DISEASES AND

TUMORS OF
LYMPHOID SYSTEM
Reactive Lymphadenitis
 Any immune response against foreign
antigens is often associated with lymph
node enlargement (lymphadenopathy)
 The infections that cause lymphadenitis
are numerous and varied and may be
acute or chronic
 In most instances the histology is non
specific
Acute Nonspecific Lymphadenitis
 May be due to a local group of nodes
draining a focal infection or be generalized
in systemic bacterial or viral infections
 The lymph nodes are swollen, gray-red and
engorged.
 Histologically large germinal centers are
seen. If the cause is pyogenic organism,
neutrophilic infiltrate in sinuses and
follicles+. In severe infection, abscess is
seen. Sinuses may form with skin.
Chronic Nonspecific Lymphadenitis
 Three patterns are known depending on
the causative agent
 Follicular hyperplasia: infection or
inflammation that activate B cell
proliferation. Prominent germinal centres
in follicles with tingeable macrophages.
Causes include rheumatoid arthritis,
toxoplasmosis and early stage of HIV
infection. Can be confused with follicular
lymphoma
Reactive Follicular Hyperplasia
Findings that favor a diagnosis of follicular
hyperplasia over follicular lymphoma
 Preservation of lymph node architercture
 Variation in the shape and size of
lymphoid nodule
 A mixed population of lymphocytes at
various stages of differentiation
 Prominent phogocytic and mitotic
activity in germinal centres
 Paracortical Hyperplasia: Reactive
changes within T cell region of the lymph
node. Causes: Viral infection, vaccinations,
drugs like phenytoin
 Sinus Histiocytosis: Distension and
prominence of the lymphatic sinusoids due
hypertrophy of lining endothelial cells and an
infiltrate of macrophages. Seen in lymph
nodes draining cancers
 Because of the overlap in clinical
presentations, the various lymphoid
neoplasms can only be distinguished based
on the appearance and molecular
characteristics of the tumor cells. It is most
helpful to focus on what the tumor cells is,
not where it resides in the patient
 Two groups of lymphomas are recognized:
Hodgkin lymphoma and non-Hodgkin
lymphomas
Cat Scratch Disease
 Self limited lymphadenitis caused by the
bacterium Bartonella henselae
 Primarily a disease of childhood
 Regional lymphadenopathy in axilla and
neck
 Nodal enlargement after feline scratch
or uncommonly after a splinter or thorn
injury
 Most patient lymph node enlargement
regresses over the next 2 to 4 months.
 Rarely patients develop enchephalits,
osteomyelitis and thrombocytopenia
 Microscopically suppurative granulomas
with stellate outline. DD
Lymphogranuloma venerium, tularemia,
atypical mycobacteria, fungal infection
 Diagnosis is based on clinical findings, a
positive skin test and distinctive
morphology in the lymph node
Neoplastic Proliferations of White cells

1. Lymphoid neoplasms including Hodgkin

lymhoma, NHL, lymphocytic leukemia,
plasma cell dyscriasis and related
condition. These tumours are composed
cells that resemble normal stages of
lymphocytic differentiation
2. Myeloid neoplasms arising from stem
cells. Includes acute myelogenous
leukemia, chronic myeloproliferative
disorders myelodysplastic syndromes
 Histiocytic neoplasms represent
proliferative lesions of histiocytes. Eg.
