A 52-year-old man with a prior follicular lymphoma now presents with rapidly growing lymphadenopathy, LDH of 1,800 U/L and B symptoms. New biopsy shows diffuse large B-cell lymphoma morphology. FISH reveals concurrent rearrangements of MYC and BCL2. What is the WHO 5th edition (2022) classification of this entity, and how does it alter clinical management compared to conventional DLBCL?
- A This is Grade 3B follicular lymphoma transformed to DLBCL; treated identically to de novo DLBCL with R-CHOP
- B High-grade B-cell lymphoma with MYC and BCL2/BCL6 rearrangements (double-hit/triple-hit); classified separately in WHO 2022 and treated with intensified regimens (DA-EPOCH-R) rather than standard R-CHOP due to inferior outcomes with R-CHOP alone ✓
- C Primary mediastinal B-cell lymphoma with secondary MYC amplification; managed with consolidation radiation after R-CHOP
- D Plasmablastic lymphoma with MYC rearrangement; managed with EPOCH-based regimen plus antiretroviral therapy if HIV-positive
Explanation
WHO 2022 (5th edition) classifies high-grade B-cell lymphoma with MYC and BCL2 rearrangements (and/or BCL6) as a distinct entity — the 'double-hit' (or 'triple-hit') lymphoma — separate from DLBCL NOS. These tumors co-overexpress MYC-driven proliferation and BCL2-driven apoptotic resistance, creating a uniquely aggressive biology. Standard R-CHOP is inadequate (PFS ~40% at 2 years). Most centers use intensified regimens such as DA-EPOCH-R or R-CODOX-M/IVAC. The context of transformation from follicular lymphoma is consistent with Richter-like transformation and characteristically involves acquisition of MYC rearrangement.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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