Dr Shwe Sin

FMHS
Universiti Tunku Abdul Rahman
By the end of the lesson, the students
should be able to :
State the definition and types of lymphoma and their
differences.
Describe the classification, clinical presentation,
diagnosis, staging and prognosis of Hodgkin and Non-
Hodgkin lymphomas.
DEFINITION
Lymphomas are a group of diseases caused by
malignant lymphocytes that accumulate in lymph
nodes and cause the characteristic clinical features of
lymphadenopathy.

Types :
Hodgkin Lymphoma (HL)
Non-Hodgkin Lymphoma (NHL)
I. HODGKINS LYMPHOMA
Definition :
Primary malignant tumour arising from the lymph
node named after Dr. Thomas Hodgkin

A clonal neoplastic disorder where the Reed-Sternberg

tumour giant cells & its variants represent the
transformed cells accompanied by a background of
appropriate inflammatory cells
W.H.O CLASSIFICATION (2008)
Classic Hodgkin lymphoma
-Nodular sclerosis
-Mixed cellularity
-Lymphocyte depleted
-Lymphocyte rich

Nodular Lymphocyte predominant

DIFFERENCE FROM N.H.L
Usually localized to a single axial node (cervical or
mediastinal)
Orderly predictable spread by contiguity
Mesenteric nodes & Waldeyers ring rarely involved.
Extra-nodal uncommon
Leukaemic conversion almost absent
 Diagnosis and histological
classification
Gross : (Usually cervical lymph node)

Painless, enlarged, discrete lymph nodes, rubbery in

consistency
Cut surface is fish flesh appearance
1. LYMPHOCYTE PREDOMINANT
Effects young males
Diffuse or nodular pattern
Frequent L & H (pop corn) cells in a background of
reactive B lymphocytes
Reed-Sternberg cells are absent
No fibrosis
Can transform into Diffuse large B cell N.H.L
CD 20 (+), CD 15 (-) and CD 30 (-)
2. NODULAR SCLEROSIS
Young females
Mediastinum lymph node involved
The lymph node is divided into nodules by sclerosing
fibrous bands
Frequently Lacunar cells (CD 15 & CD 30 positive) are
seen (multilobate nuclei surrounded by abundant pale
cytoplasm. The nucleus appear to be sitting in an
empty lacunae)
Background inflammatory cells are T lymphocytes &
histiocytes
3. MIXED CELLULARITY
Diffuse effacement of lymph node by numerous
diagnostic classical Reed-Sternberg tumour giant cells
& mononuclear Hodgkin cell (CD 15 & CD 30 positive)
R-S giant cell is a large cell with abundant amphophilic
cytoplasm. Nucleus is bilobed or binucleated & mirror
image to each other
They contain characteristic red nucleoli with a
perinuclear halo giving rise to an owl eyed appearance
The background inflammatory cells are mature
lymphocytes, polymorphs, histiocytes & eosinophils
4. LYMPHOCYTE DEPLETION
Effects older patients
Atypical R-S giant cells are seen with bizarre nuclei
(CD 15 & CD 30 positive)
Mature lymphocytes are depleted
Fibrosis & necrosis present
STAGING ANN ARBOR
Stage I : Confined to single lymph node region
(cervical/ mediastinum)
Stage II : 2 or more lymph node regions (same side of
the diaphragm)
Stage III : Involvement of lymph node (both sides of
diaphragm, splenic involvement present)
Stage IV : Disseminated involvement including bone
marrow & peripheral blood
Ann Arbor Staging
DIAGNOSIS
Clinical features
Young adults usually males except nodular sclerosis.
Male: Female = 2 : 1
Early stage painless, non-tender, asymmetrical, firm,
discrete and rubbery enlarged lymph node (usually cervical
& mediastinum)
Advanced atage-
Present with fever, which is intermittent low grade known
as Pel Ebstein fever
Pruritus, night sweat & weight loss
Opportunistic infection due to impairment of cell
mediated immunity
Investigations
For primary diagnosis
FNAC (Fine Needle Aspiration Cytology) Lymph node
Routine histology is the mainstay for diagnosis of
lymphoma
Excisional biopsy
For staging
CXR
CT scan
Bone marrow biopsy
 Prognosis
Approximately 85% of patients are cured (good
prognosis).
II. NON HODGKINS LYMPHOMA
Definition

