PATHOLOGY OF LYMPH NODE.

1. Lymph node structure

Lymphoid tissue:
-lymphoid system contain several focal concentrations of immune cells-
lymph nodes, spleen, tonsils, GIT lymphoid tissue, etc
-major accumulations of immune competent cells occur at portals of
antigen entry- the tonsils (mouth and nose, the respiratory and GIT mucosa
(for inhaled and ingested antigens, the lymph nodes (for lymph drainage of s!in
and organs, the spleen (as the "lood filter
-central lymphoid tissue- thymus and "one marro#-these are central for
development of the immune system-"ut do not participate in the immune
response in the adult
-peripheral lymphoid tissue- remaining lymphoid organs- actively involved
in immune response
lymph node structure- capsule, sinuses, germ cell follicles, mantle $one,
paracorte%, T and & cell regions
'. (anifestations of diseases of the lymphoid system
1. Immune deficiency
-depletion of lymphocytes in the tissues or "lood (lymphopenia and
a"normalities relating to su"types of ly-ct -may "e associated #ith defective
immunity
-lymphocyte depletion- occurs as a conse)uence of radiotherapy,
administration of cytoto%ic drugs, corticosteroids- general immunodeficiency-
reversi"le
-selective atrophy of lymphoid tissues- in congenital deficiency syndromes
'. *erverted immune function
-immune hypersensitivity and autoimmunity- manifestations of immune
response
major pathologic features are in the target organs of the a"normal immune
response, not in the lymphoid tissue
+. Lymphadenopathy - enlarged lymph nodes
locali$ed to one lymph node ar group, or generali$ed
,auses of lymphadenopathy:
-reactive hyperplasia-due to immune response- nonspecific, usually a local
response to introduction of antigen, most commonly "acterial, only occasionally-
generali$ed, as a response to viremia
1
-reactive hyperplasia associated #ith specific infections- infectious
mononucleosis, granulomatous pattern in tu"erculosis and histoplasmosis and
granulomatous-purulent in cat scratch disease, lymphogranuloma venereum, etc,
-lymphadenopathy of uncertain cause- sarcoidosis, associated #ith
autoimmune diseases, such as rheumatoid arthritis, lupus erythematodes, etc,
sinus histiocytosis #ith massive lymphadenopathy- -[Link] disease,
,astlemann disease, etc
-primary neoplastic proliferations- lymphomas and /odg!in disease
-secondary neoplasms- metastases- most commonly carcinomas and
melanomas
0pper ,ervical L1s - ,a of nasopharyn%, retrotonsilar region
(idcervical L1s - ,a of thyroid, upper aerodigestive tract, particularly pharyn%
and laryn%.
supraclavicular L1s - ,a of "reast, in left side -stomach, pancreas, prostate
testis, 2ircho#s Ln
3%illary L1s - ca of "reast, lungs, melanoma
Inguinal L1s - e%ternal genital organs, melanomas of lo#er e%tremities, "ut only
rarely ca from internal organs (ovary, cervi%, anal canal and even less the testis
[Link]
increase of the num"er of circulating lymphocytes in peripheral "lood- either as
a function of the immune response or as a result of neoplastic proliferations
(lymphocytic leu!emia, lymphoma
5. (onoclonal gammopathy
neoplasms of & cell derivation- may sho# evidence of plasmacytoid
differentiation-secret monoclonal IgG-that may "e detected in serum as 6(
component7 (malignant
8. 9plenomegaly
enlargment of the spleen (normal range of 1':-18: g, often result of the same
factors that cause lymphadenopathy-acute and chronic infections, inf.
mononucleosis, leu!emia, lymphomas, etc
LYMPHADENOPATHY.
