evenly
dispersed chromatin and no nucleoli (nuclear grade 1 or 2, like LCIS cells)
 Commonly signet ring cells, intracellular Lumina and targetoid cytoplasmic mucin can
be seen
 Typically, not very mitotically active with < 10 mitoses/10 HPF without necrosis and
usually given a mitotic score of 1
 Most commonly tumors are of intermediate histologic grade (Nottingham grade 2)

Histologically, there are 2 distinct features-

 Pattern A characteristic single le (Indian le) linear arrangement of stromal infiltration
by the tumor cells with very little tendency to gland formation is seen. Infiltrating
cells may be arranged concentrically around ducts in a target like pattern.
 Tumor cytology Individual tumor cells resemble cells of in situ lobular carcinoma.
They are round and regular with very little pleomorphic and infrequent mitoses.
Some tumors may show signet- ring cells distended with cytoplasmic mucin.
 98- Dysplastic changes in uterine cervix
Macroscopic:
It looks amorphous purple chunk, find darker epithelium.
Cervical dysplasia is a precancerous condition in which abnormal cell growth occurs on the
surface lining of the cervix or endo cervical canal, the opening between the uterus and
the vagina. It is also called cervical intraepithelial neoplasia (CIN).

Pathology:
The abnormal growth of cells on the surface of the cervix. Cervical dysplasia is usually
caused by certain types of human papillomavirus (HPV) and is found when a Pap test or
cervical biopsy is done. It can be mild, moderate, or severe, depending on how abnormal
the cells look under a microscope and how much of the cervical tissue is affected. Cervical
dysplasia is not cancer, but may become cancer and spread to nearby normal tissue.

The cervix is the lower, narrow end of the uterus that forms a canal between the uterus and
vagina. Before cancer cells form in tissues of the cervix, the cells of the cervix go through
abnormal changes called dysplasia. There are different types of dysplasia. Mild dysplasia,
called low-grade intraepithelial lesion (LSIL) is one type. Moderate or severe dysplasia,
called high-grade intraepithelial lesion (HSIL) is another type of dysplasia. LSIL and HSIL may
or may not become cancer

CIN The dysplastic abnormalities are:

 crowding of cells
 pleomorphism
 high nuclear cytoplasmic ratio
 coarce, irregular nuclear chromatin
 many mitoses

Koilocytes features: Nuclear enlargement Irregularity of the nuclear membrane contour

Nuclear Hyperchroomasia, clear area around the nucleus (perinuclear halo).
Dysplastic changes often occur due to chronic irritation or prolonged inflammation. On
removal of the inciting stimulus, the changes may disappear. In a proportion of cases,
however, dysplasia may progress into carcinoma in situ (cancer con ned to layers superficial
to basement membrane) or invasive cancer.

Epithelial dysplasia is characterized by cellular proliferation and cytological changes as

under:
 Increased number of layers of epithelial cells
 Disorderly arrangement of cells from basal layer to the surface layer
 Loss of basal polarity i.e. nuclei lying away from basement membrane
 Cellular and nuclear pleomorphism
 Increased nucleo cytoplasmic ratio
  Nuclear hyper chromatism
 Increased mitotic activity.

The two most common examples of dysplastic changes are the uterine cervix and
respiratory tract.

49a- Squamous Papilloma

Macroscopic:
Squamous papilloma is an Exophytic overgrowth and projection of the soft tissue associated
with human papillomavirus (HPV), with the function of the surrounding structures spared. It
is usually benign and asymptomatic, appears as pedunculated, sessile or verrucous, and
usually depends on its location
Squamous papilloma is a benign epithelial tumor of the skin. Though considered by many
authors to include common viral warts (verrucae) and condyloma acuminata, true
squamous papilloma differs from these viral lesions. If these ‘viral tumors’ are excluded,
squamous papilloma is a rare tumor.

Histologically:
Histologically, squamous papillomas are characterized by hyperkeratosis, acanthosis with
elongation of rete ridges and papillomatosis. The verrucae, in addition to these features,
have foci of vacuolated cells in the acanthotic stratum Malpighi, vertical tiers of
parakeratosis between the adjacent papillae and irregular clumps of keratohyaline granules
in the virus-infected granular cells lying in the valleys between the papillae.
It is one of the Epidermal tumors that is characterized as Benign tumors.
Papilloma can occur anywhere in the mouth and has the usual papillary or finger-like
projections.
Microscopically, each papilla is composed of vascularized connective tissue covered by
squamous epithelium.
 53- Pleomorphic adenoma of the Parotid Gland
Macroscopic:
Pleomorphic adenoma is a circumscribed, pseudo- encapsulated, rounded, at times
multilobulated, firm mass, 2-5 cm in diameter, with bosselated surface. e cut surface is grey-
white and bluish, variegated, semi translucent, usually solid but occasionally may show
small cystic spaces. e consistency is soft and mucoid.
Most common benign tumor of the salivary glands is pleomorphic adenoma. It is composed
of epithelial and stromal elements.
Pleomorphic adenomas are benign salivary gland tumors, which predominantly affect the
superficial lobe of the parotid gland. The “pleomorphic” nature of the tumor can be
explained on the basis of its epithelial and connective tissue origin.

