PATHOLOGY OF LYMPH NODE.
1. Lymph node structure
Lymphoid tissue:
-lymphoid system contain several focal concentrations of immune cellslymph 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 skin
and organs), the spleen (as the blood filter)
-central lymphoid tissue- thymus and bone marrow-these are central for
development of the immune system-but 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 zone,
paracortex, T and B cell regions
2. Manifestations of diseases of the lymphoid system
1. Immune deficiency
-depletion of lymphocytes in the tissues or blood (lymphopenia) and
abnormalities relating to subtypes of ly-ct -may be associated with defective
immunity
-lymphocyte depletion- occurs as a consequence of radiotherapy,
administration of cytotoxic drugs, corticosteroids- general immunodeficiencyreversible
-selective atrophy of lymphoid tissues- in congenital deficiency syndromes
2. Perverted immune function
-immune hypersensitivity and autoimmunity- manifestations of immune
response
major pathologic features are in the target organs of the abnormal immune
response, not in the lymphoid tissue
3. Lymphadenopathy - enlarged lymph nodes
localized to one lymph node ar group, or generalized
Causes of lymphadenopathy:
-reactive hyperplasia-due to immune response- nonspecific, usually a local
response to introduction of antigen, most commonly bacterial, only occasionallygeneralized, as a response to viremia
1
-reactive hyperplasia associated with specific infections- infectious
mononucleosis, granulomatous pattern in tuberculosis and histoplasmosis and
granulomatous-purulent in cat scratch disease, lymphogranuloma venereum, etc,
-lymphadenopathy of uncertain cause- sarcoidosis, associated with
autoimmune diseases, such as rheumatoid arthritis, lupus erythematodes, etc,
sinus histiocytosis with massive lymphadenopathy- Dorfman-Rosai disease,
Castlemann disease, etc
-primary neoplastic proliferations- lymphomas and Hodgkin disease
-secondary neoplasms- metastases- most commonly carcinomas and
melanomas
Upper Cervical LNs - Ca of nasopharynx, retrotonsilar region
Midcervical LNs - Ca of thyroid, upper aerodigestive tract, particularly pharynx
and larynx.
supraclavicular LNs - Ca of breast, in left side -stomach, pancreas, prostate
testis, Virchows Ln
Axillary LNs - ca of breast, lungs, melanoma
Inguinal LNs - external genital organs, melanomas of lower extremities, but only
rarely ca from internal organs (ovary, cervix, anal canal) and even less the testis
4.Lymphocytosis
increase of the number of circulating lymphocytes in peripheral blood- either as
a function of the immune response or as a result of neoplastic proliferations
(lymphocytic leukemia, lymphoma)
5. Monoclonal gammopathy
neoplasms of B cell derivation- may show evidence of plasmacytoid
differentiation-secret monoclonal IgG-that may be detected in serum as „M
component“ (malignant)
6. Splenomegaly
enlargment of the spleen (normal range of 120-160 g), often result of the same
factors that cause lymphadenopathy-acute and chronic infections, inf.
mononucleosis, leukemia, lymphomas, etc
LYMPHADENOPATHY.
