A 55-year-old man undergoes colonoscopy for rectal bleeding and is found to have a 4 cm polypoid lesion in the sigmoid colon. Histology shows malignant glands invading through the muscularis mucosae into the submucosa. Molecular analysis reveals microsatellite instability. This feature is associated with which hereditary syndrome?

• A Familial adenomatous polyposis (FAP)
• B Lynch syndrome (HNPCC) ✓
• C Peutz-Jeghers syndrome
• D MUTYH-associated polyposis

Explanation

Lynch syndrome (HNPCC) is caused by germline mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2), leading to microsatellite instability (MSI-H) due to the inability to correct replication errors in repetitive DNA sequences. MSI testing is a standard screening tool for Lynch syndrome. In contrast, FAP is driven by APC mutation and chromosomal instability, not microsatellite instability, and presents with hundreds to thousands of adenomatous polyps.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.