Pathology:
 Epithelial component may form various patterns like ducts, Acini, tubules, sheets
and strands of cells of ductal or myoepithelial origin. e ductal cells are cuboidal or
columnar, while the underlying myoepithelial cells may be polygonal or spindle-
shaped resembling smooth muscle cells. e material found in the Lumina of duct-like
structures is PAS-positive epithelial mucin. Focal areas of squamous metaplasia and
keratinization may be present.
Immunohistochemically, the tumor cells are immuno-reactive for epithelial
(cytokeratin, EMA, CEA) as well as myoepithelial (actin, vimentin and S-100)
antibodies.
 Stromal elements are present as loose connective tissue, and as myxoid, mucoid and
chondroid matrix, which simulates cartilage (pseudo cartilage). However, true
cartilage and even bone may also be observed in a small proportion of these tumors.
Based on morphology, immunohistochemistry, ultra- structure and molecular
characteristics, the mesenchymal matrix of the tumor has been assigned as a
product of epithelial origin and are actually modified myoepithelial cells as seen by S-
100 immunostain positivity.
e epithelial and mesenchymal elements are intermixed and either of the two
components may be dominant in any tumor.

 Metaplastic changes may be seen, e.g. adipose metaplasia, osseous metaplasia,

squamous metaplasia (sometimes with keratinization), sebaceous metaplasia and
mucinous metaplasia
 Intravascular permeation has been reported in a small percentage of cases and does
not increase the risk of recurrence or distant metastasis
o It is proposed to be a phenomenon associated with surgical manipulation (
 Other features that may be seen in pleomorphic adenoma include:
o Tyrosine crystal: dense amorphous eosinophilic floret shaped crystal
o Increased cellularity: so called cellular pleomorphic adenoma
 o Increased mitotic activity
o Myoepithelial rich area or tumor

112- Urothelial Carcinoma

Macroscopic:
It is made up of one or several purple shapes.
Transitional cell carcinoma, also called urothelial carcinoma, is a type of cancer that
typically occurs in the urinary system. It is the most common type of bladder
cancer and cancer of the ureter, urethra, and urachus. It accounts for 95% of bladder
cancer cases.
Micro papillary variant of urothelial carcinoma (UC) of the bladder is an aggressive tumor,
comprising 0.6-6% of all UC. It generally presents with high-grade and stage, and has been
reported as having a worse prognosis when compared to traditional UC.
Only about 1% of bladder cancers are adenocarcinomas. These cancer cells have a lot in
common with gland-forming cells of colon cancers. Nearly all adenocarcinomas of the
bladder are invasive.

Pathology:
The Urothelial cancer can be divided into papillary and non-papillary tumors depending on
the morphological appearance. Approximately 25% of all urothelial tumors are non-invasive
papillary tumors.
Tumor cells are graded according to the degree of nuclear atypia into four different grades,
including urothelial neoplasm of low malignant potential. The most malignant tumors are of
grade 3 and show at least focal areas of high-grade nuclear atypia and common mitotic
figures. Urothelial carcinoma grade 3 represents a tumor with more aggressive behavior and
increased risk for recurrence and metastatic spread.
Sarcomatoid variants of urothelial carcinoma exist and, furthermore, squamous cell
carcinomas and adenocarcinomas can develop in the urinary bladder. Squamous cell
carcinoma accounts for approximately 5% of all cancers in the urinary bladder. However, in
areas where schistosomiasis is endemic, squamous cell carcinomas account for
approximately 75% of all bladder carcinomas.

Different types of staging:

 T1 - lamina propria.
o Several subdivisions of T1 exist:
 T1a - superficial or in muscularis mucosae.
 T1b - beyond muscularis mucosae - into submucosa.
 T2 - muscularis propria.
Note:
 Approximately 25% of muscle invasive urothelial carcinoma on biopsy is a lower
stage in the cystectomy specimen.
o In approximately 15% of cases it is pT0 (no primary tumor identified).
 63- Lipoma
Macroscopic:
The slide itself seems really empty when looking at it- but then it resembled the alveolar-
like structure of the lungs.
A lipoma is a fatty tumor located just below the skin. It isn't cancer and is usually harmless.
A lipoma is a slow-growing, fatty lump that's most often situated between your skin and the
underlying muscle layer. A lipoma, which feels doughy and usually isn't tender, moves
readily with slight finger pressure.
 Bright yellow homogeneous fat with fine fibrous capsule (superficial lesions only)
and trabeculae
 May be very large (particularly if deep)
 Greasy cut surface

Pathology:
The mass is composed of lobules of mature white adipose tissue divided by fibrous septa
containing thin-walled capillary-sized vessels.
At low power magnification, a lipoma of the stomach is seen to be well demarcated from
the mucosa at the lower center right. This neoplasm is so well differentiated that, except for
its appearance as a localized mass, it is impossible to tell from normal adipose tissue. Benign
neoplasms are always well differentiated.
Lipomas are defined as mesenchymal tumors, which typically lie subcutaneously.[7] Less
commonly, they can also be found on internal organs, such as the stomach and bowels.
These masses are not typically attached to underlying muscle fascia. Lipomas are composed
of lobulated, slow-growing, mature adipose tissue, having minimal connective tissue stroma.
They are commonly enclosed in a thin, fibrous capsule.
Variants of lipoma defined by location include:
 Inter-muscular lipoma
 Intramuscular lipoma
 Parosteal / periosteal lipoma
 Lipoma arborescence (synovial lipomatosis)

 Superficial lipomas are most common:

upper back, shoulder, neck, and abdomen
Rare in hands, feet, lower legs, and face

 Deep lipomas may arise in deep soft tissues as well as:

thorax, mediastinum, pelvis, and, rarely, retro-peritoneum
May also occur near bone (periosteal/Parosteal lipoma)

 Intramuscular lipoma is most common within:

large muscles of thigh, upper arm, and shoulder
 64- Chondroma
Macroscopic:
On the slide, there is a big chunk of purple.
Chondroma is a lesion of mature hyaline cartilage that may be located centrally within the
bone (enchondroma) or may arise either in or beneath the periosteum (periosteal or
cortical Chondroma, respectively). It is a neoplasm of mature hyaline cartilage.
Grossly, the enchondroma is lobulated, bluish-grey, translucent, cartilaginous mass lying
within the medullary cavity.

