Term
| what is the difference between the adenomatous polyps and other polyps? |
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Definition
| adenomatous polyps are true neoplasms, while the others are mainly reparative mechanisms |
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Term
| in the colon, every adenomatous polyp is potentially __________? |
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Definition
| pre-malignant - they are benign, but are precursors to the majority of colorectal adenocarcinomas |
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Term
| what are the most common and the most clinically significant neoplastic polyps? |
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Definition
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Term
| what is the morphologic range for adenomatous polyps? |
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Definition
| they can be small pedunculated polyps to large, sessile ones |
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Term
| what is the rate of incidence for adenomatous polyps in the western world? |
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Definition
| they are present in nearly 50% of adults by the age of 50 |
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Term
| how many adenomatous polyps progress to adenocarcinomas? |
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Definition
| only a minority - regardless, all need to be checked out |
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Term
| what are adenomatous polyps characterized by? |
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Definition
| the presence of dysplasia (disorganized growth - hyperchromasia, elongation, stratification) - for ex. large N:C ratio, clumped chromatin, stratified nucleus or stratified cell, loss of polarity, etc. |
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Term
| why does a colonoscopy reduce the risk of colorectal CA? how can polyps make their presence known outside of screenings? |
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Definition
| b/c most polyps are clinically silent, usually only some large polyps bleed (gives rise to occult blood/*anemia) and some villous polyps secrete protein/potassium (leads to *hypoproteinemia/*hypokalemia) |
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Term
| if a pt over 50 has anemia, what do they need to be checked for? |
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Definition
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Term
| what characterizes colonic adenomas morphologically? |
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Definition
| they can range in size from .3 cm to 10 cm in diameter, they can be pedunculated/sessile, and they may have a raspberry-like, velvety surface |
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Term
| what characterizes colonic adenomas histologically? |
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Definition
| colonic adenomas have *large nucleoli, *eosinophilic cytoplasm, and a *reduction in goblet cells. any dysplasia is seen mostly on the *surface of the adenoma and the epithelium fails to mature as cells migrate from the crypt to the surface |
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Term
| what is gardner's syndrome? does it have a genetic correlation? |
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Definition
| gardner's syndrome is a condition associated with *FAP (familial adenomatous polyposis), *osteomas (benign bone tumors in the face/skull/mandible/long bones), and a higher risk of: colon CA, thyroid CA, fibromas, and sebaceous cysts in the epithelial lining. a mutation in the adenomatous polyposis gene in 5q is involved. |
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Term
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Definition
| a rare variant of FAP that also includes CNS tumors (particularly glioblastomas - very aggressive) |
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Term
| what are the three types of adenoma architecture? |
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Definition
| tubular, villus, or tubulo-villus |
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Term
| what does it mean to say an adenoma has tubular architecture? |
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Definition
| a tubular adenoma tends to be small, on a pedestal with cylindrical architecture |
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Term
| what does it mean to say an adenoma has villous architecture? how likely is this kind of adenoma to have dysplasia/invade? |
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Definition
| a villous adenoma is larger and more sessile (like a bush, rather than a flower), is covered by slender villi, and more finger-like than tubule. this type of adenoma is *more likely to have dysplasia/foci of invasion* |
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Term
| what does it mean to say an adenoma has tubulo-villus architecture? |
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Definition
| these adenomas can have features of both tubular and villus polyps and *will be more likely to have dysplasia than simple tubular adenomatous polyps* |
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Term
| what is a sessile serrated adenoma? |
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Definition
| a particular adenoma commonly found in the *R colon which have malignant potential but still lack typical cytological features of dysplasia. they have *serrated architecture through the full length of the glands, lateral growth and crypt dilation, and may resemble hyperplastic polyps |
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Term
| what is an intramucosal carcinoma? |
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Definition
| this occurs when a dysplastic epithelial cell penetrates the basement membrane to invade the lamina propria or muscularis mucosa. colonic mucosa lack lymphatic channels, and these have little metastatic potential if removed - however if they get past the muscularis mucosa, it is considered invasive and can metastasize |
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Term
| what is the most common malignancy of the GI tract? |
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Definition
| adenocarcinoma - which also makes up 15% of all CA deaths |
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Term
| when does incidence of GI adenocarcinoma peak? |
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Definition
| adenocarcinoma rates peak at ~60-70, several decades after the peak of adenomatous polyps. screening protocols in the US consist of colonoscopy for everyone at age 50. |
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Term
| where are adenocarcinomas more common? why? |
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Definition
| in developed countries, where diets consist of more highly refined carbohydrates and fat with a lower intake of fiber. these dietary factors can lead to potentially toxic oxidative byproducts of bacterial metabolism which come into contact with the mucosa for a longer period due to decreased stool bulk. |
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Term
| what are the two major genetic pathways which can lead to colonic adenocarcinomas? |
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Definition
| 1) the APC/beta-catenin pathway associated w/WNT and the classic adenoma-carcinoma sequence. 2) microsatellite instability associated w/defects in DNA mismatch repair |
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Term
| what is the classic adenoma-carcinoma sequence involving APC? |
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Definition
| there is a mutation of APC (adenomatous polyposis coli - tumor suppressor) in the early neoplastic process, (this has to happen to each of the the APC gene copies for adenoma formation). APC acts as a regulator of beta-catenin, a component of the WNT signaling pathway, by binding/degrading it. in the absence of APC, beta-catenin accumulates and translocates to the nucleus - promoting proliferation. |
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Term
| what are other tumor promoter/suppressor mutations in the classic adenoma-carcinoma sequence? |
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Definition
