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Classifications of lymphomas
• Lukes and Collins
• Kiel classification
• Working formulation
• REAL classification (1994)
• WHO classification (2000)
WHO CLASSIFICATIONF OF
NEOPLASMS
HAEMATOPETIC AND
LYMPHOID TISSUES
( 2000)
WHO classification based on
• Morphology
• Immunophaenotype
• Genetics
• Clinical presentation
Major groups of the WHO
classification of lymphomas
• Precursor B-cell lymphomas (immature B
cells
• Mature B-cell lymphoma (mature B-cells)
• Precursor T-cell lymphoma (immature T-cells)
• Mature T-cell lymphoma (mature T-cells)
• Hodgkin lymphoma
General principles of malignant lymphomas
• Diagnosis and classification is only possible histologically
• Final evidence of lymphoma by proof of monoclonality
• Clinical behaviour from ‘indolent’ to aggressive
• 80 to 90% of lymphomas are of B-cell origin
General principles of malignant lymphomas
• Frequently associated with abnormalities of the immune system
• All lymphoid neoplasms are derived from a single transformed cell
• Neoplastic B and T cells tend to home and grow where their normal counterparts reside
• Non Hodgkin lymphomas seem to be widespread at time of diagnosis, Hodgkin’s lymphoma follows a continuous spreading pattern
B-Cell Neoplasms
• Precursor B-cell lymphoblastic
leukemia/lymphoma
Precursor B-lymphoblastic leukaemia/lymphoma
(precursor B-cell acute lymphoblastic leukaemia)
Morphology Lymphoblasts
Immunology TdT
CD10 (CALLA)
Surface Ig
CD19, 79a
+
+ / -
-
+
Genetics No consistent abnormality
Clinical Children >> adults, aggressive
disease but frequently curable
Acute lymphocytic leukemia in marrow, medium power
Mature B-cell Lymphomas
• B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma
• B-cell prolymphocytic leukemia
• Lymphoplasmacytic lymphoma (lymphoplasmacytoid lymphoma)
• Mantle cell lymphoma
• Follicular lymphoma (follicle center lymphoma)
B-cell chronic lymphocytic
leukaemia/small lymphocytic lymphoma Morphology Predominantly small lymphocytes
Immunology Surface IgM
CD5,
CD10
CD19, 20, 79a
CD22
CD23
+
+
-
+
+ / -
+
Genetics Trisomy 12 or 13q, abnormalities
in some cases
Clinical Usually leukaemic, adults,
indolent course
Malignant lymphoma, diffuse small lymphocytic type, lymph node,
low power
Lymphoplasmacytic lymphoma
Morphology Plasmocytiod lympho-cytes,
lymphocytes, plasma cells (+ / -
Dutcher bodies),
Immunology Surface IgM
Cytoplasmic Ig
CD5, 10
CD19, 20, 22, 79a
+
+
-
+
Genetics No specific abnormalities
Clinical Adults, indolent course
Mantle cell lymphoma
Morphology Small irregularly shaped centrocyte-
like cells
Immunology Surface IgM, IgD
CD5
CD10
CD 19, 20, 22, 79a
CD23
Cyclin D1
+
+
- / +
+
-
+
Genetics t(11;14),
BCL-1 rearrangement
Clinical Adults, moderately aggressive course
(median survival 3-4 yrs)
Follicular lymphoma Morphology Mixture of germinal center blasts and
cleaved cells (centroblasts and
centrcytes
Immunology Surface Ig
CD5
CD10
CD19, 20, 22, 79a
BCL-2
+
-
+ / -
+
+
Genetetics t(14;18 and BCL-2 rearrangements in
the majority of cases
Clinical Adults. Indolent course (median survial
7 – 9 years)
Malignant lymphoma, follicular, low power
Mature B-cell Lymphomas
• Diffuse large B-cell lymphoma
– Centroblastic
– Immunoblastic
– Plasmablastic
• Subtypes:
– Mediastinal (thymic)
– Intravascular,
– Primary effusion lymphoma
Diffuse large B-cell lymphoma
