Hyperplastic and serrated polyps of the colorectum.

The serrated polyp pathway is a histopathological sequence that begins in a hyperplastic polyp, or precursor serrated aberrant crypt focus, and has the potential to end in a colonic adenocarcinoma that is CIMP-high and, in most cases, also MSI. An activating mutation of the BRAF oncogene is a marker for this pathway. There is evidence that aberrant CpG-island methylation is the molecular engine that drives the progression through sequential steps of the pathway, from hyperplastic polyp to a form of atypical hyperplastic polyp (termed sessile serrated adenoma) to dysplastic serrated polyp and, ultimately to serrated carcinoma. A second serrated pathway, identified by mutations of KRAS in serrated adenoma, is delineated less completely. Its endpoint is a colorectal carcinoma that is CIMP-low and MSS, and both the advanced serrated adenoma and carcinoma stages of this pathway show molecular genetic and morphologic features that overlap with those of the conventional APC carcinogenic pathway. Clinical studies are needed to elucidate the natural history of serrated neoplasia, and provide evidence-based guidance for risk assessment and surveillance of individuals discovered to harbor its various serrated polyp precursors.