hodgkin ’ s lymphoma introduction lymphocyte predominance classical hl nodular sclerosis mixed...
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HODGKIN’S LYMPHOMA
Introduction
Lymphocyte Predominance
Classical HLNodular Sclerosis
Mixed cellularity
Lymphocyte rich
Lymphocyte depletion
Special morphology
HODGKIN’S LYMPHOMA
Raid JastaniaJan 22/03
HODGKIN’S LYMPHOMA
Introduction
Lymphocyte Predominance
Classical HLNodular 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 2nd-3rd decade, another peak in 6th
• In Orientals – HL: 5-10% of all Lymphomas
HODGKIN’S LYMPHOMA
Introduction
Lymphocyte Predominance
Classical HLNodular 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 HLNodular Sclerosis
Mixed cellularity
Lymphocyte rich
Lymphocyte depletion
Special morphology
Staging
• Ann Arbor Staging system
I single LN region (I) or single extralymphatics (I E)
II2 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)
IIILN 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 HLNodular 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 HLNodular 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 HLNodular Sclerosis
Mixed cellularity
Lymphocyte rich
Lymphocyte depletion
Special morphology
HODGKIN’S LYMPHOMA
Introduction
Lymphocyte Predominance
Classical HLNodular Sclerosis
Mixed cellularity
Lymphocyte rich
Lymphocyte depletion
Special morphology
HODGKIN’S LYMPHOMA
Introduction
Lymphocyte Predominance
Classical HLNodular 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 HLNodular 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 HLNodular 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 HLNodular Sclerosis
Mixed cellularity
Lymphocyte rich
Lymphocyte depletion
Special morphology
HODGKIN’S LYMPHOMA
Introduction
Lymphocyte Predominance
Classical HLNodular 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 HLNodular 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 HLNodular Sclerosis
Mixed cellularity
Lymphocyte rich
Lymphocyte depletion
Special morphology
HODGKIN’S LYMPHOMA
Introduction
Lymphocyte Predominance
Classical HLNodular Sclerosis
Mixed cellularity
Lymphocyte rich
Lymphocyte depletion
Special morphology
HODGKIN’S LYMPHOMA
Introduction
Lymphocyte Predominance
Classical HLNodular 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 HLNodular Sclerosis
Mixed cellularity
Lymphocyte rich
Lymphocyte depletion
Special morphology
HODGKIN’S LYMPHOMA
Introduction
Lymphocyte Predominance
Classical HLNodular 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 HLNodular Sclerosis
Mixed cellularity
Lymphocyte rich
Lymphocyte depletion
Special morphology
HODGKIN’S LYMPHOMA
Introduction
Lymphocyte Predominance
Classical HLNodular 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 HLNodular Sclerosis
Mixed cellularity
Lymphocyte rich
Lymphocyte depletion
Special morphology
HODGKIN’S LYMPHOMA
Introduction
Lymphocyte Predominance
Classical HLNodular 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 HLNodular 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 HLNodular 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 HLNodular Sclerosis
Mixed cellularity
Lymphocyte rich
Lymphocyte depletion
Special morphology
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