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| Adenocarcinoma | ||
| Etiology •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 | ||
| Pathogenesis •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, | ||
| Epidemiology •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 •The gross appearance is dependent on the stage of the tumor •Early invasive carcinoma may maintain the appearance of the original adenoma either polypoid or sessile •More commonly, the tumor has obliterated evidence of the underlying adenoma and when first seen is a firm, white, flat, well demarcated mucosal lesion with raised rolled margins, often with central ulceration •Over time, the lesion spreads circumferentially through circular lymphatics to produce a constricting napkin-ring lesion in the mucosa •As mucosal spread occurs, tumor also invades the full thickness of the muscular wall, and only at this stage is tumor seen grossly involving the perirectal fat, or mesentery • Cecal lesions often have a different appearance because of the large volume of space in which they can grow before producing symptoms. Cecal carcinomas often cover large areas of the cecum with fungating sessile or bulky lesions which can be extensively necrotic •Because of their long growth time before discovery cecal lesions often are seen as large deeply invasive tumors with attachment to the adjacent peritoneal wall •Examples: | ||
| General Microscopic Description •Most colorectal carcinomas have a characteristic appearance which facilitates their identification in metastatic as well as primary lesions •Most lesions are at least moderately differentiated with gland formation and a lining of tall columnar cells with palisading large oval or pencil shaped nuclei with increased coarse chromatin, easily found mitoses and some mucin production •The epithelium bears a clear resemblance to the dysplastic epithelium which covers adenomas •Mucin lakes are found in 10-15% of tumors and these patients are often those with hereditary non-polyposis syndromes or ulcerative colitis •Neuroendocrine differentiation can be identified in 10% of cases but true neuroendocrine carcinoma is extremely uncommon •Examples: | ||
| Clinical Correlation •Colorectal carcinoma develops over a long period of time with an estimated doubling time of almost two years •Presenting symptoms are related to chronic blood loss with the signs and symptoms of iron deficiency anemia, increasing luminal obstruction with change in bowel habits, diameter of stool, variable constipation, diarrhea, and vague abdominal discomfort or pain. A palpable mass lesion is a late finding •Right sided tumors are most associated with blood loss and rarely with obstruction while left sided lesions present with signs of obstruction •Treatment is surgical and prognosis is related to stage at presentation •About 25% of patients will present with metastatic disease, primarily lymph nodes and liver. The overall survival is 50% | ||
| References • Cotran RS, Kumar V, Robbins SL: Robbins Pathologic Basis of Disease. 5th ed. Philadelphia, W.B. Saunders, 1994, pp. 815-817 • Sleisenger MH, Fordtran JS. Gastrointestinal disease. 5th ed. Philadelphia: Saunders, 1993, pp. 144 Please be patient during transfer. Medline will open in a new window. To return, close the Medline Window Adenocarcinoma
| Synopsis by: Martin Nadel M.D. (T67000M81403)[207]
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