lymphadenopathy -enlargement of the lymph node- the most important
manifestation of lymph node disorders
.eactive lymphoid hyperplasia
reactive lymphoid hyperplasia #ithin lymphoid tissue represents a
manifestation of immune response and consists of three components- this
condition may assume one of three major patters
-1. follicular hyperplasia- "ecause of an activation of & cell region-this
pattern is often associated #ith chronic infections #ith &-cell amntigens
2
-'. paracortical hyperplasia- represents a T cell response-this pattern is
characteri$ed "y reactive changes #ithin the T-cell $one of the lymph nodes
-+. sinus histiocytosis-accounts for macrophage response-this reactive
pattern is characteri$ed "y distention and prominence of lymphatic sinuses
-in most cases, immune response represents a com"ination of all three patterns,
any one may predominate
1.-follicular hyperplasia:
histological features: -large germinal centres- #ithin #hich "last transformation
is prominent feature
-prominent phagocytic activity in germinal centres- many apoptotic "odies
-often associated #ith chronic infections-caused "y organisms that
represent &-cell antigens
differential diagnosis:
follicular hyperplasia of the lymph node may "e confused #ith follicular
(nodular malignant lymphoma- "cl' oncoprotein
-preservation of lymph node architecture and variation in si$e and shape
of germinal centres- favors a diagnosis of hyperplasia in contrast to lymphoma
Lymphadenopathies associated #ith prominent follicular hyperplasia:
-rheumatoid arthritis
- systemic lupus erythematodes and other autoimmune diseases
- o!oplas"osis:
relatively common ilness caused "y a proto$oon To%oplasma gondii,- commonly
infects cats, may "e transmitted to humans, danger of transplacental infection
a ac)uired to%oplasmosis- occurs in adults- acute fe"rile ilness #ith generali$ed
lymphadenopathy, or enlarged cervical lymph nodes
histological features:
-e%tensive follicular hyperplasia, e%panded paracortical regions, numerous
histiocytes in clusters #ithin the paracorte% and reactive centers of follicles
-may "e confused #ith lymphoma- "iopsy is necessary
" congenital to%oplasmosis-more serious condition- infection is transmitted
from mother to fetus
-characteri$ed "y necrosis in the "rain, retinal involvement, may cause still"irth,
hydrocephalus, microcephaly, congenital "lindness, other neurologic defects
diagnosis- serologic techni)ues
-A#D$ - persise% &e%erali'e( ly"pha(e%opahy
patients infected #ith /I2, #ith anti"odies against /I2- may present #ith
persistent enlargment of lymph nodes-7persistent generali$ed
lymphadenopathy7- component of 3I-9-related comple%
histological features:
3
-the lymph node sho#s folicular and parafollicular hyperplasia- very large
follicles in early stage, irregular loss or fragmentation of mantle $one (;the rim
composed of small lymphocytes surrounding follicles, in later stage-
progressive loss of all lymphocytes from the lymph node
H#)-associae( *al(ayer ri%& ly"phoi( hyperplasia- /I2 infected
patients have a high incidence of head and nec! manifestations, including
-opportunistic infections, neoplasms (<aposi sarcoma, malignant lymphoma
-florid follicular hyperplasia that occurs #ith increasing fre)uency in e%tranodal
sites, such as =aldayer ring and salivary glands
pathologic features: nasopharyngeal and tonsillar lymphoid tissue sho#
hyperplasia-upper air#ays o"struction
histologically: follicular germinal centres are irregularly enlarged- hyperplastic
lymphoid tissue serves as reservoir for /I2, >&2 infections is important
cofactor for development of lymphoid hyperplasia
+.- paracorical ly"phoi( hyperplasia
-characteri$ed "y reactive changes #ithin the T-regions
parafollicular T-lymphocytes undergo proliferation-transformation to
immuno"lasts
-it is encountered particularly in viral infections or follo#ing administration of
certain drugs, such as phenytoin- 6immuno"lastic lymphadenopathy7
dermatopathic lymphadenopathy-form of reactive hyperplasia-
characteri$ed "y paracortical hyperplasia and the presence of numerous pale
histiocytes containing lipids and melanin
occurs in lymph nodes draining the s!in #ith chronic s!in damage, such as chronic
radiation dermatitis, psoriasis, etc
,.- si%us hisiocyosis
-characteri$ed "y distention and prominence of the lymphatic sinuses-
hypertrophy of the lining cells
-infiltration of sinuses "y activated histiocytes
-it is often encountered in lymph nodes draining cancers- may represent an
immune response to the tumor
$PE-#F#- PATTE.N$ OF LYMPHADEN#T#$
1-Gra%ulo"aous ly"pha(e%iis
-the immune response against intracellular organisms is mediated "y T
cells, lympho!ines and macrophages- results in formation of epithelioid
granulomas
tu"erculosis-(yco"acterium tu"erculosis, atypical myco"acteria, histoplasma,
etc.
