Serrated Adenoma: A Distinct Form of Non-Polypoid Colorectal Neoplasia?

Until recently, 2 major forms of colorectal polyp were recognized: the adenoma and the hyperplastic polyp. Adenomas were known to represent a precursor to colorectal cancer, whereas hyperplastic polyps were viewed as nonneoplastic, having no potential for progression to malignancy. We now recognize, however, that the lesions diagnosed as hyperplastic polyps in the past represent a heterogeneous group of polyps, some of which truly are hyperplastic, and others that truly have a significant risk for transformation to colorectal cancer. These polyps have a characteristic serrated architecture, and include not only hyperplastic polyps but also the recently recognized serrated adenomas. Serrated adenomas occur in 2 forms: the traditional serrated adenoma, which is usually a polypoid lesion endoscopically, and the sessile serrated adenoma, a flat or slightly raised, usually right-sided lesion. Serrated adenomas of both types show characteristic molecular alterations not commonly seen in traditional colorectal adenomas, and probably progress to colorectal cancer by means of a different pathway, the so-called 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.

Until 20 years ago, 2 major forms of colorectal epithelial polyp were recognized: the adenoma and the hyperplastic polyp. Adenomas have long been accepted as neoplastic, precursor lesions for colorectal adenocarcinoma. In contrast, hyperplastic polyps were for the most part regarded as innocuous lesions without neoplastic potential. It was known that hyperplastic polyps could be identified adjacent to a significant percentage of colorectal adenomas, and that they occur with higher frequency in populations at greater risk of developing colorectal cancer, but they were nevertheless felt by most to represent nonneoplastic bystander lesions.

In 1990, however, this view of colorectal polyps was challenged when Longacre and Fenoglio-Preiser published a study examining a group of polyps that showed mixed histologic features of hyperplastic and adenomatous polyps. These lesions were believed to represent not mixed tumors with 2 separate hyperplastic and adenomatous components, but a single entity in which the glands had a serrated architecture, and the cells lining them showed nuclear features reminiscent of adenoma. These lesions were termed serrated adenomas, but were felt by the investigators to represent a variant of villous or tubulovillous adenoma rather than a lesion related to hyperplastic polyps.

Subsequent scattered reports and small series of colorectal adenocarcinomas associated with giant or large hyperplastic polyps (usually defined as >1 cm), however, suggested that at least some hyperplastic polyps had malignant potential. Adenocarcinomas were also reported arising in mixed hyperplastic and adenomatous polyps. In addition, the presence of multiple hyperplastic polyps in the form of hyperplastic polyposis was clearly associated with the development of colorectal adenocarcinoma.

The concept that the lesions previously categorized as hyperplastic polyps actually represented several distinct entities emerged with the work of Torlakovic and Snover. These investigators showed that the polyps arising in patients with hyperplastic polyposis had morphologic features that were different from those of small sporadic hyperplastic polyps, and that these features could reliably be used to differentiate between the potentially precancerous polyps and those that probably did not pose a risk for progression to colorectal cancer. In 2003, this group studied a set of sporadic serrated lesions, and showed that several discrete types of sporadic serrated polyps were also identifiable, and that these polyps could generally be divided into those with abnormal proliferation, termed sessile serrated adenomas, and those with normal proliferation, termed hyperplastic polyps.

Morphologic features and classification of serrated colon polyps

As a result of the studies described earlier, it has become clear that not all serrated polyps merely represent innocuous hyperplastic polyps, but that these lesions comprise a heterogeneous group of polyps, some of which are likely associated with a significant cancer risk. The current classification of serrated colorectal polyps is summarized in Box 1 .

Box 1

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