Hodgkin's Disease

Previously called Hodgkins disease
Hodgkins Lymphoma
Hodgkin's lymphoma (HL) is a neoplasm of
lymphoid tissue defined by the presence of

the malignant Reed-Sternberg (R-S) cells
and/or Hodgkin's cells (H-cells) with an
appropriate cellular backgrounds.
Peak incidence 20-30 years in developed
countries, but is 5-20 in developing

countries like ours.
Males are more frequently involved.
Less common than NHL, arround 10% of
lymphoma ; ~ 10,000 cases per year
Aetiology of HL :
Genetic factors
Occupational exposure
Epstein-Barr virus
Reed Sternberg (R-S) Cell

A large cell, 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 so that the cell appears
binucleated or multinucleated. The
nuclear membrane is thick and sharply
defined.. There is very large, usually
rounded, highly acidophilic central
inclusion like nucleolus surrounded by
a clear hallow. When the two lobes
phase each other (mirror image) Owl
eye appearance results.
Reed-Sternberg (R-S) cells
Origin of the RS cells in HD

Malignant RS cells constitute only a small
percentage of cells in lymph nodes.

RS cells are now proved to be mainly of Bcell origin, with crippling mutations during
immunoglobulin gene somatic hypermutation
within germinal centre, which prevents
further differentiation.
Classification
Histologic Subtypes of Hodgkin
lymphoma
( WHO Classification ).
1. Classical Hodgkin lymphomas.
Nodular sclerosis - 67%. Good prognosis
Mixed-cellularity - 25%. Intermediate prognosis

Lymphocyte-rich - 3%, best prognosis.
Lymphocyte-depletion - rare & worst prognosis.
2. Nodular lymphocyte predominant
Hodgkin lymphoma. Excellent prognosis
Hodgkin's Histologic subtypes
Nodular sclerosing HL
Most common type Hodgkin's lymphoma in
US/Europe
Usually presents in the anterior mediastinum
and neck of young adult females
Characterized by fibrotic capsule and bands
subdividing tissue and
Lacunar variant Reed Sternberg cell their
pale cytoplasm retracting in formalin fixed

sections, producing empty space or lacunae
usually stage I or II
Histologic subtypes 2
Lymphocyte predominant
Usually presents with limited disease in
the neck of young adults

Associated with L and H (lymphocytic and
histiocytic) or "popcorn cell" variant RS
cell
Mixed cellularity
More extensive disease
Older patients than NS and LP
More R-S cells, eosinophils, plasma cells
Mononuclear variant R-S cells
stage III or IV disease
Lymphocyte depleted
Often presents in retroperitoneum, older
patients
Accompanied by less lymphocytes,
sclerosis and pleomorphic RS cell
variants, HIV (EBV)
Also more aggressive disease
Ancillary studies
AncillaryimmunologicstudiesassistthedxofHodgkins'
lymphoma
DistinguishHL(classicaltype)from
Immunoblastreactions
UnusualvariantsofNHL
CD15andCD30antigensingolgiandoncellmembraneofRS
cellsmostuseful
Nodular Sclerosis Hodgkins Lymphoma
The Lacunar RS cells in Nodular Sclerosis HL
Lymphocyte rich and Lymphocyte Depleted HL
classic RS
cell (mixed
cellularity)
lacunar cell
(nodular
sclerosis)
folded or
multilobated
nucleus and lies
Popcorn cell
(lymphocyte
predominance)
multiply infolded
nuclear membranes,
small nucleoli,
abundunt cytoplasm
Patternsofspread
Hodgkin'slymphomaspreadscontiguouslyvia
lymphatics
StagingasinNHLmayormaynotinclude
laparotomy/splenectomy
Clinical features
Bimodal age distribution :
young adults ( 20-30 yrs) & elderly (> 50yrs) May
occur at any age
M > F
Lymphadenopathy:
most often cervical region
asymmetrical, discrete
painless, non-tender
elastic character on palpation ( rubbery)
not adherent to skin
fluctuate in size
Contiguous spread via the lymphatic chain
eg.involvement of abdominal & thoracic LNs

