HODGKIN LYMPHOMA DR. ALEJANDRA ZARATE OSORNO HOSPITAL ESPAÑOL DE MEXICO
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1 HODGKIN LYMPHOMA DR. ALEJANDRA ZARATE OSORNO HOSPITAL ESPAÑOL DE MEXICO
2 HODGKIN LYMPHOMA CLASSIFICATION Lukes & Butler Rye WHO-2016 Linphocytic and/or histiocytic Nodular & diffuse Nodular Sclerosis Lymphocyte predominance Nodular Sclerosis Nodular Lymphocyte Predominance chl: lymphocyte rich chl: Nodular Sclerosis Mixed Cellularity Mixed Cellularity chl: Mixed Cellularity Diffuse Fibrosis Reticular Lymphocyte Depletion chl: Lymphocyte Depletion
3 HODGKIN LYMPHOMA 15% of all the lymphomas México: 15% Incidence: stable Hodgkin s disease Hodgkin Lymphoma B-cell origin Classification based on the original Lukes &Butler classification
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6 DIAGNOSTIC CRITERIA There have been changes Purely histological to histological and immunophenotypic Reclassification of the disease Change on the frequency of the subtypes Changes on the criteria for the HL diagnosis
7 IMMUNOPHENOTYPE RS cells RS + appropriate milieu HL Inmunophenotype NLP HL LP cell chl, NS: Lacunar cell chl, MC: RS+ mononuclear cells chl, LD RS+ anaplastic cells
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9 Immunophenotype Small biopsies RS cells are not necessary for the diagnosis Enough number of mononuclear cells with the appropriate immunophenotype
10 CD30 MUM-1
11 TYPES OF RS CELLS RS cells (chl) Typical (lobulated, bynucleated, multinucleated, anaplastic) - Variants - Hodgkin: mononuclear - Lacunar L-P cells (NLP HL)
12 MONONUCLEAR AND LACUNAR CELLS
13 L-P CELLS
14 RS-LIKE CELLS IN LYMPH NODES Reactive lymphadenopaties (infectious mononucleosis) EBV associted B-cell lymphoproliferative disorders Non Hodgkin Lymphomas T-cell rich B-cell lymphoma Anaplastic Large Cell Lymphoma Peripheral T-cell Lymphomas Annaplastic Variant Diffuse Large B- cell Lymphoma Malignant Melanoma Anaplastic Carcinomas Seminoma Pleomorphic Sarcomas Extramedulary Myeloid Tumor
15 Granulocyte Monocyte / macrophage Dendritic cell T-lymphocyte HODGKIN LYMPHOMA LINEAGE OF THE RS CELL B Lymphocyte germinal center
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17 CLASSICAL HODGKIN LYMPHOMA CYTOKINES AND Y QUIMOKINES Interleukines -2, -5, -6, -7, -9, - 10, -13 Interleukin 13 receptor GM-CSF Lymphotoxin A Beta-transforming growth factor (fibrosis) Eotaxin (eosinophyles) Quimokines CC (> T-cells Th2)
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19 INMUNOPHENOTYPE OF THE RS CELLS chl NLP HL RS cells L-P cells CD20 -/+ + CD3 - - CD30 + -/+ CD15 +/- - EBV +/- -/+ CD PAX-5 + weak + Bcl-6 -/+ weak + EMA - +/- OCT Bcl-2 + -
20 CD30 CD15 LMP1 CD45 CD20 PAX-5
21 CD30 CD15 LMP-1
22 CLASSICAL HOSGKIN LYMPHOMA CELL OF ORIGIN MATURE B-CEL, DERIVED FROM THE GERMINAL CENTER, IN MATURATION STAGE
23 ADVERSE PROGNOSTIC FACTORS CD15 negative CD20 + (RS cells) Abundant macrophages (CD68 Y CD163) EBV (> 45 years) Bcl-2 (RS cells) Paucity of B-cells in the reactive environment bcl-2 J Clin Oncol 2013;31: Blood 2012;120:
24
25 CLASSICAL HODGKIN LYMPHOMA FOUR SUBTYPES Similar features: Inmunophenotype Genetics Differences: Clinical characteristics Involved organs Pattern of tissular growth Fibrosis RS cell type Reactive environment Association with EBV
26 CLASSICAL HODGKIN LYMPHOMA CLINICAL FEATURES Bimodal age distribution years Adults > 55 years Associated with EBV: increased incidence in chl Particularly MC and LD Geographical variation Peripheral lymphadenopathy > 60% in I or II stages B symptoms 40%
27 FRECUENCY OF THE SUBTYPES Nodular Sclerosis 62% Mixed Cellularity: 27% Nodular Lymphocyte Predominance: 5% Lymphocyte Rich: 5% Lymphocyte Depletion: 1%» German Hodgkin Study Group» L Clin Oncol 23:5739, 2005