Langerhans cell histiocytoses
Hodgkin and Non Hodgkin lymphomas
Hodgkin lymphoma Non-Hodgkin lymphoma
 More frequent
 More often localized to a
involvement of multiple
single axial group of
peripheral nodes
nodes
 Noncontiguous spread
 Orderly spread by
 Mesenteric nodes and
contiguity
Waldeyer ring commonly
 Mesentric nodes and
involved
Waldeyer ring rarely
 Extranodal involvement
involved
 Extranodal invovement common
uncommon
The WHO Classification of
Lymphoid Neoplasm
Based on morphologic, phenotypic,
genotypic and clinical features
 Precursor B cell Neoplasm
 Peripheral B cell Neoplasm
 Precursor T cell Neoplasm
 Peripheral T cell Neoplasm
 Hodgkin Lymphoma
Precursor B Cell Neoplasam
 Precursor B cell leukemia/lymphoma (B-
cell ALL)
Peripheral B cell Neoplasm
 B cell chronic lymphocytic
leukemia(CLL)small lymphocytic
lymphoma (SLL)
 B cell prolymphocytic leukemia
 Lymphoplasmacytic lymphoma
 Mantle cell lymphoma
 Follicular lymphoma
 Extrnodal marginal zone
lymphoma(MALT lymphoma)
Peripheral B cell Neoplasms
 Splenic marginal zone lymphoma
 Nodal marginal zone lymphoma
 Hairy cell leukemia
 Plasmacytoma/plasma cell myeloma
 Diffuse large cell lymphoma
 Burkitt lymphoma
Precursor T cell Neoplasm
 Precursor T cell leukemia/lymphoma (T
cell ALL)
Peripheral T/NK cell Neoplasm
 T cell prolymphocytic leukemia
 T cell granular lymphocytic leukemia
 NK cell leukemia
 Adult T cell lymphoma/Leukemia
 Peripheral T cell lymphoma - not
otherwise specified (NOS)
 Angioimmunoblastic T cell lymphoma
Peripheral T/NK cell Neoplasms
 Anaplastic large cell lymphoma, primary
systemic type
 NK/T cell lymphoma of nasal type
 Enteropathy type T cell lymphoma
 Hepatosplenic –gamma, delta T cell
lymphoma
 Mycosis fungoides/Sezary syndrome
 Panniculitis like T cell lymphoma
Hodgkin Lymphoma
 Lymphocyte predominance, nodular
 Lymphocyte rich
 Nodular sclerosis
 Mixed cellularity
 Lymphocyte depletion
Common Lymphomas

 Small lymphocytic lymphoma/Chronic

lymphocytic leukemia
 Follicular lymphoma
 Diffuse large B cell lymphoma
 Burkitt lymphoma
 Lymphoblastic lymphoma
 Hodgkin lymphoma
Lymphoid Neoplasms
 Lymphoid neoplasms encompass a
group of entities that vary widely in their
clinical presentation and behavior
 Leukemias primarily involve the bone
marrow with spillage of neoplastic cells
into peripheral blood
 Lymphomas are tumors of lymphoid
tissue that produce masses in involved
lymph nodes or other tissue
Lymphoma versus Leukemia
 Because of the overlap in clinical
presentations, the various lymphoid
neoplasms can only be distinguished
based on the appearance and molecular
characterstics of the tumour cells. Stated
another way, for puposes of diagnosis
and prognostication, it is most helpful
to focus on what the tumour cells is,
not where it resides in the patient
 B and T cell tumors are composed of cells that
are arrested or derived from specific stage of
normal differentiation pathways
 Diagnosis and classification of these tumors
relies heavily on either immunohistochemistry
or flow cytometry that detect lineage specific
antigen and markers of maturity
 Most common NHLs are B cell derived from
follicular or post follicular B cells(most B cell
lymphomas have undergone somatic
hypermutation).They often show chromosomal
translocation involving Ig heavy chain gene
 All lymphoid neoplasms are monoclonal.