Extra nodal disease - rare
Hepatospleenomegaly
Constitutional symptoms ( B symptoms )
Night sweats,
sustained fever > 38 degree celsius,
loss of weight >10% of body weight in
6m
Fever sometimes cyclical (Pel-Ebstein fever)
Pain at the site of disease after drinking alcohol
Pallor
Pruritis
Symptoms of Bulky (>10 cm) disease
Hodgkins Lymphoma - Lymphadenopathy
Investigations
CBP :
Anemia ( normochromic / normocytic),

eosinophilia, neutrophilia, lymphopenia
ESR raised still have prognostic factor
LFT- (liver infil / obs at porta hepatis)
RFT- prior to treatment
Urate , Ca,
LDH - adverse prognosis
CXR- mediastinal mass
CT thorax / abdomen / pelvis-for staging
Other: Gallium scan, , Lymphangiography ,
Laporotomy
LN FNAC / biopsy :
Malignant REED-STERNBERG ( RS) Cell: Bi-nucleate
cell with a prominent nucleolus. Derived from B cell,

at an early stage of differentiation
Reactive background of eosinophils, lymphocytes,
plasma cells
Fibrous tissue
Staging of HD :
Ann Arbor Staging system
- Stage I : Disease in one Lymph node area.

- Stage II :Disease in two or more lymph node area on
the same side of the diaphragm.
- Stage III :Disease in lymph node areas on both sides
of the diaphragm (spleen is considered nodal).
- Stage IV : Extensive disease in liver, Bone marrow or
other extranodal sites.
Symptom status A or B.
Staging requires the use of a number of imaging,
hematological and sometimes surgical evaluation
procedures.
Ann Arbor Clinical Staging of HL
Treatment of Hodgkins Lymphoma

Depends on Clinical stage .
It generally includes radiotherapy and/or
chemotherapy.
Overall 20 yr Disease Free survival (CURE)
in those receiving radiotherapy or

chemotheapy is about 80-90%.
Prognosis
Hodgkin's lymphoma is a curable malignancy
Overall cure rate approximately 80%
With modern therapy, prognosis based more
on staging, bulk of disease, than morphologic

subtype
In long term survivors there is a risk of
secondary malignancy: (leukemia , NHL),
Solid tumors- Lung, breast

Infections
Cardiac, pulmonary, endocrinal abnormalities
International Prognostic Index (IPI)

Age
Advanced stage disease
Performance status
Elevated LDH
Presence of Extra nodal disease
Non-Hodgkin lymphoma
(NHL).
NHL are neoplasms of immune system usually
originates in the lymphoid tissues and can spread to
other organs. However, unlike Hodgkin lymphoma,
NHL is much less predictable and has a far greater
predilection to disseminate to extranodal sites.
Risk factors
: radiation, agricultural
chemicals, immunodeficiency states,

connective tissue disease
& infections : EBV (burkitts lymphoma).
Helicobacter pylori (gastric MALT)
Most lymphomas are of B cell phenotype (75-85%),
while about 20% are T cell lymphomas.
Lower grade lymphomas tend to have more mature
cells and mostly follicular patterns.
Higher grade lymphomas tend to have larger less
mature cells and diffuse patterns.

NHL s are staged using the Ann Arbor
Diagnosis of NHL
Excisional biopsy is preferred to show:
effacement , cellular morphology and nodal

architecture (follicular vs diffuse).
Immunohistochemistry to confirm cells are
lymphoid
LCA (leukocyte common antigen) CD45
Monoclonal staining with Igk or Igl
Flow cytometry:
CD 19, CD20 for B cell lymphomas
CD 3, CD 4, CD8 for T cell lymphomas
Chromosome changes/oncogenes
Behavior
Indolent grow slowly. The majority of NHLs.
are generally considered incurable with

chemotherapy and/or radiation therapy.
Aggressive rapid growth pattern. This is the
second most common form of NHL and are

curable with chemotherapy.
Very Aggressive grow very rapidly. small
proportion of NHLs and can be treated with

chemotherapy. Unless treated rapidly, these
lymphomas can be life threatening.
Normal development of B lymphocytes
Small Lymphocytic L.
B-Lymphoblastic L.
Plasma
cell
Marginal
Zone L
Follicular Lym.
Burkitts
Memory
cell
Mantel cell L.
Antigen
Large cell L
Large cell L
Immunoblast
B-cell
REAL/WHO Classification of NHL

A) Precursor : lymphoblast
B) peripheral
B-Cell Lymphomas
(>85%)
Diffuse Large B-Cell Lymphomas
(31%)
Follicular Lymphoma (22%)
Mucosa-Associated Lymphatic Tissue (MALT) Lymphoma

