Immunopathology of Lymphoma Noraidah Masir MBBCh, M.Med (Pathology), D.Phil . Department of Pathology Faculty of Medicine Universiti Kebangsaan Malaysia
Immunopathology of Lymphoma Lymphoma classification has been challenging to pathologists. Prior to mid 70s, pathologists had great difficulty in defining lymphoma categories There were many classification schemes Earlier classifications depend largely on morphology
Immunopathology of Lymphoma Previous Lymphoma Classification Schemes Rappaport classification (1966) Cell morphology and growth pattern Lukes and Collins (1974) Based on immunological concepts. But little correlation with each other. Kiel also correctly Kiel classification /Lennert Group identified morphologic types (1975) International Working Clinical prognostic groups. Does Formulation (1982) not include T cell lymphomas
Immunopathology of Lymphoma 1994 - International Lymphoma Study Group Adopted a new Availability of approach to immunohistological lymphoma Revised European-American markers classification Classification of Lymphoid Neoplasms (REAL) 2000 WHO Classification of Haematopoetic & Lymphoid (Revised 2008) Neoplasms
Immunopathology of Lymphoma WHO Classification of Lymphoid Neoplasms Every lymphoma subtype is defined by integrating • Tumour morphology, • Immunophenotype, • Genetic • Clinical features. More than 40 subtypes are recognized Each is a distinct disease entity and has corresponding counterpart in normal lymphoid tissue.
Immunopathology of Lymphoma Lymphomas are broadly categorized into 1. Precursor B and T lymphoid neoplasms 2. Mature B cell neoplasms 3. Mature T- and NK-neoplasms 4. Hodgkin lymphoma 5. Immunodeficiency-associated lymphoproliferative disorders
Immunopathology of Lymphoma Lymphoma Immunophenotyping Specific immunophenotypic features essential for diagnosis of lymphoma entities. Two major methods: 1. Immunohistochemistry 2. Flow cytometry
Immunopathology of Lymphoma B CELL NEOPLASMS • B cell neoplasms most common lymphomas • Tend to mimic stages of normal B cell differentiation. • Their resemblance to normal cell differentiation is the basis for their classification. • Knowledge of cellular composition and events in the differentiation of normal B cells is a prerequisite of understanding B cell lymphoma. • It has led to the insight of tumor genesis in the lymphoid organ
Immunopathology of Lymphoma Events in the development of B cells in the bone marrow and secondary lymphoid tissues and their characteristic phenotype at different stages of maturation.
Immunopathology of Lymphoma B cell differentiation in peripheral lymphoid tissue Naïve mature B cell from bone marrow Mature B cell Mature B cell MANTLE ZONE Memory B Antigen cell encounter Centrocyte B blast GERMINAL CENTRE Centroblast Long-living plasma cell Short-living plasma cell (Sagaert et al 2003)
Immunopathology of Lymphoma Cellular origin of B cell lymphomas Marginal zone Naïve B cell Mantle zone cells Each subtype of B Memory B cell Germinal cell lymphoma has Centre B cells its corresponding counterpart in normal lymphoid tissue. Plasmablastic cell plasma cell
Immunopathology of Lymphoma Cellular origin of B cell lymphomas MZL Mantle cell lymphoma CLL (Mutated gene) Marginal zone B CLL (unmutated V gene) Naïve B cell Mantle zone cells HCL, DLBCL (ABC-type) Primary mediastinal B cell lymphoma CLL Memory B (unmutated V cell gene) Germinal Centre B cells Follicular lymphoma Burkitt lymphoma Plasma cell neoplasm DLBCL (GC-type) Lymphocyte predominant Hodgkin lymphoma Plasmablastic cell PTLD Classical Hodgkin LPL plasma cell lymphoma PEL
Immunopathology of Lymphoma B Cell Lymphoma B Lineage-Specific Markers Detectable in Paraffin Embedded Tissues Molecule Marker Classical pan-B cell CD20, CD79a markers “Newer” CD markers CD19, CD22, CD37 Signalling molecules BLNK, PLCgamma2 Transcription factors PAX5, OCT2
Immunopathology of Lymphoma B Cell Lymphoma CD20 CD20- For regulation of B cell proliferation and differentiation CD20 DLBCL CD20 Reactive follicle Homogeneous labelling for CD20 in DLBCL TCRBCL
B Cell Lymphoma Immunopathology of Lymphoma CD20 CD20 Homogeneous labelling for CD20 in follicular lymphoma. Label tumour cells in interfollicular regions CD20 Follicular lymphoma Follicular lymphoma
Immunopathology of Lymphoma B lymphoblastic lymphoma CD20 CD79a B lymphoblastic lymphoma B lymphoblastic lymphoma In B lymphoblastic lymphoma, most tumour cells express CD79a and not CD20
Immunopathology of Lymphoma Multiple Myeloma CD20 CD79a Myeloma cells do not express CD20. Occasional CD20-positive lymphocytes as internal positive Many tumour cells express CD79a control
Immunopathology of Lymphoma B Lineage-Specific Markers Progenitor Pre B cell Immature B Mature Germinal Memory B Plasma cell B cell cell naïve B cell centre B cell cell CD20 CD79a CD19 (B lymphoblastic (Mature B cell neoplasms) (Myeloma) lymphoma)
Immunopathology of Lymphoma Using rabbit polyclonal anti CD19 antibody that is reactive on paraffin sections. Previous studies of CD19 on B cell neoplasia limited to flow cytometric analysis. Its expression in B cell neoplasm on routine tissue biopsy specimens has not been previously investigated.
