Pathologic features and biologic importance of colorectal serrated polyps

Abstract

Serrated polyps of the large intestine comprise a heterogeneous group of mucosal lesions that includes nondysplastic polyps, such as hyperplastic polyps and sessile serrated polyps, and polyps that show overt cytologic dysplasia, namely serrated adenomas and mixed hyperplastic/adenomatous polyps. These polyps have received increased recognition over the past 2 decades, as emerging evidence suggests that a subset may be precursors to colorectal carcinomas that lack chromosomal instability. Several investigators have proposed the concept of the "serrated neoplastic pathway" according to which nondysplastic serrated lesions develop progressively severe dysplasia culminating in the development of microsatellite unstable carcinomas that show DNA hypermethylation and BRAF mutations. A subset of hyperplastic polyps and sessile serrated polyps show mutations in the BRAF gene and abnormal DNA methylation, which can, ultimately, affect the promoter regions of key DNA-repair and tumor suppressor genes, such as MLH1 and MGMT, leading to their decreased transcription and microsatellite instability. On the basis of this hypothesis, many authors have proposed that sessile serrated polyps should be treated and surveilled similar to conventional adenomas, although prospective data are lacking. This review describes the clinicopathologic and molecular features of serrated polyps and discusses the current data regarding their biologic significance.