histology: caseous necrosis, granulomas composed of epithelioid histiocytes,
giant cells, lymphocytes, mar!ed fi"rosis in chronic cases
4
+-$uppurai/e &ra%ulo"aous ly"pha(e%iis
-histologic appearances are much the same as for granulomatous
lymphadenopathy, "ut #ith addition of acute suppurative inflammation-
neutrophils in the centres of granulomas
several different organisms may produce this form of lymphadenopathy-such as
--a scrach (isease-lymph nodes draining the site of the s!in scratch
G neg "acterium (afipia felis, most patients are prepu"ertal patients,
regression in t#o months
,-#%fecious "o%o%ucleosis
is caused "y >pstein-&arr virus
-characteri$ed "y fever, sore throat, peripheral "lood lymphocytosis,
generali$ed lymphadenopathy and hepatosplenomegaly
more common in children, more severe in young adults, is transmitted via the
upper respiratory tract- commonly through !issing (6!issing disease7
morphology: lymph nodes sho# Tcell hyperplasia- follicles may "e totally
o"scured, T cells sho# activation- large num"ers of T immuno"lasts- possi"le
misdiagnosis of high grade lymphoma
in peripheral "lood- large transformed lymphocytes- -o#ney cells- diagnostic
feature
0-1a2asa3i (isease - fe"rile disorder of un!no#n ethiology. ?ever and cervical
lymphadenopathy, affecting children, pharyngeal and conjunctival inflammation,
erythematous s!in rashes, arthritis. The L1s sho# fi"rin throm"i and patchy
infarcts
4 -1i3uchi ly"pha(e%iis (necroti$ing histiocytic lymphadenitis
uncommon "enign self-limited lesion of lymph nodes, characteri$ed "y presence
of large necroses, #ithout granuloma formation and #ithout suppurative
inflammation
LYMPHADENOPATH#E$ OF 5N1NO*N PATHOGENE$#$.
16 -asle"a%%7s (isease (angiofollicular hyperplasia of lymph node
-uncommon condition characteri$ed "y "enign non-progressive lymphadenopathy
or "y slo#ly gro#ing mass
there are t#o different variants of ,-
1@ hyaline-vascular form
-more common, occurs in all ages, slo#ly gro#ing mass -most commonly in the
mediastinum and the retroperitoneum, lymph nodes and soft tissues may "e
affected as #ell -"enign clinical outcome
pathogenesis- un!no#n, recent studies suggest a role of a"normal development
of germinal centres in the folicles "ecause of a"normal immune stimuli
5
histology: lymph nodes sho# a"normal follicles #ithout germinal centres (follicles
vary in si$e and shape and hypervascular interfollicular areas, lymph node
sinuses are lac!ing, fi"rosis is common
'@ plasma cell variant-systemic form, characteri$ed "y multiple foci of
infiltration and multiorgan involvement- severe prognosis
histology:lymph node sho#s large follicles #ith numerous plasma cells in the
interfollicular regions- polyclonal- some cases may progress to lymphoma
*A>(9 syndrome- polyneuropathy, organomegaly (spleen, lymp nodes, liver,
endocrinopathy (dia"etes mellitus, amenorrhea, gynecomastia, ( protein and
s!in manifestation (hypertrichosis, hemangiomas,etc-may "e associated #ith
multiple myeloma
+6 A%&ioi""u%o8lasic ly"pha(e%opahy
-relatively uncommon condition affecting older patients- #eight loss, fever, s!in
rashes, hepato-splenomegaly, generali$ed lymphadenopathy
cause is un!no#n, 5:B of patients die #ithin + years either of infection or
"ecause of development of malignant lymphoma
histology: lymph node sho#s progressive depletion of lymphoid cells #ith
o"literation of normal structure, loss of follicles and enlargement of
paracortical regions composed of numerous immuno"lasts, T lymphocytes,
histiocytes, plasma cell and proliferation of "lood vessels
,6 #""u%o8lasic ly"pha(e%opahy
represent a"normal immune response to various stimuli
histology: lymph node structure may "e completely o"literated, proliferation of
immature activated immuno"lasts, mar!ed T cell response #ith e%pansion of
paracortical regions
may closely resem"le lymhomas
some possi"le causes: -postvaccinal lymphadenopathy, lymphadenopathy in
measles and other viral infections, drug hypersensitivity, etc.
06 $i%us hisiocyosis 2ih "assi/e ly"pha(e%opahy- .osai-Dorf"a%
(isease
-the cause is un!no#n, children are commonly affected- massive cervical
lymphadenopathy, fever, mild anemia may "e present
morphology:
affected lymph node contains a"undant histiocytes that may fill the sinuses-
histiocytes contain phagocytosed lymphocytes #ithin their cytoplasm-
6emperipolesis7-the phenomenon of ingestion living cells
46 1i"uras (isease
it presents as a mass in the su"cutaneous tissue of the head and nec! region or
in major salivary glands, often associated #ith locali$ed lymphadenopathy
6
histology: lymph nodes sho# mar!ed hyperplasia of germinal centres, G,s are
often vasculari$ed, infiltration "y mature eosinophils, hyalini$ed vessels in
paracortical region
LYMPHOMA$ .