Antigen receptor genes and their
products(Immunoglobulin and T cell receptor
rearrangement) is frequently used to
differentiate monoclonal neoplasms from
polyclonal reactive process- Molecular
studies
 Immunodeficiency predisposes to lymphoid
neoplasms particularly associated with EBV
 NHL is usually widely disseminated at the
time of diagnosis show only systemic
therapies are curative
Precursor B and T cell lymphoblastic
lymphoma/leukemia
 Aggressive tumors composed of
immature lymphocytes (lymphoblasts)
 Occur predominantly in children and
young adults
 Pre B lymphoblastic tumor appear as
leukemia
 Pre T lymphoblastic tumor occur as
mediastinal mass and later spill over as
leukemia
 Both pre B and pre T lymphoblasic tumors
usually take on the clinical appearance of an
acute lymphoblastic leukemia (ALL) at some
time during their course)
 T lymphoblastic lymphoma(LL) shows sheets
of immature cells with scanty cytoplasm,
enlarged , immature nuclei with
inconspicuous nucleoli. Positive for Tdt. CD3
and CD43 are positive
 B cell LL shows positivity for CD20,
CD79,CD19 and Tdt
Acute Lymphoblastic leukemia
 Good Prognosis when the age group is
between 2 to 10 years with t(12;21) and
hyperdiploidy-ALL
Small Lymphocytic Lymphoma/Chronic
Lymphocytic Leukemia
 These two disorders are
morphologically, phenotypically and
genotypically identical differing only in
the extent of peripheral blood
involvement. CLL if lymhocytosis
exceeds 4000 cells/cmm.
 Occurs in old age, associated with
hyogammaglobulinemia, autoimmune
haemolytic anemia
 Loss of lymph node architecture by sheets of
small lymphoid cells with proliferation
centre
 IHC: CD5, CD23 and CD43 positive. 99% of
cases positive for B cell marker like CD20
and CD79a.
 Karyotype: trisomy12 and deletions of
chromosome11 and 12
 Prognosis: Median survival 4 to 6 years.
Many patient live for more than 10 years
Small Lymphocytic Lymphoma
Follicular Lymphoma(FL)
 Relatively common tumor
 Morphology: Lymph nodes are effaced by
nodular appearance with close back to back
arrangement. Nodules composed of
centrocytes with centroblasts. Graded I to 3.
 IHC: BCL2 positive, B cell marker positive,
Ki-67 index around 20%, BCL6 also positive.
CD10 can be positive
 Karyotype: t(14;18)
 Clinical Features: Occurs predominatly
in older persons. Causes painless
generalized lymphadenopathy. Spread
to bone marrow is very common.
 Natural history is prolonged but follicular
lymphoma is not easily curable
 In 40% cases progress to diffuse large B
cell lymphoma (DLBCL)
 Majority of tumors have a characteristic
t(14,18) translocation
Follicular Lymphoma
Follicular lymphoma - spleen
Follicular hyperplasia versus Follicular
Lymphoma – BCl2 Ab.
Diffuse Large B Cell
Lymphoma(DLBCL)
 Includes several forms of NHL that
share certain features including a B cell
phenotype, diffuse growth pattern and
an aggressive clinical history
 Commonest NHL (about 50% of NHL)
 The tumor has large, vesicular, irregular
nuclei with prominent nucleoli. Variable
morphology is known
 Positive for B cell markers like CD19,CD20 and
CD79a
 Different subtypes are known. EBV induced
lymphoma in acquired immune deficiency states,
primary effusion lymphoma(KSHV mediated),
Mediastinal large B cell lymphoma are some of them
 Any age can be affected. Present as rapidly
enlarging mass. Extra nodal site presentation is well
known. BM involvement is not common at the time
of diagnosis
 Aggressive tumors that are rapidly fatal if untreated.
With intensive chemotherapy remission can be
achieved in 60% to 80% of cases
DLBCL involving spleen
DLBCL
Burkitt Lymphoma
 Endemic in Africa, sporadic in other
areas. Can be associated with immune
deficiency
 Affects mainly children and young adults
 Extra nodal site is affected. Maxilla and
mandible in African patients, abdominal
tumors in sporadic cases
 High grade tumor that is among the
fastest growing human neoplasm
 Diffuse sheets of medium size tumor cells with
round to oval nuclei with two to five prominent
nucleoli. Cytoplasam is basophilic with vacuoles.
