Classifications of lymphomas

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1 Classifications of lymphomas Lukes and Collins Kiel classification Working formulation REAL classification (1994) WHO classification (2000)

2 WHO CLASSIFICATIONF OF NEOPLASMS HAEMATOPETIC AND LYMPHOID TISSUES ( 2000)

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4 WHO classification based on Morphology Immunophaenotype Genetics Clinical presentation

5 Major groups of the WHO classification of lymphomas Precursor B-cell lymphomas (immature B cells Mature B-cell lymphoma (mature B-cells) Precursor T-cell lymphoma (immature T-cells) Mature T-cell lymphoma (mature T-cells) Hodgkin lymphoma

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11 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

12 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

13 B-Cell Neoplasms Precursor B-cell lymphoblastic leukemia/lymphoma

14 Precursor B-lymphoblastic leukaemia/lymphoma (precursor B-cell acute lymphoblastic leukaemia) Morphology Lymphoblasts Immunology Genetics TdT CD10 (CALLA) Surface Ig CD19, 79a No consistent abnormality / - - Clinical Children >> adults, aggressive disease but frequently curable

15 Acute lymphocytic leukemia in marrow, medium power

16 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)

17 B-cell chronic lymphocytic leukaemia/small lymphocytic lymphoma Morphology Predominantly small lymphocytes Immunology Surface IgM Genetics CD5, CD10 CD19, 20, 79a CD22 CD23 Trisomy 12 or 13q, abnormalities in some cases - / - Clinical Usually leukaemic, adults, indolent course

18 Malignant lymphoma, diffuse small lymphocytic type, lymph node, low power

19 Lymphoplasmacytic lymphoma Morphology Immunology Genetics Plasmocytiod lympho-cytes, lymphocytes, plasma cells ( / - Dutcher bodies), Surface IgM Cytoplasmic Ig CD5, 10 CD19, 20, 22, 79a No specific abnormalities - Clinical Adults, indolent course

20 Mantle cell lymphoma Morphology Small irregularly shaped centrocytelike cells Immunology Surface IgM, IgD CD5 CD10 CD 19, 20, 22, 79a CD23 Cyclin D1 - / - Genetics t(11;14), BCL-1 rearrangement Clinical Adults, moderately aggressive course (median survival 3-4 yrs)

21 Follicular lymphoma Morphology Mixture of germinal center blasts and cleaved cells (centroblasts and centrcytes Immunology Surface Ig Genetetics CD5 CD10 CD19, 20, 22, 79a BCL-2 t(14;18 and BCL-2 rearrangements in the majority of cases - / - Clinical Adults. Indolent course (median survial 7 9 years)

22 Malignant lymphoma, follicular, low power

23 Mature B-cell Lymphomas Diffuse large B-cell lymphoma Centroblastic Immunoblastic Plasmablastic Subtypes: Mediastinal (thymic) Intravascular, Primary effusion lymphoma

24 Diffuse large B-cell lymphoma Morphology Monomorphous large cells with prominent nucleoli and basophilic cytoplasm Immunology Surface Ig 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

25 Malignant lymphoma, diffuse large B cell type, medium power

26 Malignant lymphoma, retroperitoneum, diffuse large B cell type, medium power

27 Diffuse large B-cell lymphoma

28 Malignant lymphoma, peritrabecular, bone marrow, medium power

29 Mature B-cell Lymphomas Burkitt lymphoma Plasmacytoma Plasma cell myeloma

30 Burkitt lymphoma/burkitt cell leukaemia Morphology Medium sized cells, basophilic cytoplasm, starry sky appearance, high mitotic rate Immunology Surface IgM Genetics CD5, 23 CD10 CD19, 20, 22, 79a Ki67 t(2;8), t(8;14) or t(8;22), rearrangement of c-myc - >85% Clinical Children >> adults, aggressive but curable in children, extranodal sites ie. ovary

