15-38: Nonfamilial Adenomatous & Serrated Polyps

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 (forming traditional serrated adenomas) mutations 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.

A. Adenomas

Adenomas (eFigures 15–32 and 15–33) 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 and 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.

B. Serrated Polyps

There are three types of serrated polyps: hyperplastic polyps, sessile serrated lesions (eFigure 15–34), and traditional serrated adenomas. It is believed that sessile serrated lesions (prevalence 5–15%) and traditional serrated adenomas (prevalence less than 1%) harbor an increased risk of colorectal cancer similar or greater to that of adenomas. 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.