Starry sky pattern is often seen due to
macrophages. High mitotic rate
 IHC: B lineage marker +. CD10 can be
positive.Ki67 index is nearly 100%
 Karyotype: t(8.14) some time other variants.
Over expression of MYC protein
 Although very high grade tumor, the majority of
patients can be cured with very aggressive
chemotherapy
Burkitt Lymphoma
Mantle cell lymphoma
 Constitutes 4% of all NHL. Arises from
mantle zone of normal lymphoid follicles
 Involves in diffuse or vaguely nodular pattern
 Cells are slightly larger than normal
lymphocytes and have irregular nucleus and
inconspicuous nucleoli
 Bone marrow is involved in most cases
 Frequent involvement of GIT presenting as
lymphomatoid polyposis
 Positive for Pan B cell marker like
CD19,lCD20 and CD79a. CD5 is also
positive
 Cyclin D1 positivity is characteristic
 Proliferation centre is absent
 Most patients have t(11;14). Cylin D1
gene from chromosome 11 is
translocated to 14th chromosome
 Mantle cell lymphoma is aggressive and
incurable and are associated with a
median survival of 3 to 5 years
Extranodal Marginal Zone Lymphoma
 Special category of low-grade mature B cell
tumour
 Arise from mucosal associated lymphoid
tissue (MALT) such as intestine,
salivaryglands, lung, orbit and breast.
 Occurs in the set up of Sjogren syndrome
and Hashimoto thyroiditis
 H.pylori is the cause
 Treatment with antibiotics may cause
regression
 Associated with t(1;14) involving BCL10
and IgH gene and t(11;18) involving
MALT1 and IAP2 gene
 Prognosis is excellent
 Can affect lymph node as well as spleen
Hairy Cell Leukemia
 Uncommon, indolent B cell neoplasm,
having fine, hair like cytoplasmic
projects
 Positive for Pan B cell markers,
including,
CD19,CD20,CD79a,CD11c,CD103 and
Tartarate resistant acid phophtase
 Occurs in old males with bone marrow
involvement and splenomegaly
 Pancytopenia due to marrow infiltration
and splenic sequestration can result in
pancytopenia
 Pancytopenia and infection are major
problems
 Extremely sensitive to purine
nucleosides
 Complete durable response is the rule
and overall prognosis is excellent
Mycosis Fungoides and Sezary Syndrome

 Composed of neoplastic CD4+ cells home

to the skin and they are often referred as
cutaneous T cell lymphomas (CTCL)
 Mycosis fungoides: nonspecific
erythrodermic rash progressing through
plaque phase and tumour phase
 Infiltration of epidermis and upperdermis
by neoplastic T cells whichoften have
cerebriform nuclei.
 Nodal and Visceral dissemination can
occur
 Sezary syndrome is a clinical variant
with generalized exforliative
erythroderma and tumour cells (Sezary
cells) in the peripheral blood
 Mycosis fungoides – patient may survive
for many years in early stage where as
in tumour stage of mycosis fungoides
and in sezary syndrome survival is
generally 1 to 3 years
Adult T-cell leukemia/lymphoma
 Caused by retrovirus, human T-cell
leukemia virus type 1 (HTLV-1)
 Endemic in Japan, carrbiean and west
africa and sprodically elsewhere
 Skin lesion, generalized
lymphadenopathy, hepatosplenomegaly,
hypecalcemia and variable numbers of
malignant CD4+ cells in peripheral
blood.CD25 and IL-2 receptor positive
 Most cases, extremely aggressive
disease
 In 15 to 20% of patients the course is
chronic and is clinically indistinguisbale
from cutaneous T-cell lymphoma
Peripheral T-cell lymphoma
 Heterogenous tumours that together
make up about 15% of adult NHLs.
