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)

Working Formulation - Intermediate Grade D. Malignant lymphoma, follicular (predominantly large cell) Diffuse areas Sclerosis E. Malignant lymphoma, diffuse (small cleaved cell) F. Malignant lymphoma, diffuse (mixed, small and large cell) Epithelioid cell component G. Malignant lymphoma, diffuse (large cell) Cleaved cell Noncleaved cell

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 Neoplasms I. Precursor B-cell neoplasm: B-precursor lymphoblastic leukemia/lymphoma II. Peripheral B-cell neoplasms T-Cell and Putative NK-Cell Neoplasms I. 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 Neoplasms B-cell chronic lymphocytic leukemia/prolymphocytic leukemia/small lymphocytic lymphoma Lymphoplasmacytoid lymphoma/immunocytoma Mantle cell lymphoma

Revised European-American Lymphoma Classification Peripheral B-cell Neoplasms Follicle 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 Neoplasms Marginal 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 Neoplasms Diffuse 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 Neoplasms T-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 Neoplasms Peripheral T-cell lymphomas, unspecified Provisional cytologic categories: medium sized cell, mixed medium and large cell, large cell, lymphoepithelioid cell Provisional subtype: Hepatosplenic gd T-cell lymphoma Provisional subtype: Subcutaneous panniculitic T-cell lymphoma

Revised European-American Lymphoma Classification T-Cell and Putative NK-Cell Neoplasms Angioimmunoblastic 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 Neoplasms Anaplastic 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 Disease Lymphocyte predominance Nodular sclerosis Mixed cellularity Lymphocyte depletion Provisional entity: Lymphocyte-rich classical Hodgkin’s Disease