HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology HODGKIN ’ S LYMPHOMA Raid Jastania Jan 22/03

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Definition Presence of Reed-Sternberg cells and their variants in an appropriate background of inflammatory cells 2 biologically and clinically distinct entities: –Nodular lymphocyte predominance HL –Classical HL Evidence of B-cell origin In Caucasians –HL: 25-40% of all lymphomas –Peak in 2 nd -3 rd decade, another peak in 6 th In Orientals –HL: 5-10% of all Lymphomas

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Classification REAL/WHO Classification: –Nodular Lymphocyte Predominance –Calssical: Lymphocyte-rich Mixed cellularity Nodular Sclerosis (50-80%) Lymphocyte depletion (rare) Not classifiable cases Relation to Non Hodgkin ’ s Lymphomas –HL and Follicular lymphoma –CLL can progress to HL –Difficult distinction, diffuse large B- cell, anaplastic large cell.

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Staging Ann Arbor Staging system I single LN region (I) or single extralymphatics (I E) II 2 or mare LN regions in same side of the diaphragm (II) or localized extralymphatics and LN region on the same side of the diaphrag (II E) III LN regions on both sides of the diaphragm (III), with localized area of extralymphatics (III E), or the Spleen (III S) or both (III ES) IV Diffuse one or more extralymphatics

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Nodular Lymphocyte Predominance HL 5% Of all HL Children, young and middle aged M:F 3:1 Solitary enlarged peripheral LN, neck, groin and axilla Mediastinal LN very rare Relapse is common 19-32% Median time for relapse 4 y Stage I disease excellent 95% Stage VI 24% Treatment : ? Surgery for I, limited radiation.

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Pathology Nodal architecture is obliterated Multiple, crowded, large, dark- staining nodules of small lymphocyte Eosinophils and plasma cells scanty Lympho-histiocytic ( L&H ) cells CD20+, bcl-6+, and EMA+ CD30- CD3+ T-cells form rosettes around the L&H cells PCR of microdissected L&H cells showed clonal rearrangement of Ig genes (B-cell nature)

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Pathology Trasformation to Large cell Lymphoma: –3-4% transform to diffuse large cell lymphoma –Localized disease, favorable prognosis –Overgrowth of L&H cells or NHL Diffuse Lymphocyte predominance HL: –Rare –Minor nodular component on reticulin stain –More likely to be stage III or IV –Difficult to differentiate with T cell rich B cell lymphoma and lymphocyte rich classical HL

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Classical Hodgkin ’ s Lymphoma Presents with lymphadenopathy Extranodal disease is uncommon Spread: –Contiguous pattern –Similar to carcinomas –To spleen following para aortic LN –Then blood borne spread The neoplastic Reed-Sternberg cells –Diagnostic R-S cells –Mononuclear R-S cells –Lacunar cells –Pleomorphic R-S cells –Mummified cells

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Reed-Sternberg Cells Histogenesis controversial –Histiocyte, interdigitating dendritic cells, Follicular dendritic cells, myeloid cells and lymphocyte –B-cell lineage B-cell specific activator protein and sometimes CD20 Ig gene rearragement –Immuno: CD45RB (LCA) – CD30+, CD15+(para nuclear globules with or without membranous staining) B-cell markers, like CD20 occasionally –Genetics: Ig gene rearrangement in single neoplastic cell microdissection

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Classical Hodgkin ’ s Lymphoma Association with EBV: –40-50% of cases in the West, and 100% in underdeveloped countries and patients with AIDS –MC type 60%, NS type 35% –Stronger association in the head and neck region and at the extremes of life

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Nodular Sclerosis 5-year survival 80% Pathology: –The capsule is thickened with multiple fibrous bands and nodularity –Lacunar cells with small lymphocytes, plasma cells, eosinophils, neutrophils and histiocytes –Syncytial variant of NSHL –Necrosis, geographic –The cellular phase: lack fibrous bands Subclassification/grading: –British National Lymphoma Investigation (BNLI) Grade I (54% 5-year survival) Grade II (37% 5-year survival ): –Any of : > 25% of cellular nodule contain numerous bizarre R-S cells –>25% of cellular nodules show lymphocyte depletion –>80% of cellular nodules show a fibrohistiocytic pattern

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Mixed Cellularity Cervical and supraclavicular LN Complete remission in 70% Pathology: –Background of small lymphocytes, plasma cells, eosinophils, and histiocytes –Mononuclear and diagnostic R-S cells –Focal necrosis, secondary fibrosis

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Lymphocyte-rich HL Often early stage disease Uncommon in the mediastinum Worse survival than N-LPHL 5-year survival 80% Pathology: –Mononuclear and rare diagnostic R-S cells –Not L&H cells

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Lymphocyte depletion HL Prognosis poor, 80% dying within 3 years Pathology: –2 recognized types Diffuse fibrosis type- rare R-S cells Reticular type- abundant diagnostic and pleomorphic R-S cells

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Anaplastic Large Cell Lymphoma, Hodgkin ’ s-like Young adult with LN involvement and large mediastinal mass Patients do poorly with therapy for HL, but good with aggressive chemo for NHL Pathology: –Cohesive growth of large bizarre neoplastic cells –Architecture resemble HL, capsular thickening, nodular growth, sclerosis band –Admixed reactive cells –Most called nodular sclerosis, syncytial, NS2 or LDHL, reticular type –Immuno: like ALCL CD30+, LCA+/-, EMA+/-, CD15+/-, CD3-/+

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Special morphologic features of classical HL Interfollicular HL –Can be in any type. Inter follicular growth Foamy Histiocytes in HL –Confusion with xanthogranulomas Epithelioid histiocytes –Mimic the pattern of Lennert ’ s lymphoma HL in monocytoid B-cell clusters Treatment altered HL In the Spleen: –The number of nodules should be counted –First affect the pulp, in a periarteriolar location or in the marginal zone In the Liver: –First in the portal areas In the marrow: –Focal or diffuse fibrosis with non specific infiltrates –Marrow eosinophilia

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Prognostic Factors in Classical HL Stage Histologic type Sex and age: male and old, worse prognosis B symptoms Total tumor burden Response to treatment Vascular invasion Lack of CD15, expression of CD20

HODGKIN ’ S LYMPHOMA Introduction Lymphocyte Predominance Classical HL  Nodular Sclerosis  Mixed cellularity  Lymphocyte rich  Lymphocyte depletion Special morphology Thanks