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