Hamartomatous Polyposis Syndromes - Peutz-Jeghers Syndrome (PJS), Juvenile Polyposis Syndrome (JPS), Cowden Syndrome (CS), Cronkhite-Canada (CC), Tuberous Sclerosis (TS) Peutz-Jeghers Syndrome (PJS): - "Spots + Hamartomas + GI Cancer + Uterine, Breast and Pancreas + Sex Cord Tumor → PJS" - Autosomal Dominant I STKII Gene Mutation - Classic mucocutaneous pigmentation, spots cross vermillion border on lips - Hamartomatous polyps throughout GI Tract - Genetic testing if FHx, ≥ 2 GI hamartomatous polyps, and/or pigmentation - Sx 2nd/3rd decade 2/2 large polyps bleeding/obstructing/intussusception - Histologically distinct hamartomatous polyps → Arborizing pattern w/ muscularis mucosa extending into branching fronds I "Pseudo-invasion" from epithelial infolding → Polyp epithelium from site of removal → Adenoma and cancer can occur in polyps Juvenile Polyposis Syndrome (JPS): - "Juvenile Polyps + CRC + Gastric CA JPS" - Autosomal Dominant I Mutation in SMAD4 (aka MADH4) or BMPR1A gene → Tumor suppressor gene in TGF-ß family - Criteria: >5 Juvenile colon polyps, juvenile polyps outside the colon, or FHx of JPS + Juvenile polyp - Small to >3cm polyps, Proximal>Distal, in 1st decade (dozens to 100s): Smooth, reddish, w/ white exudate, w/o fissures/lobulations - Histo: Epithelium from site of removal, abundant lamina propria w/ benign elongated cystically dilated glands | lack smooth muscle core - Sx 1st/2nd decade 2/2 large polyps bleeding/obstructing/intussusception Cowden Syndrome (CS): - "Varied polyps + PTEN + Trichilemmomas" - PTEN gene mutation - Colon polyps in 95%, throughout colon → Likely risk of CRC - Varied polyp types - Esophagus: Diffuse glycogenic acanthosis - Stomach/Small bowel: Hamartomatous - can be a/w autism, MR - Trichilemmomas (bumpy skin lesion) - Variant: Bannayan-Riley-Ruvalcaba: PTEN + Hamartomatous polyps + subcutaneous lipomas + macrocephaly +hemangioma Cronkhite-Canada (CC): - Non-inherited I GI Hamartomas + Nail Abnl + Hair Loss + Protein Losing Enteropathy Tuberous Sclerosis (TS): - AD, GI hamartomas, many organ system involvement by Dean Ehrlich MD @DeanEhrlich_MD #Hamartomatous #Polyposis #Syndromes #diagnosis #management #gastroenterology
