A germinal center

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A germinal center
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B - cells
T - cells
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Malignant Lymphomas

• Hodgkins Disease
• Non - Hodgkins Lymphomas

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HODGKINS DISEASE
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Definition

• Hodgkins Disease encompasses a group of
  disorders that differ from NHL by
• Arise in a single node / chain of nodes spreads
  characteristically to contiguous lymph nodes
• Reid - Sternberg cells

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Epidemiology

• 50 of Malignant Lymphomas
• Incidence is bimodal
• Agent - EBV virus

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WHO Classification of HD

• Nodular Sclerosis
• Mixed Cellularity
• Lymphocyte - rich
• Lymphocyte depletion
• Lymphocyte predominance

CLASSICAL HODGKINS
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Macroscopy

• Enlargement of cervical nodes most frequent
• Individual nodes discrete Rubbery
• C/S grayish tan or pale tan

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Hodgkin Lymphoma - Gross
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Microscopy

• RS cells in a appropriate background of
• Non Neoplastic inflammatory cells--
  lymphocytes , plasma cells , eosinophils

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Reid - Sternberg cell

• True neoplastic element in HD
• Classic RS cells are large ,15 - 45 microns ,
  binucleate / bilobed
• Nucleus contains large inclusion like owl eyed
  nucleoli surrounded by a clear halo.
• Cytoplasm - abundant amphophilic

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Variants of RS cell

• Mononuclear variant
• Lacunar cells
• L H variants

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R-S cell (Mononuclear variant)
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R-S cells (Lacunar variant)
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Lacunar cells
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R-S Cells - Multinucleate
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Lymphohistiocytic (L H) variant
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Mummified R-S cell
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SIGNIFICANCE OF DIFFERENT RS CELLS

• Typical RS cell Lymphocyte depleted gt Mixed
  Cellularity gt Nodular Sclerosis gt Lymphocyte
  Predominant.
• Lacunar Cell? Nodular Sclerosis
• LH Cell (Pop Corn cell) ? Lymphocyte
  predominant.
• Mummified cell? Classical HD

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Spread of HD Staging

• Spread is predictable
• Nodal disease precedes splenic disease
• Splenic disease precedes liver disease
• Liver disease precedes BM involvement extra
  nodal involvement.

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Liver that is involved with Hodgkin's disease
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ANN ARBOR CLASSIFICATION

• STAGE DISTRIBUTION OF DISEASE
• I. Involvement of a single lymph node region (I)
  or involvement of a single extra-lymphatic
  organ/site IE
• II. Involvement of 2 /more LN regions on
  same side of diaphragm II or with
  involvement of limited contiguous
  extra-lymphatic organ /site IIE

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• III. LN regions on both sides of diaphragm
  which may include spleen / limited contiguous
  EL organ /site .
• IV. Disseminated foci of involvement.

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Nodular Sclerosis

• 65 - 75
• Characterized by
• - Collagen bands
• - Lacunar cells
• - polymorphous background of
  lymphocytes , eosinophils , plasma cells
  macrophages
• L cervical ,supraclavicular , mediastinal
• women, adolescents, young adults.
• Prognosis is Excellent

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HD - NS
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Mixed Cellularity

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• classic RS cells mononuclear variants plentiful
• diffuse effacement by a heterogeneous population
  of small lymphocytes , eosinophils , plasma cells
  , benign macrophages
• Men , older age, B- symptoms , advanced tumor
  stage.

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HD - MC
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Lymphocyte Predominance

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• Nodal effacement by vaguely infiltrate of small
  lymphocytes admixed with benign histiocytes
• Classic RS cells few , L H variants common.
• Men , lt 35 , limited disease
• prognosis good.

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HD - lymphocyte predominance
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Hodgkins Lymphoma Lymphocyte depleted

• Many Reed-Sternberg cells and variants are
  present.
• This type of HD is not common.
• Worst prognosis.

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Lymphocyte Depletion type
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Clinical Features
NHL
HD

• single axial group multiple
  peripheral nodes
• spread by contiguity non contiguous
  spread
• mesenteric Waldeyers mesenteric Waldeyers
• not involved
  involved
• extranodal uncommon extranodal common

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NON - HODGKINS LYMPHOMAS
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NHL

• 6th leading cause of cancer death
• Recent increase especially in patients with AIDS
• In 65 NHL arise in LN, 35 NHL arise in
  lymphoid tissue of parenchymal organs
• Potential spread to other LN , Other tissues
  like liver, spleen, BM

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CLASSIFICATION

• NHL may originate in T cells, B cells,
  histiocytes.
• 80 - 85 B cell
• Remainder - T cell
• CD2, CD3, CD4, CD7, CD8 T cell
• CD10, CD19, CD20, surface Ig B cell

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• Many tumors of B cells may recapitulate
  the follicular pattern
• Other B cell tumors , T cell tumors , histiocytic
  tumors - diffuse pattern
• The morphologic changes reflect the stage of
  differentiation or activation at which the tumor
  cells are frozen

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CLASSIFICATIONS

• The Working Formulation for Clinical Use
• - LOW
• - INTERMEDIATE
• - HIGH GRADE
• Each group is further divided based on
  architecture , cytologic appearance of cells
• Also contains a miscellaneous group to include
  histiocytic T cell tumors

