1. 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)

2. 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

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

4. 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

5. 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

6. 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

7. 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

8. LBCL BL
Children
LBCL BL
Adults

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

10. 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

11. 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

12. 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:

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

14. 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

15. 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

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

17. 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

18. 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