POLYP / SYNDROME
GENETICS · MECHANISM
FEATURES
CANCER RISK · CLUE
Hyperplastic polyp
most common non-neoplastic
Delayed shedding of surface epithelium
Small, rectosigmoid; serrated ("sawtooth") crypts on surface
Essentially none
BRAF mutation, CpG island hypermethylation (CIMP) → MLH1 silencing
Flat, right colon; serration extends to crypt base
Precancerous via the serrated / MSI pathway
APC loss → KRAS → TP53 (adenoma-carcinoma sequence)
Small, pedunculated; tubular glands
Lowest-risk adenoma
Same pathway
Large, sessile, "cauliflower"; may secrete mucus → watery diarrhea, hypokalemia
Highest-risk adenoma (size > 1 cm, villous, high-grade dysplasia)
Regenerating mucosa between ulcers
IBD, especially UC
Not neoplastic itself
Juvenile polyp · juvenile polyposis
Sporadic hamartoma; syndrome: SMAD4 or BMPR1A (AD)
Child < 5 with painless rectal bleeding; may prolapse
Single polyp: none · syndrome (many polyps): ↑ CRC
STK11 (LKB1), autosomal dominant
Hamartomatous polyps throughout the GI tract (intussusception); mucocutaneous hyperpigmentation of lips, mouth, hands, genitalia
↑ colorectal, breast, pancreatic, gastric, ovarian/testicular cancers
Familial adenomatous polyposis
APC on chr 5q, AD; 2-hit
Hundreds to thousands of adenomas from adolescence; CHRPE (retinal pigment lesions)
~100% CRC by ~40 → prophylactic colectomy · duodenal adenomas
FAP variant (APC)
Polyposis + osteomas (skull, mandible), supernumerary teeth, desmoid tumors, epidermoid cysts, fibromas
Same colon risk as FAP
APC or mismatch-repair genes
Polyposis + CNS tumor: medulloblastoma (APC) or glioblastoma (MMR)
"Turcot = Turban" (brain)
MUTYH-associated polyposis
Autosomal recessive base-excision repair defect (G:C → T:A)
Tens to hundreds of adenomas, often later onset
Siblings affected, parents not
PTEN, AD
Hamartomatous GI polyps, trichilemmomas, macrocephaly
↑ breast, thyroid (follicular), endometrial cancer