Lymphoproliferative Disorders II:

Hodgkin’s Lymphoma and Non-

Hodgkin’s Lymphoma
Dilip K. Das, MBBS, MD, PhD, DSc, FRCPath.
Department of Pathology, Faculty of
Medicine,
Kuwait University
Hodgkin’s Lymphoma: History and Pathognomonic Cells

• In 1832, Thomas Hodgkin, an English physician (1798-1866),

described peculiar morbid anatomical appearance of lymph nodes in
some autopsy cases.
• In 1865, Wilks applied the eponymous term ‘Hodgkin’s disease’ to it.
• Carl von Sternberg (1898) and Dorothy Reed (1902) independently
described the pathognomonic cell of Hodgkin’s disease, presently
called Hodgkin cell and Reed-Sternberg cell (R-S cell).
• The Hodgkin cell is a large mononucleated cell and Reed-Strenberg
cell is a binucleated, multilobated or mulinucleated cell with
prominent eosinophilic nucleoli.
Hodgkin’s Lymphoma: Constituent Cells and
the Origin of Neoplastic Cells
• The malignant cell of Hodgkin’s
lymphoma forms only a small
percentage of the cellular
population within the affected
lymph nodes. The bulk of the
tissue is made up of reactive
lymphocytes, macrophages,
plasma cells, and eosinophils,
attracted into the cellular mileau
by a variety of cytokines
secreted by the Hodgkin’s and R-
S cells.
 Classification of Hodgkin’s Lymphoma
World Health Organization (WHO)
Classification:
2. Classical Hodgkin’s lymphoma (HL)
• lymphocyte rich classical HL
• mixed cellularity
• Lymphocyte depleted
• Nodular sclerosis
7. Nodular lymphocyte predominant Hodgkin’s
lymphoma
Classical Hodgkin’s Lymphoma: Clinical
and Gross Anatomical Features
• Peak incidence in 3rd and 4th
decades.
• Lymphadenopathy in upper half of
the body (cervical, axillary, and
mediastinal). Enlarged lymph nodes
are typically rubbery, discrete and
mobile. Mediastinal involvement
common (40%). Disease starts in
lymph node or thymus and spread
via lymphatics in a contiguous
fashion. Spleen appears key to
hematogenous dissemination.
• A third of patients have systemic
symptoms (weight loss, fever, and
night sweats).
• Affected lymph nodes are enlarged
with smooth surface and cut
surface is homogeneously white.
 Classical Hodgkin’s Lymphoma:
Histopathology
A. Lymphocyte rich classical
Hodgkin’s lymphoma (LRCHL):
Scattered or scanty classical
Hodgkin and R-S cells in a
lymphocyte rich background.
B. Mixed cellularity: An admixture of
lymphocytes, histiocytes, plasma
cells, Hodgkin’s cell and R-S cells,
the latter are relatively abundant
compared to classical LRCHL. A B
C. Lymphocyte depleted: Numerous
Hodgkin’s cells and R-S cells with
depletion of lymphocytes.
D. Nodular sclerosis: Cellular
nodules, which are separated by
bands of collagen. Within the
nodules mixed infiltrate and
special Hodgkin cell variants
called laculnar cells (cells which
appear to sit in a space or lacuna).
C D
 Nodular Lymphocyte Predominant
Hodgkin’s Lymphoma
• Differs markedly from clinical
presentation of classical Hodgkin’s
lymphoma.
• Peak age is a decade older and
marked male predominance.
• Most patients (90%) have
asymptomatic localized disease and
unusual sites (e.g. inguinal LN)
involved.
• Histologically: Nodular growth
pattern but no collagen band
formation, abundant lymphocytes,
paucity of typical Hodgkin’s cells,
and a distinct R-S cell variant called
‘popcorn’ cell.
• Overall survival is excellent and
superior to that in classical
Hodgkin’s lymphoma.
 Immunophenotyping of Hodgkin’s Lymphoma

• In vast majority of cases,

Hodgkin’s and R-S cells show
clonal immunoglobulin gene
rearrangement, indicationg their
B-lymphocyte origin. Further,
somatic hypermutation of
immunoglobulin gene indicate
that the cells are of germinal
center origin. Hence, the term
Hodgkin’s disease is replaced
with Hodgkin’s lymphoma.
• Neoplastic cells in classical
Hodgkin’s lymphoma: CD45–,
CD30+,CD15+.
• Neoplastic cells in nodular
lymphocytic predominance
Hodgkin’s lymphoma: CD45+,
CD30–, CD15–, CD20+.

