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Adenomas and serrated polyps may be non-polypoid (flat, slightly elevated, or depressed), sessile, or pedunculated (containing a stalk). Their significance is that over 95% of cases of adenocarcinoma of the colon are believed to arise from these lesions. Early detection and removal of these precancerous lesions through screening programs has resulted in a 34% reduction in deaths from colorectal cancer since 2000. It is proposed that there is a polyp → carcinoma sequence whereby nonfamilial colorectal cancer develops through a continuous process from normal mucosa to adenomatous or serrated polyp and later to carcinoma. An estimated 75% of cancers arise in adenomas after inactivation of the APC gene leads to chromosomal instability and inactivation or loss of other tumor suppressor genes. The remaining 25% of cancers arise through the serrated pathway in which hyperplastic polyps develop Kras mutations (forming traditional serrated adenomas) or BRAF oncogene activation (forming sessile serrated lesions) with widespread methylation of CpG-rich promoter regions that leads to inactivation of tumor suppressor genes or mismatch repair genes (MLH1) with microsatellite instability.
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Adenomas (eFigures 17–32 and 17–33) are present in more than 30% of men and 20% of women over the age of 50. Most adenomas are smaller than 5 mm and have a low risk of becoming malignant. Adenomas are classified as “advanced” if they are 1 cm or larger or contain villous features or high-grade dysplasia. In the general population, the prevalence of advanced adenomas is 6%. Advanced lesions are believed to have a higher risk of harboring or progressing to malignancy. It has been estimated from longitudinal studies that it takes an average of 5 years for a medium-sized polyp to develop from normal-appearing mucosa and 10 years for a gross cancer to arise.
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There are three types of serrated polyps: hyperplastic polyps, sessile serrated lesions (eFigure 17–34), and traditional serrated adenomas. It is believed that sessile serrated lesions (prevalence 5–12%) and traditional serrated adenomas (prevalence less than 1%) entail an increased risk of colorectal cancer similar or greater to that of adenomas and account for up to 20–30% of colorectal cancers. Many pathologists cannot reliably distinguish between hyperplastic polyps and sessile serrated lesions. Diminutive hyperplastic polyps (less than 5 mm) are extremely common (prevalence 20–30%), especially in the rectum, and believed to be without significant risk.
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