Serrated polyposis syndrome: molecular, pathological and clinical aspects

Abstract

Hyperplastic polyps have traditionally been considered not to have malignant potential. New pathological classification of serrated polyps and recent discoveries about the serrated pathway of carcinogenesis have revolutionized the concepts and revitalized the research in this area. Until recently, it has been thought that most colorectal cancers arise from conventional adenomas via the traditional tumor suppressor pathway initiated by a mutation of the APC gene, but it has been found that this pathway accounts for only approximately 70%-80% of colorectal cancer (CRC) cases. The majority of the remaining colorectal cancer cases follow an alternative pathway leading to CpG island methylator phenotype carcinoma with BRAF mutation and with or without microsatellite instability. The mechanism of carcinomas arising from this alternative pathway seems to begin with an activating mutation of the BRAF oncogene. Serrated polyposis syndrome is a relatively rare condition characterized by multiple and/or large serrated polyps of the colon. Clinical characteristics, etiology and relationship of serrated polyposis syndrome to CRC have not been clarified yet. Patients with this syndrome show a high risk of CRC and both sporadic and hereditary cases have been described. Clinical criteria have been used for diagnosis and frequent colonoscopy surveillance should be performed in order to prevent colorectal cancer. In this review, we try to gather new insights into the molecular pathogenesis of serrated polyps in order to understand their possible clinical implications and to make an approach to the management of this syndrome.

Keywords: Colorectal cancer; CpG island methylator phenotype; Hyperplastic polyps; Serrated pathway; Serrated polyposis.

Figure 1

Model of serrated pathway of colorectal carcinogenesis. MVHP: Microvesicular hyperplastic polyp; SSA: Sessile serrated adenoma; MGMT: Methylguanine methyltransferase; MSI: Microsatellite instability; MSS: Microsatellite stable; CRC: Colorectal cancer; CIMP: CpG island methylator phenotype; GCSP: Goblet cell serrated polyp; TSA: Traditional sessile adenomas.

Figure 2

Segment of colectomy in a case of serrated polyposis. Polyps are frequently small (arrows) and flat, making their endoscopic detection difficult.

Figure 3

Endoscopic appearance of serrated polyps. A and B: Sessile serrated adenoma (SSA) (arrows) as flat polyp on conventional optical colonoscopy; C: Narrow-band imaging appearance of polyp (arrow) seen in panel A; D: Chromoendoscopy image of SSA revealing Kudo II pattern (Images courtesy of Dr. Adolfo Parra, Hospital Central de Asturias, Oviedo, Spain).

Figure 4

Confocal endomicroscopy of (A) tubular adenoma, low-grade dysplasia and (B) serrated polyp. Both types of polyps show different shape as well as differences in the cellular structures (Images courtesy of Dr. Maria Pellisé, Hospital Clinic, Barcelona, Spain).

Figure 5

Pathological types of serrated polyps. A: Microvesicular serrated polyp; B: Sessile serrated adenomas; C: Traditional serrated adenoma; D: Mixed polyp.