31 Malignant lymphoma, Burkitt type, karyotype, diagram

32 Burkitt lymphoma

33 Burkitt lymphoma Endemic (African) Burkitt lymphoma Sporadic (nonendemic) Burkitt lymphoma Burkitt like lymphoma related to HIV patients

34 High grade, B-cell Burkitt like lymphoma

35 Plasma cell myeloma/plasmacytoma Morphology Plasma cells Immunology Genetics Surface Ig Cytoplasmic Ig EMA CD19, 20, 22 CD79a t(11;14) in a few cases - - / - / - Clinical Adults. Lytic bone lesions, less commonly soft tissue tumour. Relapse after plateau phase

36 Multiple myeloma, lesions in skull

37 Multiple myeloma, lesions in skull, radiograph

38 Multiple myeloma, lesions in bone marrow

39 Multiple myeloma, bone marrow, low power

40 Multiple myeloma, bone marrow, medium power

41 Multiple myeloma, bone marrow smear, high power

42 Immunosecretory disorders (clinical manifestation of diverse lympoid neoplasms) Clinical syndrome Waldenstrom s macroglobulinaema Underlying neoplasm Lymphoplasmocytic lymphoma Heavy chain disease (HCD) gamma HCD alpha HCD Mu HCD Lymphoplasmocytic lymphoma Extranodal marginal cell lymphoma (immunoproliferative small intestinal disorder) B-cell chronic lymphocytic leukaemia Immunoglobulin deposition disease Systemic light chain disease Primary amyloidosis Plasma cell myeloma, monoclonal gammopathy Plasma cell myeloma, monoclonal gammopathy

43 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

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47 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)

48 Splenic marginal zone B-cell lymphoma Morphology Immunology Genetics Small centrocyte like cells, moncytoid B cells, lymphocytes, plasma cells Surface Ig CD5, 10 CD19, 20, 22, 79a CD23 No specific abnormalities - - Clinical Splenomegaly.?Always leukaemic

49 Marginal zone B-cell lymphoma of MALT type Morphology Immunology Genetics Small centrocyte like-cells, monocytoid B cells, lymphocytes, plasma cells Surface Ig CD5, 10 CD19, 20, 22, 79a CD23 t(11;18 in many cases, trisomy 3 in some cases - - Clinical Indolent course, often localized. May transform to large cell lymphoma

50 MALT lymphomas of the gastrointestinal tract: Mostly B-cell lymphomas Enteropathy associated T-cell lymphoma

51 Pulmonary lymphomas Bronchial tissue

52 Malignant lymphomas of salivary glands Associated with Sjögren`s syndrome

53 Malignant lymphoma of the thyroid Associated with Hashimoto thyroiditis

54 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

55 Hairy cell leukaemia Morphology Small lymphoid cells with bean shape nuclei and pale cytplasm Immunology Genetics Surface Ig CD5, 10, 23 CD11c, 25 CD19, 20, 22, 79a CD103 (MLA) No specific abnormalities - Clinical Adults, often with slenomegaly and pancytotopenia,indolent course

56 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)

57 Post-transplantation lymphoproliferative disorder (PTLD), medium power

58 T and NK-cell neoplasms

59 T-Cell Neoplasms Precursor T-cell lymphoblastic leukemia/lymphoma

60 Precursor T-lymphoblastic lymphoma/leukaemia (precursor T-cell acute lymphoblastic leukaemia) Morphology Lymphoblasts, identical cytology to B lymphoblasts Immunology TdT CD1a CD3 CD7 CD4 /-8 Genetics SCL / TAL-1 rearrangements 25% / - / - Clinical Frequently involves mediastinum, adolescents and young adults, highly aggressive but potentially curable

61 T-Cell Neoplasms Angioimmunoblastic T-cell lymphoma Peripheral T-cell lymphoma (unspecified) Adult T-cell leukemia/lymphoma (HTLV1) Systemic anaplastic large cell lymphoma (Tand null-cell types) Primary cutaneous anaplastic large cell lymphoma