-lymphomas are primary neoplasms of lymphoid tissue derived from lymphocytes,
their precursor and derivates
- most lymphomas arise from the lymph nodes, the usual presentation is as a
locali$ed or generali$ed lymphadenopathy-nodal lymphomas
-less commonly (in a"out one third of cases lymphomas may "e primary in
e%tranodal lymphoid tissue, such as the tonsils, GI tract mucosa, spleen, etc-
e%tranodal lymphomas
malignant lymphomas are classified in t#o major groups
-non-/odg!in lymphomas- characteri$ed "y diffuse or nodular
proliferation of neoplastic lymphoid cells
-/odg!in disease-malignant lymphoma, characteri$ed "y presence
of neoplastic diagnostic /odg!in and .eed-9tern"erg cells #ithin a"undant
reactive non-neoplastic infiltrate composed of lymphocytes, leu!ocytes, plasma
cells, histiocytes,etc.
NON-HODG1#N LYMPHOMA$
"a9or feaures:
-lymphomas are of monoclonal origin- can "e documented "y clonal gene
rearrangements or monoclonal IgG production- monoclonality-vast majority of
neoplastic proliferations arise from one clone of lymphocytes- monoclonal, on the
other hand reactive lymphoid proliferation as a part of immune response sho#s
polyclonal proliferation
monoclonal nature can "e esta"lished "y:
-the presence of monoclonal light and@or heavy chain of IgG
-presence of a clonal chromosomal a"erration- for e%ample the C,14
translocation in &ur!itt lymphoma
-clonal T receptor rearrangement (T-1/Ls
-all forms of lymphoma have the potential to disseminate to the other
lymph nodes, "lood, "one marro#, spleen, etc. - neoplastic lymhocytes may
circulate in the "lood in 1/Ls and may "e #idely distri"uted throughout the
#hole "ody
-if "one marro# involvement and neoplastic lymphoid cells circulating in
peripheral "lood predominate, or if these constitute the first recogni$ed
manifestation of the disease- the process is called leu!emia
7
-if the proliferation affects primarily lymph nodes or e%tranodal lymphoid
tissue and presents as a mass in lymph node- the process is called lymphoma
Important features of 1/L-
-age dependency-1/L is a group of tumors that encompasses a #ide
spectrum of disorders, differing in patients age at onset- incidence of su"types
of malignant lymphomas varies greatly #ith age, for e%ample lympho"lastic L-
occurs in children and young adults and is rare in old patients, in contrast
lymphocytic L occurs almost only in old age
-1/Ls can derive of T or &-cells - T and & cell lymphomas- 1/Ls derived
from & cell are more common
-1/Ls may sho# nodular(follicular or diffuse gro#th pattern,
immunostaining #ith anti"odies to "cl-' oncogene helps in distinguishing
follicular hyperplasia (germinal centre are negative from nodular 1/L- positive
-LA$$#F#-AT#ON OF NON-HODG1#N LYMPHOMA$.
-lymphomas sho# e%treme degree of variation in clinical "ehavior and response
to therapy
-the aim of classification is to identify homogenous su"groups that "ehave in a
predicta"le #ay
lo#-grade lymphomas -5-year survival rate ranges from 5:-D:B clinically
indolent, longer survival times, "ut rarely cured "y therapy
intermadiate grade- 5-year survival rate ranges from +5-45B
high-grade lymphomas- 5-year survival rate ranges from ':-+'B , aggressive
"ehavior, "ut are responsive to therapy, "y current very effective treatment
protocols potentially cura"le
-each prognostic group contains several types of lymphoma
*HO classificaio% (pu"lished '::1- classification of tumors of
hematopoietic and lymhatic tissues is a result of several years of
discussions and consensus meetings, it is going to "e accepted
: -ELL LYMPHOMA$
-more common than T-cell 1/L, most of them are derived of the lymphoid
cells of the lymph node follicles - follicular centre cell lymphomas
&-cell neoplasms are divided into three major categories
a; Precursor :-cell %eoplas"s
8; Maure :-cell %eoplas"s
c; :-cell proliferaio%s of u%cerai% "ali&%a% poe%ial
8
A( a; P.E-5.$O. :--ELL NEOPLA$M$
LYMPHO:LA$T#- LYMPHOMA <LE51EM#A;
-histologically this tumor is composed of neoplastic cells that are identical #ith
lympho"lasts of 3LL- small to medium si$ed uniform cells #ith large nuclei and
scanty cytoplasm, many mitoses
-"ecause of "iological identity of lympho"lasts of leu!emia and lymphoma, the
difference is ar"itrary
-#hen the process is confined to a mass lesion #ithout "lood and marro#
involvement- diagnosis is lymphoma
-#ith e%tensive marro# and "lood involvement, lympho"lastic leu!emia is a
appropriate term
-predominantly affects males, most pateints under ': years of age
-accounts for less that 5B of all 1/Ls, "ut a"out 4:B of childhood lymphomas
clinically: rapidly gro#ing tumor in the mediastinum or as a"dominal mass
disease is rapidly progressing- early dissemination to "one marro# and "lood
a( 8; MAT5.E :--ELL NEOPLA$M$