 Lobulated on low power

 Plump tumor cells with fine punctate calcification
 Nuclear Hyperchroomasia common
 May have focal fibrosis
 May have osteoclast-like giant cells, histiocytes-like cells, vacuoles resembling
lipoblasts
 Well- circumscribed lobulated masses o bluish firm cartilage. Overlying bone is
thinned/eroded

Pathology:
The most common locations are the metaphyseal region of short tubular bones of hands
and feet.
Chondroma is a benign cartilage in bone tumor, encapsulated, with a lobular growing
pattern. Tumor cells (chondrocytes, cartilaginous cells) resemble normal cells and produce
the cartilaginous matrix (amorphous, basophilic material). Characteristic are the vascular
axes within the tumor, which make the distinction with normal hyaline cartilage.
Tumor shows stages of cartilage formation. Mesenchymal tissue is seen at periphery. Most
mature cartilage is seen at center. Consists of highly vaculated physaliphorous cells
surrounded my mucoid material. Gross: soft lobule gelatinous with areas of hemorrhages.

The coexistence of multiple enchondroma with multiple soft tissue haemangioma

constitutes a familial syndrome called Maffucci’s syndrome. There is also Ollier’s syndrome
that involves multiple unilateral enchondromas.
Maffucci’s syndrome is a disorder that primarily affects the bones and skin. It is
characterized by multiple enchondromas (benign enlargements of cartilage), bone
deformities, and haemangioma (tangles of abnormal of blood vessels).
Most common locations for enchondroma are short tubular bones of the hands and feet,
and less commonly, they involve the ribs or the long bones.

Histologically, the tumor has characteristic lobulated appearance. e lobules are composed
of normal adult hyaline cartilage separated by vascularized fibrous stroma. Foci of
calcification may be evident within the tumor. Enchondroma is distinguished from
chondrosarcoma by the absence of invasion into surrounding tissues and lack of cellular
features of malignancy.
Lobules of mature hyaline cartilage surrounded by vascularized fibrous stroma.
Chondrocytes irregular distributed. Occasionally dark nuclei and binuclear forms may be
seen (not indicative of malignancy in children but more sinister in adults.

65- Cavernous Haemangioma of Liver

Macroscopic:
On the slide, it looks and appears as - pink-red squarish chunk.
Haemangioma is the commonest benign tumor of the liver. Majority of them are
asymptomatic and discovered incidentally. Rarely, a haemangioma may rupture into the
peritoneal cavity.
Grossly, haemangioma appear as solitary or multiple, circumscribed, red-purple lesions,
commonly subscapular and varying from a few millimeters to a few centimeters in diameter.
They are commonly cavernous type giving the sectioned surface a spongy appearance.

Pathology:
The Haemangioma are lined by endothelial cells with a thin fibrous stroma. They are also
known as cavernous or capillary hepatic haemangioma.
Large, cavernous blood-filled spaces, lined by single layer of epithelium, separated by
connective tissue. May later undergo fibrosis/calcification.

Histologically, haemangioma of the liver shows characteristic large, cavernous, blood-filled

spaces, lined by a single layer of endothelium and separated by connective tissue. Some
haemangioma may undergo progressive fibrosis and may later get calcified.
Hemangiomas of the liver are usually of cavernous type. They consist of variably-sized
vascular channels lined by flattened endothelial cells. The vascular channels are separated
by fibrous stroma. Organizing thrombi are frequently present and as they
undergo sclerosis, the entire lesion may be replaced by a fibrous nodule.

Higher magnification show large dilated vascular spaces separated by thin fibrous
septa. Secondary changes such as hyalinization and calcification may be seen in chronic
cases.

Treatment & Prognosis: Asymptomatic cavernous hemangiomas discovered incidentally on

imaging studies are not treated. Symptomatic lesions can be surgically excised. The
prognosis is excellent.

 Cavernous hemangiomas
o Circumscribed proliferation of variably sized, dilated and thin walled vessels
lined by a single layer of flat endothelial cells
o No cytologic atypia or mitosis
o Vascular spaces separated by fibrous septa containing small vessels
o Focal thrombi, calcification, hyalinization, extra medullary hematopoiesis and
stromal edema may be present
o May have irregular interface with surrounding hepatic parenchyma
  Sclerosing / sclerosed haemangioma
o Abundant fibrotic stroma that compresses and replaces lesion vessels
o Only vague outline of residual vessels may be present; elastin or trachoma
may aid in highlighting such vessels
 Capillary haemangioma
o Lobular proliferation of small, thin walled vessels lined by a single layer of
bland endothelial cells
68- Osteosarcoma
Macroscopic:
The slide appears as a pink square- like chunk.
Osteosarcoma is a malignant neoplasm of the bone and is the most common histological
form of primary bone cancer. It is most prevalent in children and young adults, as it is
associated with the formation and growth of bone.
Osteosarcoma or osteogenic sarcoma is the most common primary malignant tumor of the
bone. The tumor is characterized by formation of osteoid or bone, or both, directly by
sarcoma cells. The tumor is thought to arise from primitive osteoblast-forming
mesenchyme. Depending upon their locations within the bone, osteosarcomas are classified
into 2 main categories: central (medullary or classic) and surface (Parosteal and periosteal).