lymphadenopathy -enlargement of the lymph node- the most important
manifestation of lymph node disorders
Reactive lymphoid hyperplasia
reactive lymphoid hyperplasia within 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- because of an activation of B cell region-this
pattern is often associated with chronic infections with B-cell amntigens
2
-2. paracortical hyperplasia- represents a T cell response-this pattern is
characterized by reactive changes within the T-cell zone of the lymph nodes
-3. sinus histiocytosis-accounts for macrophage response-this reactive
pattern is characterized by distention and prominence of lymphatic sinuses
-in most cases, immune response represents a combination of all three patterns,
any one may predominate
 1.-follicular hyperplasia:
histological features: -large germinal centres- within which blast transformation
is prominent feature
-prominent phagocytic activity in germinal centres- many apoptotic bodies
-often associated with chronic infections-caused by organisms that
represent B-cell antigens
differential diagnosis:
follicular hyperplasia of the lymph node may be confused with follicular
(nodular) malignant lymphoma- bcl2 oncoprotein
-preservation of lymph node architecture and variation in size and shape
of germinal centres- favors a diagnosis of hyperplasia in contrast to lymphoma
Lymphadenopathies associated with prominent follicular hyperplasia:
-rheumatoid arthritis
- systemic lupus erythematodes and other autoimmune diseases
- toxoplasmosis:
relatively common ilness caused by a protozoon Toxoplasma gondii,- commonly
infects cats, may be transmitted to humans, danger of transplacental infection
a) acquired toxoplasmosis- occurs in adults- acute febrile ilness with generalized
lymphadenopathy, or enlarged cervical lymph nodes
histological features:
-extensive follicular hyperplasia, expanded paracortical regions, numerous
histiocytes in clusters within the paracortex and reactive centers of follicles
-may be confused with lymphoma- biopsy is necessary
b) congenital toxoplasmosis-more serious condition- infection is transmitted
from mother to fetus
-characterized by necrosis in the brain, retinal involvement, may cause stillbirth,
hydrocephalus, microcephaly, congenital blindness, other neurologic defects
diagnosis- serologic techniques
-AIDS - persistent generalized lymphadenopathy
patients infected with HIV, with antibodies against HIV- may present with
persistent enlargment of lymph nodes-“persistent generalized
lymphadenopathy“- component of AIDS-related complex
histological features:
3
-the lymph node shows folicular and parafollicular hyperplasia- very large
follicles in early stage, irregular loss or fragmentation of mantle zone (=the rim
composed of small lymphocytes surrounding follicles), in later stageprogressive loss of all lymphocytes from the lymph node
HIV-associated Waldayer ring lymphoid hyperplasia- HIV infected
patients have a high incidence of head and neck manifestations, including
-opportunistic infections, neoplasms (Kaposi sarcoma, malignant lymphoma)
-florid follicular hyperplasia that occurs with increasing frequency in extranodal
sites, such as Waldayer ring and salivary glands
pathologic features: nasopharyngeal and tonsillar lymphoid tissue show
hyperplasia-upper airways obstruction
histologically: follicular germinal centres are irregularly enlarged- hyperplastic
lymphoid tissue serves as reservoir for HIV, EBV infections is important
cofactor for development of lymphoid hyperplasia
 2.- paracortical lymphoid hyperplasia
-characterized by reactive changes within the T-regions
parafollicular T-lymphocytes undergo proliferation-transformation to
immunoblasts
-it is encountered particularly in viral infections or following administration of
certain drugs, such as phenytoin- „immunoblastic lymphadenopathy“
dermatopathic lymphadenopathy-form of reactive hyperplasiacharacterized by paracortical hyperplasia and the presence of numerous pale
histiocytes containing lipids and melanin
occurs in lymph nodes draining the skin with chronic skin damage, such as chronic
radiation dermatitis, psoriasis, etc
 3.- sinus histiocytosis
-characterized by distention and prominence of the lymphatic sinuseshypertrophy of the lining cells
-infiltration of sinuses by activated histiocytes
-it is often encountered in lymph nodes draining cancers- may represent an
immune response to the tumor
SPECIFIC PATTERNS OF LYMPHADENITIS
1-Granulomatous lymphadenitis
-the immune response against intracellular organisms is mediated by T
cells, lymphokines and macrophages- results in formation of epithelioid
granulomas
tuberculosis-Mycobacterium tuberculosis, atypical mycobacteria, histoplasma,
etc.
histology: caseous necrosis, granulomas composed of epithelioid histiocytes,
giant cells, lymphocytes, marked fibrosis in chronic cases
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2-Suppurative granulomatous lymphadenitis
-histologic appearances are much the same as for granulomatous
lymphadenopathy, but with addition of acute suppurative inflammationneutrophils in the centres of granulomas
several different organisms may produce this form of lymphadenopathy-such as
-Cat scratch disease-lymph nodes draining the site of the skin scratch
G neg bacterium (afipia felis), most patients are prepubertal patients,
regression in two months
3-Infectious mononucleosis
is caused by Epstein-Barr virus
-characterized by fever, sore throat, peripheral blood lymphocytosis,
generalized lymphadenopathy and hepatosplenomegaly
more common in children, more severe in young adults, is transmitted via the
upper respiratory tract- commonly through kissing („kissing disease“)
morphology: lymph nodes show Tcell hyperplasia- follicles may be totally
obscured, T cells show activation- large numbers of T immunoblasts- possible
misdiagnosis of high grade lymphoma
in peripheral blood- large transformed lymphocytes- Downey cells- diagnostic
feature
4-Kawasaki disease - febrile disorder of unknown ethiology. Fever and cervical
lymphadenopathy, affecting children, pharyngeal and conjunctival inflammation,
erythematous skin rashes, arthritis. The LNs show fibrin thrombi and patchy
infarcts
5 -Kikuchi lymphadenitis (necrotizing histiocytic lymphadenitis)
uncommon benign self-limited lesion of lymph nodes, characterized by presence
of large necroses, without granuloma formation and without suppurative
inflammation
LYMPHADENOPATHIES OF UNKNOWN PATHOGENESIS.
