Lukes and Collins Kiel classification Working formulation ... · •All lymphoid neoplasms are derived from a single ... •Mu HCD B-cell chronic lymphocytic leukaemia ... • Splenic

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

• 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

CD19, 20, 79a

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),

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

CD 19, 20, 22, 79a

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

CD19, 20, 22, 79a

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

• 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

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

• Burkitt lymphoma

• Plasmacytoma

• Plasma cell myeloma

Burkitt lymphoma/Burkitt cell

leukaemia

Morphology Medium sized cells, basophilic

cytoplasm, ‘starry sky’ appearance,

high mitotic rate

CD5, 23

CD19, 20, 22, 79a

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.

Malignant lymphoma,

Burkitt type, karyotype,

diagram

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

Cytoplasmic Ig

CD19, 20, 22

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

CD5, 10

CD19, 20, 22, 79a

Clinical Splenomegaly. ?Always leukaemic

Marginal zone B-cell lymphoma of

MALT type

Morphology Small centrocyte like-cells,

‘monocytoid B cells’, lymphocytes,

plasma cells

CD5, 10

CD19, 20, 22, 79a

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

CD5, 10, 23

CD11c, 25

CD19, 20, 22, 79a

CD103 (MLA)

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

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

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

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

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

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

Immunology CD3

Variable expression of other T cell

markers

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

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

CD56, 57

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

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

Immunology CD3, CD56, CD 45RO

CD4, CD8, CD5

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

Lukes and Collins Kiel classification Working formulation ... · •All lymphoid neoplasms are derived from a single ... •Mu HCD B-cell chronic lymphocytic leukaemia ... • Splenic

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