A lymph node biopsy shows effacement of architecture by large cells with prominent nucleoli, brisk mitoses and a high Ki-67 (~90%). IHC: CD10+, BCL6+, BCL2 strong, MUM1 negative, CD5 negative. Which cell-of-origin subtype (Hans classifier) does this immunophenotype represent and what is its prognostic significance?
- A Activated B-cell (ABC) subtype — poorer prognosis due to NF-kB activation
- B Germinal centre B-cell (GCB) subtype — more favourable prognosis with R-CHOP ✓
- C Unclassified subtype — prognosis intermediate between GCB and ABC
- D Double-expressors (DE-DLBCL) — automatically classified as high-grade B-cell lymphoma
Explanation
The Hans classifier uses CD10, BCL6 and MUM1 to assign GCB vs non-GCB (ABC) subtypes. CD10 positive → automatically GCB subtype. GCB-DLBCL has significantly better outcomes with R-CHOP compared to ABC-DLBCL, which relies on constitutive NF-kB activation (often via MYD88/CD79B mutations). Although this tumor is BCL2-strong, BCL2 overexpression without cytogenetic rearrangement defines 'double-expressor' (DE) status (co-expression of MYC ≥40% and BCL2 ≥50%), which carries a worse prognosis within DLBCL NOS but does NOT upgrade the WHO classification to high-grade B-cell lymphoma, which requires confirmed gene rearrangements.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.