Serrated Polyps and Colorectal Cancer: New Pathway to Malignancy

Abstract

Until recently, two major forms of colorectal epithelial polyp were recognized: the adenoma and the hyperplastic polyp. Adenomas were perceived to represent the precursor to colorectal cancer, whereas hyperplastic polyps were viewed as innocuous lesions with no potential for progression to malignancy. We now recognize, however, that the lesions formerly classified as hyperplastic actually represent a heterogeneous group of polyps, some of which have a significant risk for neoplastic transformation. These serrated polyps include not only hyperplastic polyps but also traditional serrated adenomas and sessile serrated adenomas. These polyps demonstrate characteristic molecular alterations not commonly seen in colorectal adenomas, and they probably progress to colorectal cancer by means of a new pathway: the serrated neoplasia pathway. The morphologic features of serrated colorectal lesions, the molecular alterations that characterize them, and their role in colorectal cancer development are discussed herein.

Serrated colorectal polyps in inflammatory bowel disease

“…The morphologic, clinical, and molecular characteristics of sporadic colorectal serrated polyps are well-recognized, [2][3][4][5]8,23 and have resulted in consensus recommendations for short-and long-term patient management. 7,24,25 The present study addresses the dearth of available data regarding such lesions in patients with inflammatory bowel disease by means of a retrospective evaluation of serrated polyps diagnosed during the course of endoscopic surveillance.…”

“…1,2 Sessile serrated adenoma/polyps are usually located in the proximal colon, predominate in women, and harbor BRAF mutations, whereas traditional serrated adenomas are usually left sided, occur more often in men, and contain KRAS mutations. [3][4][5] The significance of serrated polyps in the general population with respect to carcinoma risk stratification, endoscopic surveillance, and management is becoming increasingly clear and has recently been incorporated into clinical consensus guidelines. [6][7][8] Patients with extensive, longstanding colonic inflammatory bowel disease, mainly ulcerative and Crohn's colitis, face an increased risk of developing colorectal cancer compared with the general population.…”

Mucinous Adenocarcinomas with Intra-Abdominal Dissemination: A Review of Current Therapy

“…The key element of this pathway is dysfunction in DNA mismatch repair enzymes that results from germline mutations in one of several DNA mismatch repair genes, most commonly MLH1 or MSH2. The result is the development of microsatellite instability (MSI) in tumors derived through this genetic pathway [33].…”

Traditional serrated adenoma has two pathways of neoplastic progression that are distinct from the sessile serrated pathway of colorectal carcinogenesis

“…1 However, the biological significance of these two morphological patterns is still unknown. Although some pathologists diagnose tumors with combined features as mixed hyperplastic/adenomatous polyps or mixed polyps with a description of the constituent components, 17,18 mixed polyps have also been reported to share similar molecular changes and implicate morphological progression to malignancy. 13,19 Jass et al 13 reported that traditional serrated adenoma with dysplastic epithelium resembling conventional adenoma displayed a high frequency of KRAS mutation, whereas Kim et al 7 linked this traditional serrated adenoma to a lower frequency of BRAF mutation.…”