Double-Hit Lymphoma with MYC and BCL2 rearrangements

Epidemiology and Etiology:

• Elderly (median 51-65y)
• Extremely rare < 18y
• 2-8% in unselected series of DLBCL
• 4% in Vancouver series of 1260 DLBCL
• Prior history of indolent lymphoma in a minority
• 43% (23 FL, 1 CLL)

Common sites:

Gross features:

• Advanced stage (majority)
• Extranodal involvement
• BM and/or PB (59%)
• CNS (9-50%)
• Pleural effusions (commonly)

Histologic features:

Immunophenotype:

Marker:	Sensitivity:	Specificity:
BCL2	95%
CD10	88%
BCL6	75%
MUM1/IRF4 (neg)	83%
MIB1 (range 50-100%, median 90%)

Molecular features:

• MYC translocation:
• 66% of cases in Mitelman have an IG gene partner (compare to 98% in BL)
• 49% of those cases with MYC-IG rearrangement are with IGK or IGL (compare to 18% in BL)
• t(8;9)(q24;p13) (PAX5) most common non-IG partner
• other non-IG partners:
• 1p36
• 3p25
• 3q27 (BCL6)
• 4p13
• 5q13
• 12p11
• 13q31
• Complex karyotype
• Multiple alterations in addition to the BCL2 and MYC translocations in almost all cases in Vancouver series

Other features:

• Elevated LDH (majority)
• High IPI risk profile (3 or 4/5)
• Poor prognosis:
• Median OS 0.2-1.5 years
• For a small series of B-ALLs, median survival 2.8 months
• In Mitelman database:
• ~30% are mature B cell neoplasm, NOS
• ~15% are FL
• But all studies showed deficits in histology or clinical follow-up
• Associated with blastic/blastoid morphology
• ~35% are DLBCL (some of these may be “Burkitt-like lymphoma” as diagnosed in the past)
• ~15% are BL
• ~3% were lymphoblastic lymphoma/leukemia
• But many are incompletely documented without data on expression of TdT or CD34

References:

• Blood (2011);117(8):2319-2331
• Cancer Genetics and Cytogenetics 171 (2006) 52e56
• BLOOD (2009) VOLUME 114, NUMBER 11:2273-2279.