-mature &-cell neoplasms comprise over C5 B of all non /odg!in lymphomas
#orld#ide
the most common types #ithin this category- are large &-cell lymphoma and
follicular lymphoma
-classification is "ased on morphology and immunophenotype- mature &-cell
neoplasms are clonal proliferations of & cell in different stages of
differentiation
The major entities include:
$MALL LYMPHO-YT#- LYMPHOMA-<$LL;
-chronic lymphocytic leu!emia and small lymphocytic lymphoma represent one
neoplasm
-diagnosis of 9LL is made in a"sence of "one marro# involvement
-lymph node infiltration has diffuse gro#th pattern
-histologically- 9LL consists of small uniform lymphocytes #ith dar!-staining
nuclei #ihout atypia, scanty cytoplasm, mitotic figures are rare
-clinically- older patients are affected, the disease has prolonged slo#ly
progressive course, most patient are first asymptomatic
-typically the patients have generali$ed lymphadenopathy and
hepatosplenomegaly,
-"one marro# involvement is present in almost all cases in the course of disease
-a"out 4:B of patients have neoplastic lymphocytes in peripheral "lood
MANTLE -ELL LYMPHOMA
- &-cell neoplasm composed of monomorphous small to medium-si$ed lymphoid
cells #ith irregular nuclei #hich resem"le centrocytes
9
-(,L comprises appro%imately +-1:B of lymphomas
-it occurs mostly in middle age, slight male predominance
sites of involvement- lymph nodes, spleen, "one marro#
histologically: vagualy nodular diffuse infiltration, most cases- typical
cytogenetic a"normality #ith translocation t(11,14()1+,)+' resulting in
overe%pression of cyclin -1
prognosis: mantle cell lymphoma has median survival +-5 years, "ut most patients
cannot "e cured
D#FF5$E [Link] :--ELL LYMPHOMA
-is a diffuse proliferation of large si$ed neoplastic &-cells, constitute a"out +:-
4:B of adult lymphomas in #estern countries
the medium age is Dth decade, "ut age range is #ide
clinically- patients typically present #ith a rapidly enlarging mass #ith lymph
node involvement
histologically: -al#ays diffuse gro#th pattern, composed of large immuno"lasts-
large polymorphic cells #ith many mitoses, prominent nucleoli, in some cases-
plasmacytoid differentiation- #ith monoclonal IgG
prognosis: aggressive "ut potentially cura"le neoplasm, rapidly fatal if
untreated, "ut usually favora"le response to chemotherapy-complete remission
can "e achieved in 8:-C:B of the patients, a"out 5:B remain disease-free for
several years
FOLL#-5LA. LYMPHOMA$
-is a neoplasm of follicle centre & cells (centrocytes and centro"lasts #hich has
at least partially follicular gro#th pattern
- follicular lymphomas constitute a"out +5B of adult lymphomas in the 09, the
incidence is lo#er in 3sia, #orld#ide E a"out ':B
clinically:
-neoplasm affects predominantly adults, #ith median age of 8: years
-most patients have #idespread disease at diagnosis, including lymphadenopathy-
fre)uently generali$ed at onset
-"one marro# is often involved (4:B at the time of diagnosis
histologically: lymph node is infiltrated "y neoplastic &-cells #ith cleaved nuclei,
scanty cytoplasm- nuclear chromatin is coarse, nuclei indistinct, mitoses
infre)uent (centrocytes and in addition to small cleaved lymphocytes- there are
large cleaved and non-cleaved cells (centro"lasts- more mitoses, larger nuclei,
irregular contours of nuclei, distinctive nucleoli
cytogenetic a"normalities:
-virtually in all cases, the tumor cells have cytogenetic a"normalities, mostly a
translocation t(14:1C- "rea!point on chromosome 1C- at the site of proto-
oncogene "cl-' (present in D5 to F:B of cases
10
prognosis: in most cases lo# response to chemotherapy- impossi"le to
eradicate completely neoplastic cells
-in '5 to +:B of patients- follicular lymphoma progress to high-grade large &-
cell lymphoma
:5.1#TT LYMPHOMA
-is highly aggressive lymhoma often presenting at e%tranodal sites
the neoplasm e%ists in t#o variants:
endemic &L- this tumor #as descri"ed in 3frica, #here it is associated #ith
>pstein-&arr viral infection-
-it represents one of most common malignant tumors of childhood in
3frica, *apua, 1e# Guinea
sporadic &L- this variant is seen throughout the #orld mostly among young
adults and children
- incidence is lo#, 1-'B of all lymphomas
histologically: "oth variants- tumor consists of small closely pac!ed lymphoid
cells #ith regular round nuclei- many mitoses- many apoptotic "odies- starry s!y
pattern-
-"oth african and related non-endemic cases- similar histological features,
children and young adults are affected, in "oth form the tumor rarely arises
#ithin lymph nodes
-african cases- involvement of ja#s is the most common site, #hereas a"dominal
tumors are typical of non-african cases ("o#el, ovaries, retroperitoneum
prognosis: leu!emic transformation is not very common, the tumor responds to
