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Lynch Syndrome — RACP Adult Medicine MCQ

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ModerateGeneral Internal MedicineLynch SyndromeRACP Adult Medicine

A 55-year-old man is being assessed for hereditary cancer risk. He has a personal history of colon cancer at age 45, endometrial cancer in his sister at age 48, and ovarian cancer in his mother at age 52. Immunohistochemistry of his colon cancer shows loss of MLH1 and PMS2 staining. What is the most likely underlying syndrome?

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Correct answer: E — Li-Fraumeni syndrome

Lynch syndrome (HNPCC) is an autosomal dominant condition caused by germline mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2). It accounts for ~3% of all colorectal cancers. The characteristic feature is loss of MMR protein staining on IHC (in this case MLH1/PMS2 – paired loss as PMS2 is the obligate partner of MLH1). Lynch syndrome increases the risk of colorectal, endometrial, ovarian, gastric, urological, and other cancers. All CRC patients should undergo universal MMR IHC/MSI testing (regardless of age or family history). Surveillance includes colonoscopy every 2 years from age 25.

Reference: Cancer Council Australia – 2019 – Hereditary CRC Guidelines; eviQ – 2024 – Lynch Syndrome