28 Subtype Clinical features RS cells Histological Variants Differential Diagnosis Lymphocyte Rich, 5% 43 years Males Stages I or II Mediastinum EBV <25% Typical Lacunar like or LPlike Few lymphocytes and plasma cells Nodular Diffuse LP HL Mantle cell lymphoma TCRBCL CLL/LPL Nodular Sclerosis, 62% 28 years Females Stages I or II Mediastinum EBV<25% Lacunar cells Mononuclear RS cells Fibrosis Eosinophils Necrosis Cellular Phase Syncitial Variant Histological Subtipes Grades I and II Mediastinal primary BCL Gray zone Lymphoma ALCL DLBC with sclerosis Germinal cell tumor Metastases Reactive lymphadenopatie Retroperitoneal fibrosis Mixed Cellularity, 27% 37 years Males Stages III and IV Abdomen, retroperitoneum, bone marrow EBV>50% Typical RS cells All variant No lacunar cells Reactive environment Fibrosis Focal and Interfolicular Diffuse Nodular Infectious mononucleosis PTCL AIBTL TCHRBCL Mucocutaneous ulcer EBV associated LP disorders Lymphocyte Depletion 1% >55 years Males Stages III an d IV Abdomen, retroperitoneum, BM Pleomorphic RS cells Necrosis Fibrosis Scarse lymphocytes Diffuse fibrosis Reticular Sarcomatoid ALCL Sarcoma PTCL
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30 LYMPHOCYTE RICH
31 chl, NODULAR SCLEROSIS
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34 MONONUCLEAR AND LACUNAR CELLS
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36 chl, NODULAR SCLEROSIS, SYNCITIAL VARIANT
37 SV, NS CD45 CD30 CD15 MUM-1
38 chl, MIXED CELLULARITY Medium age 37 years Male Stages III and IV Frequent B symptoms Peripheral lymphadenopathy, spleen, liver, bone marrow EBV associated > 50% Increased frequency in HIV +
39
40 INFECTIOUS MONONUCLEOSIS CD30 EBER
41 ANAPLASTIC LARGE CELL LYMPHOMA, HODGKIN LIKE
42 Reactive Lymphadenopathy Metastatic Nasopharyngeal carcinoma CK
43 chl, LYMPHOCYTE DEPLETION Less frequent, < 1% 30 to 40 years old or > 55 years Male predominance (60-75%) Clinical stage III or IV, most aggressive B symptoms: 80% EBV: 95% with HIV + and developing countries Differential diagnosis: ALCL Involved organs Abdomen and retroperitoneum Bone marrow Diffuse growth pattern
44 chl, LYMPHOCYTE DEPLETION, DF CD30 LMP-1
45 chl, LYMPHOCYTE DEPLETION, RETICULAR CD30 LMP-1
46 HL, NODULAR LYMPHOCYTE PREDOMINANCE 5% of HL, males, fourth decade Stages I-II, 5 to 25% advanced stage, unfavorable evolution Rarely EBV associated Involvement sites: Cervical, axillary and inguinal lymph nodes Mediastinum, spleen and bone marrow: rare Favorable response to therapy with jate relapses Stage III-IV Unfavorable evolution Evolution to DLBCL 3-5% or TCHRBCL Note in the dx the origin from a NLPHL
47 NODULAR LP HL Frequency: 5% Inmunophenotype (B-cell CD20+, PAX-5+, bcl-6+) Histological variants (6 types) Differential diagnosis: Progressive transformation of the germinal centers T-cell rich B cell lymphoma Follicular lymphoma chl, lymphocyte rich Peripheral T cell lymphoma, NOS Chronic lymphocytic leukemia /small lymphocytic lymphoma
48
49 CD20
50 EMA bcl-6 CD57 CD21
51
52 CD57 EBER
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54 TCHRBCL CD20 CD3
55 NODULAR LP vs TCHRBCL LH, NLP TCHRBCL Patrón nodular Yes Not CD CD CD30 -/+ - CD15 -/+ - EMA +/- -/+ CD57 (PD-1) +/- -/+ CD TIA-1 - -/+ CD8 - +
56 CLASSICAL HODGKIN LYMPHOMA SECONDARY SITES (BONE MARROW AND LIVER) Mononuclear cells expressing CD15 and CD30 Appropriate reactive cellular environment Classical RS cells are not required if the diagnosis was made in another site Bone marrow: stage IV Vascular disemination
57 CD30 LMP-1
58 chl, EXTRANODAL Very rare (except in HIV +) 0.25% of chl Initial differential diagnosis: DLBCL Mostly by contiguous extension or retrogradous lymphatic disemination Site GI tract Lung, most common Skin 0.5% (T-cell CD30 + cutaneous lymphoproliferative disorders) Waldeyer s ring Bone
59 HODGKIN LYMPHOMA PATHOLOGY OF THE RELAPSING DISEASE Modern therapy success > 30% relapsing 1 to 13% late relapse (3 to 4 years) More frequent: Advanced stages Systemic symptoms Bulky mediastinal disease Most frequent subtype: nodular sclerosis Previously involved sites
60 HODGKIN LYMPHOMA CAUSES OF DEATH Chemotherapy complications Secondary neoplasms, hearth disease and infections < 40% persistent disease Secondary neoplasms: Solid tumors Acute myeloid leukemia Non Hodgkin lymphoma
61 THANK YOU VERY MUCH FOR YOUR ATTENTION
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