 Although several rare distinctive
subtypes fall under this heading, most
tumours in this group are unclassfiable
 Generally present as disseminated
disease, are aggressive and respond
poorly to therapy
Multiple Myeloma and Related Plasma
Cell Disorders
Six major variants
1. Multiple Myeloma
2. Localized plasmacytoma
3. Lymphoplasmacytic lymphoma
4. Heavy chain disease
5. Primary or immunocyte-associated
amyloidosis
6. Monoclonal gammopathy of
undetermined significance
 All originate from a clone of B cells that
differentiates into plasma cells and
secretes a single complete or partial
immunoglobulin
 Serum contains excessive amount of
immunoglobulin – M component
 All are common in middle-aged and
elderly persons
Multiple Myeloma
 Most common of the malignant plasma
cell dyscrasias
 Clonal proliferation of neoplastic plasma
cells in the bone marrow associated with
multifocal lytic lesions throughout
skeletal system
 Dysregulation of D cyclins seems to be
of general importance in multiple
myeloma
 Most common M component is IgG(60%),
followed by IgA (20%to25%); only rarely
IgM,IgD, or IgE. 15 to 20 % of cases only
kappa or lambda light chain – Light chain
disease with Bence Jone proteinuria
 Osteolytic lesions in vertebral column,
ribs, skull, pelvis, femur, clavicle and
scapula.
 Radiologicaly punched out osteolytic
lesions
 Microscopic appearance: Increased
neoplastic plasma cells
 Cytokines produced by tumours cells like IL-6,
TNC produce RANK-ligand which promotes
osteolysis by osteoclastic giant cells
 With progressive disease, spleen, liver, kidney,
lung, lymph nodes show increased malignant
plasma cells
 Terminally leukemic picture may emerge
 Myeloma Nephrosis is a dinstictive feature of
multiple myeloma
 Proteinaceous casts in distal tubles and collecting
ducts surrounded by multinucleated giant cells,
epithelial cells become necrotic or atrophic.
Metastatic calcification and pyelonephritis can
occur. Tumour plasma cells are also seen
 In contrast to multiple myeloma,
lymphoplasma cytic lymphoma is not
associated with lytic skeletal lesions.
Lymphocytes, plasma cells,
lymphoplasma cytic cells are seen
diffusely infiltrating lymph node, spleen,
bone marrow and some time liver
 Lymphoplasma cytic lymphoma is
associated with IgM macroglublinemia
Clinical Features:
 Peak age is 50 to 60 years
 Bone pain,pathological fracture and
hypercalcemia can occur
 Hypercalcemia can cause neurologic
manifestation such as confusion and
lethargy
 Anemia can result due to bone marrow
infiltration
 Recurrent infection due to decreased
normal immunoglobulin. Staphyo,
strepto, E.coli can cause serious infection
 Hyperviscosity syndrome due to
excessive production and aggregation of
myelooma protein and this more
characteristic of lymphoplasmacytic
lymphoma
 Renal insufficency occurs in as many as
50% of cases. It is due to toxic effects of
Bence-Jones protein on renal epithelial
cells of tubules, hypercalcemia and
recurrent bacterial infection
 Amyloidosis develops in 5 to 10% of
cases
Diagnosis of Multiple myeloma
 Diagnosis is suspected when focal,
punched-out radioloical defects in the bone
is present particularly in vertebrae or
calvarium.
 Serum electrophoresis in 99% cases show
monoclonal peak (1% of cases it is non
secretory myeloma)
 Examination of the bone marrow is used to
confirm the presence of plasma cell
proliferation
Lymphoplasmacytic lymphoma
 Composed of a mixed population of B
cells that range from small lymphocytes to
plasmacytic lymphocytes and plasma cells
 Behaves like indolent B-cell lymphoma
 Involves multiple lymphnodes, bone
marrow and spleen
 Serum IgM is increased causing
Waldenstrom macroglubonemia
 Does not produce lytic bone lesions
 Affects older persons.