Morphology Monomorphous large cells with
prominent nucleoli and basophilic
cytoplasm
Immunology Surface Ig
Cytoplasmic Ig
CD5, CD10
CD19, 20, 22, 79a
+ / -
- / +
- / +
+
Genetics t(14;18) 30%, BCL-6 rearrangend 40%
and / or mutated 75%
Clinical Children or adults, aggressive, but
may be curable
Malignant lymphoma, diffuse large B cell type, medium power
Malignant lymphoma, retroperitoneum , diffuse large B cell type,
medium power
Diffuse large B-cell lymphoma
Malignant lymphoma, peritrabecular, bone marrow, medium power
Mature B-cell Lymphomas
• Burkitt lymphoma
• Plasmacytoma
• Plasma cell myeloma
Burkitt lymphoma/Burkitt cell
leukaemia
Morphology Medium sized cells, basophilic
cytoplasm, ‘starry sky’ appearance,
high mitotic rate
Immunology Surface IgM
CD5, 23
CD10
CD19, 20, 22, 79a
Ki67
+
-
+
+
>85%
Genetics t(2;8), t(8;14) or t(8;22), rearrangement
of c-myc
Clinical Children >> adults, aggressive but
curable in children, extranodal sites ie.
ovary
Malignant lymphoma,
Burkitt type, karyotype,
diagram
Burkitt lymphoma
Burkitt lymphoma
• Endemic (African) Burkitt lymphoma
• Sporadic (nonendemic) Burkitt
lymphoma
• Burkitt like lymphoma related to HIV+
patients
High grade, B-cell Burkitt like lymphoma
Plasma cell myeloma/plasmacytoma
Morphology Plasma cells
Immunology Surface Ig
Cytoplasmic Ig
EMA
CD19, 20, 22
CD79a
-
+
- / +
-
+ / -
Genetics t(11;14) in a few cases
Clinical Adults. Lytic bone lesions, less
commonly soft tissue tumour.
Relapse after plateau phase
Multiple myeloma, lesions in skull
Multiple myeloma, lesions in skull, radiograph
Multiple myeloma, lesions in bone marrow
Multiple myeloma, bone marrow, low power
Multiple myeloma, bone marrow, medium power
Multiple myeloma, bone marrow smear, high power
Immunosecretory disorders (clinical manifestation
of diverse lympoid neoplasms) Clinical syndrome Underlying neoplasm
Waldenstrom’s macroglobulinaema Lymphoplasmocytic lymphoma
Heavy chain disease (HCD)
•gamma HCD Lymphoplasmocytic lymphoma
•alpha HCD Extranodal marginal cell lymphoma
(immunoproliferative small intestinal
disorder)
•Mu HCD B-cell chronic lymphocytic
leukaemia
Immunoglobulin deposition disease
•Systemic light chain disease Plasma cell myeloma, monoclonal
gammopathy
•Primary amyloidosis Plasma cell myeloma, monoclonal
gammopathy
Mature Lymphomas
• Marginal zone B-cell lymphoma of
mucosa-associated lymphoid tissue
(MALT) type
– Nodal marginal zone lymphoma with or
without monocytoid B-cells
• Splenic marginal zone B-cell lymphoma
• Hairy cell leukemia
Extranodal lymphomas MALT (Mucosa Associated Lymphoid Tissue)
• Arising from marginal zone cells
(centrocyte like cells surrounding the
follicles = marginal zone)
• Preceded by autoimmune disease of
the organ involved
• MALT lymphocytes tend to remain
localized (“homing” to mucosal sites)
Splenic marginal zone B-cell
lymphoma
Morphology Small centrocyte like cells,
‘moncytoid B cells’, lymphocytes,
plasma cells
Immunology Surface Ig
CD5, 10
CD19, 20, 22, 79a
CD23
+
-
+
-
Genetics No specific abnormalities
Clinical Splenomegaly. ?Always leukaemic
Marginal zone B-cell lymphoma of
MALT type
Morphology Small centrocyte like-cells,
‘monocytoid B cells’, lymphocytes,
plasma cells
Immunology Surface Ig
CD5, 10
CD19, 20, 22, 79a
CD23
+
-
+
-
Genetics t(11;18 in many cases, trisomy 3 in
some cases
Clinical Indolent course, often localized.