CD30 CD15
Non-Hodgkin Lymphoma: Definition and
Morphologic Basis.
Definition:
• In histology, lymphomas constitute
a homogeneous neoplastic cell
population, due to multiplication of
one or more elements normally
present in the lymph node to the
point of destruction of nodal
architecture. The tumor growth
pattern is either as cohesive cellular
aggregates called follicular or
nodular pattern or as diffuse
infiltration.
Other histologic and cytologic features:
• The neoplatic cells tend to infiltrate
the capsule of the lymphoid organ
they involve.
• Cytologically, the neoplastic cells
are monotypic but have
resemblance with their non-
neoplastic counterpart.
• One type of neoplastic cell can
transform/differentiate
morphologically different cell type.
Reactive Follicular Hyperplasia of the Lymph Node
Immunologic and Gednetic Basis of NHL
Immunologic Basis:
Immunologically, lymphomas are expanded
clones of lymphocytic precursors or
functional cell types (B- or T-cell), which
appear to develop from a block or switch on
(derepression) of lymphocytic
transformation.
B-cell neoplasms are sIg+ and or cIg+, and
express panB-cell markers (CD19, CD20,
CD22, and CD79α).
T-cell neoplasms express T-cell markers
such as CD2, CD3, CD5, CD7, CD4, and CD8,
but CD3 is considered lineage specific.

Genetic Basis:
Genetically in most lymphoid neoplasms
antigen receptor gene rearrangement
precedes transformation. As a result, the
daughter cells derived from the malignant
progenitor share same antigen receptor gene
configuration and sequence and synthesize
identical antigen receptor protein (either Ig or
T-cell receptor).
 Extracted from the WHO Classification of Neoplastic
Diseases of the Lymphoid Tissues: 1997
(Summary of Main Entries)

• B-cell neoplasms: • T-cell neoplasia:

• Precursor B-cell (B- lymphoblastic
lymphoma/leukemia)
• Mature (peripheral) B-cell
neoplasms
• B-cell CLL/small lymphocytic lymphoma
• B-cell prolymphocytic leukemia
• Lymphoplasmacytic lymphoma
• Mantle cell lymphoma
• Follicular lymphoma
• syndrome
Marginal zone lymphoma (extranodal or
MALT, Nodal, and Splenic)
• lymphoma
Hairy cell leukemia
• Diffuse large B-cell lymphoma and its
subtypes (Burkitt lymphoma,
immunoblastic lymphoma)
• Plasmacytoma, and plasma cell myeloma
• Precursor T-cell (T-lymphoblastic)
lymphoma/leukemia
• Mature (peripheral) T-cell
neoplasms
• T-prolymphocytic leukemia
• T-cell granular lymphocytic
leukemia
• Aggressive NK cell leukemia
• Mycosis fungoides and Sezary
• Angioimmunoblastic T-cell
• Peripheral T-cell lymphoma:
Lymphoepithelioid (Lennert’s),
Immunoblastic
• Adult T-cell leukemia/
lymphoma (HTLV 1+)
• Anaplastic large cell lymphoma
(ALCL) (T and Null celltypes)
• Intestinal T-cell lymphoma
 Non-Hodgkin Lymphoma: Selected Sub-Types

1. B-cell CLL/small lymphocytic

lymphoma.
2. Follicular lymphoma.
3. Diffuse large B-cell
lymphoma.
4. Marginal zone lymphoma
(extranodal MALT).
5. Burkitt lymphoma.
6. Precursor T-lymphoblastic
lymphoma/leukemia.
7. Anaplastic large cell
lymphoma.
 B-cell CLL/Small Lymphocytic Lymphoma

• Exclusively a disease of adults

and affected lymph nodes are
enlarged with smooth surface
and homogeneous white cut
surface.
• Are tumors of immature small
lymphocytes. Normal lymph
nodal architecture is replaced
by a monotonous infiltrate of
small lymphocytes. Disease is
almost invariable disseminated
with liver, spleen and bone
marrow infiltration.
• The cells are of B-cell lineage
and tissue manifestation of B-
cell CLL. B-cell associated
antigens are expressed.
• Genetic features:
Immunoglobulin heavy and light
chain genes are rearranged.