1/ Castlemann´s disease (angiofollicular hyperplasia of lymph node)
-uncommon condition characterized by benign non-progressive lymphadenopathy
or by slowly growing mass
there are two different variants of CD
1/ hyaline-vascular form
-more common, occurs in all ages, slowly growing mass -most commonly in the
mediastinum and the retroperitoneum, lymph nodes and soft tissues may be
affected as well -benign clinical outcome
pathogenesis- unknown, recent studies suggest a role of abnormal development
of germinal centres in the folicles because of abnormal immune stimuli
5
histology: lymph nodes show abnormal follicles without germinal centres (follicles
vary in size and shape) and hypervascular interfollicular areas, lymph node
sinuses are lacking, fibrosis is common
2/ plasma cell variant-systemic form, characterized by multiple foci of
infiltration and multiorgan involvement- severe prognosis
histology:lymph node shows large follicles with numerous plasma cells in the
interfollicular regions- polyclonal- some cases may progress to lymphoma
POEMS syndrome- polyneuropathy, organomegaly (spleen, lymp nodes, liver),
endocrinopathy (diabetes mellitus, amenorrhea, gynecomastia), M protein and
skin manifestation (hypertrichosis, hemangiomas,etc)-may be associated with
multiple myeloma
2/ Angioimmunoblastic lymphadenopathy
-relatively uncommon condition affecting older patients- weight loss, fever, skin
rashes, hepato-splenomegaly, generalized lymphadenopathy
cause is unknown, 50% of patients die within 3 years either of infection or
because of development of malignant lymphoma
histology: lymph node shows progressive depletion of lymphoid cells with
obliteration of normal structure, loss of follicles and enlargement of
paracortical regions composed of numerous immunoblasts, T lymphocytes,
histiocytes, plasma cell and proliferation of blood vessels
3/ Immunoblastic lymphadenopathy
represent abnormal immune response to various stimuli
histology: lymph node structure may be completely obliterated, proliferation of
immature activated immunoblasts, marked T cell response with expansion of
paracortical regions
may closely resemble lymhomas
some possible causes:
-postvaccinal lymphadenopathy, lymphadenopathy in
measles and other viral infections, drug hypersensitivity, etc.
4/ Sinus histiocytosis with massive lymphadenopathy- Rosai-Dorfman disease
-the cause is unknown, children are commonly affected- massive cervical
lymphadenopathy, fever, mild anemia may be present
morphology:
affected lymph node contains abundant histiocytes that may fill the sinuseshistiocytes contain phagocytosed lymphocytes within their cytoplasm„emperipolesis“-the phenomenon of ingestion living cells
5/ Kimuras disease
it presents as a mass in the subcutaneous tissue of the head and neck region or
in major salivary glands, often associated with localized lymphadenopathy
histology: lymph nodes show marked hyperplasia of germinal centres, GCs are
often vascularized, infiltration by mature eosinophils, hyalinized vessels in
paracortical region
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LYMPHOMAS.
-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
localized or generalized lymphadenopathy-nodal lymphomas
-less commonly (in about one third of cases) lymphomas may be primary in
extranodal lymphoid tissue, such as the tonsils, GI tract mucosa, spleen, etcextranodal lymphomas
malignant lymphomas are classified in two major groups
-non-Hodgkin lymphomas- characterized by diffuse or nodular
proliferation of neoplastic lymphoid cells
-Hodgkin disease-malignant lymphoma, characterized by presence
of neoplastic diagnostic Hodgkin and Reed-Sternberg cells within abundant
reactive non-neoplastic infiltrate composed of lymphocytes, leukocytes, plasma
cells, histiocytes,etc.
