Colon Polypectomy

A Brief History of Serrated Colorectal Polyps

Before 1996, the majority of colorectal polyps were divided into 2 groups, the hyperplastic polyp (HPP), which, in many Western series, constituted the most common polyp, and adenomas, which were divided into several subgroups based predominantly on the degree of villous architecture.[1] A number of less common polyps (juvenile retention polyps, various forms of hamartomatous polyps, inflammatory polyps, and others) were considered more or less curiosities in general practice. Although there was some controversy about the significance of HPP and adenomas in the 1960s and 1970s, a consensus developed that adenomas, particularly those with a villous component, were precursors to colorectal carcinoma and that HPPs were not.[1] Challenges to the concept were raised from time to time, including arguments that adenomas with no villous components did not develop into carcinoma and that HPPs in the lower colon were markers for the development of adenomas in the higher reaches of the colon; however, by the last decade of the 20th century, there was relatively little debate about the overall concept of a dichotomy between these 2 types of polyps.

Nevertheless, there were clues suggesting that this dichotomy might not be so clear. For example, early on there were reports of “hyperplastic polyp” at the margin of a significant percentage of adenomas.[2] HPPs also were recognized as occurring in much higher frequency in populations at risk for the development of colorectal carcinoma.[3] Occasional HPPs were recognized as becoming large, particularly in the ascending colon, and occasional large HPPs with adenocarcinoma were seen but rarely reported.[4,5] Urbanski et al[6] in 1984 reported, in what may turn out to be a prescient article, a case of adenocarcinoma arising in a “mixed hyperplastic-adenomatous” polyp and suggested that this phenomenon was an underdiagnosed condition. Subsequently, Longacre and Fenoglio-Preiser[7] analyzed a group of polyps with mixed features of HPP and adenoma and concluded that most of these cases, rather than representing a mixed tumor, were actually adenomas with a serrated configuration, leading to the term serrated adenoma. Although serrated adenoma now was recognized as a discrete entity, in general it nevertheless was considered a variant of villous or tubulovillous adenoma (TVA), and recommendations for management followed the general guidelines for traditional adenomas.

In 1996 Torlakovic and Snover,[8] in a review of a series of patients with so-called hyperplastic polyposis, suggested that this was a condition with a high propensity for the development of adenocarcinoma, despite the consensus at that time that this syndrome was not associated with an increased risk. This premalignant risk subsequently was confirmed by several other groups and today is generally accepted.[9-11] Perhaps more important, this same article analyzed the morphologic features of the polyps of “hyperplastic polyposis” compared with small sporadic HPPs and concluded that there were significant morphologic differences that would allow histologic distinction of these 2 lesions.[8] It was thought that the polyps of hyperplastic polyposis bore some features in common with the serrated adenomas described by Longacre and Fenoglio-Preiser[7] but maintained a sessile configuration, and the term sessile serrated adenoma (SSA) was coined to distinguish these lesions from the more pedunculated lesions of what might now be termed traditional serrated adenoma (TSA).[12] These similar features included serration, architectural distortion, occasional small areas with superficial cytologic dysplasia and eosinophilic change identical to that seen in a majority of TSAs, and occasional transition from SSA to TSA. Because of these features and the now accepted risk for carcinoma, it was recommended that this condition be renamed serrated adenomatous polyposis. Use of such a term was considered important to avoid mismanagement by clinicians accustomed to the concept that all HPPs were indolent and, in essence, could be ignored.

It is of some historic interest that the original draft of that manuscript[8] used the term sessile serrated adenomatosis, but the name was changed at the recommendation of reviewers to serrated adenomatous polyposis. In retrospect, this was unfortunate, because the term serrated adenomatous polyposis sometimes has been misconstrued to mean a colon with multiple TSAs, a condition that has yet to be described. It also would seem that some have interpreted the article as describing a new entity when the intent was to rename the old lesion, HPP. This fact, however, may be responsible in part for the failure of most pathologists to recognize this condition under any name other than hyperplastic polyposis.

Another observation of this article was that there were a number of other lesions in the literature that were considered HPPs that, after careful review of published illustrations (and personal observations), were most likely SSA rather than HPPs.[8] These included mucosal hyperplasia of the appendix, “inverted” HPPs, and, most important, mixed tubular adenoma-hyperplastic polyps (which are better termed mixed sessile serrated adenoma-tubular adenoma)[1,4,13] (to be discussed further). Abnormal proliferation characterized a lesion in which the proliferation zone did not occupy its normal location in the basal third to half of the crypt but had migrated upward in the crypt, often in an irregular manner such that on one side of a crypt the proliferation zone was higher than on the other side or, in some cases, occupied only 1 side of the crypt. The proliferation zone may or may not have been truly expanded but was positioned abnormally. This alteration was noted to be associated with a number of other histologic findings (detailed subsequently). The lesions were termed sessile serrated adenomas, in keeping with the terminology coined earlier in serrated adenomatous polyposis (hyperplastic polyposis).

From 1996 until 2003, the concept of a serrated lesion with bland cytologic features that was not an HPP was not generally accepted, although there were scattered reports from the United States and Japan of presumably neoplastic serrated lesions described with a variety of terms such as serrated adenoma, polypoid and superficial types and serrated adenoma types 1 and 2, which might have been describing the same lesion as SSA.[14,15] In 2003, Torlakovic et al[12] reported their study of sporadic serrated lesions (excluding TSAs and mixed lesions) using cluster and discriminant analysis and identified several discrete clusters of polyps that generally could be subdivided into polyps with “abnormal” proliferation and those with “normal” proliferation.

The group with normal proliferation, which seemed to constitute the group of polyps fitting the general distribution and morphologic features of the lesions originally described as HPPs, could be subdivided into 3 types based on the character of their mucin — microvesicular, goblet cell, and mucin-poor. The lesions designated as SSAs demonstrated a decrease in staining for hMLH1 and hMSH2, and this fact, along with review of the literature (see subsequent text), suggested that SSA was a likely candidate to be the precursor lesion for some colorectal adenocarcinomas with microsatellite instability (MSI).

In 2003, Goldstein et al[16] reported a histologic analysis of lesions originally diagnosed as HPPs that had been removed at sites where MSI-high colon cancers were later diagnosed. This analysis revealed findings essentially identical to those of Torlakovic et al,[12] and Goldstein et al[16] also recommended the term sessile serrated adenoma for this lesion. Their data more directly supported the concept that SSA was the precursor to at least some MSI-high colon cancers.