NHL originates from B lymphocytes, T lymphocytes,

Histiocytes or NK cells
Majority (85 %) are B cell in origin and the remainder
are T cell in origin (15%)
Differences from Hodgkins
Lymphoma
NHL can be extra-nodal as well as nodal
Can involve the mesenteric & Waldeyers ring
Spread is not contiguous (i.e generalized)
Can disseminate to bone marrow and can cause
leukaemic conversion.
Etiology and Pathogenesis
Oncogenes
Abnormal activation of Growth promoting oncogenes such as
c-myc , c-abl and Bcl- 2 oncogene
Oncogenic Viral and bacterial infections
Oncogenic DNA virus EBV is associated with endemic type
of Burkitt lymphoma and HHV-8 is associated with
Primary effusion lymphoma
Oncogenic RNA virus HTLV-1 is associated with Adult T-
cell Leukaemia & Lymphoma and HIV-1 is associated with
Primary CNS Lymphoma
Oncogenic bacterial infection H.pylori Gastric NHL
Immunodeficiency & Autoimmunity
Immunodeficiency states are closely associated with
Large B cell type of Peripheral NHL in AIDS &
transplant recipients

Autoimmune states such as Atrophic autoimmune

gastritis, Hashimotos thyroiditis & Sjogrens syndrome
associated with B-MALTomas
CLASSIFICATION
Numerous classifications in NHL, fairly confusing and
controversial
1. Rapperports Classification (1966)
2. Luke & Collins Classification (1974)
3. Kiels Classification
4. Working formulation Classification
5. REAL Classification
6. WHO Classification of Lymphoma (N.H.L is
combined with H.L)
W.H.O Classification of Lymphoid
neoplasm
I.Precursor B cell neoplasm
Precursor B acute Lymphoblastic Leukaemia &
Lymphoblastic Lymphoma
II.Precursor T cell neoplasm
Precursor T acute Lymphoblastic Leukaemia &
Lymphoblastic Lymphoma
III.Peripheral B cell neoplasm
Chronic Lymphocytic Leukaemia/ Small Lymphocytic
Lymphoma
Follicular Lymphoma
Lymphoplasmacytic Lymphoma
Mantle cell Lymphoma
Marginal zone Lymphoma
Diffuse large B cell Lymphoma
Burkitts Lymphoma
Hairy cell Leukaemia
Multiple Myeloma
IV.Peripheral T cell neoplasm & NK cell
neoplasm
Mycosis Fungoides / Sezary Syndrome
Peripheral T cell Lymphoma
Adult peripheral T cell Leukaemia / Lymphoma
 Follicular Lymphoma
It is the most common form of NHL (45 %
of adult lymphomas)
Morphology:
Histology
Predominant follicular growth pattern is
observed in involved lymph nodes
The neoplastic cells closely resemble normal
germinal centre B cells
 Immunophenotype CD 10 and Pan B cell
marker CD 19 & CD 20 positive
Genotype t (14:18)
Clinical Features:
Affects middle aged adults presenting with
painless generalized lymphadenopathy
May transform into a Diffuse Large B cell
NHL (30 50 %)
Diffuse Large B cell Lymphoma
20 % of NHL
It mainly presents as aggressive Lymphoma
Types:
Immunodeficiency type arising in AIDS
patients associated with EBV infection
Transformation from previous Hodgkin
Lymphoma
 Burkitt Lymphoma
Types:
Endemic / African type
Non endemic / Sporadic type
Aggressive type occuring in HIV patients
They are all histologically identical
Clinical Features:
Lymphoma (usually extranodal) than leukemia and
30 % of childhood NHL
The endemic type involves mandible and it is
strongly associated with EBV
The lymphoma runs an aggressive course
Histology:

They contain cells with scanty blue cytoplasm, oval

nuclei with coarse chromatin & several nucleoli
Scattered tingible body macrophages with ingested
nuclear debris are present among the tumour cells
producing characteristic Starry Sky appearance
Immunophenotyping Pan B cell marker CD 19, CD
20 & CD 10 positive
Genotyping t (8:14)
 Mycosis Fungoides/ Sezary
syndrome
Mycosis Fungoides extranodal cutaneous
T cell lymphoma affecting CD 4 Helper T
cells

Sezary Syndrome extranodal cutaneous T

cell lymphoma with leukemic component
 Staging of NHL
Ann Arbor Staging, similar to that of
Hodgkin Lymphoma
 Investigations for NHL
Biopsy and histology
Immunophenotyping
Cytogenetic & molecular study
For staging CT, MRI and bone marrow
biopsy
Immuno markers
Myeloid markers: CD13, CD33, CD117
T cells markers: CD1, CD2, CD3, Cd4, CD8,
Cd5, CD6, CD7
B cells markers: CD19, CD20, CD22, CD9,
Cd10, CD79 and
 References
Essential Hoffbrand (A.V Hoffbrand and P.A.H Moss)
6th Edition
Robbins basic pathology, 9th Edition