Sessile serrated polyps: Cancer risk and appropriate surveillance
ABSTRACTSessile serrated polyps are a recently recognized type of neoplastic polyp that develops along a molecular pathway different from that of conventional adenomas. While the clinical significance of the serrated pathway to colorectal cancer is clear, further study is needed to understand a patient’s lifetime colorectal cancer risk posed by serrated neoplasms and the optimal postpolypectomy surveillance interval.
KEY POINTS
- From 20% to 30% of colorectal cancers arise through the serrated polyp pathway (the serrated neoplasia pathway.)
- Histologically, serrated polyps have a serrated or sawtooth appearance from the folding in of the crypt epithelium. Types of serrated polyps include hyperplastic polyps, traditional serrated adenomas, and sessile serrated polyps (also known as sessile serrated adenomas).
- Guidelines for surveillance after polypectomy of serrated lesions recommend that patients with a large (≥ 10-mm) or a sessile serrated polyp with cytologic dysplasia or a traditional serrated adenoma be followed more closely than patients with a sessile serrated polyp smaller than 10 mm. Patients with small rectosigmoid hyperplastic polyps should be followed the same as people at average risk.
Sessile serrated polyps are a type of polyp recently recognized to be a precursor of colorectal cancer. They arise from a pathway of genetic alterations different from the pathway that causes the more common and well-understood conventional adenomas (also called tubular adenomas, tubulovillous adenomas, and villous adenomas).
We do not yet know enough about the lifetime colorectal cancer risk for individuals with sessile serrated polyps, nor do we know the optimal surveillance interval for patients who have these polyps on colonoscopy. It is believed that sessile serrated polyps may be the cause of a substantial number of “interval” colorectal cancers—ie, cancers that occur after colonoscopy but before the next scheduled examination.
Serrated polyps get their name from their jagged appearance on microscopy. In the past, all serrated colorectal lesions were called hyperplastic polyps. But with the advent of molecular and genetic diagnostics and with the ability to recognize the subtle morphologic differences of serrated lesions, they have been reclassified into those without malignant potential (hyperplastic polyps) and those that are neoplastic (sessile serrated polyps and traditional serrated adenomas) (Table 1).
In this article, we discuss the evolving understanding of the different types of serrated polyps, and we offer our thoughts on a reasonable postpolypectomy surveillance plan in patients with these lesions. We focus on sessile serrated polyps, the most common form of serrated polyp with cancerous potential, since it may be one of our greatest challenges in optimal colorectal cancer prevention.
CLINICAL SCENARIO
A 65-year-old woman with no family history of colorectal cancer undergoes screening colonoscopy, during which three polyps are found and removed—a 3-mm tubular adenoma in the sigmoid colon, an 8-mm sessile serrated polyp at the hepatic flexure, and a 2-mm hyperplastic polyp in the rectum. When should she undergo follow-up colonoscopy?
Based on the number, size, and pathologic makeup of the polyps in this patient, we would recommend follow-up surveillance colonoscopy in 5 years.
THE SERRATED POLYP PATHWAY: A DIFFERENT PATH TO COLORECTAL CANCER
Colorectal cancer is the third most common cancer in the United States.1 From 70% to 80% of these cancers arise from adenomatous polyps via the adenoma-carcinoma pathway. This molecular pathway develops through chromosomal instability (CIN) and involves the loss of heterozygosity (the loss of function of one allele). This leads to the progressive accumulation of mutations in tumor-suppressor genes such as adenomatous polyposis coli (APC) and p53, and oncogenes such as KRAS. The result of these mutations is the development of adenomatous polyps that lead to microsatellite-stable colorectal cancers (Figure 1).2
More recently, studies have shown that the other 20% to 30% of colorectal cancers likely arise through a separate pathway, called the serrated polyp pathway or serrated neoplasia pathway. In contrast to CIN, this pathway is characterized by methylation of CpG islands (CIMP–CpG island methylation phenotype, CIMP) in the promoter regions of specific genes.3 Central to the serrated polyp pathway is progressive methylation in colonic mucosa; mutation in the BRAF oncogene, activating cell proliferation leading to a sessile serrated polyp; and epigenetic silencing of the DNA mismatch repair gene hMLH1, which is a key step in the progression to a sessile serrated polyp with dysplasia, which may rapidly become a microsatellite-unstable colorectal cancer.4
Histologically, serrated polyps have a serrated or sawtooth appearance from the folding in of the crypt epithelium, and they include hyperplastic polyps, traditional serrated adenomas, and sessile serrated polyps (sessile serrated adenomas).
Sessile serrated polyps and traditional serrated adenomas (which are rare) are thought to be precancerous, whereas hyperplastic polyps do not have malignant potential.
