|Adenoma of Colon ( Adenomatous Polyp)|
The dysplasia-adenoma-carcinoma sequence occurs in the setting of increasing loss of heterozygosity in genes involved in: DNA replication accuracy (mismatch repair)-Chromosomes 2 and 3; tumor suppression-Chromosomes 5,18, and 17; and oncogene activation-chromosomes 5,17,and 18
A hereditary predisposition to cancer is found in 1% of colorectal carcinoma patients with the Adenoma Polyposis Coli Syndrome involving Chr.5, and in 5-10% of patients with Hereditary Non-Polyposis (Lynch Syndromes) gene changes on Chr 2 and 3
For each patient loss of heterogosity must occur in multiple genes
Two pathways are commonly hypothesized to account for the known environmental, dietary and genetic predispositions to colorectal carcinoma. Both eventuate in loss of gene heterozygosity
The first of these postulate mucosal damage either through dietary induction of increased bile acid production or the direct affect of dietary and environmental carcinogens. This leads to increased mucosal cellular proliferative activity and an increase risk for gene match failure
The second postulates a direct genotoxic affect possibly mediated through production of oxygen free radicals
As increased numbers of defective gene growth regulators are formed, increased abnormal cellular activity eventuates in carcinoma,
Colorectal carcinoma is a disease of the older population except for people with hereditary non-polyposis and polyposis syndromes or chronic inflammatory bowel disease
The male/female ratio for rectal carcinoma is 2/1 while the male/female ratio of right sided lesions is 1/1
The remarkably higher incidence in more affluent countries and the change in incidence in migrants to the area of migration suggests a strong environmental affect which most studies relate to high dietary fat, low fiber and high refined carbohydrates
|General Gross Description|
Colonic adenomas are localized proliferations of dysplastic epithelium which are initially flat, but with increased growth project from the mucosa forming polyps.
Adenomas are classified by their gross appearance as either sessile (flat) or pedunculated (having a stalk).
Small adenomas (<0.5mm) have a smooth tan surface. Penduculated polyps have a head with a cobblestone or lobulated red-brown surface. Sessile polyps have a more delicate villous surface much like a sea anemone.
Pedunculated polyps are more likely to be tubular or tubulovillous histologic type and sessile lesions are more likely villous adenomas
While it is impossible to predict the presence or absence of carcinoma based on the gross appearance of polyps, larger polyps have a higher incidence of concurrent malignancy than small polyps. Sessile polyps have a higher incidence of malignany than pedunculated polyps of the same size.
Sessile polyps are most common in the cecum and rectum while overall pedunculated polyps are equally split between the sigmoid-rectum, and the remainder of the colon.
|General Microscopic Description|
By definition adenomas are composed of dysplastic epithelium. The nuclei are enlarged, cigar-shaped with an increase in nuclear chromatin, increased N/C ratio, crowding and loss of polarity within glands. There is often a decrease in mucous production.
Three subtypes of colonic adenomas are recognized: tubular; tubulovillous: and villous.
Villous adenomas have more than 50% of the dysplastic epithelium arranged in tall fingerlike villous projections similar to the villi seen in normal small intestinal mucosa.
Tubular adenomas have more than 75% of their epithelium arranged in tube like fashion which when cut accros looks like rows of transected gunbarrels.
Tubulovillous lesions have 25-50% villous component the rest being tubular.
Pedunculated adenomas are predominantly tubular with an increasing villous component as they grow larger.
Sessile adenomas are predominantly villous.
As a general rule, adenomas become more sessile as they become larger, and sessile lesions have a higher degree of dysplasia that tubular lesions.
Cotran RS, Kumar V, Robbins SL: Robbins Pathologic Basis of Disease. 5th ed. Philadelphia, W.B. Saunders, 1994, pp. 809-818.
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|Adenoma of Colon ( Adenomatous Polyp)
||Synopsis by: Martin Nadel M.D. (T67000M81400)