Significance of serrated polyps of the colon

Abstract

The fundamental view that colon adenocarcinomas arise only from conventional adenomas has been challenged by the now recognized hyperplastic polyp-serrated adenoma-adenocarcinoma pathway. This article describes the history of the serrated adenoma (both the traditional serrated adenoma and the sessile serrated adenoma) as well as the histology and endoscopic appearance of these lesions in comparison with hyperplastic polyps and mixed polyps. Although the exact pathway is the subject of ongoing research, compelling histologic associations and molecular phenotypes that define the model of the serrated polyp-carcinoma sequence, including microsatellite instability, BRAF/KRAS mutations, and CpG island methylator phenotype, provide strong evidence that this is a genuine pathway. Management of serrated neoplasia of the colon includes careful colonoscopy, complete removal of colonic polyps, sampling fields of diminutive polyps of the rectosigmoid, and basing surveillance on histology of removed polyps.

Figure 1

The histology and schematic of the serrated polyp-carcinoma sequence. Diagram shows the putative (?s represent areas of greatest uncertainty) progression of a subset of hyperplastic polyps (HPs), which are typically (+) CIMP and (+) BRAF, into a Sessile Serrated Adenoma (SSA) that may have hypermethylation of the DNA mismatch repair gene hMLH1 gene and subsequently into a Mixed Polyp that more often has hypermethylation of hMLH1 and may show evidence of microsatellite instability particularly in areas of high grade dysplasia that are thought to progress to microsatellite unstable colorectal carcinomas. The origin of the Traditional Serrated Adenomas is less clear; some authors have proposed that these polyps arise from a subset of sessile serrated adenomas or from a subset of HPs such as the goblet cell-rich HPs based on their higher frequency of K-ras rather than BRAF mutations and the higher frequency of hypermethylation of another DNA repair gene MGMT rather than hMLH-1. Photographs courtesy of Russell Nash M.D.