Proposed WHO Classification of Lymphoid neoplasm B cell neoplasm Precursor B cell neoplasm Precursor B-lymphoblastic leukemia/lymphoma (precursor B-ALL) T cell neoplasm Precursor T-cell and NK-cell neoplasm Precursor T-lymphoblastic lymphoma/leukemia (precursor T-ALL)

Mature (peripheral) B cell neoplasm B-cell chronic lymphocytic leukemia/SLL Lymphoplasmacytic lymphoma Splenic marginal zone B-cell lymphoma Hairy cell leukemia Plasma cell myeloma/plasmacytoma Extra-nodal marginal zone B cell lymphoma of MALT type Nodal marginal zone B cell lymphoma Follicular lymphoma Mantle cell lymphoma

Mature (peripheral) B cell neoplasm (cont’d) Diffuse large B cell lymphoma Mediastinal B cell lymphoma Primary effusion lymphoma Burkitt lymphoma/Burkitt cell leukemia

Mature (peripheral) T cell neoplasm T-cell prolymphocytic leukemia T-cell granular lymphocytic leukemia Aggressive NK-cell leukemia Adult T-cell leukemia/lymphoma (HTLV1) Extranodal NK/T cell lymphoma, nasal type Enteropathy type T cell lymphoma Hepatosplenic gamma delta T cell lymphoma Subcutaneous panniculitis-like T cell lymphoma Mycosis fungoides/Sezary syndrome

Mature (peripheral) T cell neoplasm (cont’d) Anaplastic large cell lymphoma, T/null cell, primary cutaneous Peripheral T cell lymphoma, NOS Angioimmunoblastic T cell lymphoma Anaplastic large cell lymphoma, T/null cell, primary systemic

Hodgkin's lymphoma (Hodgkin's disease) Nodular lymphocyte predominant Hodgkin's lymphoma Classical Hodgkin's lymphoma Nodular sclerosis Hodgkin's lymphoma (grades 1 and 2) Lymphocyte-rich classical Hodgkin's lymphoma Mixed cellularity Hodgkin's lymphoma Lymphocyte depletion Hodgkin's lymphoma

Pediatric Follicular Lymphoma Rare lymphoma subtype in children (1-2%) 60% present in head and neck Tonsils, nasopharynx Other sites: lymph nodes, GI tract, testis Many differences with FL in adults Usually Grade II-III Bcl-2 usually negative (both protein & bcl-2R) Male: Female ratio 3:1 85% present with Stage I or II disease 75% CR with low relapse rate

LBCL BL Children LBCL BL Adults

Burkitt-like lymphoma should exist? Burkitt-like lymphoma should be included in: Diffuse large B cell lymphoma or Morphologic variant of Burkitt lymphoma

Burkitt and Burkitt-like Lymphomas May show follicular colonization Cytologically tumor cells resemble the small blasts of the dark zone of the GC High rate of somatic mutations of Ig VH BCL-6+, CD 10+ Evidence favors a germinal center derivation

Burkitt-like Lymphomas Similar to BL, but with greater variation in nuclear morphology MIB-1 100%, CD10 +, bcl-2 - Cytogenetics or molecular genetics desirable for diagnosis - should have a c-myc translocation This morphologic variant more common in immunodeficiency states

In the WHO classification The term “Burkitt-like lymphoma” is retained Burkitt-like lymphoma will be considered a variant of Burkitt lymphoma Intermediate morphology C-myc translocations High proliferative fraction Major criteria:

BURKITT LYMPHOMA Morphologic Variants Classical Burkitt lymphoma Atypical Burkitt/ Burkitt- like With plasmacytoid differentiation (HIV -associated) Subtypes, clinical genetic Endemic Sporadic Immunodeficiency-associated

Anaplastic Large Cell Lymphoma Paradigm for process used to define disease entities (REAL) First recognized based on Morphology - sinusoidal growth Antigenic phenotype - CD30+ Studies of molecular pathogenesis led to new diagnostic tools RT-PCR and ALK-1 monoclonal antibody New diagnostic tools define the borderlands of the disease

Anaplastic Large Cell Lymphoma Clinical Features Presents most commonly in lymph nodes Cutaneous involvement variable Most common in children, young adults Frequent presence of systemic symptoms “B” symptoms or high IPI less often predict poor outcome (in contrast to most other NHL) Aggressive natural history but good response to chemotherapy

DISTRIBUTION OF ANAPLASTIC LARGE CELL LYMPHOMA BY AGE (267 cases) Sex Ratio= 1.34 Number of cases Age

Survival of 154 patients with ALCL 100 ALK+ (n=132) Survival 75 ALK - (n=22) p<0.001 50 25 60 120 180 240 Months

Clinical Significance of ALK + in Anaplastic Large Cell Lymphoma ALK+ cases are seen in younger age groups Children and young adults; M>>F ALK+ cases have better prognostic than ALK-, irrespective of other clinical features; i.e. age, stage or IPI Conclusion: ALK+ ALCL is probably a distinct disease entity, separate from ALK- ALCL