Pathology:
The disease Osteosarcoma is composed of spindle cells. The pink osteoid formation seen
here is consistent with differentiation that suggests osteosarcoma.
Sarcoma cells characterized by variation in cellular size and shape containing Osteoid and
Osteoclast –like giant cells.

Histologically, osteosarcoma shows considerable variation in pattern from case-to-case and

even within a tumor from one area to the other. However, the following two features
characterize all classic forms of osteosarcomas
1. Sarcoma cells
The tumor cells of osteosarcomas are undifferentiated mesenchymal stromal cells which
show marked pleomorphism and polymorphism i.e. variation in size as well as shape. e
tumor cells may have various shapes such as spindled, round, oval and polygonal and bizarre
tumor giant cells. The tumor cells have variable size and show hyperchromatism and
atypical mitoses. Histochemically, these tumor cells are positive for alkaline phosphatase.
Immunohistochemically, sarcoma cells of osteosarcoma express vimentin, osteocalcin,
osteonectin and type I collagen.
2. Osteogenesis
The anaplastic sarcoma cells form osteoid matrix and bone directly; this is found
interspersed in the areas of tumor cells. In addition to osteoid and bone, the tumor cells
may produce cartilage, fibrous tissue or myxoid tissue.

There are 5 different variants

 62a- Leimyosarcoma
Macroscopic:
Leimyosarcoma is a rare type of cancer that begins in smooth muscle tissue. Smooth muscle
tissue is found in many areas of the body, such as the digestive system, urinary system,
blood vessels and uterus. Leimyosarcoma most often begins in the abdomen or uterus.
Grossly, the tumor may be of variable size but is usually quite large, pedunculated and
lobulated mass into the lumen.
Aside from colorectal carcinoma, other malignant tumors which are encountered
sometimes in the large bowel are Leimyosarcoma. The site that is affected is the Smooth
muscle of the myometrium.

Pathology:
Microscopically, Leimyosarcoma is characterized by high cellularity and presence of mitotic
figures. Tumor is usually well-differentiated.
Cellular leiomyoma has preponderance of smooth muscle elements and may superficially
resemble Leimyosarcoma but is distinguished from it by the absence of mitoses.

Histologically, though there are usually some areas showing whorled arrangement of
spindle-shaped smooth muscle cells having large and hyper chromatic nuclei, the hallmark
of diagnosis and prognosis is the number of mitoses per high power field (HPF). The
essential diagnostic criteria are: more than 10 mitoses per 10 HPF with or without cellular
atypia, or 5-10 mitoses per 10 HPF with cellular atypia. More the number of mitoses per
10HPF worse are the prognosis. Leimyosarcoma is liable to recur after removal and
eventually metastasizes to distant sites such as lungs, liver, bone and brain.

Soft Tissue Leimyosarcoma is a relatively rare malignant tumor. It may be difficult to be

distinguished from gastrointestinal stromal tumors and Schwann cell neoplasms. To make a
correct identification of soft tissue Leimyosarcoma, Immunostaining with several smooth
muscle differentiation markers (actin, calponin and desmin), and negative staining results
with S100 (to rule out Schwann cell neoplasm), c-kit and CD34 (to rule out gastrointestinal
stromal tumors) is needed.
 74- Neurinoma
Macroscopic:
It is a benign tumor that may develop on the hearing and balance nerves near the inner ear.
The tumor results from an overproduction of Schwann cells -- small sheet-like cells that
normally wrap around nerve fibers like onion skin and help support the nerve
Schwannoma is most commonly seen as a gray or red mottled edematous mass in the
subcutis of the flank or neck area near the salivary glands;
Tumors of the peripheral nerves are commonly benign and include Schwannoma
(neurilemmoma) and neurofibroma. Both of them arise from Schwann cells but
neurofibroma contains large amount of collagen. Rarely, their malignant counterpart,
malignant peripheral nerve sheath tumor, develops particularly in patients with von
Recklinghausen’s neurofibromatosis.

 Usually solitary
 Capsule derived from the epineurium
 Nerve of origin may be present at the periphery - does not penetrate substance of
tumor
 Dumbbell tumor: in posterior mediastinum, originates from or extends into vertebral
canal
 Small tumors may be difficult to differentiate from neurofibroma due to the fusiform
appearance
 Large tumors have an eccentric position in relation to the nerve
 Cut section is light tan and glistening and may show yellow patches
 Large tumors may be cystic

Pathology:
 Biphasic: compact hypercellular Antoni A areas and myxoid hypocellular Antoni
B areas (may be absent in small tumors)
 Nuclear palisading around fibrillary process (Verocay bodies) is often seen in cellular
areas
 Large, irregularly spaced vessels are most prominent in Antoni B areas
 Cells are narrow, elongated and wavy with tapered ends interspersed with collagen
fibers
 Tumor cells have ill defined cytoplasm, dense chromatin
 Often displays degenerative nuclear atypia (ancient change)
 Rare mitotic figures
 Blood vessels may show gaping tortuous lumina having thickened hyalinized walls;
may have thrombi
 Dilated vessels surrounded by or invested by hemorrhage can be seen
 May have foamy macrophages
  Lymphoid aggregates
 Amianthoid fibers or collagenous spherules: large nodular masses of collagen with
radiating edges
 No axons except where nerve is attached
 Malignant transformation can show malignant epithelioid cells and may rarely show
divergent differentiation as angiosarcoma-like areas

75- Meningioma
Macroscopic:
Meningiomas are tumors that are derived from the meningothelial cells, the epithelial cells
of the meninges. They are common intracranial tumors, and have a female preponderance.
They are typically rounded lesions that arise from the Dura and grow slowly to compress the
underlying brain.
Size can vary from 1 or 2 cm up to 7cm. Although most lesions are solitary, they may be
multiple. Infiltration of the skull by tumor may occur, causing local bony thickening.
The most common tumor arising from the Pia-arachnoid is meningioma accounting for 20%
of intracranial tumors.

