Lymphoma Classification

• Lymphoma first used in 1858

• Old terminology– Hodgkin’s Disease– Lymphosarcoma– Reticulum cell sarcoma– Giant follicle lymphoma

Rye Classification

• Classification for Hodgkin’s Disease

• Conference in Rye NY 1965

• Modification of Lukes-Butler classification

• Divided HD into four histologic types

Rye Classification

• Lymphocyte predominance (LP)

• Nodular sclerosis (NS)

• Mixed cellularity (MC)

• Lymphocyte depletion (LD)

Rappaport Classification

• Rappaport proposed classification in 1966

• Nodular or Diffuse– Lymphocytic, well differentiated– Lymphocytic, poorly differentiated– Mixed lymphocytic-histiocytic– Histiocytic– Undifferentiated

Modified Rappaport Classification

• Nodular– Lymphocytic, poorly differentiated– Mixed lymphocytic-histiocytic– Histiocytic

Modified Rappaport Classification

• Diffuse– Lymphocytic, well differentiated– Lymphocytic, intermediate differentiation– Lymphocytic, poorly differentiated– Mixed lymphocytic-histiocytic– Undifferentiated, Burkitt’s type– Undifferentiated, non-Burkitt’s type– Histiocytic– Lymphocytic

New Classification Schemes

• British National Lymphoma Investigation (1974)

• Lukes and Collins (1974)

• Dorfman (1974)

• Kiel (1974)

• World Health Organization (1976)

Lukes and Collins Classification

• Attempt to correlate lymphoma to current understanding of normal immune system

• proposed immunologic subtypes could be recognized by morphology

Lukes and Collins Classification

• Undefined cell type• T cell types

– Small lymphocytic– Mycosis fungoides / Sezary syndrome (cerebriform)– Convoluted lymphocytic– Immunoblastic sarcoma (T cell)

• Histiocytic• Unclassifiable

Lukes and Collins Classification

• B cell types– Small lymphocytic– Plasmacytoid lymphocytic– Follicular center cell

• small cleaved

• large cleaved

• small noncleaved

• large noncleaved

– Immunoblastic sarcoma (B cell)

Kiel Classification

• Proposed by Lennert and a European consortium

• Updated in 1988

Kiel Classification

• Low Grade Malignancy– Lymphocytic– Lymphoplasmacytoid– Centrocytic– Centroblastic-centrocytic

• Follicular

• Follicular and Diffuse

• Diffuse

Kiel Classification

• High Grade Malignancy– Centroblastic– Lymphoblastic

• Burkitt’s type

• Convoluted cell type

– Immunoblastic

Updated Kiel Classification (B Cell)

• Low Grade– Lymphocytic: CLL, PLL and hairy cell leukemia– Lymphoplasmacytic/cytoid (LP immunocytoma)

• Plasmacytic

• Centroblastic/centrocytic– follicular

– diffuse

• Centrocytic

Updated Kiel Classification (B Cell)

• High Grade– Centroblastic– Immunoblastic– Large Cell Anaplastic (Ki-1)– Burkitt’s lymphoma– Lymphoblastic

• Rare Types

Updated Kiel Classification (T Cell)

• Low Grade– lymphocytic: CLL and PLL– Small cerebriform cell: MF and SS– Lymphoepithelioid (Lennert’s lymphoma)– Angioimmunoblastic (AILD)– T zone– Pleomorphic, small cell (HTLV 1+/-)

Updated Kiel Classification (T Cell)

• High Grade– Pleomorphic, medium and large cell ( HTLV 1 +/-)– Immunoblastic (HTLV 1 +/-)– Large cell anaplastic (Ki 1 )– Lymphoblastic

• Rare Types

Working Formulation

• Collaborative international study sponsored by NCI

• Published new terminology in 1982

• A Working Formulation of Non-Hodgkin’s Lymphoma for Clinical Usage

• Not a new classification but a means o translation from one classification to another