62 Angioimmunoblastic T-cell lymphoma Morphology Immunology Genetics Architecture effaced, arborizing high endothelial venules, no secondary follicles, mixed infiltrate of lymphocytes, blasts and atypical clear cells T-cell phaenotype, large follicular dendritic cell clusters around proliferating venules No specific abnormalities Clinical Systemic disease with lymphadenopathy, fever, weight loss and skin rash, polyclonal hypergammaglobulinaeimia, aggressive course

63 Adult T-cell lymphoma/leukaemia (HTLV1) Morphology Pleomorphic infiltrate of small and large lymphoid cells Immunology CD2, 3, 4, 5, 25 CD7 - Genetics Integrated HTLV-1 genome present Clinical Adults, commonest in Japan and Carribean, hypercalcaemia, leukaemia, bone lysis, commonly aggressive, rarely indolent

64 Anaplastic large cell lymphoma, T/null cell Morphology Bizarre large cells, sometimes R-S like or multinucleated, abundant cytoplasm, cohesive cells, intrasinusoidal spread Immunology Genetics T or null phenotype CD30 EMA ALK 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

65 Peripheral T-cell lymphoma, not otherwise characterized Morphology Immunology CD3 Genetics Atypical lymphocytes of varying sizes, variable reactive background elements, e.g. macrophages, vessels etc. Variable expression of other T cell markers No specific abnormalities / - Clinical Adults, aggressive course but potentially curable

66 T-cell lymphomas T-cell prolymphocytic leukemia T-cell large granular lymphocytic leukemia NK-cell leukemia Extranodal NK/T-cell lymphoma, nasaltype (angiocentric lymphoma) Mycosis fungoides Sezary syndrome

67 T-cell prolymphocytic leukaemia Morphology Small lymphoid cells, with some nuclear irregularity Immunology CD2, 3, 5, 7 CD4 CD8 Genetics inv14(q11;32) 75%, trisomy 8q - / Clinical Adults, often leukaemic, more aggressive than B cell chronic lymphocytic leukamia

68 T-cell granular lymphocytic leukaemia Morphology Small to medium lymphoid cells with eccentric round or oval nuclei, azurophilic cytoplasmic granules Immunology CD2 CD3, 8 CD16 CD56, 57 Genetics No specific abnormalities / - - / Clinical Adults, usually leukaemic, neutropenia /- anaemia, indolent course

69 Mycosis fungoides/sezary syndrom Morphology Small to medium-sized cells with cerebriform nuclei epidermal infiltration Immunology CD2, 3, 4, 5 CD7, 8, 25 - Genetics No specific abnormalities Clinical Adults, principally localized skin but may involve blood and lymph nodes

70 Extranodal NK/T-cell lymphoma nasal-type (angiocentric lymphoma) Morphology Broad spectrum of cell sizes, eosinophils, histiocytes, large R-S cells Immunology CD3, CD56, CD 45RO CD4, CD8, CD5 EBV Genetics No specific chromosomal abnormality /- - Clinical More common in Asia, involves face and nose, but occasionally elsewhere

71 T-Cell Neoplasms Subcutaneous panniculitis-like T-cell lymphoma Enteropathy type intestinal T-cell lymphoma Hepatosplenic / T-cell lymphoma

72 Clinical staging of Hodgkin and non-hodgkin lymphomas (Ann Arbor Classification) Stage* Distribution of disease I II III IV Involvement of a single lymph node region (I) or involvement of a single extralymphatic organ or site (I E ). 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 (II E ). Involvment of lymph node regions on both sides of the diaphragm (III), which may include the spleen (III S ) and/or limited contiguous extralymphatic organ or site (III E, III ES ). 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%

73 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)

74 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

2010 Hematopoietic and Lymphoid ICD-O Codes - Alphabetical List THIS TABLE REPLACES ALL ICD-O-3 Codes

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