Pathology:
Microscopically, Meningiomas are divided into 5 subtypes:
Meningotheliomatous (syncytial), fibrous (fibroblastic), transitional (mixed), angioplasty
and anaplastic (malignant)
1. Meningotheliomatous (syncytial) meningioma. This pattern of meningioma
resembles the normal arachnoid cap cells. The tumor consists of solid masses
of polygonal cells with poorly-defined cell membranes (i.e. syncytial
appearance). The cells have round to oval, central nuclei with abundant,
finely granular cytoplasm. Some amount of collagenous stroma is present
that divides the tumor into irregular lobules.
2. Fibrous (fibroblastic) meningioma. A less frequent pattern is of a spindle-
shaped fibroblastic tumor in which the tumor cells form parallel or interlacing
bundles. Whorled pattern and psammoma bodies are less common features
of this type.
3. Transitional (mixed) meningioma. This pattern is characterized by a
combination of cells with syncytial and fibroblastic features with conspicuous
whorled pattern of tumor cells, often around central capillary-sized blood
vessels. Some of the whorls contain psammoma bodies due to calcification of
the central core of whorls (Fig. 30.17). Other forms of degenerative changes
like xanthomatous and myxomatous degeneration may also be encountered,
in transitional variety. These first three histologic patterns constitute a
spectrum of lesions rather than three distinct entities.
4. Angioplasty meningioma. An angioblastic meningioma includes 2 patterns:
haemangioblastic pattern resembling haemangioblastoma of the cerebellum,
and haemangiopericytic pattern which is indistinguishable from
haemangiopericytoma elsewhere in the body. Both types of angioblastic
meningiomas have high rate of recurrences.
5. Anaplastic (malignant) meningioma. Rarely, a meningioma may display
features of anaplasia and invade the underlying brain or spinal cord. This
 pattern of meningioma is associated with extraneural metastases, mainly to
the lungs.

72- Malignant Melanoma

Macroscopic:
They are malignant tumors that are derived from the melanocytes, usually identifiable by
their melanin content.
Malignant melanoma or melanocarcinoma arising from melanocytes is one of the most
rapidly spreading malignant tumors of the skin that can occur at all ages but is rare before
puberty. The tumor spreads locally as well as to distant sites by lymphatic and by blood.
Some high risk factors associated with increased incidence of malignant melanoma are as
under:
i) Persistent change in appearance of a mole.
ii) ii) Presence of pre-existing naevus (especially dysplastic naevus).
iii) iii) Family history of melanoma in a patient of atypical mole. Higher age of the
patient.
iv) iv) More than 50 moles 2 mm or more in diameter

Pathology:
i) Lentigo maligna melanoma. This often develops from a pre-existing lentigo (a flat
naevus characterized by replacement of basal layer of epidermis by naevus cells).
It is essentially a malignant melanoma in situ. It is slow growing and has good
prognosis.
ii) Superficial spreading melanoma. This is a slightly elevated lesion with variegated
color and ulcerated surface. It often develops from a superficial spreading
melanoma in situ (pagetoid melanoma) in 5 to 7 years. The prognosis is worse
than for lentigo maligna melanoma.
iii) Acral lentigenous melanoma. This occurs more commonly on the soles, palms
and mucosal surfaces (Fig. 26.30). The tumor often undergoes ulceration and
early metastases. The prognosis is worse than that of superficial spreading
melanoma.
iv) Nodular melanoma. This often appears as an elevated and deeply pigmented
nodule that grows rapidly and undergoes ulceration. This variant carries the
worst prognosis

Melanin pigment may be present (melanotic) or absent (amelanotic melanoma) without any
prognostic influence. The pigment, if present, tends to be in the form of uniform fine
granules (unlike the benign naevi in which coarse irregular clumps of melanin are present).
At times, there may be no evidence of melanin in H&E stained sections but Fontana-Masson
stain or DOPA reaction reveals melanin granules in the cytoplasm of tumor cells.
Immunohistochemically, melanoma cells are positive for HMB-45 (most specific), S-100 and
Melan-A.
 84- Undifferentiated Small cell Carcinoma of then Lungs
Macroscopic:
Small cell carcinomas are frequently hilar or central in location, have strong relationship to
cigarette smoking and are highly malignant tumors. They are most often associated with
ectopic hormone production because of the presence of neurosecretory granules in
majority of tumour cells which are similar to those found in argentaffin or Kulchitsky cells
normally found in bronchial epithelium.
- small cell carcinoma (about 90%);
- combined small cell carcinoma (about 10%)
Although it is possible to distinguish a number of different histological sub-classes of lung
cancer by light microscopy, the most important current clinical distinction is between small
cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Based primarily on its
clinical behavior, SCLC, a neuroendocrine lesion, is considered as a separate entity to the
non-small cell carcinomas.
In a person with small cell cancer, the cancerous cells appear small and round under a
microscope. The cells of non-small cell lung cancer are larger.
By immunohistochemistry, these tumour cells are positive for neuroendocrine markers:
chromogranin, neuron-specific enolase (NSE) and synaptophysin. Small cell carcinomas have
3 subtypes:
o Oat cell carcinoma is composed of uniform, small cells, larger than
lymphocytes with dense, round or oval nuclei having diffuse chromatin,
inconspicuous nucleoli and very sparse cytoplasm (oat = a form of grain).
These cells are organized into cords, aggregates and ribbons or around small
blood vessels forming pseudorosettes.
o Small cell carcinoma, intermediate cell type is composed of cells slightly
larger than those of oat cell carcinoma and have similar nuclear
characteristics but have more abundant cytoplasm. These cells are organised
into lobules.
o Combined oat cell carcinoma is a tumour in which there is a definite
component of oat cell carcinoma with squamous cell and/or adenocarcinoma
Pathology:
 Round / oval blue cells with minimal cytoplasm; usually small to medium sized
 Nuclear features: finely dispersed chromatin, no distinct nucleoli, molding,
smudging, high mitotic rate
 Stroma: thin, delicate, scant, fibrovascular
 Necrosis and apoptosis of individual cells common
 Patterns: sheets, clusters, ribbons, rosettes, peripheral palisading
  Other / rarer feature:
 Azzopardi phenomena: basophilic nuclear material lining blood vessel walls
 Metastatic cells usually have more cytoplasm
 Scattered giant cells