May transform to large cell
lymphoma
MALT lymphomas of the
gastrointestinal tract:
• Mostly B-cell lymphomas
• Enteropathy associated T-cell
lymphoma
Pulmonary lymphomas
• Bronchial tissue
Malignant lymphomas of
salivary glands
• Associated with Sjögren`s syndrome
Malignant lymphoma of the
thyroid
• Associated with Hashimoto thyroiditis
Others
• Malignant lymphomas of the orbit
• Malignant lymphomas of the skin
– B-cell
– T-cell (Mycosis fungoides, Sezary syndrome)
• Other sites:
– Brain, testis, breast, bone
Hairy cell leukaemia
Morphology Small lymphoid cells with bean
shape nuclei and pale cytplasm
Immunology Surface Ig
CD5, 10, 23
CD11c, 25
CD19, 20, 22, 79a
CD103 (MLA)
+
-
+
+
+
Genetics No specific abnormalities
Clinical Adults, often with slenomegaly and
pancytotopenia,indolent course
Categories of post-transplant
lymphoproliferative disorders (PTLD)
1. Early lesions
1. Reactive plasmacytic hyperplasia
2. Infectious mononucleosis-like
2. PTLD – polymorphic
1. Polyclonal (rare)
2. Monoclonal
3. PTLD monomorphic (classified according to lymphoma
classification)
1. B-cell lymphomas
2. T-cell lymphomas
3. Other types (rare)
Post-transplantation lymphoproliferative disorder (PTLD), medium
power
T and NK-cell neoplasms
T-Cell Neoplasms
• Precursor T-cell lymphoblastic
leukemia/lymphoma
Precursor T-lymphoblastic lymphoma/leukaemia
(precursor T-cell acute lymphoblastic leukaemia)
Morphology Lymphoblasts, identical cytology to B
lymphoblasts
Immunology TdT
CD1a
CD3
CD7
CD4 +/-8
+
+ / -
+ / -
+
+
Genetics SCL / TAL-1 rearrangements 25%
Clinical Frequently involves mediastinum,
adolescents and young adults, highly
aggressive but potentially curable
T-Cell Neoplasms
• Angioimmunoblastic T-cell lymphoma
• Peripheral T-cell lymphoma (unspecified)
• Adult T-cell leukemia/lymphoma (HTLV1)
• Systemic anaplastic large cell lymphoma (T- and null-cell types)
• Primary cutaneous anaplastic large cell lymphoma
Angioimmunoblastic T-cell
lymphoma
Morphology Architecture effaced, arborizing high endothelial
venules, no secondary follicles, mixed infiltrate of
lymphocytes, blasts and atypical clear cells
Immunology T-cell phaenotype, large follicular
dendritic cell clusters around
proliferating venules
Genetics No specific abnormalities
Clinical Systemic disease with lymphadenopathy, fever,
weight loss and skin rash, polyclonal
hypergammaglobulinaeimia, aggressive course
Adult T-cell lymphoma/leukaemia
(HTLV1+)
Morphology Pleomorphic infiltrate of small and
large lymphoid cells
Immunology CD2, 3, 4, 5, 25
CD7
+
-
Genetics Integrated HTLV-1 genome present
Clinical Adults, commonest in Japan and
Carribean, hypercalcaemia,
leukaemia, bone lysis, commonly
aggressive, rarely indolent
Anaplastic large cell lymphoma,
T/null cell
Morphology Bizarre large cells, sometimes R-S like or
multinucleated, abundant cytoplasm, cohesive
cells, intrasinusoidal spread
Immunology T or null phenotype
CD30
EMA
ALK
+
+ / -
+ / -
Genetics t(2;5) causing fusion of
ALK and NPM genes in
majority of cases
Clinical Systemic form aggressive but potentially curable,
rare primary cutaneous disease, mainly in adults
is more indolent but incurable
Peripheral T-cell lymphoma, not
otherwise characterized
Morphology Atypical lymphocytes of varying sizes,
variable reactive background
elements, e.g. macrophages, vessels
etc.