NON-HODGKIN LYMPHOMAS
major features:
-lymphomas are of monoclonal origin- can be documented by 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 shows
polyclonal proliferation
monoclonal nature can be established by:
-the presence of monoclonal light and/or heavy chain of IgG
-presence of a clonal chromosomal aberration- for example the 8,14
translocation in Burkitt lymphoma
-clonal T receptor rearrangement (T-NHLs)
-all forms of lymphoma have the potential to disseminate to the other
lymph nodes, blood, bone marrow, spleen, etc. - neoplastic lymhocytes may
circulate in the blood in NHLs and may be widely distributed throughout the
whole body
-if bone marrow involvement and neoplastic lymphoid cells circulating in
peripheral blood predominate, or if these constitute the first recognized
manifestation of the disease- the process is called leukemia
-if the proliferation affects primarily lymph nodes or extranodal lymphoid
tissue and presents as a mass in lymph node- the process is called lymphoma
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 Important features of NHL-age dependency-NHL is a group of tumors that encompasses a wide
spectrum of disorders, differing in patients age at onset- incidence of subtypes
of malignant lymphomas varies greatly with age, for example lymphoblastic Loccurs in children and young adults and is rare in old patients, in contrast
lymphocytic L occurs almost only in old age
-NHLs can derive of T or B-cells - T and B cell lymphomas- NHLs derived
from B cell are more common
-NHLs may show nodular(follicular) or diffuse growth pattern,
immunostaining with antibodies to bcl-2 oncogene helps in distinguishing
follicular hyperplasia (germinal centre are negative) from nodular NHL- positive
 CLASSIFICATION OF NON-HODGKIN LYMPHOMAS.
-lymphomas show extreme degree of variation in clinical behavior and response
to therapy
-the aim of classification is to identify homogenous subgroups that behave in a
predictable way
low-grade lymphomas -5-year survival rate ranges from 50-70% clinically
indolent, longer survival times, but rarely cured by therapy
intermadiate grade- 5-year survival rate ranges from 35-45%
high-grade lymphomas- 5-year survival rate ranges from 20-32% , aggressive
behavior, but are responsive to therapy, by current very effective treatment
protocols potentially curable
-each prognostic group contains several types of lymphoma
 WHO classification (published 2001)- classification of tumors of
hematopoietic and lymhatic tissues is a result of several years of
discussions and consensus meetings, it is going to be accepted
 B CELL LYMPHOMAS
-more common than T-cell NHL, most of them are derived of the lymphoid
cells of the lymph node follicles - follicular centre cell lymphomas
B-cell neoplasms are divided into three major categories
a) Precursor B-cell neoplasms
b) Mature B-cell neoplasms
c) B-cell proliferations of uncertain malignant potential
Ad a) PRECURSOR B-CELL NEOPLASMS
 LYMPHOBLASTIC LYMPHOMA (LEUKEMIA)
-histologically this tumor is composed of neoplastic cells that are identical with
lymphoblasts of ALL- small to medium sized uniform cells with large nuclei and
scanty cytoplasm, many mitoses
8
-because of biological identity of lymphoblasts of leukemia and lymphoma, the
difference is arbitrary
-when the process is confined to a mass lesion without blood and marrow
involvement- diagnosis is lymphoma
-with extensive marrow and blood involvement, lymphoblastic leukemia is a
appropriate term
-predominantly affects males, most pateints under 20 years of age
-accounts for less that 5% of all NHLs, but about 40% of childhood lymphomas
clinically: rapidly growing tumor in the mediastinum or as abdominal mass
disease is rapidly progressing- early dissemination to bone marrow and blood
ad b) MATURE B-CELL NEOPLASMS
-mature B-cell neoplasms comprise over 85 % of all non Hodgkin lymphomas
worldwide
the most common types within this category- are large B-cell lymphoma and
follicular lymphoma
-classification is based on morphology and immunophenotype- mature B-cell
neoplasms are clonal proliferations of B cell in different stages of
differentiation
The major entities include:
 SMALL LYMPHOCYTIC LYMPHOMA-(SLL)
-chronic lymphocytic leukemia and small lymphocytic lymphoma represent one
neoplasm
-diagnosis of SLL is made in absence of bone marrow involvement
-lymph node infiltration has diffuse growth pattern
-histologically- SLL consists of small uniform lymphocytes with dark-staining
