Hodgkin's Lymphoma
Introduction of lymphoma
The lymphomas are malignant
tumors of lymphoid tissue
,characterized by the abnormal
proliferation B or T cells in
lymphoid tissue .
Hodgkin’s lymphoma
Introduction:
Hodgkin lymphoma (formerly called Hodgkin's disease) is a
group of cancers characterized by Reed-Sternberg cells in an
appropriate reactive cellular background.
An important clinical feature is its tendency to arise within
lymph node areas and to spread in an orderly fashion to
contiguous areas of lymph nodes .
Hodgkin lymphoma has a bimodal age distribution with one
peak in the 20s and 30s, and a second peak over the age of 50.
Etiology
Infection
Genetics
Occupational
Origin of Hodgkin's Lymphoma
Evidence is now that the majority of classical HL have clonal Ig
rearrangement, with somatic hypermutation clearly identifying
that H-RS cells as a neoplastic, germinal center derived
B- cells.
Nodular lymphocyte predominant HL(NLPHL), as well is
believed now to be derived from a B-cell as indicated by clonal
VDJ rearrangements of the immunoglobulin heavy chain locus
in the malignant lympocytic and histiostic cells (L & H-cells ).
Histopathologic Classification
WHO 1997
Nodular lymphocyte predominant
Classical HL
Lymphocyte rich CHL
Nodular sclerosis
Mixed cellularity
Lymphocyte depletion
Unclassified
Classical Hodgkin's lymphoma(CHL)
 This variant comprises about 95% ,of all HL cases, and shows
typical bimodal age distribution.
 Each histological subtype is characterized by a series of clinical
, morphological, phenotypic, and genetotypic features (nodular
sclerosis, mixed cellularity ,lymphocyte depleted, and
lymphocyte rich HL).
 In CHL, classical RS-cells can be easily detected.
Diagnostic RS cells
 Diagnostic RS-cells are large cells (20-50 Mm) in diameter or more with
abundant weakly acidophilic or amphophilic cytoplasm, which may appear
homogenous or granular and lacks a pale zone in the Golgi area , The
nucleus is bilobed or polylobed .
 The nuclear membrane is thick and sharply defined. The nuclear pattern is
usually vesicular but with some coarse chromatin clumps scattered
throughout .There is very large ,variously shaped, but usually rounded,
highly acidophilic central inclusion like nucleolus surrounded by a clear
halo. When the two lobes face each other (mirror image) owl eye
appearance results.
 Cells with this set of features but lacking nuclear lobation are referred to as
mononuclear variant of RS cells or H-cells (Hodgkin's cells).
Classical RS cells
Nodular sclerosis Hodgkin's lymphoma (NSHL)
Morphology
In most cases, NSHL has at least a partially nodular pattern, with fibrosious
bands separating the nodules.
Areas of necrosis are common, and diagnostic RS- cells are rare.
The characteristic neoplastic cells, the lacunar type of RS-cells, have
multilobated nuclei and small nucleoli with abundant pale cytoplasm that
retracts in formalin- fixed sections, producing an empty space or lacunae.
The background usually contains several lymphocytes, histiocytes, plasma
cells, eosinophils and neutrophils.
Mixed Cellularity Hodgkin's lymphoma(MCHL)
Morphology
The appearance is usually diffuse or vaguely nodular, without bands forming
sclerosis.
Fine interstitial fibrosis may be present, and classical diagnostic R-S-cells
are easily identified.
The background infiltrate typically consists of lymphocytes, epitheliod
histiocytes, eosinophils, and plasma cells, but lymphocytes may
predominate, giving rise to a differential diagnosis of nodular lymphocyte
predominance Hodgkin's lymphoma(NLPHL) .
Lymphocyte depleted Hodgkin's lymphoma(LDHL)
Morphology
The pattern in LDHL is diffuse and often appears hypocellular ,due to the
presence of fibrosis , necrosis, and a paucity of inflammatory cells.
Large number of classical RS-cells are present with a bizarre pleomorphic
sarcomatous variants.
Confluent sheets of RS-cells may be present but rarely predominate .
Lymphocyte Rich Classical Hodgkin's Lymphoma
(LRCHL)
Morphology
Some cases of the CHL with RS-cells of the classical type or lacunar
type may have a background infiltrate that consist predominantly of
lymphocytes, with rare or no eosinophils, the term lymphocyte rich
CHL was proposed.
Nodular lymphocyte predominance Hodgkin's lymphoma
(NLPHL)
Morphology
NLPHL is defined as having at least a partial nodular growth pattern, diffuse
areas are present in a minority of the cases .
The RS-cells variant of NLPHL differ from the "classic" RS-cells : they
have vesicular, polylobated nuclei and distinct but small, usually peripheral
nucleoli, without perinuclear halos, called L&H-cells (lymphocytes and/or
histiocytes of Luke's and Butler) or "Popcorn cell".
The classical RS are not usually found.
The background is predominantly lymphocytes. Any clusters of epitheliod
histiocytes, plasma cells, eosinophils and neutrophils are rarely seen.
NLPHL
Nodular LPHL and Classical HL Morphologic and
Immunophenotypic Features.
Characteristic
CHL
NLPHL
Diffuse, Interfollicular, Nodular
Nodular, at least in part
R-S Mononuclear or Lacunar
Lymphomcytic/Histiocytic or
Popcorn
Lymphocytes ,histiocytes, eosinophils,
plasma.
Lymphocytic, Histiocytic.
Fibrosis
Common
Rare
CD15
+ ( 85% )
(-)
CD30
+ ( > 95% )
(-)
CD20
(- / +)
(+)
CD45
(-)
(+)
Epithelial Membrane Antigen
(-)
(+)
Nuclear BCL 6 ( PTN in R-S cells )
(-)
(+)
+ ( 50% )
(-)
T -cells > B-cells
B-cells > T-cells
(-)
(+)
Rearranged, Clonal, Mutated,
“Crippled”
Rearranged, Clonal, Mutated,
Ongoing
Pattern
Tumour Cells
Background
EBV ( in R-S ) cells
Background Lymphocytes
CD57 T-cells
Ig genes
General symptoms:
I. Fever
II.Weight loss
III.Loss of appetite
Symptoms of Hodgkin’s lymphoma:
IV.Night sweats
V.Pruritus
VI.lethargy
Examination
 Local symptoms:
I. Enlarged, painless, non-tender, superficial lymph nodes
II.Alcohol-induced pain ‫ــــ‬Rarely, patients with Hodgkin’s
lymphoma complain of severe pain following alcohol
ingestion.
The pain typically occurs within a few minutes after the
ingestion of even a small amount of alcohol. The
mechanism is unknown.
Signs of HL:
1. Lymph node enlargement
2. Cachexia
3. Anemia
4. Splenomegaly
5. Hepatomegaly
6. Jundice. rarely
Diagnosis
BLOOD:
(FBC, Film, ESR, LFT, LDH, Urate , Ca.)
Lymph node excision biopsy , image guided needle
biopsy.
Chest X-ray, CT of thorax, abdominal, pelvis
and bone marrow biopsy‫ـــــــ‬staging of HL