aggressive chemotherapy- long remissions are reported- in many cases relaps-
long survival in a"out 5:B #ith appropriate treatment
T - -ELL LYMPHOMA$
less common than & cell lymphomas
PE.#[Link] T--ELL LYMPHOMA
-(ost patients present #ith lymph node involvement, "ut any site may "e
affected
-it is composed of polymorphic T-cell neoplastic elements
-it accounts for a"out 5:B of T-cell derived lymphomas
clinically: many patients present #ith advanced disease, it is among the most
aggressive lymphomas, prognosis is poor
MY-O$#$ F5NGO#DE$ AND $E=A.Y $[Link]
- these are mature T-cell lymphomas presenting in the s!in #ith
patches@pla)ues and characteri$ed "y epidermal and dermal infiltrate composed
of small to medium si$ed T-cells
mycosis fungoides is histologically characteri$ed "y cutaneous infiltrates
composed of polymorphic small to medium-si$ed lymphoid neoplastic cells- in
11
most patients slo# "ut permanent progression of the disease- #ith involvement
of internal organs
clinical course is slo#ly progressive "ut fatal in all cases, poor prognosis
associated #ith development of lymphadenopathy, sepsis is a fre)uent terminal
complication
9e$ary syndrome-is characteri$ed clinically "y infiltrates in the s!in,
lymphadenopathy and presence of 9e$ary cells (neoplastic in peripheral "lood
*rognosis is related to stage- patients #ith limited s!in disease have good
prognosis, in more advanced stages #ith e%tracutaneous dissemination E
aggressive "ehaviour
E>[Link] N16T--ELL LYMPHOMA? NA$AL TYPE
-is predominantly e%tranodal lymphoma, characteri$ed "y prominent necrosis, it
is angiocentric
-mostly composed of 1< cells (,-58 positive, the nasal cavity is most common
site
clinically: the patients present #ith epista%is, e%tensive destructive lesion in
middle part of face (so-called lethal midline granuloma
the lymphoma can e%tend to paranasal sinuses, nasopharyn%, oral cavity, palate,
etc
prognosis is varia"le, some patients may respond #ell to therapy, the other die
of disseminated disease despite aggressive treatment
AD5LT T--ELL LE51EM#A-LYMPHOMA
his is uncommon T-cell neoplasm, that is endemic in Gapan and ,ari"ean
-caused "y /LT2-1 virus,- this is oncogenic retrovirus- has strong tropism for
,-4 cells (similarly as /I2
clinically: very aggressive disease #ith a median survival of a"out C month #ith
therapy, present #ith lymphadenopathy, hepatospolenomegaly, s!in lesions, etc.
E>[Link] MAL#GNANT LYMPHOMA$
-lymphomas that arise at sites other than lymph nodes
-can arise at any site in the "ody, "ut the commonest sites include - major
lymphoid tissue sites, such as the spleen, =aldayer ring, salivary glands, GIT,
s!in, testis,etc
great majority are of &-cell origin-the commonest of them is gastric lymphoma-
MALT ly"ho"a-
-malignant lymphomas arising in mucosa-associated lymphoid tissue ((3LT
(3LT lymphoma - lo#-grade &-cell lymphoma composed of medium-si$ed
lymphoid cells #ith pale cytoplasm, resem"ling centrocytes (,,L cells, #ith
plasma cell differentiation-presence of lympho-epithelial lesions
12
-tends to remain locali$ed for long periods, seldom disseminates to "one
marro#, responds favora"ly to local therapy-
(ajor sites for developing of (3LT lymphoma-stomach, salivary glands
1@ (3LT(&-cell gastric lymphoma -the most common of all e%tranodal
lymphomas
-disease of the si%th and seventh decades, "ut !no#n also in younger
patients
-clinical symptoms include dyspepsia, a"dominal pain, at endoscopy-
findings similar to those seen in chronic gastritis and peptic ulcers
prognosis: -remains locali$ed to the stomach, in a minority of cases-gastric
lymph nodes may "e involved later, (L does not disseminate, prognosis is related
to stage of the tumor- good result of surgery alone- the response of gastric
(3LT lymphoma to eradication of /. pylori
overall prognosis is considera"ly "etter than that of nodal lymphoma of similar
histological grade
'@ (3LT (&-cell salivary gland lymphoma
in patients over 5: years, mar!ed female preponderance
-most cases arise in patients #ith lymphoepithelial sialadenitis L>93 and
9jogren syndrom
L>93-salivary gland lesion consisting of infiltrates composed of polyclonal &
cells and plasma cells, and epi-myoepithelial islands, inflammatory infiltrates may
replace salivary gland tissue- acinar cell atrophy
9jogren syndrome- autoimmune disease presenting #ith !eratoconjunctivitis,
rheumatoid arthritis, %erostomia and enlargement of salivary glands (L>93- "ut
not all patients #ith L>93 have 99
enlargement of salivary glands, later-involvement of intraparotideal and cervical
lymph nodes, histologically-similar as gastric (3LT lymphoma
prognosis: indolent "ehavior #ith long survival- surgery, no tendency to involve
"one marro#
HODG1#N D#$EA$E.