nuclei wihout atypia, scanty cytoplasm, mitotic figures are rare
-clinically- older patients are affected, the disease has prolonged slowly
progressive course, most patient are first asymptomatic
-typically the patients have generalized lymphadenopathy and
hepatosplenomegaly,
-bone marrow involvement is present in almost all cases in the course of disease
-about 40% of patients have neoplastic lymphocytes in peripheral blood
 MANTLE CELL LYMPHOMA
- B-cell neoplasm composed of monomorphous small to medium-sized lymphoid
cells with irregular nuclei which resemble centrocytes
-MCL comprises approximately 3-10% of lymphomas
-it occurs mostly in middle age, slight male predominance
sites of involvement- lymph nodes, spleen, bone marrow
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histologically: vagualy nodular diffuse infiltration, most cases- typical
cytogenetic abnormality with translocation t(11,14)(q13,q32) resulting in
overexpression of cyclin D1
prognosis: mantle cell lymphoma has median survival 3-5 years, but most patients
cannot be cured
 DIFFUSE LARGE B-CELL LYMPHOMA
-is a diffuse proliferation of large sized neoplastic B-cells, constitute about 3040% of adult lymphomas in western countries
the medium age is 7th decade, but age range is wide
clinically- patients typically present with a rapidly enlarging mass with lymph
node involvement
histologically: -always diffuse growth pattern, composed of large immunoblastslarge polymorphic cells with many mitoses, prominent nucleoli, in some casesplasmacytoid differentiation- with monoclonal IgG
prognosis: aggressive but potentially curable neoplasm, rapidly fatal if
untreated, but usually favorable response to chemotherapy-complete remission
can be achieved in 60-80% of the patients, about 50% remain disease-free for
several years
 FOLLICULAR LYMPHOMAS
-is a neoplasm of follicle centre B cells (centrocytes and centroblasts) which has
at least partially follicular growth pattern
- follicular lymphomas constitute about 35% of adult lymphomas in the US, the
incidence is lower in Asia, worldwide – about 20%
clinically:
-neoplasm affects predominantly adults, with median age of 60 years
-most patients have widespread disease at diagnosis, including lymphadenopathyfrequently generalized at onset
-bone marrow is often involved (40%) at the time of diagnosis
histologically: lymph node is infiltrated by neoplastic B-cells with cleaved nuclei,
scanty cytoplasm- nuclear chromatin is coarse, nuclei indistinct, mitoses
infrequent (centrocytes) and in addition to small cleaved lymphocytes- there are
large cleaved and non-cleaved cells (centroblasts)- more mitoses, larger nuclei,
irregular contours of nuclei, distinctive nucleoli
cytogenetic abnormalities:
-virtually in all cases, the tumor cells have cytogenetic abnormalities, mostly a
translocation t(14:18)- breakpoint on chromosome 18- at the site of protooncogene bcl-2 (present in 75 to 90% of cases)
prognosis: in most cases low response to chemotherapy- impossible to
eradicate completely neoplastic cells
-in 25 to 30% of patients- follicular lymphoma progress to high-grade large Bcell lymphoma
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 BURKITT LYMPHOMA
-is highly aggressive lymhoma often presenting at extranodal sites
the neoplasm exists in two variants:
endemic BL- this tumor was described in Africa, where it is associated with
Epstein-Barr viral infection-it represents one of most common malignant tumors of childhood in
Africa, Papua, New Guinea
sporadic BL- this variant is seen throughout the world mostly among young
adults and children
- incidence is low, 1-2% of all lymphomas
histologically: both variants- tumor consists of small closely packed lymphoid
cells with regular round nuclei- many mitoses- many apoptotic bodies- starry sky
pattern-both african and related non-endemic cases- similar histological features,
children and young adults are affected, in both form the tumor rarely arises
within lymph nodes
-african cases- involvement of jaws is the most common site, whereas abdominal
tumors are typical of non-african cases (bowel, ovaries, retroperitoneum)
prognosis: leukemic transformation is not very common, the tumor responds to
aggressive chemotherapy- long remissions are reported- in many cases relapslong survival in about 50% with appropriate treatment
 T - CELL LYMPHOMAS
less common than B cell lymphomas
 PERIPHERAL T-CELL LYMPHOMA
-Most patients present with lymph node involvement, but any site may be
affected
-it is composed of polymorphic T-cell neoplastic elements