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REAL Classification
NHL

• 1994 Revised European-American
• classification of Lymphoid neoplasms,
• Tumors of B cells
• Tumors of T cells NK cells
• Hodgkins Lymphoma

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WHO Classification of Lymphomas(1997)

• Precursor B-cell neoplasms (neoplasms of
  immature B-cells),
• Peripheral B-cell neoplasms (neoplasms of
  mature B-cells)
• Precursor T-cell neoplasms (neoplasms of
  immature T-cells),
• Peripheral T-cell and NK-cell neoplasms
  (neoplasms of mature T-cells natural killer
  cells),
• Hodgkin Lymphoma (neoplasms of
• Reed-Sternberg cells and variants)

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WHO classification
NHL

• I. Precursor B cell Neoplasms
• Precursor B Lymphoblastic
  Leukemia/Lymphoma

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WHO classification
NHL

• II. Peripheral B-cell Neoplasms
• Chronic lymphocytic leukaemia/small
  lymphocytic lymphoma,
• B-cell prolymphocytic leukaemia,
• Lymphoplasmacytic lymphoma,
• Splenic and nodal marginal zone lymphomas,
• Extranodal marginal zone lymphoma,
• Mantle cell lymphoma,

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WHO classification
NHL

• II. Peripheral B-cell Neoplasms
• Follicular lymphoma,
• Marginal zone lymphoma,
• Hairy cell leukaemia,
• Plasmacytoma/plasma cell myeloma,
• Diffuse large B-cell lymphoma,
• Burkitt's lymphoma

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WHO classification
NHL

• III. Precursor T-cell Neoplasms
• Precursor T-lymphoblastic leukaemia / lymphoma,

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WHO classification
NHL

• IV. Peripheral T-cell and NK-cell Neoplasms
• 1. T-cell prolymphocytic leukaemia,
• Large granular lymphocytic leukaemia,
• Mycosis fungoides/Sezary syndrome,
• Peripheral T-cell lymphoma, unspecified,
• Anaplastic large cell lymphoma,
• Angioimmunoblastic T-cell lymphoma,

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WHO classification
NHL

• IV. Peripheral T-cell and NK-cell Neoplasms
• 7. Enteropathy-associated T-cell lymphoma,
• 8. Panniculitis-like T-cell lymphoma,
• 9. Hepatosplenic ?d T-cell lymphoma,
• 10. Adult T-cell leukaemia/lymphoma,
• 11. NK/T-cell lymphoma, nasal type,
• 12. NK-cell leukaemia

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Immune markers

• B-cells
• CD10, CD19, CD20, CD21, CD23, CD79a,

• T-cells
• CD1, CD3, CD4, CD5, CD8

All Leukocytes CD45
NK-cells CD16, CD56
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Multiple enlarged lymph nodes high grade
non-Hodgkin's lymphoma (NHL) tends to involve a
single node.
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PRECURSOR B- AND T-CELL NEOPLASMS

• Acute Lymphoblastic
• Leukemia / Lymphoma

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Precursor B- and T-cell Neoplasms

• ACUTE LYMPHOBLASTIC LEUKAEMIA / LYMPHOMA
• Pre-B or Pre-T lymphocytes (lymphoblasts),
• About 85 B-cell type childhood leukaemias
• 15 T-cell lymphomas adolescent males,
• Morphologically indistinguishable,
• (immunophenotyping for subclassification)
• Condensed chromatin, inconspicuous nuceloli,
  scant agranular cytoplasm

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ALL
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Pre-T cell lymphomas

• ALLs with lymphomatous presentation,
• Mediastinal masses (thymic involvement),
• Lymphadenopathy and splenomegaly,
• Same morphology as pre-B cell ALL,

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PERIPHERAL B-CELL NEOPLASMS- Chronic
lymphocytic leukaemia (CLL)/Small lymphocytic
lymphoma (SLL)
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PERIPHERAL B-CELL NEOPLASMS- Chronic
lymphocytic leukaemia (CLL)/Small lymphocytic
lymphoma (SLL)

• Morphologically, phenotypically, and
  genotypically indistinguishable,
• Differ in peripheral blood lymphocytosis,
• Absolute lymphocyte count gt4000/cmm CLL
• Most common leukemia of adults in west,
• Less common in Asian countries,
• SLL 4 of NHL,

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SLL - lymphnode
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SLL - LN
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Smudge cell
CLL
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CLL/SLL liver infiltration
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CLL/SLL Clinical features

• Variable leucocyte count
• - Leucopenia to gt 200,000/cmm.,
• Disrupts immune function
• - Susceptibility to infections,
• - 10 to 15 - autoantibodies
• (hemolytic anemia, thrombocytopenia)

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FOLLICULAR LYMPHOMA
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Follicular Lymphoma

• Most common in US,
• 45 of adult lymphomas,
• Middle age,
• Afflicts males and females equally,
• Less common in Europe, rare in Asia,
• Neoplastic cell germinal centre B-cells,

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ENLARGED MESENTERIC LYMPHNODES
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Mixture of Centrocytes and centroblasts