 IgM macroglobulin produces hyperviscosity
syndrome known as Waldenstrom
macroglobulinemia with following features
 Visual impairment due to retinal hemorrage
and exudate
 Neurological problems such as headaches,
dizziness, tinnitus, deafness and stupor due
to sluggish blood flow and sluding
 Bleeding due to macroglobulin forming
complexes with platelets and clotting factors
 Cryoglobulinemia related to precipitation
of macroglobulin at low tempature
producing Raynaud phenomenon and
cold utricarida
 Median survival in multiple myeloma and
lymphoplasmacytic lymphoma is 4 to5
years
Localized Plasmacytoma
 Solitary lesions involving the skeleton or the
soft tissue
 Skeletal lesions occur at the same site as
multiple myleoma where as soft tissue
lession occur in upper respiratory tract.
 Solitary skeletal plasmacytoma most often
develop in to MM after a period of 5 to 10
years
 Extraosseous plasma cytoma is often cured
by local resection
Heavy Chain disease
 Not a specific entity but a group of
proliferations in which only heavy chain is
produced mostly IgA.
 It is a variant of Maltoma of small intestine
(medittarean lymphoma-IPSIT)
 Lesson common igG heavy chain disease
often presents as diffuse
lymphadenopathy and
hepatosplenomegaly and histologically
resembles lymphoplasmacytic lymphoma
Primary or Immunocyte-Associated
Amyloidosis
 Monoclonal proliferation of plasma cells
that secrete free light chains underlies
this form of amyloidosis
Monoclonal Gammopathy of
Undeetermined Significance (MGUS)
 Term applied to monoclonal gammopathies
that detected in asympotomatic individuals
 M protein is found in the serum of 1% to
3% of asymptomatic health persons older
than 50 years
 MGUS is a precurosor lesion that should
be considered a form of neoplasia
 Rate of development of full fledged
neoplasia is 1% per year.
 In genral, patients with MGUS have less
than 3gm/dL of monoclonal protein in
the serum and no Bence-Jones
proteinuria
 Diagnosis of MGUS should be made
with caution and only after careful
exclusion of all other forms of
monoclonal gammopathies
Hodgkin Lymphoma
 Distinctive group of neoplasm that arises almost
invariably in a single lymph node or chain of
lymph nodes
 Spread to contiguous lymph nodes
 Morphologically characterized by the presence
of distinctive neoplastic giant cells called Reed-
Sternberg(RS) cells with non malignant
inflammatory cell background
 Distinctive clinical features including systemic
symptoms like fever etc.,
 Different type of treatment
Hodgkin Lymphoma
 Lymphocyte  Lymphocyte Rich
Predominance  Nodular Sclerosis
 Mixed Cellularity
Immunophenotype:  Lymphocyte depleted
Neoplastic cells are
positive for LCA, CD20 Immunophenotype:
and other B lineage Neoplastic cells are
marker. CD30,CD15 are positive for
negative CD30,CD15,LMP and
negative for LCA
Lymphocyte Classical Hodgkin
Predominance Lymphoma
Hodgkin and Non Hodgkin lymphomas
Hodgkin lymphoma Non-Hodgkin lymphoma
 More frequent
 More often localized to a
involvement of multiple
single axial group of
peripheral nodes
nodes
 Noncontiguous spread
 Orderly spread by
 Mesenteric nodes and
contiguity
Waldeyer ring commonly
 Mesentric nodes and
involved
Waldeyer ring rarely
 Extranodal involvement
involved
 Extranodal invovement common
uncommon
Reed-Sternberg (RS) Cell
 RS cell, Hodgkin mononuclear cells are
seen with appropriate inflammatory
background in Classical Hodgkin
lymphoma
 RS cell is a large cell with an enlarged
multilobated nucleus, exceptionally
prominent eosinophilic nucleoli surrounded
by perinucleolar halo (owl eye
appearance).Mirror image is formed and
nuclear membrane is distinct
Reed Sternberg Cell
 Classical RS cells are common in mixed