-it accounts for about 50% of T-cell derived lymphomas
clinically: many patients present with advanced disease, it is among the most
aggressive lymphomas, prognosis is poor
 MYCOSIS FUNGOIDES AND SEZARY SYNDROME
- these are mature T-cell lymphomas presenting in the skin with
patches/plaques and characterized by epidermal and dermal infiltrate composed
of small to medium sized T-cells
mycosis fungoides is histologically characterized by cutaneous infiltrates
composed of polymorphic small to medium-sized lymphoid neoplastic cells- in
most patients slow but permanent progression of the disease- with involvement
of internal organs
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clinical course is slowly progressive but fatal in all cases, poor prognosis
associated with development of lymphadenopathy, sepsis is a frequent terminal
complication
Sezary syndrome-is characterized clinically by infiltrates in the skin,
lymphadenopathy and presence of Sezary cells (neoplastic) in peripheral blood
Prognosis is related to stage- patients with limited skin disease have good
prognosis, in more advanced stages with extracutaneous dissemination –
aggressive behaviour
 EXTRANODAL NK/T-CELL LYMPHOMA, NASAL TYPE
-is predominantly extranodal lymphoma, characterized by prominent necrosis, it
is angiocentric
-mostly composed of NK cells (CD56 positive), the nasal cavity is most common
site
clinically: the patients present with epistaxis, extensive destructive lesion in
middle part of face (so-called lethal midline granuloma)
the lymphoma can extend to paranasal sinuses, nasopharynx, oral cavity, palate,
etc
prognosis is variable, some patients may respond well to therapy, the other die
of disseminated disease despite aggressive treatment
 ADULT T-CELL LEUKEMIA-LYMPHOMA
his is uncommon T-cell neoplasm, that is endemic in Japan and Caribean
-caused by HLTV-1 virus,- this is oncogenic retrovirus- has strong tropism for
CD4 cells (similarly as HIV)
clinically: very aggressive disease with a median survival of about 8 month with
therapy, present with lymphadenopathy, hepatospolenomegaly, skin lesions, etc.
 EXTRANODAL MALIGNANT LYMPHOMAS
-lymphomas that arise at sites other than lymph nodes
-can arise at any site in the body, but the commonest sites include - major
lymphoid tissue sites, such as the spleen, Waldayer ring, salivary glands, GIT,
skin, testis,etc
great majority are of B-cell origin-the commonest of them is gastric lymphoma MALT lymhoma-malignant lymphomas arising in mucosa-associated lymphoid tissue (MALT)
MALT lymphoma- low-grade B-cell lymphoma composed of medium-sized
lymphoid cells with pale cytoplasm, resembling centrocytes (CCL cells), with
plasma cell differentiation-presence of lympho-epithelial lesions
-tends to remain localized for long periods, seldom disseminates to bone
marrow, responds favorably to local therapy-
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Major sites for developing of MALT lymphoma-stomach, salivary glands
1/ MALT(B-cell) gastric lymphoma -the most common of all extranodal
lymphomas
-disease of the sixth and seventh decades, but known also in younger
patients
-clinical symptoms include dyspepsia, abdominal pain, at endoscopyfindings similar to those seen in chronic gastritis and peptic ulcers
prognosis: -remains localized to the stomach, in a minority of cases-gastric
lymph nodes may be involved later, ML does not disseminate, prognosis is related
to stage of the tumor- good result of surgery alone- the response of gastric
MALT lymphoma to eradication of H. pylori
overall prognosis is considerably better than that of nodal lymphoma of similar
histological grade
2/ MALT (B-cell ) salivary gland lymphoma
in patients over 50 years, marked female preponderance
-most cases arise in patients with lymphoepithelial sialadenitis LESA and
Sjogren syndrom
LESA-salivary gland lesion consisting of infiltrates composed of polyclonal B
cells and plasma cells, and epi-myoepithelial islands, inflammatory infiltrates may
replace salivary gland tissue- acinar cell atrophy
Sjogren syndrome- autoimmune disease presenting with keratoconjunctivitis,
rheumatoid arthritis, xerostomia and enlargement of salivary glands (LESA)- but
not all patients with LESA have SS
enlargement of salivary glands, later-involvement of intraparotideal and cervical
lymph nodes, histologically-similar as gastric MALT lymphoma
prognosis: indolent behavior with long survival- surgery, no tendency to involve
bone marrow
HODGKIN DISEASE.
