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Lymphoma Classification
• Lymphoma first used in 1858
• Old terminology– Hodgkin’s Disease– Lymphosarcoma– Reticulum cell sarcoma– Giant follicle lymphoma
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Rye Classification
• Classification for Hodgkin’s Disease
• Conference in Rye NY 1965
• Modification of Lukes-Butler classification
• Divided HD into four histologic types
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Rye Classification
• Lymphocyte predominance (LP)
• Nodular sclerosis (NS)
• Mixed cellularity (MC)
• Lymphocyte depletion (LD)
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Rappaport Classification
• Rappaport proposed classification in 1966
• Nodular or Diffuse– Lymphocytic, well differentiated– Lymphocytic, poorly differentiated– Mixed lymphocytic-histiocytic– Histiocytic– Undifferentiated
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Modified Rappaport Classification
• Nodular– Lymphocytic, poorly differentiated– Mixed lymphocytic-histiocytic– Histiocytic
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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
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New Classification Schemes
• British National Lymphoma Investigation (1974)
• Lukes and Collins (1974)
• Dorfman (1974)
• Kiel (1974)
• World Health Organization (1976)
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Lukes and Collins Classification
• Attempt to correlate lymphoma to current understanding of normal immune system
• proposed immunologic subtypes could be recognized by morphology
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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
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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)
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Kiel Classification
• Proposed by Lennert and a European consortium
• Updated in 1988
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Kiel Classification
• Low Grade Malignancy– Lymphocytic– Lymphoplasmacytoid– Centrocytic– Centroblastic-centrocytic
• Follicular
• Follicular and Diffuse
• Diffuse
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Kiel Classification
• High Grade Malignancy– Centroblastic– Lymphoblastic
• Burkitt’s type
• Convoluted cell type
– Immunoblastic
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Updated Kiel Classification (B Cell)
• Low Grade– Lymphocytic: CLL, PLL and hairy cell leukemia– Lymphoplasmacytic/cytoid (LP immunocytoma)
• Plasmacytic
• Centroblastic/centrocytic– follicular
– diffuse
• Centrocytic
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Updated Kiel Classification (B Cell)
• High Grade– Centroblastic– Immunoblastic– Large Cell Anaplastic (Ki-1)– Burkitt’s lymphoma– Lymphoblastic
• Rare Types
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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+/-)
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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
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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
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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
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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
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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
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Working Formulation - Miscellaneous
• Composite
• Mycosis fungoides
• Histiocytic
• Extramedullary plasmacytoma
• Unclassifiable
• Other
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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
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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
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Revised European-American Lymphoma Classification
• Peripheral B-cell NeoplasmsB-cell chronic lymphocytic leukemia/prolymphocytic
leukemia/small lymphocytic lymphoma
Lymphoplasmacytoid lymphoma/immunocytoma
Mantle cell lymphoma
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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
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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
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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
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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
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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
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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
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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
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Revised European-American Lymphoma Classification
• Hodgkin’s DiseaseLymphocyte predominance
Nodular sclerosis
Mixed cellularity
Lymphocyte depletion
Provisional entity: Lymphocyte-rich classical Hodgkin’s Disease