Immunology CD3
Variable expression of other T cell
markers
+ / -
Genetics No specific abnormalities
Clinical Adults, aggressive course but
potentially curable
T-cell lymphomas
• T-cell prolymphocytic leukemia
• T-cell large granular lymphocytic leukemia
• NK-cell leukemia
• Extranodal NK/T-cell lymphoma, nasal-type (angiocentric lymphoma)
• Mycosis fungoides
• Sezary syndrome
T-cell prolymphocytic leukaemia
Morphology Small lymphoid cells, with some
nuclear irregularity
Immunology CD2, 3, 5, 7
CD4
CD8
+
+
- / +
Genetics inv14(q11;32) 75%, trisomy 8q
Clinical Adults, often leukaemic, more
aggressive than B cell chronic
lymphocytic leukamia
T-cell granular lymphocytic
leukaemia
Morphology Small to medium lymphoid cells with
eccentric round or oval nuclei,
azurophilic cytoplasmic granules
Immunology CD2
CD3, 8
CD16
CD56, 57
+
+ / -
+
- / +
Genetics No specific abnormalities
Clinical Adults, usually leukaemic, neutropenia
+/- anaemia, indolent course
Mycosis fungoides/Sezary
syndrom
Morphology Small to medium-sized cells with
cerebriform nuclei epidermal infiltration
Immunology CD2, 3, 4, 5
CD7, 8, 25
+
-
Genetics No specific abnormalities
Clinical Adults, principally localized skin but
may involve blood and lymph nodes
Extranodal NK/T-cell lymphoma nasal-type
(angiocentric lymphoma)
Morphology Broad spectrum of cell sizes,
eosinophils, histiocytes, large R-S
cells
Immunology CD3, CD56, CD 45RO
CD4, CD8, CD5
EBV
+/-
-
+
Genetics No specific chromosomal abnormality
Clinical More common in Asia, involves face
and nose, but occasionally elsewhere
T-Cell Neoplasms
• Subcutaneous panniculitis-like T-cell
lymphoma
• Enteropathy type intestinal T-cell
lymphoma
• Hepatosplenic / T-cell lymphoma
Clinical staging of Hodgkin and non-Hodgkin
lymphomas (Ann Arbor Classification)
Stage* Distribution of disease
I Involvement of a single lymph node region (I) or involvement of a
single extralymphatic organ or site (IE).
II Involvement of 2 or more lymph node regions on the same side of the
diaphragm alone (II) or with involvement of limited contguous
extralymphatic organs or tissue (IIE).
III Involvment of lymph node regions on both sides of the diaphragm
(III), which may include the spleen (IIIS) and/or limited contiguous
extralymphatic organ or site (IIIE , IIIES).
IV Multiple or disseminated foci of involvement of one or more
extralymphatic organs or tissues with or without lymphatic involvement
*Further division on basis of absence (A) or presence (B) of the following
symptoms: significant fever, night sweats, unexplained loss of normal body
weight of more than 10%
Histiocytic and dendritic-cell neoplasms
• Macrophage/Histiocytic neoplasm
– Histiocytc sarcoma
• Dendritic-cell neoplams
– Langerhans cell histiocytosis
– Langerhans cell sarcoma
– Interdigitating dendritic cell sarcoma/Tumour
– Follicular dendritic cell sarcoma/tumour
– Dendritic cell sarcoma, not otherwise
– Specified (NOS)
Langerhans cell histiocytosis CD1+, Birbeck granules
• Letterer-Siwe disease – Acute disseminated cutaneous lesions before 2
years of age, infiltration of bone marrow rapidly fatal
• Multifocal disease (eosinophilic granuloma) – Combination of skull defects, diabetes insipidus
and exophthalmus = Hand-Schueller-Christian triad
• Unifocal lesions (eosinophilic granuloma) – Often indolent
