2. Special Problems in B-Cell Lymphomas
• Burkitt lymphoma in adults
Perkins AS, Friedberg JW, Rochestor U, NY
• Primary mediastinal B-cell lymphoma
Johnson PWM, Davies AJ, U Southampton, UK
• Marginal zone lymphomas
Kahl B, Yang D, U Wisconsin
3. Burkitt Lymphoma: Diagnostic Features
• High rate of proliferation (Ki-67 > 95%)
• Activation of MYC gene at 8q24 (Giemsa
banding or FISH)
• Relative simplicity of karyotype
• No cleaves or folds in nuclear contour
• Lack of Tdt positivity
4. Key Clinical Features
• Bulky abdominal mass, B symptoms,
laboratory evidence of tumor lysis
• 70% bone marrow involvement
• 40% leptomeningeal involvement
5. Treatment
• Intensive, short duration chemotherapy
(high-dose alkylating agents, CNS
prophylaxis)
• ALL-like regimen
• Therapy included consolidation with auto-
SCT
6. OS According to Age
All cases > 40 yrs
• CODOX-M/IVAC 71% 39%
• ALL-like 51% 40%
• Hyper-CVAD 57% 17% (> 60 yrs)
89% (rituximab-
based)
7. Conclusion
• A highly curable malignancy
• Inferior outcome in patients age > 40
years
• Important to differentiate from “atypical
Burkitt”
8. Primary Mediastinal B-Cell Lymphoma
• Median age 37 years
• Stage I/II 74%
• Elevated LDH 77%
• Bulk (>10 cm) 75%
• Pleural or pericardial 50%
effusion
9. Treatment
• Role of third generation regimen
• Role of rituximab
• Consolidating radiotherapy
• How to evaluate residual mass?
• Role of HDT
10. Role of Third Generation Regimen
• Three large retrospective (one population-
based) studies showed superior OS for
MACOP-B, VACOP-B compared to CHOP
(70% vs 50%, p < 0.05)
11. Role of Rituximab
• Addition of rituximab to dose-adjusted
EPOCH (n = 44) was associated with
favorable EFS and OS (87% and 93%, p <
0.05)
• Retrospective population-based study did
not showed superiority of R-CHOP over 3rd
generation regimen
12. Consolidating Radiotherapy
• Mediastinal radiotherapy is essential in
patients achieving PR after initial
chemotherapy (increased CR rate from
42% to 95%)
• Role in patients with CR is questionable in
particular those treated with rituximab-
based regimen
13. How to Evaluate Residual Mass?
• FDG-PET is the tool of choice
• All patients with positive PET relapsed
compared to 26% in patients with negative
PET
• Gallium scan is less expensive but time-
consuming and low spatial resolution
14. Role of HDT
• No role in patients with first CR
• In chemosensitive relapse and refractory
disease, the long-term OS were 40-70%
and 50-60%, respectively
15. Nodal MZL
• Median age 60 years
• Male : female 1:1
• Present in advanced stage with non-bulky
widespread lymphadenopathy
• 1/3 had bone marrow involvement
16. Nodal MZL
• Clinical course resembled other nodal
indolent lymphomas
• Prognosis less favourable compared to
MALT, splenic MZL and FL. Roughly
comparable to SLL.
• 16% transformed to large-cell in 4.5 years
• Apply same treatment approach as FL
17. Splenic MZL
• Present with moderate to massive
splenomegaly
• Cytopenias due to splenic sequestration
(main factor) and marrow involvement
• Best diagnostic tool is bone marrow
examination
• Differentiate with HCL by showing
negative staining to CD25 and CD103
18. Splenic MZL
• Splenectomy is the treatment of choice
• In asymptomatic patients using watch and
wait policy, median time to treatment is 3
years
• Systemic chemotherapy (favored purine
analogues) is indicated in patients
contraindication to splenectomy or had
heavy burden of disease outside spleen
19. Splenic MZL
• 5-year OS 76%
• Three adverse poor prognostic factors:
hemoglobin < 12 g/dl, serum albumin <
3.5 g/dl and LDH > ULN
20. Gastric MALT Lymphomas
• Comprised 30% of all MALT lymphomas
• Endoscopy showed erythema, erosions,
ulceration. Masses are uncommon.
• Establish H. pylori status is essential (histologic
examination, biopsy urease test, urea breath
test, stool antigen test and selorogy).
• 90% of patients had H. pylori infection
• t(11;18) evaluation by FISH
21. Treatment
• 75% of stage IE patients with H. pylori infection
and without t(11;18) will respond to H. pylori
eradication
• Response is quite slow. Complete response is
established in one year.
• Repeat endoscopy every 3-6 months until
normalization of gastric mucosa then annually
• Routine biopsy of normal appearing mucosa is
not recommended
22.
23. Treatment
• Low-dose radiotherapy is indicated in
patients with H-pylori negative or failure to
H. pylori eradication (100% OS)
• Patients with advanced disease were
treated with the same principle as patients
with advanced stage FL
24. Non-gastric MALT Lymphomas
• Comprised 70% of all MALT lymphomas
• Association with infectious agents
- B burgdorfi: cutaneous MALT lymphoma
- C psittaci: conjunctival MALT lymphoma
- C jejuni: IPSID
• Frequency of associations and role of
antimicrobial therapy are still under
investigations
29. Addition of Etoposide to CHOP/CHOP-
Like Regimen
• CHOEP vs CHOP : EFS 71% vs 50% (p
=.01)(GNHLG)
• VIP/ABVD vs CHOP : no difference in OS
and EFS (GOELAMS)
30. Subtype-Specific Therapies
• Cutaneous ALCL: local excision with or
without radiotherapy
• ALK pos ALCL : CHOP
• Localized NK/T lymphoma, nasal type:
- primary radiotherapy is the principal
treatment. Chemotherapy provide
additional benefit?
- Initial RT vs initial CT : CR 83% vs 20%
(Li et al, JCO 2006)
31. Conclusions
• Outcome is unsatisfactory with CHOP
• Therapies should be tailored according to
the subtypes
• Large well-designed RCTs coorporating
novel therapies are urgently needed.
32. WHO 2008
B-Cell Lymphomas (New Addition)
• Primary cutaneous follicle center cell lymphoma
• DLBCL, NOS
- T-cell/histiocyte rich large B-cell lymphoma
- Primary DLBCL of CNS
- Primary cutaneous DLBCL, leg type
• DLBCL of chronic inflammation
• ALK-pos large B-cell lymphoma
• Plasmablastic lymphoma
• Large B-cell lymphoma associated with Castleman
disease
• B-cell lymphoma, intermediate beteween DLBCL and BL
• B-cell lymphoma, intermediate beteween DLBCL and HL
34. DLBCL of Chronic Inflammation
• Long standing chronic inflammation
• Associated with EBV infection
• Involve narrow space, body cavities
• Prototype : pyothorax-ass-lymphoma.
• Poor pg, 5-yr OS 25-30%
35. Hydroa Vacciniiforme-Like Lymphoma
• Children/adolescence of Asian, Native
Americans, South Americans
• Associated with EBV
• Associated with insect bites, sun
sensitivity