113a- Serous papillary adenocarcinoma of the Ovary

Macroscopic:
Serous surface papillary carcinoma of the ovary is a rare peritoneal neoplasm found in
postmenopausal women that is histologically characterized by an exophytic papillary tumor
originating from the surface epithelium of the ovary.
Histologically, the ovarian structure consists of covering by coelomic epithelium, outer
cortex and inner medulla.
They are called serous tumors because of the presence of clear, watery, serous fluid in these
predominantly cystic tumors. Majority are bilateral.
Histogenesis of the serous tumors is by metaplasia from the surface (coelomic) epithelium
or mesothelium which differentiates along tubal-type of epithelium.

Pathology:
Cyst-adenocarcinoma has multilayered malignant cells which show loss of polarity, presence
of solid sheets of anaplastic epithelial cells and definite evidence of stromal invasion.
Papillae formations are more frequent in malignant variety and may be associated with
psammoma bodies but mere presence of psammoma bodies is not indicative of malignancy.
Psammoma bodies can be found in organs such as the thyroid, ovaries, endometrium, and
the lining of the central nervous system. They are involved in both cancerous and benign
tumors, and can also be a sign of chronic inflammation.
 Papilla growing from the wall
inwards towards the Lumen of
the Cyst; Its Fibro vascular Axis

86- Chronic Myelogenous Leukemia

Macroscopic:
Chronic Myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a cancer
of the white blood cells. It is a form of leukemia characterized by the increased and
unregulated growth of myeloid cells in the bone marrow and the accumulation of these
cells in the blood. It is associated with Philadelphia Chromosome in more than 95% of the
cases it is found in all haemopoietic cell lines.
By WHO definition, CML is established by identification of the clone of hematopoietic stem
cell that possesses the reciprocal translocation between chromosomes 9 and 22, forming
Philadelphia chromosome.
Pathology:
The bone marrow is grossly hypercellular mainly due to neutrophils and their precursors
with an increase in the immature: mature ratio. The cytoplasm of the immature cells
appears to mature more rapidly than the nucleus. Megakaryocytes show hypolobation.
In Juvenile, the laboratory finding show Thrombocytopenia, which Is a WBC that is lower
than in Classic CML, and an increase in the proportion of fetal hemoglobin.

Bone marrow (chronic phase):

o Hypercellular marrow with absolute myeloid hyperplasia and myelocyte bulge
o Myeloid to erythroid ratio ≥ 10:1
o Layer of immature granulocytes (5 - 10 cells in thickness) around the bone
trabeculae (2 - 3 cells layer in normal marrow)
o No significant dysplasia
Bone marrow (accelerated phase):
- 10 - 19% blasts
- Large clusters or sheets of small, abnormal megakaryocytes associated with marked
reticulin or collagen fibrosis may be considered presumptive evidence of accelerated
phase
Bone marrow (blast phase):
- ≥ 20% blasts in marrow or blood or the presence of an extra medullary proliferation
of blasts
- Approximately 70% have myeloid blasts (may include neutrophil, monocytes,
megakaryocytic, basophilic, eosinophilia or elytroid blasts) and approximately 30%
have lymphoid blasts (usually B lymphoblast but T and NK blasts have been reported)
-
87- Chronic Lymphocytic Leukemia- Liver
Macroscopic:
Infiltration of the Liver by hematologic malignancies is an uncommon cause of liver failure.
B-Cell Chronic Lymphocytic Leukemia (CLL) is a usually indolent disease that may infiltrate
the liver, but based on a review of the literature, has never been reported to induce
acute liver failure. Chronic lymphocytic leukemia involving the liver. The leukemic infiltrates
are confined to the portal tracts.
The small Whitish-Gray Nodules scattered throughout the parenchyma represent Leukemic
infiltrates in the Periportal areas
Pathology:
Leukemia is a monoclonal malignant proliferation of stem cells of bone marrow, with
replacement of normal bone marrow by leukemic cells, accumulation in peripheral blood
and infiltration of organs (i.e., lymph nodes, spleen, liver, kidney).
As a result of bone marrow infiltration, one or all series are suppressed, generating
pancytopenia (anemia, neutropenia and thrombocytopenia). Leukemia classification, based
upon clinical and histogenetic criteria: Acute Leukemias (proliferation of young, immature
elements) Chronic Leukemias (monoclonal proliferation of non-functional lymphoid and
myeloid elements) Lymphocytic (lymphoid) Granulocytic (myeloid) Chronic lymphocytic
(lymphoid) leukemia is a malignant lymphoid proliferation, similar to a low-grade
lymphoma, but affecting mainly the bone marrow and the peripheral blood.