(7.5%)
Small Lymphocytic Lymphoma-Chronic Lymphocytic
Leukemia (7%)
Mantle Cell Lymphoma (6%)
Mediastinal (Thymic) Large B-Cell Lymphoma (2.4%)
Lymphoplasmacytic Lymphoma-Waldenstrom
Macroglobulinemia (<2%)
Nodal Marginal Zone B-Cell Lymphoma (<2%)
Splenic Marginal Zone Lymphoma (<1%)
C)Precursor :lymphoblast
D) peripheral T and NK Cell Lymphomas
(~12%)
Extranodal T or NK-Lymphoma
Cutaneous T-Cell Lymphoma (Szary
Syndrome and Mycosis Fungoides)

Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-Cell Lymphoma
NCI Working Formulation for Lymphoma CLassification
Low Grade NHL

Diffuse small lymphocytic (CLL/SLL).
Follicular small Cleaved cell.
Follicular mixed small and large cell.
Intermediate Grade NHL
Diffuse Small Cleaved.

Diffuse mixed small and large.
Diffuse large cell lymphoma.
Follicular large cell lymphoma.
High Grade NHL (all
diffuse)
Immunoblastic Lymphoma
Small non-cleaved, Burkitts Lymphoma.
Lymphoblastic lymphoma
Precursor B and T cell neoplasms:
This encompasses Precursor B and T ALL
and Lymphoblastic lymphomas.

Acute lymphoblastic Leukemia: Extensive
bone marrow and peripheral blood
involvement. (Includes L1 and L2 but not
L3 FAB subtypes); Majority are of
precursor B origin.
Lymphoblastic Lymphoma:
Lymphoma presentation
with a mass lesion and < 25% blasts in
marrow; Majority are of precursor T
origin. (80-85%)
Clinical features of LL
In the T LL, Mediastinal mass is quite
common (up to 80% in some series).

In B LL no mediastinal mass is usually
present.
High rates of marrow involvement are
expected.
Mediastinal Mass in T Lymphoblastic Lymphoma
LN Biopsy in LYMPHOBLASTIC
LYMPHOMA /ALL
High Grade NHL-Lymphoblastic Lymphoma-Bone marrow
Mantle
Cell
Lymphoma
Disease of the elderly.
Generalized nodal and extranodal disease.
Most have marrow involvement.

About half have splenic involvement.
Lymphoid polyps in large and small bowel.
About one third have peripheral lymphocytosis.
Mantel cell lymphoma

Small uniform cells
Follicular Lymphoma
Most common form in States, not common in
Iraq.
Middle aged and elderly.
Indolent disease.
often asymptomatic, not curable
Variable composition of small cleaved follicular
centre cells and large non-cleaved Follicular
centre cells.
Follicular lymphoma, involving a lymph node
A, Nodular aggregates of lymphoma cells are present throughout. B, At

high magnification, small lymphoid cells with condensed chromatin and
Mixed Small and Large Follicular lymphoma
Marginal Zone
Lymphoma
Disease of Middle aged.
May involve LN, spleen, extranodal
tissue including MALT (mucosal

associated )
Associated with chronic infection
& Autoimmune (e.g. Hashimotos
thyroiditis) or infectious (e.g.
Helicobacter pylori).
Indolent , but poor response to therapy.
Diffuse Large B-cell

Lymphoma
adults (Mainly middle aged), and less so
in children (in Western countries and in
Iraq)
Rapidly enlarging mass, nodal or
extranodal.
Aggressive, rapidly fatal if untreated.
Most common type of lymphoma
Diffuse large B-cell lymphoma. The tumor cells have large nuclei with
open chromatin and prominent nucleoli. They express pan B markers as
Burkitt lymphoma
Clinical: 3 types
1. Endemic: African EBV , jaw
2. Sporadic: North America , abdominal mass
3. Immunosuppressed (HIV)
Aggressive tumor, high grade
Strictly of B cells (non cleaved)
Pathology: medium size, high mitosis,
apoptosis, Starry sky pattern
JAW MASS IN BURKITTS LYMPHOMA
Burkitt lymphoma. The tumor cells and their nuclei are fairly uniform, giving a
monotonous appearance. Note the high mitotic activity and prominent nucleoli. The
"starry sky" pattern produced by interspersed, lightly staining
Burkitt cells are monomorphic, medium sized cells

with rounded nuclei, multiple nucleoli, basophilic
cytoplasm and cytoplasmic vacuoles, With high rates
of proliferation (mitotic figures) and spontaneous
cell death (Starry sky appearance)
Burkitts Lymphoma Imprint of a Lymph node
Peripheral Tand NK-Cell

neoplasms
Peripheral T-cell Lymphoma unspecified.
Mycosis Fungoides and Sezary Syndrome.
Anaplastic large cell lymphoma
Adult T cell lymphoma Leukemia.
Others .
All these share some common features :

