Neoplastic intestinal disorders Flashcards
Intraluminal projections of mucosa that are formed of a non-neoplastic mixture of inflammatory cells, stromal and epithelial components
Inflammatory polyp
Microscopy of a polyp shows inflamed granulation tissue with mixed inflammatory infiltrates, erosion, and epithelial hyperplasia.
Inflammatory polyp
Polyp formed by piling up of goblet and absorptive cells from decreased epithelial turnover and delayed shedding of surface epithelial cells
Hyperplastic polyp
Polyp formed by piling up of goblet and absorptive cells from being adjacent to or overlying any mass or inflammatory lesion
Hyperplastic polyp
Chief significance of hyperplastic polyps
Must be distinguished from sessile serrated adenomas
Smooth, nodular protrusion of the L colonic mucosa, often on the crests of mucosal folds. Microscopy shows mature goblet and absorptive cells with serrated surface.
Hyperplastic polyp
Premalignant polyp caused by germline mutations in tumor suppressor genes or proto-oncogenes. Associated with extraintestinal manifestations
Hamartomatous polyp
Polyp type of juvenile polyposis
Hamatomatous polyp
Inheritance of juvenile polyposis
Autosomal dominant
Treatment of juvenile polyposis
Colectomy –> limit hemorrhage
Extraintestinal manifestations related to hamartomatous polyps
Pulmonary AVMs
Other congenital manifestations
Mutations seen <50% of pts with hamartomatous polyps
SMAD4
BMPR1A
Gene mutation associated with both juvenile polyposis and hereditary hemorrhagic telangiectasia
SMAD4
<3 cm reddish polyp, typically pedunculated with a smooth surface. Cystic spaces are characteristic.
Hamartomatous polyp
Microscopy of colon polyp shows normal or attenuated muscularis mucosae, lamina propria expanded by mixed inflammatory infiltrates, and cystically dilated crypts filled with mucin and inflammatory debris.
Hamartomatous polyp
Precursors to colorectal adenocarcinomas
Colonic adenomas
Small, pedunculated polyps composed of rounded glands. Mucosal surface is smooth, appearing white or red.
Tubular adenoma
White granular mucosa distinct form the normal mucosa on a small sessile polyp with mixed architecture.
Serpentine appearance of tubulovillous adenoma
Larger and sessile colonic polyp covered by slender villi. Diffuse nodular appearance.
Villous adenoma
Conditions associated with villous adenomatous polyp
Hypoproteinemia
Secretory diarrhea
Hypokalemia
Most important characteristic of adenomatous polyps that correlates with malignancy
Size
Microscopy of polyp found in the R colon shows serrated architecture through the full length of the glands, including the crypt base, crypt dilation, and lateral crypt growth
Sessile serrated adenoma
Inheritance of Peutz-Jeghers syndrome
Autosomal dominant
Hereditary syndrome characterized by multiple GI hamartomatous polyps and mucocutaneous hyperpigmentation. Associated with a markedly increased risk of several malignancies throughout childhood and adulthood. Commonly presents between 10-15 yo.
Peutz-Jeghers syndrome
Tumor that can be present at birth in Peutz-Jeghers syndromes
Sex cord tumors of the testes
Mutation found in most cases of Peutz-Jeghers syndrome
Loss of function mutation in STK11
Most common location of polyps in Peutz-Jeghers syndromes
Small intestine
Syndrome associated with arborizing network microscopy of polyp
Peutz-Jeghers
Mutation in Cowden syndrome
PTEN –> PI3K/AKT pathway
Hereditary syndrome associated with hamartomatous and inflammatory intestinal polyps, lipomas, and ganglioneuromas. Mean age of presentation <15 yo
Cowden syndrome
Standard of care for familial adenomatous polyposis
Prophylactic colectomy
Common extracolonic sites for neoplasia in familial adenomatous polyposis
Ampulla of Vater
Stomach
Congenital hypertrophy of the retinal pigment epithelium is associated with what hereditary syndrome
Familial adenomatous polyposis
Gene mutations associated with familial adenomatous polyposis
APC
MUTYH
Mean age of presentation in classic FAP
10-15 yo
Mean age of presentation in attenuated FAP
40-50 yo
Mean age of presentation in Gardner syndrome and Turcot syndrome
10-15 yo
Mean age of presentation in MUTYH associated polyposis
30-50 yo
Extra-GI manifestations in Gardner syndrome
Osteomas
Thyroid and desmoid tumors
Skin cysts
Extra-GI manifestations in Turcot syndrome
Medulloblastoma
Glioblastoma
Gene associated with autosomal dominant FAP
APC
Most common mutations in hereditary non-polyposis colorectal carcinoma
MSH2
MLH1
Inheritance of hereditary non-polyposis colorectal carcinoma
Autosomal dominant
Hereditary cancer syndrome associated with consequences in mismatch repair deficiency and resulting microsatellite insufficiency.
Lynch syndrome
Pharmacologic chemoprevention of colorectal adenocarcinoma
COX-2 inhibitors
Most common maligancy of GI tract
Colorectal adenocarcinoma
Stepwise accumulation of multiple mutations in colorectal adenocarcinoma
APC –> beta-catenin –> KRAS –> TP53, LOH, and SMAD
Mutation in TGFBR2 results in what?
Uncontrolled cell growth
How to identify microsatellite instability?
Absence of immunohistochemical staining for mismatch repair proteins
Molecular genetic analysis of microsatellite sequences
Colorectal adenocarcinoma that produces abundant mucin is associated with what prognosis?
Poor
Dysplastic epithelial cells breach the basement membrane to invade the lamina propria. May extend into, but not through the muscularis mucosa. Complete polypectomy is generally curative and there is little metastatic potential.
Intramucosal carcinoma
