GI polyps and carcinoma Flashcards
Define polyp
morbid excrescence
Sessile vs pedunculated polyp
Sessile: mass without a stalk. Pedunculated: mass with a stalk
architecture of polyps
tubular ( no villi, tubular structures) and villous (long villi projections)
adenoma
precursor to malignancy
adenocarcinoma
invasive
What does it mean that non-neoplastic polyps are usually syndromic
They are associated with a genetic syndrome that overall predisposes to cancer development
List types of non-neoplastic polyps
inflammatory polyps, hamartomatous polyps and hyperplastic polyps
presentation and cause of inflammatory polyps
Often present with bleeding. Often due to mucosal prolapse (very common in the rectum). Cycles of injury and healing result in “polyp” formation = inflamed colonic mucosa with ulceration/erosion, epithelial hyperplasia
What are hamartomatous polyps
Childhood “tumor-like” over-growth / mature tissue / developing where it is normally present (e.g. colonic tissue developing in the colon). Types: juvenile (sporadic and syndromic), Cowden (syndromic), Bannayan-Ruvalcaba-Riley (syndromic), Cronkhite-Canada (syndromic) and Peutz-Jeghers (syndromic)
Where do polyps occur
variable locations in lower GI tract
Juvenile polyp histology
Cystically dilated crypts, surface erosion. syndromic juvenile polyps often have foci of dysplasia
Peutz-Jeghers polyps histology
complex glandular architecture separated by increased smooth muscle bundles
Polyps clinical consequences
risk of future GI carcinoma and extra-GI manifestations
Peutz-Jeghers syndrome mean age, genes, GI lesions, extra-GI manifestations (not on test)
10-15yrs, LKB1/STK11 genes, causes arborizing hamartomatous polyps (Small intestine > colon > stomach) and colonic adenocarcinoma. Extra GI: mucocutaneous pigmented lesions and increased risk of other cancers
Juvenile polyposis mean age, genes, GI lesions, extra-GI manifestations (not on test)
<5 years, SMAD4/BMPR1A genes, juvenile hamartomatous polyps with risk of gastric, small intestinal, colonic, and pancreatic adenocarcinoma. Extra GI: Pulmonary arteriovenous malformations, digital clubbing
Cowden syndrome, Bannayan-Ruvalcaba-Riley syndrome mean age, genes, GI lesions, extra-GI manifestations (not on test)
<15 yrs, PTEN gene, Hamartomatous polyps, lipomas, ganglioneuromas, inflammatory polyps, risk of colon cancer. Extra GI: Benign skin tumors, benign and malignant thyroid and breast lesions
Cronkhite-Canada syndrome mean age, genes, GI lesions, extra-GI manifestations (not on test)
> 50 yrs, no known genes, Hamartomatous colon polyps, crypt dilatation and edema in nonpolypoid mucosa. Extra GI: Nail atrophy, hair loss, abnormal skin pigmentation, cachexia, and anemia
For hyperplastic polyps: list location, age, size, histology, dysplasa
Left colon including rectum, increases with age, small (<0.5cm), Delayed maturation with overgrowth of superficial epithelium (absorptive and goblet cells) resulting in SERRATED architecture and sessile nodule, NO dysplasia
Compare the two common types of serrated polyps
Hyperplastic polyps are not pre-malignant, left side of colon, crypts are star shaped. Sessile serrated polyps/adenoma are pre malignant and dysplastic, right side of colon
What characteristic is most important in risk of adenoma malignancy
size! Larger size means larger risk of malignancy.
villous vs tubular adenomas risk of malignancy
Villous adenomas contain foci of invasion more frequently than tubular adenomas
What are adenomatous/dysplastic changes
Increased number of cells piling up on each other, Loss of basal-orientation of nucleus and darker nuclei, Reduced mucin production and reduced cytoplasm, Increased mitotic activity
What is high grade dysplasia called
carcinoma in situ
Describe tubular adenoma
has stalk and tubular appearance
Describe villous adenoma
sessile (no stalk), villi with fibrovascular core,
Risk factors for colorectal cancer
age, long standing ulcerative colitis, FAP/HNPCC, red meat, alcohol, smoking,
Are most colorectal cancers spontaneous or familial
sporadic
What are the main molecular pathways in adenoma-carcinoma sequence
classical: WNT/APC/ beta-catenin. Microsatellite instability: defects in mismatch repair. K-Ras/MAP kinase/ P13 kinase signaling
Describe WNT pathway
in resting cells, Beta catenin binds APC forming destruction complex, and beta catenin is destroyed. When WNT binds its receptor, the destruction complex is deactivated so intracellular beta catenin levels rise. Beta catenin goes to nucleus and binds TCF transcription factor which turns on cell cycle genes and causes proliferation
How do APC mutations affect cell proliferation
When APC is mutated, destruction of Beta catenin doesn’t occur, so cell proliferation occurs continuously
Polyps cell proliferation
There is no increase in the rate of cell proliferation in the early stage of polyp formation. Polyps represent An increase in the size of the proliferating crypt compartment
Which gene is most commonly mutated in colon cancer
APC
What is familial adenomatous polyposis
autosomal dominant APC mutations - incrased risk of colon cancer and lots of polyps. 100% develop invasive adenocarcinoma before age 30
Describe K-Ras/MAPK/P13K signaling
EGFR > Ras >Raf > MEK1/2 > MAPK leads to cellular proliferation. P13K activates a signaling molecule that inhibits Raf and leads to cell survival
Cetuximab MOA
Blocks P13K leading to cell death, and blocks Ras leading to stopped cell proliferation
What is Lynch syndrome
Hereditary Non-Polyposis Colorectal Cancer - develop cancer at earlier age than sporadic types. Tends to be right sided. Due to inherited mutation of mismatch repair gene allele, then acquire second allele mutation over time leading to microsatellite instability
Which colon cancers feature high rates of mismatch repair mutations
hereditary non-polyposis colorectal cancer and sporadic cancers
symptoms of early vs advanced colon carcinoma
early: no symptoms or fatigue, weight loss, anemia. Advanced: constipation, urgency, narrowing of stool, cramping/pain, blood loss, weight loss
Colon cancer detection
colonscopy, barium enema, blood in stool, DNA/mutations
Define carcinoma
-Invasion of dysplastic epithelial cells into and beyond the lamina propria
Adenocarcinoma histology
invading into muscularis propria, desmoplastic (fibrotic) response, dirty necrosis in lumen of some glands
Where does colon cancer most commonly metastasize to
liver
histology and genetics of sporadic colon cancer
APC mutation- tubular villous adenoma, typical adenocarcinoma. DNA mismatch repair/ MSH2,MLH1 mutations- sessile, serrated adenoma, mucinous adenocarcinoma
Histology and genetics of familial adenomatous polyposis
APC mutations- tubular, villous adenoma, typical adenocarcinoma. DNA mismatch repair/MUTYH mutation- sessile, serrated adenoma, mucinous adenocarcinoma
histology and genetics of hereditary nonpolyposis colorectal cancer
DNA mismatch repair/ MSH2, MLH1 mutations. Sessile serrated adenoma, mucinous adenocarcinoma