Chronic lymphocytic (lymphoid) leukemia (liver). Tumor lymphocytic infiltrate into the portal
tracts, which appear very enlarged, lacking normal structures. These tumor lymphoid cells
resemble normal lymphocytes (small, monomorphic, round hyperchromatic homogenous
nuclei, reduced cytoplasm), but are immature, monoclonal and non-functional. With
evolution, the tumor cells will infiltrate the lobules.

88a- Hodgkin’s Disease- Mixed Cellular Type

Macroscopic:
Hodgkin's disease (HD) is a type of Lymphoma, which is a blood cancer that starts in the
lymphatic system. The lymphatic system helps the immune system get rid of waste and fight
infections. HD is also called Hodgkin disease, Hodgkin lymphoma, and Hodgkin's
lymphoma.
Hodgkin’s disease (HD) primarily arises within the lymph nodes and involves the Extranodal
sites secondarily.

Pathology:
1. Lymphocyte-predominance type
The lymphocyte-predominance type of HD is characterized by proliferation of small
lymphocytes admixed with a varying number of histiocytes forming nodular or di use
pattern.
 Nodular form is characterized by replacement of nodal architecture by numerous
large neoplastic nodules.
 Diffuse form does not have discernible nodules but instead there is di use
proliferation of cells.

2. Nodular-sclerosis type
Nodular sclerosis is the most frequent type of HD, seen more commonly in women than in
men. It is characterized by two essential features.
 Bands of collagen: Variable amount of fibrous tissue is characteristically present in
the involved lymph nodes. Occasionally, the entire lymph node may be replaced by
dense hyalinised collagen.
 Lacunar type RS cells: Characteristic lacunar type of RS cells with distinctive
pericellular halo are present. These cells appear lacunar due to the shrinkage of
cytoplasm in formalin fixed tissue. e pericellular halo is not seen if the tissue is fixed
in Zenker’s fluid. In addition to these 2 characteristics, the nodules between the
fibrous septa consist predominantly of lymphocytes and macrophages, sometimes
with foci of necrosis.

3. Mixed-cellularity type
 This form of HD generally replaces the entire affected lymph nodes by
heterogeneous mixture of various types of apparently normal cells. These include
proliferating lymphocytes, histiocytes, eosinophils, neutrophils and plasma cells.
Some amount of fibrosis and focal areas of necrosis are generally present. Typical RS
cells are frequent

RS Cells = Reed–Sternberg cells (also known as lacunar histiocytes for certain types) are
distinctive, giant cells found with light microscopy in biopsies from individuals with Hodgkin
lymphoma. They are usually derived from B lymphocytes, classically considered crippled
germinal center B cells.

94- Thyroid Papillary Adenocarcinoma

Macroscopic:
Papillary carcinoma (PTC) is the most common form of well-differentiated thyroid cancer,
and the most common form of thyroid cancer to result from exposure to radiation. Papillary
carcinoma appears as an irregular solid or cystic mass or nodule in a
normal thyroid parenchyma.
It can occur at all ages including children and young adults but the incidence is higher with
advancing age. The tumor is found about three times more frequently in females than in
males.
Grossly, papillary carcinoma may range from microscopic foci to nodules up to 10 cm in
diameter and is generally poorly delineated. Cut surface of the tumor is greyish-white, hard
and scar-like. Sometimes the tumor is transformed into a cyst, into which numerous papillae
project and is termed papillary cyst adenocarcinoma.

Pathology:
Histologically, the following features are present:
1. Papillary pattern:
Papillae composed of fibro vascular stalk and covered by single layer of tumor cells is
the predominant feature. Papillae are often accompanied by follicles.
2. Tumor cells:
The tumor cells have characteristic nuclear features due to dispersed nuclear
chromatin imparting it ground glass or optically clear appearance and clear or
oxyphilic cytoplasm. These tumor cells, besides covering the papillae, may form
follicles and solid sheets.
3. Psammoma bodies:
Half of papillary carcinomas show typical small, concentric, calcified spherules called
Psammoma bodies in the stroma

Microscopy shows branching papillae having fibro vascular stalk covered by a single layer of
cuboidal cells having ground-glass nuclei (inbox). Colloid- filled follicles and solid sheets of
tumor cells are also present.
71- Choriocarcinoma
Macroscopic:
Choriocarcinoma is a malignant, trophoblastic cancer, usually of the placenta. It is
characterized by early Haematogenous spread to the lungs. It belongs to the malignant end
of the spectrum in Gestational Trophoblastic Disease (GTD). It is also classified as a germ cell
tumor and may arise in the testis or ovary.
Choriocarcinoma in females is of 2 types—Gestational and non- Gestational. Gestational
choriocarcinoma of placental origin is more common and considered separately later. Pure
primary non-gestational choriocarcinoma of ovarian origin is rare while its combination with
other germ cell tumors is seen more often.