cellularity
 Variants of RS cells – Lacunar cell in
Nodular Sclerosis. Popcorn cell in
Lymhocyte predominance, Anaplastic
RS cell in lymphocyte depleted
 Nodular Sclerosis, Mixed Cellularity are
the common types, others are less
common
Clinical Staging of Hodgkin and NHL –
Ann Arbor Classification
Stage Distribution of Disease
I Involvement of a single lymph node region (I) or
involvement of a single extralymphatic organ or tissue
(I E)
II Involvement of two or more lymph node regions on the
same side of the diaphragm alone (II) or with
involvement of limited contiguous extralymphatic
organs or tissue (II E)
III Involvement of lymph node regions on both sides of the
diaphragm (III), which include the spleen (IIIs), limited
contguous extralymphatic organ or site (III E) or both
(III-ES)
IV Multiple or disseminated foci of involvement of one or
more extralymphatic organs or tissues with or without
lymphatic involvement
Nodular Sclerosis, Hodgkin
Lymphoma
 Most common form
 Most patients are adolescents or young
adults
 Propensity to involve the lower cervical,
supraclavicular and mediastinal lymph nodes
 Prognosis is excellent
 Nodules separated by collagenous bands.
Presence of Lacunar type of RS cells- large
cells with single multilobate nucelus with
multiple small nucleoli and abudant, pale
staining cytoplasm
Nodular Sclerosis Hodgkin
Lymphoma
Mixed Cellularity Hodgkin
Lymphoma
 Most common type in patients older than
50 years and in developing countries
 Male predominance
 Classic RS cells are plentiful within a
distinctive hetergenous cellular infiltrate
comprising of neutrophils, eosinophils,
plasma cells along with fibrosis and
necrosis
 More patients have disseminated
disease and systemic manifestations
HL – Mixed Cellularity
Lymphocyte Predominance Hodgkin
Lymphoma
 Comprise 5% of Hodgkin lymphoma
 Patient presents with isolated cervical
lymphadenopathy and prognosis is excellent
 Morphology: Formation of poorly formed
nodules, presence of POPCORN cells with
back ground of lymphocytes and histiocytes.
Other type of reactive cells are absent or
scanty. B cell origin, originates from follicles.
Positive for LCA and CD20. CD15 and CD30
negative
 Popcorn cells have a delicate
multilobed, puffy nucleus that is likened
to the appearance of popcorn or
elephant foot.
 The cells have rearranged and
somatically hypermutated igH gene
which strongly supports a follicular B cell
origin
Aetiology and Pathogenesis
 Hodgkin lymphoma is a neoplasm arising from germinal
center B cells (have immunoglobulin gene rearrangement
and have undergone somatic hypermutation)
 EBV genome is present in the RS cells in 70% cases of
mixed cellularity cases and small fraction of nodular
sclerosis
 Hyperactivation of NF-kB(a transcription factor) may be a
central event in the genesis, growth and survival of RS
cells
 The characterstic, non enoplastic inflammatory
background is due to secretion of cytokines by RS cells,
including IL-5,IL-13,TGF beta
 Younger patients with more favorable
histology tend to present in clinical stage I
or II and usually free of systemic
manifestation
 Patients with disseminated disease have
systemic symptoms(type B symptoms such
as fever,weight loss,pruritis,anemia) with
less favorable histology
 Clinical stage is the most important
prognostic factor
 5 year survival with stage 1-A or II-A is
close to 100%, even with stage IV-A or IV-B,
survival rate is 50%
 Radiotherapy protocols can lead to
secondary malignancies including lung
cancer, breast cancer and melanoms
 As a result, current efforts are aimed at
developing less genotoxic therapeutic
regimens that decrease therapy-related
complications while preserving a high
cure rate