All are diffuse.
Prominent vascular network
Compartmentaliztion of the tumor into nests
separated by collagen strands.
Wide range ot tumor cell size and nuclear
configuration .
Have a high incidence of marrow involvement.
Peripheral T cell NHL

Adult T-Cell leukemia/lymphoma :
Is associated with HTLV-1 (human T-cell
Leukemia Lymphoma virus) infection.
It is an aggressive disease presenting
with
1.generalized lymphadenopathy,
2.skin manifestations,
3.hepatosplenomegaly,
5.hypercalcaemia and
6.leucocytosis with multilobulated
lymphoid cells.
Peripheral T-cell NHL

Mycosis Fungoides :
a cutaneous T cell Lymphoma.
multiple skin lesions progressing from patches to
plaques then tumors;
Disease is often indolent but progressive.
Histologically it shows upper dermal neoplastic T
cells infiltrates with cerebriform nuclei and
epidermal invasion (epidermotropism)
In its final stages it infiltrates Lymph nodes and
visceral organs.
1.Typical Eczematoid lesions at

presentation in Mycosis Fungoides
Peripheral T-cell NHL

Sezary Syndrome :
It is the leukemic phase of mycosis
fungoides
It presents clinically with generalized
exfoliative erythroderma.
The peripheral blood shows sezary cells,
which are abnormal lymphoid with
cerebriform nuclei.
Exfoliative Erythroderma Sezary Syndrome
Sezary cells in the peripheral blood in Sezary

syndrome (lymphoid cells with cerebriform nuclei.
Comparison between HL and NHL
NHL
Hodgkins
B, less so T
Uncommon
Common
Discontiguous
Contiguous
Extranodal
Common
Uncommon
Mediastinal
Uncommon
Common
Abdominal
Common
Uncommon
Bone marrow
Common
uncommon
Uncommon
rare
common
In Majority
Origin
Site of Disease
Localized
Nodal spread
B systemic symptoms
Possible cure

Hodgkin's Disease

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Previously called Hodgkins disease

lymphoid tissue defined by the presence of

Peak incidence 20-30 years in developed

countries, but is 5-20 in developing

Reed Sternberg (R-S) Cell

acidophilic or amphophilic cytoplasm,

Reed-Sternberg (R-S) cells

Origin of the RS cells in HD

percentage of cells in lymph nodes.

Mixed-cellularity - 25%. Intermediate prognosis

Hodgkin's Histologic subtypes

Most common type Hodgkin's lymphoma in

pale cytoplasm retracting in formalin fixed

Usually presents with limited disease in

the neck of young adults

Nodular Sclerosis Hodgkins Lymphoma

The Lacunar RS cells in Nodular Sclerosis HL

Lymphocyte rich and Lymphocyte Depleted HL

eg.involvement of abdominal & thoracic LNs

Constitutional symptoms ( B symptoms )

Hodgkins Lymphoma - Lymphadenopathy

Anemia ( normochromic / normocytic),

cell with a prominent nucleolus. Derived from B cell,

- Stage I : Disease in one Lymph node area.

Ann Arbor Clinical Staging of HL

Treatment of Hodgkins Lymphoma

in those receiving radiotherapy or

on staging, bulk of disease, than morphologic

Solid tumors- Lung, breast

International Prognostic Index (IPI)

chemicals, immunodeficiency states,

while about 20% are T cell lymphomas.

Lower grade lymphomas tend to have more mature

cells and mostly follicular patterns.

Higher grade lymphomas tend to have larger less

mature cells and diffuse patterns.

Excisional biopsy is preferred to show:

effacement , cellular morphology and nodal

are generally considered incurable with

Aggressive rapid growth pattern. This is the

second most common form of NHL and are

Very Aggressive grow very rapidly. small

proportion of NHLs and can be treated with

Normal development of B lymphocytes

REAL/WHO Classification of NHL

Mucosa-Associated Lymphatic Tissue (MALT) Lymphoma

Syndrome and Mycosis Fungoides)

NCI Working Formulation for Lymphoma CLassification

Low Grade NHL

Intermediate Grade NHL

Diffuse Small Cleaved.

High Grade NHL (all

Precursor B and T cell neoplasms:

This encompasses Precursor B and T ALL

and Lymphoblastic lymphomas.

common (up to 80% in some series).

Mediastinal Mass in T Lymphoblastic Lymphoma

High Grade NHL-Lymphoblastic Lymphoma-Bone marrow