A 67-year-old man has serum protein electrophoresis showing an M-spike of 4.2 g/dL (IgG kappa), bone marrow biopsy with 38% plasma cells, serum free light chain ratio of 320, and lytic bone lesions on whole-body PET-CT. Revised ISS (R-ISS) staging is used in myeloma. Which combination correctly identifies Stage III R-ISS?
- A ISS Stage II + t(4;14) alone
- B Serum β2-microglobulin > 5.5 mg/L regardless of cytogenetics
- C ISS Stage III + high-risk cytogenetics (del 17p, t(4;14), t(14;16)) OR high LDH ✓
- D ISS Stage III + standard-risk cytogenetics + normal LDH
Correct answer: C. ISS Stage III + high-risk cytogenetics (del 17p, t(4;14), t(14;16)) OR high LDH
Explanation
R-ISS (Revised International Staging System, Palumbo et al. JCO 2015) incorporates ISS stage, cytogenetics, and LDH. R-ISS Stage III = ISS Stage III (β2-M ≥ 5.5 mg/L + albumin < 3.5 g/dL) AND [high-risk cytogenetics: del(17p), t(4;14), or t(14;16)] OR high serum LDH. R-ISS Stage I = ISS I + standard-risk cytogenetics + normal LDH. R-ISS Stage II = neither I nor III. An ISS Stage III patient with standard-risk cytogenetics and normal LDH is R-ISS Stage II, not III.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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