| mutations in *K-RAS promote growth and prevent apoptosis. mutations in *SMAD2/SMAD4 (tumor suppressor genes) lead to lack of regulation of the TGF-beta pathway and overproliferation. tumor suppressor *p53 is also mutated in 70-80% of colon CA. *telomerase is also found expressed in colon CA. |
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Term
| what is the progression of the classic adenoma-carcinoma pathway? |
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Definition
| first hit: inherited/acquired mutation of CA suppressor genes such as APC. second hit: methylation abnormalities and inactivation of normal alleles (such as APC/beta-catenin). at this point an adenoma has formed. protooncogene mutations in K-RAS, p53, telomerase, SMAD, etc then carry the adenoma to a adenocarcinoma. |
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Term
| what characterizes the DNA mismatch repair pathway? |
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Definition
| mutations accumulate in microsatellite repeats, leading to instability, some of which are located in the coding or promoter regions of genes involved in the regulation of cell growth. this inculdes mutations in *TGF-beta (lead to uncontrolled cell growth), *pro-apoptotic BAX, and the *oncogene BRAF. |
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Term
| what is the phenotypic difference in adenocarcinoma formation between the classic adenoma-carcinoma pathway and the microsatellite instability pathway? |
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Definition
| the classic adenoma-carcinoma pathway leads to more pedunculated and excavated carcinomas, while the microsatellite instability pathway leads more to sessile serrated adenomas then to excavated carcinomas |
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Term
| what is the phenotypic difference in adenocarcinoma formation between the classic adenoma-carcinoma pathway and the microsatellite instability pathway? |
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Definition
| the classic adenoma-carcinoma pathway leads to more pedunculated and excavated carcinomas, while the microsatellite instability pathway leads more to sessile serrated adenomas then to excavated carcinomas |
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Term
| what is the presentation of adenocarcinomas? does their location inform their appearance? |
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Definition
| adenocarcinomas are usually distributed evenly throughout the colon - however depending on whether they are in the proximal or distal portions of the colon, there are some phenotypic differences. |
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Term
| what is the phenotypic difference in adenocarcinoma formation between the classic adenoma-carcinoma pathway and the microsatellite instability pathway? |
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Definition
| the classic adenoma-carcinoma pathway leads to more pedunculated and excavated carcinomas, while the microsatellite instability pathway leads more to sessile serrated adenomas then to excavated carcinomas |
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Term
| what is the presentation of adenocarcinomas? does their location inform their appearance? |
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Definition
| adenocarcinomas are usually distributed evenly throughout the colon - however depending on whether they are in the proximal or distal portions of the colon, there are some phenotypic differences. |
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Term
| how do proximal tumors on the R side of the bowel tend to appear? |
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Definition
| proximal tumors on the R side of the bowel tend to be polypoid, exophytic, rarely obstructive and extend along one edge of the colon. they are also more more hyperemic, friable and may report diarrhea and darker (bloody) stools |
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Term
| how do distal tumors on the L side of the bowel tend to appear? |
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Definition
| distal tumors on the L side of the bowel tend to be annular (napkin ring) tumors which cause luminal narrowing and sometimes obstruction - which can lead to constipation, cramping, and thin stools |
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Term
| what are the histologic features of adenocarcinomas? does this change depending on location in the colon? |
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Definition
| the histologic features of adenocarcinomas are the same regardless of location in the colon and consist of tall columnar cells (resembles dysplastic epithelium in adenomas), a strong desmoplastic response (characteristic firmness), some glands in poorly differentiated areas, and abundant mucin may be produced in tumors associated with a poorer prognosis (mucin spread may spread CA). |
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Term
| how do pts with proximal tumors on the R side of the bowel tend to present? |
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Definition
| pts may experience fatigue and jaundice due to iron deficiency anemia |
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Term
| how do pts with distal tumors on the L side of the bowel tend to present? |
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Definition
| these pts may experience occult bleeding, changes in bowel habits (over years), and cramping of the LLQ |
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Term
| what are the 2 most important prognostic factors for adenocarcinomas? |
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Definition
| depth of invasion and presence/absence of lymph node metastasis |
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Term
| what characterizes adenocarcinoma metastasis? |
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Definition
| metastasis may involve the lymph nodes, bones and lungs - though the most common site of metastasis is the liver (where it may appear as multiple, creamy-tan colored lesions w/a dimple) |
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Term
| what is familial adenomatous polyposis (FAP)? |
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Definition
| an autosomal dominant mutation in the APC tumor suppressor gene, leading to 100-1000s of polyps involving the colonic mucosa, of which 1-2 will defintely become malignant. |
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Term
| what is the treatment for FAP? |
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Definition
| prophylactic colectomy - however this does not eliminate risk to other organ systems |
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Term
| what are extra-intestinal manifestations associated with FAP? |
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Definition
| gardner syndrome (intestinal polyps, osteomas of the mandibule/skull/long bones, epidermal cysts, desmoid tumors, thyroid tumors, and dental abnormalities) and turcot syndrome (intestinal adenomas and tumors of the CNS) |
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Term
| what is hereditary non-polyposis colorectal cancer (HNPCC)/lynch synrome? |
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Definition
| this is a term for familial clustering of CA at the colorectum, endometrium, stomach, ovary, ureters, brain, small bowel, hepatobiliary tract and skin. this usually occurs in younger people, on the R side of the colon. this is due to genetic abnormalities in proteins needed for detection, repair, removal of errors that occur during DNA replication (such as *MSH2/MLH1*). |
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Term
| what characterizes tumors of the anal canal histologically? |
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Definition
| the anal canal is lined by squamous cells, therefore tumors in this area may have glandular differentiation, but many will be SCCs. *pure SCCs here are associated with HPV and *immature cells may have a basaloid pattern. there can be a squamous/mucinous differentiation, and since in the anus there is a transition from the adenomatous mucosa -> squamous mucosa, there is *potential for mixed tumors. |
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