Lymphoma

dr. Isbandiyah, SpPD

Overview

Concepts, classification
Epidemiology
Clinical presentation
Diagnosis
Staging
Three important types of lymphoma

Conceptualizing lymphoma
neoplasms of lymphoid origin, typically
causing lymphadenopathy
lymphomas as clonal expansions of cells at
certain developmental stages

A practical way to think of lymphoma

Category

NonHodgkin
lymphoma

Hodgkin
lymphoma

Survival of
untreated
patients

Curability

To treat or
not to treat

Indolent

Years

Generally
not curable

Generally
defer Rx if
asymptomatic

Aggressive

Months

Curable in
some

Treat

Very
aggressive

Weeks

Curable in
some

Treat

All types

Variable
months to
years

Curable in
most

Treat

Epidemiology
5th most frequently diagnosed cancer overall
for both males and females
males > females
incidence
NHL increasing over time
Hodgkin lymphoma stable

Lymphoma classification
(based on 2001 WHO)
B-cell neoplasms
Precursor B-cell neoplasms (2 types)
Mature B-cell neoplasms (19)
B-cell proliferations of uncertain malignant potential (2)

T-cell & NK-cell neoplasms

Precursor T-cell neoplasms (3)

Mature T-cell and NK-cell neoplasms (14)
T-cell proliferation of uncertain malignant potential (1)

Hodgkin lymphoma
Classical Hodgkin lymphomas (4)
Nodular lymphocyte predominant Hodgkin lymphoma (1)

Clinical manifestations
Variable
severity: asymptomatic to extremely ill
time course: evolution over weeks, months, or
years

Systemic manifestations
fever, night sweats, weight loss, anorexia, pruritis

Local manifestations
lymphadenopathy, splenomegaly most common
any tissue potentially can be infiltrated

Other complications of lymphoma

bone marrow failure (infiltration)
CNS infiltration
immune hemolysis or thrombocytopenia
compression of structures (eg spinal cord,
ureters) by bulky disease
pleural/pericardial effusions, ascites

Diagnosis requires an adequate

biopsy
Diagnosis should be biopsy-proven before
treatment is initiated
Need enough tissue to assess cells and
architecture
open bx vs core needle bx vs FNA

Staging of lymphoma
Stage I

Stage II

Stage III

Stage IV

A: absence of B symptoms
B: fever, night sweats, weight loss

Staging Workup
CBC, chemistries, urinalysis
USG or CT scans of chest, abdomen and
pelvis
Bone marrow biopsy and aspirate
(Lumbar puncture)
AIDS lymphoma
T cell lymphoblastic lymphoma
High grade lymphoma with positive marrow

Three types of lymphoma worth

knowing about

Follicular lymphoma
Diffuse large B-cell lymphoma
Hodgkin lymphoma

Follicular lymphoma
most common type of indolent lymphoma
usually widespread at presentation
often asymptomatic
not curable (some exceptions)
associated with BCL-2 gene rearrangement
[t(14;18)]
cell of origin: germinal center B-cell

Diffuse large B-cell lymphoma

most common type of aggressive
lymphoma
usually symptomatic
extranodal involvement is common
cell of origin: germinal center B-cell
treatment should be offered
curable in ~ 40%

Hodgkin lymphoma

Thomas Hodgkin
(1798-1866)

Hodgkin lymphoma
cell of origin: germinal centre B-cell
Reed-Sternberg cells (or RS variants) in the
affected tissues
most cells in affected lymph node are
polyclonal reactive lymphoid cells, not
neoplastic cells

Reed-Sternberg cell

RS cell and variants

classic RS cell

lacunar cell

popcorn cell

(mixed cellularity)

(nodular sclerosis)

(lymphocyte
predominance)

Hodgkin lymphoma
Histologic subtypes
Classical Hodgkin lymphoma
nodular sclerosis (most common subtype)
mixed cellularity
lymphocyte-rich
lymphocyte depleted

Epidemiology

less frequent than non-Hodgkin lymphoma

overall M>F
peak incidence in 3rd decade

Clinical manifestations:
lymphadenopathy
contiguous spread
extranodal sites relatively uncommon except
in advanced disease
B symptoms

Treatment by Stage

Chemotherapy Regimens
MOPP
Mechlorethamine, Oncovin,
Procarbazine, Prednisone
ABVD
Adriamycin, Bleomycin, Vinblastine,
Dacarbazine

Long term complications of

treatment
infertility
MOPP > ABVD; males > females
premature menopause

secondary malignancy
skin, AML, lung, MDS, NHL, thyroid, breast...

cardiac disease after Adriamycin treatment.

Non-Hodgkins Lymphoma

Types of Lymphoma
Indolent (low grade)
Life expectancy in years, untreated
85-90% present in Stage III or IV
Incurable

Intermediate
Aggressive (high grade)
Life expectancy in weeks, untreated
Potentially curable

Commonly Used
Classifications

Working Formulation

Rappaport

Low Grade

Small lymphocytic

Follicular small cleaved

Follicular mixed

Diffuse well-differentiated
lymphocytic
(DWDL or WDLL)
Nodular poorly
differentiated
lymphocytic (NPDL)
Nodular mixed
lymphocytic-histiocytic
(NM)

Commonly Used
Classifications

Working Formulation

Rappaport

Intermediate Grade

Follicular large cell

Diffuse small cleaved cell
Diffuse mixed
Diffuse large cell

Nodular histiocytic (NH)

Diffuse poorly
differentiated
lymphocytic (DPDL)
Diffuse mixed
lymphocytichistiocytic (DM)
Diffuse histiocytic (DHL)

Commonly Used
Classifications
Working Formulation
Rappaport
High Grade

Large cell immunoblastic

Diffuse histiocytic
(DHL)

Lymphoblastic lymphoma

Diffuse lymphoblastic
Small noncleaved cell
Burkitts
Non-Burkitts

Diffuse
undifferentiated (DU)

Etiology of NHL
Immune suppression
congenital (Wiskott-Aldrich)
organ transplant (cyclosporine)
AIDS
increasing age

DNA repair defects

ataxia telangiectasia
xeroderma pigmentosum

Etiology of NHL
Chronic inflammation and antigenic stimulation
Helicobacter pylori inflammation, stomach
Chlamydia psittaci inflammation, ocular adnexal
tissues
Sjgrens syndrome

Viral causes
EBV and Burkitts lymphoma
HTLV-I and T cell leukemia-lymphoma
HTLV-V and cutaneous T cell lymphoma
Hepatitis C

Clinical Features

Lymphadenopathy
Cytopenias
Systemic symptoms
Hepatosplenomegaly
Fever
Night sweats

Treatment Options:
Indolent lymphomas
WDLL, NPDL
10-15% in Stage I or II
potentially curable
local radiotherapy

85-90% Stage III or IV

incurable
treatment does not prolong survival

Reasons to Treat in
Advanced Indolent Lymphomas

Constitutional symptoms
Anatomic obstruction
Organ dysfunction
Cosmetic considerations
Painful lymph nodes
Cytopenias

Treatment Options in
Advanced Indolent Lymphomas

Observation only.
Radiotherapy to site of problem.
Systemic chemotherapy

oral agents: chlorambucil and prednisone

IV agents: CHOP, COP, fludarabine, 2-CDA.

Antibody against CD20: Rituxan, Bexxar,

Zevalin.
Stem cell or bone marrow transplant.

CHOP Chemotherapy
Cyclophosphamide (Cytoxan)
Hydroxydaunorubicin
(Adriamycin)
Oncovin (vincristine)
Prednisone