Chapter 36, Ep 4 of 5: Hamartomatous Polyposis and Diffuse Gastric Cancer

Episode four moves from adenoma to hamartoma, where the dominant risk shifts away from colorectal cancer. STK11 drives Peutz-Jeghers, and the resection threshold is calibrated to intussusception rather than cancer, so any small bowel polyp over one centimeter comes out. PTEN drives Cowden, where the cancer burden tracks baseline PI3K signaling into breast and thyroid and the GI role is recognition through mixed-histology polyposis. CDH1 flips the algorithm hardest: multifocal submucosal signet-ring disease beneath intact mucosa makes endoscopy unreliable, so prophylactic total gastrectomy between twenty and thirty is the standard of care. The thread is constant, the gene dictates the histology, the histology dictates the natural history, and the natural history dictates whether the answer is surveillance, polyp-by-polyp resection, or removal of the organ.   Topics covered Peutz-Jeghers, STK11, and buccal pigmentation Arborizing hamartomas and intussusception risk Small bowel resection thresholds Peutz-Jeghers multi-organ cancer surveillance PTEN hamartoma spectrum and Cowden Hereditary diffuse gastric cancer and CDH1 Prophylactic total gastrectomy The Cambridge surveillance protocol GAPPS as the HDGC differential   Key decisions Resect any Peutz-Jeghers small bowel polyp greater than one centimeter, any symptomatic polyp regardless of size, and any polyp showing rapid growth, because growth velocity predicts intussusception better than absolute size. Start Peutz-Jeghers surveillance young with baseline EGD and colonoscopy at age eight to ten plus small bowel capsule or MR enterography, avoiding CT enterography because of cumulative radiation across decades. Enroll STK11 carriers in pancreatic surveillance on the gene alone, unlike BRCA, ATM, PALB2, and Lynch, because STK11 lifetime pancreatic risk clears the absolute-risk threshold without a family-history modifier. Read Cowden as a breast and thyroid syndrome, with annual thyroid ultrasound from diagnosis, breast MRI and mammography from the early thirties, and no prophylactic thyroidectomy because the cancers are follicular and papillary rather than medullary. Recommend prophylactic total gastrectomy with Roux-en-Y reconstruction between ages twenty and thirty for confirmed CDH1 carriers, because random biopsy misses multifocal submucosal signet-ring foci that sit beneath grossly intact mucosa. Offer the Cambridge protocol of annual EGD with thirty to fifty random biopsies only as a fallback for CDH1 carriers awaiting or declining surgery, counseling explicitly that surveillance failure is documented despite rigorous adherence. Add annual breast MRI plus mammography from age thirty for female CDH1 carriers, because lobular breast cancer risk reaches forty to fifty-five percent and mammography detects it less reliably.   For the full chapter with MCQs, tables, and primary-guideline references, visit www.boardpearls.com. Questions or feedback: [email protected]. (00:00) - Peutz-Jeghers, STK11, and buccal pigmentation (02:05) - Arborizing hamartomas and intussusception (03:03) - The small bowel resection threshold (04:36) - Multi-organ cancer surveillance (05:33) - The recognition cancers to memorize (06:57) - The PTEN spectrum and Cowden (10:56) - CDH1 and hereditary diffuse gastric cancer (13:00) - The Cambridge surveillance fallback (14:56) - GAPPS as the differential