A 70-year-old male with CLL develops rapid lymph node enlargement, B symptoms, and elevated LDH. Biopsy reveals transformation to diffuse large B-cell lymphoma. This transformation carries a particularly poor prognosis. The risk of this complication is highest in CLL cases with which molecular feature?

• A Del(13q14) as the sole cytogenetic abnormality
• B Trisomy 12 with mutated IGHV genes
• C Del(11q22-23) involving ATM with mutated IGHV
• D Unmutated IGHV with complex karyotype and TP53 disruption ✓

Explanation

Richter transformation (RT) from CLL to DLBCL occurs in 2–8% of CLL patients and carries a median survival of under 12 months. RT risk is highest with unmutated IGHV (somatic hypermutation absent, indicating germinal center non-participation), complex karyotype (≥3 abnormalities), TP53 deletion/mutation (del17p), and NOTCH1 mutations. Del(13q14) as the sole abnormality confers the best prognosis in CLL; trisomy 12 is intermediate; del(11q) without TP53 disruption is intermediate-risk.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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