- is a disorder involving primarily the lymphoid tissue
-it arises almost al#ays in a single lymph node- commonly in cervical lymph node
-it is separated from non /odg!in lymphomas for characteristic
histological features and systemic manifestations
-/- is characteri$ed morphologically "y the presence of distinctive
neoplastic cells called diagnostic .eed-9tern"erg cells, admi%ed #ith a"undant
reactive inflammatory "ac!ground infiltrate-
-the patients may present #ith systemic manifestations, such as fever,
#eight loss, night s#eats
common malignancy- accounts for +:-4:B of all lymphomas
13
*athologic features of /-:
-presence of diagnostic .eed-9tern"erg cells- giant "inucleated or
multinucleated large cells #ith conspicuous large inclusion-li!e eosinophilic
nucleoli #ith a clear halo around them, t#o halves of the cell often appear as a
mirror image of each other
-diagnostic /odg!in cell- large mononuclear cell #ith large single often
multilo"ulted or polypoid nucleus- prominent 6o#l-eyed7 nucleoli surrounded "y
clear halo
- lacunar cells- particular variant of the .9 cell, this cell is large and has a
single hyperlo"ated nucleus #ith multiple small nucleoli and an a"undant pale-
staining cytoplasm #ith #ell-defined "orders- the cells appear such as lying in
clear spaces (lacunae- fi%ation artefact "ecause of shrin!age of the cytoplasm
-neoplastic cells are typically dispersed #ithin an a"undant reactive infiltrate
composed of varia"le num"ers of lymphocytes, plasma cell, histiocytes,
neutrophils, and eosinophils
-/- is one of the most common malignancies in young adults
9tage of disease- means distri"ution of disease
the staging of /- is of great importance -very important prognostic factor in
/-- stage is an e%pression of the e%tent of spread of the neoplams- the course,
choice of therapy, and prognosis is related to the stage of disease
clinical stage-criteria for staging #ere esta"lished "ased on clinical
history and physical e%amination, radiologic studies, la"oratory test
pathologic stage -"ased on histologic findings in tissue removed "y "iopsy
(lymph nodes, spleen, "one marro#, liver, etc.- pathologic staging is more e%act
9tage I - involvement of a single L1 region or single e%tralymphoid site
9tage II - involvement of ' or more L1 regions on the same side of diaphragm
9tage III - Involvement of "oth sides of diaphragm, may include spleen and only
limited e%tranodal sites.
9tage I2 - (ultiple or disseminated involvement of one or more e%tralymphatic
organs or tissues #ith or #ithout lymph node involvement
,linically, the patients in all stages are further divided into ' prognostic groups-
A <a8se%ce;-#ith "etter prognosis and : <prese%ce;-#ith #orse prognosis- :
sy"po"s-include une%plained #eight loss of greater than 1:B of normal "ody
#eight, significant fever, and night s#eats - #orse prognosis
-LA$$#F#-AT#ON OF HODG1#N D#$EA$E
.H>9 ,L399I?I,3TIA1: - classification is "ased on relative proportion
of diagnostic neoplastic cells and inflammatory reactive "ac!ground infiltration:
- 4 su"types of /-- #ith prognostic and therapeutic implications
1@ /- #ith lymphocyte predominance
14
-this variant is characteri$ed "y the presence of numerous lymphocytes and fe#
classic 9. cells- the "est prognosis, most often in cervical nodes
it may occur in nodular and diffuse variant- typically present in stage I-
progresses slo#ly
-affects young patients
'@ /- -nodular sclerosis
-this su"type has good prognosis, usually presents in early stage, more common
in females, typically presents in '
nd
decade to early thirties
cervical lymph nodes are involved, or mediastinal mass
histologically characteri$ed "y nodular gro#th pattern "ecause of the presence
of "road "ands of collagen that divide the lymphoid tissue into circumscri"ed
nodules - presence of lacunar cells-is a variant of 9. or / cells #ith a"undant
pale-loo!ing cytoplasm
-classic .9 cells are infre)uent
-prognosis is e%cellent, especially #hen seen in clinical stages I and II
+@ /--mi%ed cellularity
-this form has intermediate prognosis- rapidly progressive, "ut good response to
therapy
histologically-the involvement of the lymph node is diffuse, typical .9 cells are
plentiful, there are fe#er lymphocytes then in type 1, prominent mi%ed infiltrate
composed of lymphocytes, plasma cells, neutrophils and eosinophils,
-the disease may "e diagnosed at any stage, "ut if compared #ith type 1 and '
/-, more patients have disseminated /- at diagnosis- more often systemic
manifestation- #orse prognosis
4@ /-- lymphocyte depleted
this form has the #orst prognosis of all-typically presents in stage III or I2-
lymph node are replaced "y destructive process- numerous neoplastic 9. cells,
diffuse fi"rosis, lo#er num"ers of reactive cells
often refractory to therapy-most patients are old- these have usually
aggressive form of the disease
*ALDAYE. .#NG LYMPHOMA$
The palatine tonsils, nasopharyngeal and ligual lymphoid tissues constitute the
major parts of =.
