A 62-year-old woman with familial adenomatous polyposis (FAP) has undergone colectomy with ileal pouch-anal anastomosis (IPAA). Annual surveillance of the pouch reveals a 1.2 cm tubulovillous adenoma in the ileal pouch. The molecular basis for ongoing adenoma formation in the ileal pouch in FAP patients is:
- A De-novo methylation of the APC promoter in ileal epithelium
- B FAP patients have MSI-H in pouch epithelium causing rapid mutations
- C Germline APC mutation causing constitutive Wnt pathway activation in all epithelial cells ✓
- D Bile acid reflux into the ileal pouch triggers somatic KRAS mutations
Correct answer: C. Germline APC mutation causing constitutive Wnt pathway activation in all epithelial cells
Explanation
FAP is caused by germline APC mutations causing constitutive activation of the Wnt/β-catenin signalling pathway in all intestinal epithelial cells throughout the gastrointestinal tract including the ileal pouch. Since the germline mutation is present in every cell, ileal pouch mucosa retains the same adenoma-forming propensity as colonic mucosa. This explains why pouch adenomas develop over time and mandates lifetime endoscopic surveillance of the pouch in FAP patients. Sulindac and celecoxib can partially suppress pouch polyp formation but do not eliminate the risk.
Reference: Bailey & Love's Short Practice of Surgery, 27th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.