Choriocarcinoma, which is a rare, highly malignant tumor that may be associated

with sexual precocity, can arise in one of three ways:

 As a primary gestational choriocarcinoma associated with ovarian pregnancy

 As a metastatic choriocarcinoma from a primary gestational choriocarcinoma arising

in other parts of the genital tract, mainly the uterus

 As a germ cell tumor differentiating in the direction of trophoblastic structures and

arising admixed with other neoplastic germ cell elements

Choriocarcinoma of the ovary may also be divided into two broad groups:
1. Gestational choriocarcinoma, encompassing the first two groups mentioned above

2. Non-gestational choriocarcinoma, a germ cell tumor that differentiates toward

trophoblastic structures

Pathology:
Microscopically, the characteristic features are as under:
i) Absence of identifiable villi.
ii) Masses and columns of highly anaplastic and bizarre cyto trophoblast and
syncytiotrophoblasts cells which are intermixed.
iii) Invariable presence of hemorrhages and necrosis.

131- Adenocarcinoma of Prostate Gland

Macroscopic:
An adenocarcinoma is a type of cancer that arises in the cells of glands. Most cells in
the prostate gland are of the glandular type, which means that adenocarcinoma is the most
common type of cancer to occur in the prostate.
Thus, it is common to classify carcinoma of the prostate into the following 4 types:
1. Latent carcinoma: is this found unexpectedly as a small focus of carcinoma in the
prostate during autopsy studies in men dying of other causes. Its incidence in autopsies has
been variously reported as 25-35%.
2. Incidental carcinoma: About 15-20% of prostatectomies done for BEP reveal incidental
carcinoma of the prostate.
3. Occult carcinoma: is this the type in which the patient has no symptoms of prostatic
carcinoma but shows evidence of metastases on clinical examination and investigations.
4. Clinical carcinoma: Clinical prostatic carcinoma is the type detected by rectal examination
and other investigations and con formed by pathologic examination of biopsy of the
prostate.

Pathology:
 Pattern depends on Gleason grade
 Small glands, sometimes medium to large glands, papillary or cribriform glands or
solid growth, single cells or necrosis
 Cytoplasm usually finely granular, may be clear/foamy due to intracellular lipid
 Nuclear enlargement, Hyperchroomasia, prominent nucleoli (>3 microns is specific
for malignancy, >1 micron is suggestive)
 75% of high grade PIN may abuts carcinoma

1. Architectural disturbance: In contrast to convoluted appearance of the glands seen

in normal and hyperplastic prostate, there is loss of intra-acinar papillary
convolutions. e groups of Acini are either closely packed in back-to-back
arrangement without intervening stroma or are haphazardly distributed.

2. Stroma Normally: Fibro muscular sling surrounds the Acini, whereas malignant Acini
have little or no stroma between them. The tumor cells may penetrate and replace
the fibro muscular stroma.

3. Tumor cells e outer basal layer seen in the normal or benign Acini is lost. e tumor
cells may be clear, dark and eosinophilic cells. Clear cells have foamy cytoplasm, dark
cells have homogeneous basophilic cytoplasm, and eosinophilic cells have granular
cytoplasm. e cells may show varying degree of anaplasia and nuclear atypia but is
generally slight.

20-PAS- Gastric Cancer

Macroscopic:
Gastric carcinoma is most commonly located in the region of gastric canal (pre-pyloric
region) formed by lesser curvature, pylorus and antrum. Other less common locations are
the body, cardia and fundus.
Pathogenically, a sequential evolution of all gastric carcinomas from an initial stage of in situ
carcinoma con ned to mucosal layers called early gastric carcinoma (EGC) has been found.
EGC eventually penetrates the muscularis or beyond, resulting in advanced gastric
carcinoma. Accordingly, gastric carcinomas are broadly classified into 2 main groups:
. Early gastric carcinoma (EGC).
. Advanced gastric carcinoma (which has 5 further major gross subtypes):
 Ulcerative carcinoma
 Fungating (Polypoid) carcinoma
 Scirrhous carcinoma(Linitisplastica)
 Colloid(Mucoid)carcinoma
 Ulcer-cancer

Early Gastric Carcinoma

It must be distinguished from certain related terms as under:
  Epithelial dysplasia is cellular atypia seen in intestinal metaplasia such as in atrophic
gastritis and pernicious anemia.

 Carcinoma in situ in the stomach is a state of severe cellular atypia or dysplasia,

without invasion across the basement membrane of the glands.

Advanced Gastric Carcinoma:

When the carcinoma crosses the basement membrane into the muscularis propria or
beyond, it is referred to as advanced gastric carcinoma. Advanced gastric carcinoma has
following 5 patterns:
a. Ulcerative Carcinoma
b. Fungating (polypoid) Carcinoma
c. Scirrhous Carcinoma (Linitis plastic)
d. Colloid (Mucoid) Carcinoma
e. Ulcer Cancer

These Carcinoma may spread via 3 ways:

Direct Spread,
This is done via local extension is the most common feature of gastric carcinoma. e spread
occurs mainly from the loose submucosal layer but eventually muscularis and serosa are
also invaded.

Lymphatic Spread,
Metastases to regional lymph nodes occur early, especially in the Scirrhous carcinoma. The
groups of lymph nodes involved are along the lesser and greater curvature around the
cardia and supra-pancreatic lymph nodes. Involvement of left supraclavicular lymph node,
Virchow or Troisier’s sign, is sometimes the presenting feature of gastric carcinoma.

Haematogenous Spread,
Blood spread of gastric carcinoma may occur to the liver, lungs, brain, bones, kidneys and
adrenals. It occurs more commonly with the poorly- differentiated carcinoma.

Clinical Signs:
Gastric carcinoma may have diverse presentations. e usual clinical features are as under:
. Persistent abdominal pain
. Gastric distension and vomiting
. Loss of weight (cachexia)
. Loss of appetite (anorexia)
. Anemia, weakness, malaise