Adenomatous polyps

What is the gross appearance of proximal adenocarcinoma?

- Grow into bowel - polypoid, exophytic mass along one edge of the colon - rarely obstructive

What are the clinical features of FAP?

- 100-thousands of polyps - CRC in 100% of untreated patients - Prophylactic colectomy which prevents CRC but does not lower the risk for neoplasias in other areas

Colonic adenomas is present in what percent and are signals for what?

- 50% of adults in west by age 50 - benign but precursors to colorectal adenocarcinomas - Majority do not progress to adenocarcinoma

What mutation is associated w/ Gardner syndrome?

- 5q

What are the 2 major genetic pathways for colonic adenocarcinoma?

- APC/B-catenin pathways associated w/WNT and exhibits classic adenoma-carcinoma path - Microsatellite instability which is associated w/defects in DNA mismatch repair. - BOth involve stepwise accumulations of mutations

What is Gardner syndrome? What types of cancers are you at a higher risk for?

- Familial adematous polyposis - Characterized by sebaceous cysts, osteomas (skull, mandible, long bones) - Risk of THYROID cancer and FIBROMAS as well as COLON carcinoma

What 2 syndromes is FAP associated with?

- Gardner - Turcot

What is the gross appearance of Distal adenocarcinoma?

- Grow into bowel - Napkin ring tumors/annular leading to luminal narrowing and obstruction

What is HEreditary non-polyposis CRC?

- Lynch syndrome - cluster of familial cancers at several sits including the colorectum, endometrium, stomach, ovary, uters, brain, small bowel, hepatobiliary tract, and skin

What is the DNA mismatch repair pathway (4 steps)?

- Microsatellite instability lets mutations accumulate int eh microsatellite repeats - These microsatellite sequences may be in coding or promoter regions of genes for cell growth regulation - TGF-B (uncontroleld cell growth)and pro-apoptic BAX mutation - BRAF oncogene mutation

What is the classic adenoma-carcinoma sequence (7 steps)?

- Mutation of adenomatous polyposis coli tumor suppressor gene (APC) - Adenoma form after each copy of APC gene is inactivated - APC normal function is to help degrade B- catenin of the WNT pathways so w/ no functional copies B-catenin accumulates leading to nucleus promoting proliferation -KRAS mutation prevents apoptosis and promotes growth - Additional mutations in tumor suppressors like SMAD2 and SMAD4 of TGF-B signalling - Loss of TGF-B lets cell grow crazy - Tumor suppressor gene P53 mutation and expression of telomerase

What is turcot's syndrome?

- Rare familial adenomatous polyposis - Central nervous system tumors especially glioblastomas

What is a sessile serrated adenoma?

- Right colon w/no cytological features of dysplasia. Have malignant potential - May resemble hyperplastic polyps - Serrated architecture

What are the 3 types of adenoma architecture?

- Tubular: small, pedunculated, rounded, tubular glands - Tubularvillous: Mix of both types - villous: larger, sessile, covered in slender villi. MOre likely to be foci of invasion

What are the 4 patterns of tumors of the anal canal?

- Typical glandular/squamous patterns of differentiation - basaloid pattern: immature cells. Can be mixed with squamous or mucinous differentiation - Squamous cells ca associated with HPV

What is Familial adenomatous polyposis (FAP)

- autosomal dominant. mutation of tumor suppressor gene adenomatous polyposis coli (APC) - GEne normally maeks a protein which regulates B-catenin of WNT pathway to regulate epithelial proliferation

What are the 2 most important prognostic factors for adenocarcinoma?

- depth of invasion and presence/absence of lymph node metastases

Where is adenocarcinoma more common and what is the role of dietary factors?

- developed countries - DIets that have high refined carbs and fat w/lower intake of fiber may lead to toxic oxidative products of bacterial metabolism which come in contact with mucosa for a long time due to decreased stool bulk. LEads to cancer

What do right sided adenocarcinoma cause?

- fatigue and jaundice due to iron deficiency anemia

What is an intramucosal carcinoma?

- happens when dysplastic epithelial cells penetrate the basement membrane to invade the lamina propria or muscularis mucosa - COlonic mucosa lack lymphatic channels and have LITTLE METASTASIS ability - If cancer gets int eh muscularis mucosa it's considered invasive and can metastasize

What is the mostcommon site of adenocarcinoma metastasis and where else does it spread?

- liver - can also spread lymph nodes, bones, and lungs

What do left sided adenocarcinoma cause?

- occult bleeding, changes in bowel habits and cramping of LLQ

What do colonic adenomas look like?

- succulent velvety surface like a raspberry (from epithelium faailing to mature as cells migrate form crypt to surface) - Dysplasia has nuclear hyperchromasia, elongation, large nucleoli, eosinophilic cytoplasm, reduction of goblet cells and stratification - Villous form of these polyps may secrete protein and potassium leading to HYPOPROTEINEMIA AND HYPOKALEMIA

What is the histology for both types of adenocarcinoma?

- tall columnar cells like dysplastic epithelium in adenomas - strong DESMOPLASTIC response making tumor FIRM - few glands form poorly differentiated lesions - some make abundant MUCIN associated with WORSE prognosis

Where does colon cancer occur in HNPCC and what age? What causes the cancer?

- younger age in RIGHT colon - caused by inherited mutation in genes that encode proteins for detection, excision and repair errors. Leads to microsatellite instability -MSH2 and MLH1 are often mutated

Name this malignancy: - Most common malignancy of the GIT - 15% of all cancer deaths - Peaks at 60-70 years old

Adenocarcinoma