- is a disorder involving primarily the lymphoid tissue
-it arises almost always in a single lymph node- commonly in cervical lymph node
-it is separated from non Hodgkin lymphomas for characteristic
histological features and systemic manifestations
-HD is characterized morphologically by the presence of distinctive
neoplastic cells called diagnostic Reed-Sternberg cells, admixed with abundant
reactive inflammatory background infiltrate-the patients may present with systemic manifestations, such as fever,
weight loss, night sweats
common malignancy- accounts for 30-40% of all lymphomas
Pathologic features of HD:
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-presence of diagnostic Reed-Sternberg cells- giant binucleated or
multinucleated large cells with conspicuous large inclusion-like eosinophilic
nucleoli with a clear halo around them, two halves of the cell often appear as a
mirror image of each other
-diagnostic Hodgkin cell- large mononuclear cell with large single often
multilobulted or polypoid nucleus- prominent „owl-eyed“ nucleoli surrounded by
clear halo
-lacunar cells- particular variant of the RS cell, this cell is large and has a
single hyperlobated nucleus with multiple small nucleoli and an abundant palestaining cytoplasm with well-defined borders- the cells appear such as lying in
clear spaces (lacunae)- fixation artefact because of shrinkage of the cytoplasm
-neoplastic cells are typically dispersed within an abundant reactive infiltrate
composed of variable numbers of lymphocytes, plasma cell, histiocytes,
neutrophils, and eosinophils
-HD is one of the most common malignancies in young adults
Stage of disease- means distribution of disease
the staging of HD is of great importance -very important prognostic factor in
HD- stage is an expression of the extent of spread of the neoplams- the course,
choice of therapy, and prognosis is related to the stage of disease
clinical stage-criteria for staging were established based on clinical
history and physical examination, radiologic studies, laboratory test
pathologic stage-based on histologic findings in tissue removed by biopsy
(lymph nodes, spleen, bone marrow, liver, etc.)- pathologic staging is more exact
Stage I - involvement of a single LN region or single extralymphoid site
Stage II - involvement of 2 or more LN regions on the same side of diaphragm
Stage III - Involvement of both sides of diaphragm, may include spleen and only
limited extranodal sites.
Stage IV - Multiple or disseminated involvement of one or more extralymphatic
organs or tissues with or without lymph node involvement
Clinically, the patients in all stages are further divided into 2 prognostic groupsA (absence)-with better prognosis and B (presence)-with worse prognosis- B
symptoms-include unexplained weight loss of greater than 10% of normal body
weight, significant fever, and night sweats - worse prognosis
CLASSIFICATION OF HODGKIN DISEASE
RYES CLASSIFICATION: - classification is based on relative proportion
of diagnostic neoplastic cells and inflammatory reactive background infiltration:
- 4 subtypes of HD- with prognostic and therapeutic implications
1/ HD with lymphocyte predominance
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-this variant is characterized by the presence of numerous lymphocytes and few
classic SR cells- the best prognosis, most often in cervical nodes
it may occur in nodular and diffuse variant- typically present in stage Iprogresses slowly
-affects young patients
2/ HD -nodular sclerosis
-this subtype has good prognosis, usually presents in early stage, more common
in females, typically presents in 2nd decade to early thirties
cervical lymph nodes are involved, or mediastinal mass
histologically characterized by nodular growth pattern because of the presence
of broad bands of collagen that divide the lymphoid tissue into circumscribed
nodules - presence of lacunar cells-is a variant of SR or H cells with abundant
pale-looking cytoplasm
-classic RS cells are infrequent
-prognosis is excellent, especially when seen in clinical stages I and II
3/ HD-mixed cellularity
-this form has intermediate prognosis- rapidly progressive, but good response to
therapy