-lymphoid tissue of =. "elongs to (3LT and is located at the gate#ay of
the respiratory and GIT tract
appro%imately 5 to 1:B of patients #ith non-/odg!in lymphomas (1/L
have =. as the primary site of lymphoma
8:B affect tonsils, +5B nasopharyn%, follo#ed "y "ase of tongue (less
than 1:B
15
(ost common types of =. lymphomas
-"y far the most common is -L&,L (diffuse large &-cell lymphoma- 4:B
is high grade lymphoma, clinically aggressive #ith fast dissemination
-mantle cell lymphoma ((,L- +:B
-follicular lymphoma (?L- mar!ed predilection to tonsils
-,LL
-(3LT lymphoma- indolent e%tranodal ly
$#NONA$AL LYMPHOMA$
-.epresent a distinctive su"set of e%tranodal head and nec! lymphomas
appearing in nose and paranasal sinuses
-sinonasal lymphomas are also one of the possi"le causes of lethal
midline granuloma- a clinical term for destructive and progressive lesions
affecting the midline of the face
The sinonasal lymphomas are of &-cell or T@1<-cell lineages and have a "road
"iologic spectrum from lo# rgade to high grade lymphomas
-can "e either primary etranodal or secondary (involvement of the nose
and paranasal sinuses "y systemic lymphoma
incidence: seem to reflect distinct geographical and pro"a"ly racial differences-
relatively rare in =estern countries (comprise only a"out 1.5B of all ly, in 3sian
and 9outh 3merican populations they represent the second most common type of
e%tranodal lymphomas (after stomach- C to 1+B of all cases of lymphoma
-incidence of secondary sinonasal lymphoas: the sites in head and nec! are often
involved "y systemic lymphomas
,linical presentation and prognosis of sinonasal lymphomas: differs in relation to
the lymphoma type and its localisation
9ymptoms of 7sinusitisI are common, due to tumor mass- nasal o"struction
-the patients complain of nasal stuffiness and discharge, facial s#elling and pain
1asal &-ly- may also present as smooth surfaced mucosal s#elling and polypoid
lesion, causing epista%is or o"struction
1asal T-ly local destructive gro#th #ith "leeding, ulcerations of mucosal
surfaces, "one destruction, pain, facial s#elling- so called lethal midline
granuloma
*lasmacytoma has less aggressive clinical course, #ith this e%ception, most
sinonasal ly- have poor clinical outcome
(ost common &-cell sinonasal lymphomas:
--L&,L- in #estern population -L&,L is fre)uently encountered in the
upper air#ays, accounting for a"out 4:B of all sinonasal ly
-sinonasal ly of plasmacytic type: e%tramedullary sinonasal plasmocytoma-
16
are most fre)uently tumors of mature plasma cells
(ost common sinonasal T@1< cell lymphomas:
-sinonasal 1<@T cell lymphoma (e%tranodal 1<@T lymphoma, nasal type-
the tumor celll accumulate around "lood vessel
-typical clinical presentation- angioinvasive and angiodestructive gro#th pattern-
associated #ith necroses and ulcerations of the mucosal surfaces "ecause of
ischemia
-e%ulcerations of mucosal surface, "one and cartilage erosions
9i$e and shape of cells is different, usually small
-often associated #ith prominent inflammatory reaction-pro"lem to
differentiate from reactive inflammatory conditions
-poor prognosis "ecause of local destructive gro#th
(3LT LH(*/A(3 A? 93LI23.H GL31-9 31- LH(*/A>*IT/>LI3L
9I3L3->1ITI9 399A,I3T>- =IT/ 9GAG.>1 9H1-.A(>
17