HODGKIN LYMPHOMA

DR. ALEJANDRA ZARATE OSORNOHOSPITAL ESPAÑOL DE MEXICO

HODGKIN LYMPHOMA CLASSIFICATION

Lukes & Butler Rye WHO-2016Linphocyticand/or histiocyticNodular & diffuse

Lymphocytepredominance

NodularLymphocytePredominancecHL: lymphocyterich

Nodular Sclerosis

Nodular Sclerosis

cHL: Nodular Sclerosis

Mixed Cellularity Mixed Cellularity cHL: MixedCellularity

Diffuse FibrosisReticular

LymphocyteDepletion

cHL: LymphocyteDepletion

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

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

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

ImmunophenotypeSmall biopsies

• RS cells are not necessary for the diagnosis

• Enough number of mononuclear cells with the appropriate immunophenotype

CD30 MUM-1

TYPES OF RS CELLS

• RS cells (cHL)– Typical

(lobulated, bynucleated, multinucleated, anaplastic)

- Variants- Hodgkin:

mononuclear- Lacunar

• L-P cells (NLP HL)

MONONUCLEAR AND LACUNAR CELLS

L-P CELLS

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

HODGKIN LYMPHOMALINEAGE OF THE RS CELL

• Granulocyte• Monocyte /

macrophage• Dendritic cell• T-lymphocyte

• B Lymphocyte– germinal center

CLASSICAL HODGKIN LYMPHOMACYTOKINES 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)

INMUNOPHENOTYPE OF THE RS CELLScHL NLP HL

RS cells L-P cellsCD20 -/+ +CD3 - -CD30 + -/+CD15 +/- -EBV +/- -/+CD45 - +PAX-5 + weak +Bcl-6 -/+ weak +EMA - +/-OCT-2 - +Bcl-2 + -

CD30 CD15

CD45 CD20 PAX-5

LMP1

CD30 CD15 LMP-1

CLASSICAL HOSGKIN LYMPHOMACELL OF ORIGIN

MATURE B-CEL, DERIVED FROM THE GERMINAL CENTER, IN

MATURATION STAGE

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

• J Clin Oncol 2013;31:256-262

• Blood 2012;120:3280-3287

bcl-2

CLASSICAL HODGKIN LYMPHOMAFOUR SUBTYPES

• Similar features:– Inmunophenotype– Genetics

• Differences:– Clinical characteristics– Involved organs– Pattern of tissular growth– Fibrosis – RS cell type– Reactive environment– Association with EBV

CLASSICAL HODGKIN LYMPHOMACLINICAL FEATURES

• Bimodal age distribution– 15-35 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%

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

Subtype Clinicalfeatures

RS cells HistologicalVariants

DifferentialDiagnosis

Lymphocyte Rich, 5%

43 yearsMalesStages I or IIMediastinumEBV <25%

TypicalLacunar –like or LP-likeFew lymphocytesand plasma cells

NodularDiffuse

LP HLMantle cell lymphomaTCRBCLCLL/LPL

NodularSclerosis,62%

28 yearsFemalesStages I or IIMediastinumEBV<25%

Lacunar cellsMononuclear RS cellsFibrosisEosinophilsNecrosis

Cellular PhaseSyncitialVariantHistologicalSubtipesGrades I and II

Mediastinal primary BCLGray zone LymphomaALCLDLBC with sclerosisGerminal cell tumorMetastasesReactive lymphadenopatieRetroperitoneal fibrosis

Mixed Cellularity, 27%

37 yearsMalesStages III and IVAbdomen, retroperitoneum, bone marrowEBV>50%

Typical RS cellsAll variantNo lacunar cellsReactive environmentFibrosis

Focal and Interfolicular

DiffuseNodular

Infectious mononucleosisPTCLAIBTLTCHRBCLMucocutaneous ulcerEBV associated LP disorders

LymphocyteDepletion 1%

>55 yearsMalesStages III an d IVAbdomen, retroperitoneum, BM

Pleomorphic RS cellsNecrosisFibrosisScarselymphocytes

Diffuse fibrosisReticularSarcomatoid

ALCLSarcomaPTCL

LYMPHOCYTE RICH

cHL, NODULAR SCLEROSIS

MONONUCLEAR AND LACUNAR CELLS

cHL, NODULAR SCLEROSIS, SYNCITIAL VARIANT

CD45 CD30 CD15

SV, NS

MUM-1

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 +

CD30

EBER

INFECTIOUS MONONUCLEOSIS

ANAPLASTIC LARGE CELL LYMPHOMA, HODGKIN LIKE

CK

Reactive Lymphadenopathy

Metastatic Nasopharyngeal carcinoma

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

cHL, LYMPHOCYTE DEPLETION, DF

CD30 LMP-1

CD30 LMP-1

cHL, LYMPHOCYTE DEPLETION, RETICULAR

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

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

CD20

EMA bcl-6

CD57 CD21

CD57

EBER

TCHRBCL

CD20 CD3

NODULAR LP vs TCHRBCL

LH, NLP TCHRBCLPatrón nodular Yes NotCD20 + +CD45 + +CD30 -/+ -CD15 -/+ -EMA +/- -/+CD57 (PD-1) +/- -/+CD21 + -TIA-1 - -/+CD8 - +

CLASSICAL HODGKIN LYMPHOMASECONDARY 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

CD30 LMP-1

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

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

HODGKIN LYMPHOMACAUSES OF DEATH

• Chemotherapy complications• Secondary neoplasms, hearth disease and

infections• < 40% persistent disease

• Secondary neoplasms:– Solid tumors– Acute myeloid leukemia– Non Hodgkin lymphoma

THANK YOU VERY MUCH FOR YOUR

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