Sporadic and syndromic hyperplastic polyps & serrated adenomas of the colon: Classification, molecular genetics, natural history, and clinical management

The traditional understanding of the evolution of colorectal cancer was based on four straightforward propositions. First, most colorectal cancers arise in precancerous polyps. Second, there are two main types of colorectal polyps: hyperplastic polyps and adenomas. Third, the adenoma is fundamentally an epithelial neoplasm, with malignant potential, whereas the hyperplastic polyp is fundamentally a benign epithelial lesion with no malignant potential. Fourth, adenomas progress to carcinomas through a single linear sequence of genetic alterations involving particular tumor suppressor genes (eg, APC and p53) and oncogenes (eg, KRAS). These propositions were easy to comprehend and to translate into clinical management guidelines and were supported by considerable circumstantial evidence. Therefore, although decades of study identified exceptions to these propositions, the contrary data received no attention. In the last few years, however, these exceptions have been organized to demonstrate an alternative pathway of colorectal carcinogenesis: the serrated pathway involving hyperplastic polyps or related lesions. This article briefly presents the evidence for the serrated pathway, provides diagnostic criteria for clinically significant serrated polyps, and suggests how these data can be translated into safe and effective guidelines for cancer prevention. Because of the incomplete understanding of the behavior of serrated polyps, any clinical management plan must be tentative. The authors therefore highlight key areas warranting further research.