A 68-year-old man with plasma cell myeloma undergoes cytogenetic workup. FISH shows del(17p13.1) with loss of TP53 and translocation t(4;14)(p16;q32). Which prognostic risk group does this combination confer per the Revised International Staging System (R-ISS)?
- A R-ISS Stage III — high risk ✓
- B R-ISS Stage I — standard risk
- C R-ISS Stage II — intermediate risk
- D Cannot be classified without FISH for del(1p) status
Correct answer: A. R-ISS Stage III — high risk
Explanation
The R-ISS defines Stage III myeloma by ISS stage III (high serum beta-2-microglobulin and low albumin) OR presence of high-risk cytogenetics: del(17p), t(4;14), or t(14;16). This patient has both del(17p13.1) — which eliminates one TP53 allele — and t(4;14), which dysregulates FGFR3 and NSD2 (MMSET). The combination of two high-risk cytogenetic lesions virtually assures R-ISS Stage III. del(1p) is an additional risk factor used in more refined scores but is not required for R-ISS.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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