Working Formulation - Low Grade

A. Malignant lymphoma (small lymphocytic)Consistent with CLL

Plasmacytoid

B. Malignant lymphoma, follicular (predominantly small cleaved cell)Diffuse areas

Sclerosis

C. Malignant lymphoma, follicular (mixed, small cleaved and large cell)Diffuse areas

Sclerosis

Working Formulation - Intermediate Grade

D. Malignant lymphoma, follicular (predominantly large cell)Diffuse areas

Sclerosis

E. Malignant lymphoma, diffuse (small cleaved cell)Sclerosis

F. Malignant lymphoma, diffuse (mixed, small and large cell)Sclerosis

Epithelioid cell component

G. Malignant lymphoma, diffuse (large cell)Cleaved cell

Noncleaved cell

Sclerosis

Working Formulation - High Grade

H. Malignant lymphoma (large cell, immunoblastic)Plasmacytoid

Clear cell

Polymorphous

Epithelioid cell component

I. Malignant lymphoma (lymphoblastic)Convoluted cell

Nonconvoluted cell

J. Malignant lymphoma (small noncleaved cell)Burkitt’s

Follicular areas

Working Formulation - Miscellaneous

• Composite

• Mycosis fungoides

• Histiocytic

• Extramedullary plasmacytoma

• Unclassifiable

• Other

Revised European-American Lymphoma Classification

• Consensus conference in Berlin Germany in 1993

• 19 hematopathologists - The International Lymphoma Study Group

• Define diseases which can be reliably recognized with currently available morphologic, immunologic, and genetic techniques

Revised European-American Lymphoma Classification

• B-Cell NeoplasmsI. Precursor B-cell neoplasm: B-precursor lymphoblastic

leukemia/lymphoma

II. Peripheral B-cell neoplasms

• T-Cell and Putative NK-Cell NeoplasmsI. Precursor T-cell neoplasms: T-precursor lymphoblastic

leukemia/lymphoma

II. Peripheral T-cell and NK-cell neoplasms

• Hodgkin’s Disease

Revised European-American Lymphoma Classification

• Peripheral B-cell NeoplasmsB-cell chronic lymphocytic leukemia/prolymphocytic

leukemia/small lymphocytic lymphoma

Lymphoplasmacytoid lymphoma/immunocytoma

Mantle cell lymphoma

Revised European-American Lymphoma Classification

• Peripheral B-cell NeoplasmsFollicle center lymphoma

Provisional cytologic grades: I (small cell), II (mixed small and large cell), III (large cell)

Provisional subtype: diffuse, predominantly small cell type

Revised European-American Lymphoma Classification

• Peripheral B-cell NeoplasmsMarginal zone B-cell lymphoma

Extranodal (MALT type +/- monocytoid B cells)

Provisional category: nodal (+/- monocytoid B cells)

Provisional entity: splenic marginal zone lymphoma (+/- villous lymphocytes)

Hairy cell leukemia

Plasmacytoma/myeloma

Revised European-American Lymphoma Classification

• Peripheral B-cell NeoplasmsDiffuse large B-cell lymphoma

Subtype: primary mediastinal (thymic) B-cell lymphoma

Burkitt’s lymphoma

Provisional category: high-grade B-cell lymphoma, Burkitt’s-like

Revised European-American Lymphoma Classification

• T-Cell and Putative NK-Cell NeoplasmsT-cell chronic lymphocytic leukemia/prolymphocytic

leukemia

Large granular lymphocytic leukemia (LGL)T-cell type

NK-cell type

Mycosis fungoides/Sezary syndrome

Revised European-American Lymphoma Classification

• T-Cell and Putative NK-Cell NeoplasmsPeripheral T-cell lymphomas, unspecified

Provisional cytologic categories: medium sized cell, mixed medium and large cell, large cell, lymphoepithelioid cell

Provisional subtype: Hepatosplenic T-cell lymphoma

Provisional subtype: Subcutaneous panniculitic T-cell lymphoma

Revised European-American Lymphoma Classification

• T-Cell and Putative NK-Cell NeoplasmsAngioimmunoblastic T-cell lymphoma

Angiocentric lymphoma

Intestinal T-cell lymphoma (+/- enteropathy associated)

Adult T-cell leukemia/lymphoma

Revised European-American Lymphoma Classification

• T-Cell and Putative NK-Cell NeoplasmsAnaplastic large cell lymphoma (ALCL), CD30+ T- and

null cell types

Provisional entity: Anaplastic large cell lymphoma, Hodgkin’s-like

Revised European-American Lymphoma Classification

• Hodgkin’s DiseaseLymphocyte predominance

Nodular sclerosis

Mixed cellularity

Lymphocyte depletion

Provisional entity: Lymphocyte-rich classical Hodgkin’s Disease