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Hyperplastic Polyps - account for 90% of all polyps in the colorectum and affect > 50% of ppl >60 Complications Hyperplastic polyposis syndrome These have no malignant potential, but its important to distinguish them from a sessile serrated adenoma (a premalignant lesion that may look very similar)!

1) Starfish appearance (due to failure of cells to die off) instead of normal daisy appearance of glands 2) In hyperplasia the problem is failure of cells to slough off (resulting in hyperplasia). In many cancers, the problem is failure of cells to die 3) Note that through the apical side is hyperplastic, but the base looks normal (key for distinguishing from serrated adenomas)

1) This is a juvenile polyp, a focal hamartomatous malformation of mucosal elements Hamartomatous = means the polyp has all of the tissue seen in a normal polyp, but, the polyp has abnormal architecture 2) These can be sporadic or syndromic (Mutation in SMAD4 = Juvenile polyposis syndrome, Mutation in PTEN = Cowden syndrome)

Generally, dont worry if its sporadic and singular (1 polyp) because there is limited to no malignant potential But if there are more than 5 found in the colon and/or rectum, this would be juvenile polyposis syndrome and there is an increased risk of adenocarcinoma Worry if these arise in association with one of the above syndromes Worry if there is a family history of juvenile polyps (because this is likely syndromic) FYI solitary juvenile polyps most commonly occur in the rectum and present with rectal bleeding

Histo appearance: Arborizing network of smooth muscle proliferation with overlying normal mucosa This is a hamartomatous polyp associated with Peutz-Jeghers syndrome The Peutz-Jegher polyp itself has no malignant potential, but there is an increased risk for cancer of the GI tract, pancreas, ovaries, uterus, breast, and lung Physical features in P-J syndrome: Melanotic mucosa and cutaneous pigmentation (macules around lips, mouth that look like freckles, but are in the mucosa look on inside of lip)

L: Sessile adenoma M: Pedunculated adenoma R: Villous adenoma By definition, an adenoma has low-grade dysplasia and has the potential to become malignant

Yes, both do! Risk of adenomas becoming cancerous (adenocarcinomas) correlates with their size (big = bad) Higher risk: 1cm (larger size) Villous architecture

Tubular adenoma - A tubular adenoma has dysplasia only in the crypts, whereas a villous adenoma is dysplasia stretching to form a test-tube

a solitary pedunculated adenoma of the colon with no evidence of malignancy, and with elongated, deep crypts (looks tubular)
Slide A: Slide B: small focus of dysplastic, non-mucin secreting epithelial cells lining a colonic crypt higher N:C ratio nuclei pseudostratified (no longer sitting at the base of the basement membrane) nuclei are larger hyperchromasia

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higher N:C ratio nuclei pseudostratified (no longer sitting at the base of the basement membrane) nuclei are larger hyperchromasia

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1) Villous adenoma simply look at the extent of dysplasia. If dysplasia is finger like (or villous like) it is villous as opposed to tubular (crypt dysplasia only) Important because its an adenoma with a high likelihood of progressing to invasive adenocarcinoma, AND if it does so in the descending colon, it produces an annular adenocarcinoma that has a tendency to obstruct the bowel.

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1) Arrows

(L) basal dilation of the crypts, (R) basal crypt serration

2) Sessile serrated adenoma, which looks like a hyperplastic polyp, but what distinguishes it is the funny dilatation of the base of the crypts Other typical features of SSA include crypts that run horizontal to the basement membrane (horizontal crypts) and crypt branching. The most common of the aforementioned 4 features is basal dilation of the crypts. 3) Important because it should be treated as though it is a tubular adenoma (ie has nuclear dysplasia and thus has neoplastic potential), even though it does not look like one 4) Pathogenesis: Microsatellite instability Germline or somatic mutation of mismatch repair genes (MLH1, MSH2 genes) alteraCon of a second allele microsatelilite instability accumulated mutations in genes that regulate growth, differentiation, apoptosis This is different from the pathway in most cancers

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This is familial adenomatous polyposis (FAP) 1) Germline mutation of APC gene (5q21). Inheritance is autosomal dominant (patients are heterozygous for the mutation, thus each cell only needs 1 more hit to knock out the other allele) 2) 100 is diagnostic. Generally find 500-2500

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1) Polyps are histologically identical to tubular adenomas 2) Manage w/ total protocolectomy after diagnosis. Sample the largest polyps for evidence of cancer. 3) Prognosis: nearly 100% progress to colon cancer by age 40

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L: polypoid mass M: ulcerative mass R: fungating mass

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1) HNPCC (hereditary non-polyposis colorectal cancer) aka Lynch syndrome 2) Also at risk of cancers of other epithelial organs (stomach; if female endometrial, ovary) 3) Phenotype of the heterozygote state is apparently normal, but when a somatic mutation inactivates the other allele of the DNA mismatch repair gene, the tissue develops a hypermutable phenotype, which accelerates multi-step carcinogenesis (along the usual sequence) 4) Most commonly affected genes: MLH1, MSH-2

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Colon cancer invading through muscularis propria (externa) (T3) The epithelium is adenomatous, dysplastic

this is CARCINOMA

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Encircled area represents cells trying to recapitulate glands, but the cells are abnormal (elevated N:C ratio) Arrows dirty necrosis, a key feature typical of colorectal cancer, comprised of luminal debris (necrotic debris + few neutrophils) This is an adenocarcinoma (its making glands)

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Mets to liver Carcinoid syndrome, due to production of serotonin by adenocarcinoma cells in the metastatic lesions

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Neuroendocrine cells Characteristic salt and pepper nuclear chromatin; nested appearance Associated with carcinoid syndrome

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