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|
Villous adenomas are sessile lesions with a papillary surface similar to a sea anemone.
Partly polypoid lesions may be seen but these have a broad base rather than a stalk.
|General Microscopic Description|
In villous adenomas the fingerlike proliferation resembles the villi of normal small intestinal mucosa except that the normal epithelial tissue covering is replaced by dysplastic epithelium.
These cells have enlarged cigar-shaped nuclei with increased nuclear chromatin, crowding and pseudopalisading.
Scattered mitoses may be seen but are not helpful in making the diagnosis which depends on >50% of the dysplastic mucosa having a villous pattern.
Mucin production is often decreased but some lesions show a marked increase in mucin. These patients may exhibit hypokalemia through loss of K+ in mucin.
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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||Synopsis by: Martin Nadel M.D. (T67000M82611)