CD20
 Follicular lymphoma
• Commonest type of NHL and a disease
of late adult life. Lymph nodes are
enlarged. Involvement of bone marrow,
liver, and spleen is common.
• Derived from (or differentiated towards)
germinal center B-cells.
• Pure follicular or mixed follicular and
diffuse pattern. Contain an admixture
of centroblasts and centrocytes
(neoplastic B-cells). Centrocytes
predominate in most cases. Non-
neoplastic follicular dendritic cells, and
T-cells are also present.
• Express pan B-cell associate antigens.
• Chromosomal translocation t(14;18)
(q32;q21) involving the
immunoglobulin heavy chain promoter
region on chromosome 14 and the anti-
apoptotic gene bcl-2 on chromosome
18. This translocation causes
constitutive over-expression of bcl-2
protein, rendering follicular lymphoma
relatively resistant to apoptosis.

CD20 Bcl 2
 Diffuse large B-cell lymphoma.
• Usually a disease of adults. Majority
of patients present with rapidly
progressive nodal disease but
extra-nodal involvement is common.
• May arise de novo or as a result of
the transformation of follicular
lymphoma.
• Histology: Characterized by a
diffuse outgrowth of large B-cells,
which may display centroblastic or
immunoblastic cytology.
• Express one or more B-cell associated
antigens.
• Common cytogenetic abnormalities are t
(14;18) translocation resulting in
deregulation of bcl-2, and translocations
involving the 3q27 breakpoint with over-
expression and mutation of bcl-6 gene,
which is associated with extra-nodal
presentation and more favorable clinical
course.

Ig λ
 Extranodal Marginal Zone Lymphoma (MALT
Lymphoma)
• Most commonly occurs in
gastrointestinal tract. Other sites
are thyroid, salivary gland, skin and
orbit. Remain localized for a long
period and have an indolent natural
history, often with very good
prognosis.
• Histology: Reactive germinal center
surrounded by a population of
neoplastic B-cells, morphologically
similar to lymph node marginal zone CD20
B-cells (centrocyte-like marginal
zone B-cells, monocytoid B-cells,
plasmacells). May show impressive
degree of plasma cell
differentiation.
• Express B-cell associated antigens.
• Novel karyotypic abnormalities, t(11;18)
and t(1;14); the latter is associated with
mutation and gain of function of bcl-10
gene.
 Burkitt Lymphoma
• Burkitt lymphoma may be endemic
(para-equatorial Africa), non-endemic
(American, Indian) and
immunodeficiency associated.
• The disease affects mostly children
and adolescents.
• Associated with Epstein-Barr (EB)
virus infection and malaria.
• Commonly involves extranodal sites
(jaw bone involvement more common
in endemic type and GIT in non-
endemic type).
• Histology: Tightly packed medium-
sized lymphoid cells with round nuclei,
multiple nucleoli, interspersed with
phagocytic macrophages, which impart
a ‘starry sky’ appearance. High
proliferation rate with almost 100%
cells in cycle. Smears show
cytoplasmic lipid vacuoles.
• Express B-cell associated antigens, and
CD10.
• A distinctive type of B-cell lymphoma,
associated with specific chromosomal
translocation t(8;14)(p24;q32) involving c-
myc gene at 8p24 and Ig heavy chain gene
locus at 14q32.
 Precursor T-lymphoblastic
lymphoma/leukemia
• Precursor T-cell
lymphoma/leukemia tend to involve
the mediastinum in adolescent
boys.
• Histology: Diffuse sheets of small to
medium-sized lymphoid cells with
high nucleo-cytoplasmic ratio,
moderately condensed to dispersed
chromatin and indistinct nucleoli.
may have a distinct convoluted
morphology.
• Express the nuclear antigen TdT. T-
lymphoblasts variably express T-cell
antigens.
• Rearrangement of antigen receptor
genes variable.
• Bone marrow infiltration is frequent.
 Anaplastic Large Cell Lymphoma (ALCL)
• Most common in children and
young adults.
• May be nodal but frequent
extranodal disease as well.
• Histology: Wide spectrum of
appearance including small cell,
lymphohistiocytic, giant cell, and
sarcomatoid. Characteristic
Doughnut and R-S-like cells.
• CD45+, CD30+, CD15–. Often of T-cell
lineage.
• Particular chromosomal translocation,
t(2;5) (p23;q35), which leads to
expression of a fusion protein containing
tyrosine kinase called anaplastic
lymphoma kinase (ALK).
• Despite aggressive histological
appearance, ALCL has a good overall
survival.

LCA CD30
Thank You