histologically-the involvement of the lymph node is diffuse, typical RS cells are
plentiful, there are fewer lymphocytes then in type 1, prominent mixed infiltrate
composed of lymphocytes, plasma cells, neutrophils and eosinophils,
-the disease may be diagnosed at any stage, but if compared with type 1 and 2
HD, more patients have disseminated HD at diagnosis- more often systemic
manifestation- worse prognosis
4/ HD- lymphocyte depleted
this form has the worst prognosis of all-typically presents in stage III or IVlymph node are replaced by destructive process- numerous neoplastic SR cells,
diffuse fibrosis, lower numbers of reactive cells
often refractory to therapy-most patients are old- these have usually
aggressive form of the disease
WALDAYER RING LYMPHOMAS
The palatine tonsils, nasopharyngeal and ligual lymphoid tissues constitute the
major parts of WR
-lymphoid tissue of WR belongs to MALT and is located at the gateway of
the respiratory and GIT tract
approximately 5 to 10% of patients with non-Hodgkin lymphomas (NHL)
have WR as the primary site of lymphoma
60% affect tonsils, 35% nasopharynx, followed by base of tongue (less
than 10%)
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Most common types of WR lymphomas
-by far the most common is DLBCL (diffuse large B-cell lymphoma)- 40%
is high grade lymphoma, clinically aggressive with fast dissemination
-mantle cell lymphoma (MCL)- 30%
-follicular lymphoma (FL)- marked predilection to tonsils
-CLL
-MALT lymphoma- indolent extranodal ly
SINONASAL LYMPHOMAS
-Represent a distinctive subset of extranodal head and neck lymphomas
appearing in nose and paranasal sinuses
-sinonasal lymphomas are also one of the possible causes of lethal
midline granuloma- a clinical term for destructive and progressive lesions
affecting the midline of the face
The sinonasal lymphomas are of B-cell or T/NK-cell lineages and have a broad
biologic spectrum from low rgade to high grade lymphomas
-can be either primary etranodal or secondary (involvement of the nose
and paranasal sinuses by systemic lymphoma)
incidence: seem to reflect distinct geographical and probably racial differencesrelatively rare in Western countries (comprise only about 1.5% of all ly), in Asian
and South American populations they represent the second most common type of
extranodal lymphomas (after stomach)- 8 to 13% of all cases of lymphoma
-incidence of secondary sinonasal lymphoas: the sites in head and neck are often
involved by systemic lymphomas
Clinical presentation and prognosis of sinonasal lymphomas: differs in relation to
the lymphoma type and its localisation
Symptoms of “sinusitis” are common, due to tumor mass- nasal obstruction
-the patients complain of nasal stuffiness and discharge, facial swelling and pain
Nasal B-ly- may also present as smooth surfaced mucosal swelling and polypoid
lesion, causing epistaxis or obstruction
Nasal T-ly local destructive growth with bleeding, ulcerations of mucosal
surfaces, bone destruction, pain, facial swelling- so called lethal midline
granuloma
Plasmacytoma has less aggressive clinical course, with this exception, most
sinonasal ly- have poor clinical outcome
Most common B-cell sinonasal lymphomas:
-DLBCL- in western population DLBCL is frequently encountered in the
upper airways, accounting for about 40% of all sinonasal ly
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-sinonasal ly of plasmacytic type: extramedullary sinonasal plasmocytomaare most frequently tumors of mature plasma cells
Most common sinonasal T/NK cell lymphomas:
-sinonasal NK/T cell lymphoma (extranodal NK/T lymphoma, nasal type)the tumor celll accumulate around blood vessel
-typical clinical presentation- angioinvasive and angiodestructive growth patternassociated with necroses and ulcerations of the mucosal surfaces because of
ischemia
-exulcerations of mucosal surface, bone and cartilage erosions
Size and shape of cells is different, usually small
-often associated with prominent inflammatory reaction-problem to
differentiate from reactive inflammatory conditions
-poor prognosis because of local destructive growth
MALT LYMPHOMA OF SALIVARY GLANDS AND LYMPHOEPITHELIAL
SIALADENITIS ASSOCIATED WITH SJOGREN SYNDROME
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