Sessile serrated adenomas: why conventional endoscopy is okay for unconventional polyps.

Abstract

Sessile serrated adenomas (SSA) are premalignant flat lesions localized predominantly in the proximal colon, which, until recently, had often been unrecognized by the endoscopist [1]. Pereyra et al. [2] report in this issue of Digestive Diseases and Sciences that these lesions can be successfully identified using conventional colonoscopy. Compared with the understanding of genetic mutations accompanying the more common adenomatous polyps (chromosomal instability pathway), the pattern of DNA alterations present in SSA-related colorectal cancer (CRC) development follows the serrated pathway, likely related to molecular abnormalities that involve CpG islands methylation, referred to as the CpG island methylator phenotype or CIMP [3]. Activating mutations of the mitogen-activated protein kinase pathway comprise components of the oncogenes BRAF or KRAS [4, 5]. Since tumor progression to CRC may be accelerated compared with the chromosomal instability pathway, SSAs are hence strongly associated with interval CRC. It is fascinating that these changes at the molecular level could have a phenotypic expression recognizable to the observant endoscopist. Pereyra et al. [1] reported that these lesions are identifiable by luminal surface features such as excess proximal localization, flat morphology, red surface color, and the presence of a mucus cap, as shown in their paper. Endoscopic presentation is subtle: Polyps in Pereyra’ s study were few (1.6 per patient) and small (43 % were 5 mm or smaller), requiring heightened awareness for identification, which, reassuringly, were recognized without specialized endoscopic equipment, facilitating their complete removal and pathological review. Since SSA progression to CRC can be prevented through polypectomy [1], awareness of these lesions among endoscopists and pathologists is important. Since criteria for pathological diagnosis of SSA are evolving, SSA may be underdiagnosed [6]. As noted in Pereyra’ s study, there was initially low inter-observer agreement among the pathologists in the diagnosis of SSA. The endoscopist’s ability to alert pathologists about a possible SSA will likely improve surveillance planning. East et al. [4] discussed the evolution of CRC, calling attention to the concern that most CRCs have their origin in two types of precancerous epithelial polyps: hyperplastic and adenomas. For more than a half century, all colorectal epithelial polyps were assumed to be either adenomatous with malignant potential or hyperplastic, a fundamentally benign lesion without malignant potential. Adenomas progress to carcinomas within a single linear sequence of genetic alterations of the tumor suppressor genes APC, p53, or mismatch repair (MMR) genes as well as oncogenes such as KRAS. Exceptions to these polyp types were reported over time, but received little attention until 1990 when Longacre and Fenoglio-Preiser addressed the concept of an intermediate type of polyp. In their study of more than 18,000 colorectal polyps, 110 (0.6 %) were diagnosed as serrated adenomas [7]. Most of these polyps had not been discerned as having aberrant histology. Nevertheless, about one-third had been classified as hyperplastic polyps and another third as atypical adenomas, while final third (0.2 % of all polyps) were described as ‘‘intermediate lesions.’’ Such variant classification obfuscated the correct identification of these lesions: 11 % of the serrated adenomas were severely dysplastic or had foci of intramucosal carcinoma, indicating that these lesions are precancerous S. J. Lanspa H. T. Lynch (&) Department of Preventive Medicine and Public Health, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA e-mail: htlynch@creighton.edu