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Hodgkin lymphomas

Hodgkin lymphomas. Monirath Hav, MD, PhD fellow Pathology Department Ghent University Hospital. Adapted from WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues 2008 edition. Definition. HLs share the following characteristics: Usually arise in LNs (cervical regions)

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Hodgkin lymphomas

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  1. Hodgkin lymphomas Monirath Hav, MD, PhD fellow Pathology Department Ghent University Hospital Adapted from WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues 2008 edition

  2. Definition HLs share the following characteristics: • Usually arise in LNs (cervical regions) • In young adults • Small number of scattered large RS cells in heterogenous background • Tumour cells often ringed by T lymphocytes in a rosette-like manner

  3. Subclassification • Nodular Lymphocyte Predominant HL (NLPHL) • Classical HL 4 subtypes • Nodular sclerosis • Mixed cellularity • Lymphocyte rich • Lymphocyte depleted

  4. Ann Arbor staging StageDefinition I Involvement of a single LN region or lymphoid structure II Involvement of >= 2 LN regions on the same side of the diaphragm III Involvement of LN regions or structures on both sides of the diaphragm III1 with or without splenic, hilar, celiac or portal nodes III2 with paraaortic, iliac or mesenteric nodes IV Involvement of extranodal sites(s)

  5. NLPHL - introduction Synonyms: • Jackson and Parker: Hodgkin's paragranuloma • Lukes and Butler: Lymphocytic and/or histiocytic (L&H) predominance Hodgkin's disease • Kiel group: nodular paragranuloma • Rye: Lymphocytic predominance Hodgkin's disease • REAL: Nodular lymphocyte predominance Hodgkin's disease

  6. NLPHL - introduction • Monoclonal B cell neoplasm • Neoplastic cells: popcorn cells or lymphocyte predominant cells (LP cells) • Age: 30-50 yo • Sex: male predominance • Main DD: T-cell/histiocyte-rich large B cell lymphoma

  7. NLPHL - morphology • Nodular or diffuse infiltrates • Predominantly small lymphocytes, histiocytes, and intermingled LP cells • LP/popcorn cell: large cell, scant cytoplasm, one large nucleus (folded or multilobated), multiple basophilic nucleoli • Occasionally  reactive follicles with PTGC adjacent to the lesion or may proceed or follow NLPHL • Unlike in classical HL, neutrophils & eosinophils are seldom seen

  8. NLPHL - Immunophenotype • LP cells are: • Positive for CD20, CD79a, CD75, BCL6 & CD45 • Usually negative for CD15 & CD30 • Ringed by CD3+ and CD57+ cells (rosette formation) • LP cells are EBV negative but it may be + in surrounding cells

  9. NLPHL – Differential diagnosis • NLPHL with prominence of extranodular LP cells is associated with a propensity to develop a diffuse pattern resembling THRLBCL (THRLBCL-like). This is seen more frequently in patients with recurrence. It’s good practice to label cases of NLPHL with such features as THRLBCL-like NPLHL and to distinguish them from primary THRLBCL. • Main DD: THRLBCL  usually BM involvement, CD57-, no small B cells in the background

  10. NLPHL – Prognosis • Develops slowly but with fairly frequent relapses • Responsive to therapy  rarely fatal • Stage I & II: 10 y OS > 80%

  11. CHL - introduction • Monoclonal, mostly B cell neoplasm • Neoplastic cells: • Nodular sclerosis : lacunar cells • Mixed cellularity: HRS? • Lymphocyte rich: HRS? • Lymphocyte depleted: HRS? • Incidence: 95% of HL • Age: bimodal  1 peak at 15-35 yo and another peak in late life • Sex: N/A • Pathogenesis: EBV!

  12. CHL - morphology • Diffuse pattern • HRS cells in rich inflammatory background • Classical diagnostic RS cell: large cell, abundant cytoplasm, at least 2 nuclear lobes or 2 nuclei, prominent eosinophilic nucleoli, with nuclear halo resembling viral inclusion • Unlike in NLPHL, neutrophils & eosinophils are frequently seen

  13. CHL - Immunophenotype • HRS cells are: • Positive for CD30 & CD15 (membrane + golgi spot staining) • Positive for MUM1 but negative for CD138 (Syndecan) • Usually negative for CD45, CD75, & CD68 • CD20 and CD79a are less often expressed • PAX5 is app. 95% expressed (weak in HRS cells but strong in reactive B cells) • HRS cells are EBV positive

  14. CHL - prognosis • Modern radiation and chemotherapy have made CHL curable in >85% of cases • Staging determines therapy • Histologic subtypes are less important as predictive factors

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