Fig. 15.38B ), sometimes to the point of obstruction. Both forms grow into the bowel wall over time and may be palpable as firm masses (
Fig. 15.38C ). The general microscopic characteristics of right- and left-sided colonic adenocarcinomas are similar. Most tumors are composed of tall columnar cells that resemble dysplastic epithelium found in adenomas (
Fig. 15.39A ). The invasive component of these tumors elicits a strong stromal desmoplastic response, which is responsible for their characteristic firm consistency. Some poorly differentiated tumors form few glands (
Fig. 15.39B). Others may produce abundant mucin that accumulates within the intestinal wall, and these carry a poor prognosis. Tumors also may be composed of signet ring cells similar to those in gastric cancer (
Fig. 15.39C
The availability of endoscopic screening combined with the recognition that most carcinomas arise within adenomas presents a unique opportunity for cancer prevention. Unfortunately, colorectal cancers develop insidiously and may therefore go undetected for long periods. Cecal and other right-sided colon cancers most often are called to clinical attention by the appearance of fatigue and weakness due to iron-deficiency anemia.Thus, it is a clinical maxim that the underlying cause of iron-deficiency anemia in an older male or postmenopausal female is gastrointestinal cancer until proven otherwise. Left-sided colorectal adenocarcinomas may produce occult bleeding, changes in bowel habits, or cramping left lower-quadrant discomfort.
Although poorly differentiated and mucinous histologic patterns are associated with poor prognosis, the two most important prognostic factors are depth of invasion and the
MLH1, MSH2 (MSH6, PMS1, PMS2)
Microsatellite instability/ "mutator phenotype" Accumulated mutations in genes that regulate growth, differentiation, and/or apoptosis
TGF  RII, BAX, BRAF,
TCF-4, IGF2R, others
Fig. 15.37 Morphologic and molecular changes in the mismatch repair pathway of colon carcinogenesis. Defects in mismatch repair genes result in micro-satellite instability and permit accumulation of mutations in numerous genes. If these mutations affect genes involved in cell survival and proliferation, cancer may develop. LOH, Loss of heterozygosity.