Immunopathology of Lymphoma CD19 Tonsil Lymph node CD19 labels the GC and mantle CD19 also labels reactive zone cells of a B lymphoid follicle plasma cells found in tonsils in a comparable fashion to CD20
CD19 Immunopathology of Lymphoma Double immunofluorescent labelling TCRBCL TCRBCL Weak CD19 expression CD19 absent LPHD Myeloma CD19 expression is absent in myeloma and LPHD
Immunopathology of Lymphoma CONCLUSIONS CD19 was expressed in most B cell neoplasms In contrast to CD20, CD19 was absent/weak in FL, DLBCL, TCRBCL, myeloma, PTLD, cHodgkin lymphoma and lymphocyte predominant Hodgkin lymphoma Significance of CD19 loss in B cell neoplasms?
Immunopathology of Lymphoma Immunophenotypic profile of B cell lymphomas ALL CLL MCL MZL FL HCL LPL Burkitt CD5 - + + -/+ - - - - CD10 + - - - + - - + CD19 + + + + + + + + CD20 -/+ + + + + + + + CD23 - + - -/+ - - - - CD25 - - - - - + - - CD103 - - - - - + - - Cyclin D1 - - + - - - - - BCL2 + + + + +/- + + - BCL6 - - - - + - - + TdT + - - - - - - -
Immunopathology of Lymphoma Immunophenotypic profile of B cell lymphomas ALL CLL MCL MZL FL HCL LPL Burkitt CD5 - + + -/+ - - - - CD10 - - - + - - + + CD19 + + + + + + + + CD20 -/+ + + + + + + + CD23 - + - -/+ - - - - CD25 - - - - - + - - CD103 - - - - - + - - Cyclin D1 - - + - - - - - BCL2 + + + + +/- + + - BCL6 - - - - + - - + TdT - - - - - - - +
Immunopathology of Lymphoma Immunophenotypic profile of B cell lymphomas ALL CLL MCL MZL FL HCL LPL Burkitt CD5 - + -/+ - - - - + CD10 + - - - + - - + CD19 + + + + + + + + CD20 -/+ + + + + + + + CD23 - - -/+ - - - - + CD25 - - - - - + - - CD103 - - - - - + - - Cyclin D1 - - + - - - - - BCL2 + + + + +/- + + - BCL6 - - - - + - - + TdT + - - - - - - -
Immunopathology of Lymphoma Immunophenotypic profile of B cell lymphomas ALL CLL MCL MZL FL HCL LPL Burkitt CD5 - -/+ - - - - + + CD10 + - - - + - - + CD19 + + + + + + + + CD20 -/+ + + + + + + + CD23 - - -/+ - - - - + CD25 - - - - - + - - CD103 - - - - - + - - Cyclin D1 - - - - - - - + BCL2 + + + + +/- + + - BCL6 - - - - + - - + TdT + - - - - - - -
Immunopathology of Lymphoma Immunophenotypic profile of B cell lymphomas ALL CLL MCL MZL FL HCL LPL Burkitt CD5 - + + -/+ - - - - CD10 + - - - - - + + CD19 + + + + + + + + CD20 -/+ + + + + + + + CD23 - + - -/+ - - - - CD25 - - - - - + - - CD103 - - - - - + - - Cyclin D1 - - + - - - - - BCL2 + + + + + + - +/- BCL6 - - - - - - + + TdT + - - - - - - -
Immunopathology of Lymphoma Immunophenotypic profile of B cell lymphomas ALL CLL MCL MZL FL HCL LPL Burkitt CD5 - + + -/+ - - - - CD10 + - - - + - - + CD19 + + + + + + + + CD20 -/+ + + + + + + + CD23 - + - -/+ - - - - CD25 - - - - - - - + CD103 - - - - - - - + Cyclin D1 - - + - - - - - BCL2 + + + + +/- + + - BCL6 - - - - + - - + TdT + - - - - - - -
Immunopathology of Lymphoma Immunophenotypic profile of B cell lymphomas ALL CLL MCL MZL FL HCL LPL Burkitt CD5 - + + -/+ - - - - CD10 + - - - + - - + CD19 + + + + + + + + CD20 -/+ + + + + + + + CD23 - + - -/+ - - - - CD25 - - - - - + - - CD103 - - - - - + - - Cyclin D1 - - + - - - - - BCL2 + + + + +/- + + - BCL6 - - - - + - - + TdT + - - - - - - -
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