Serrated Polyps With “Intermediate Features” of Sessile Serrated Polyp and Microvesicular Hyperplastic Polyp

Abstract

Sessile serrated polyps (SSPs) have been implicated in the pathogenesis of proximal colonic carcinomas, but they lack well-defined diagnostic criteria and their features overlap considerably with those of microvesicular hyperplastic polyps (MVHPs). We have noted that morphologic features of SSPs are often present in small, distally located MVHPs, suggesting that these polyps represent points on a continuum, rather than distinct entities. We evaluated the molecular features of diminutive (<1 cm) nondysplastic serrated polyps that met at least 4 of the 7 "SSP-like" morphologic criteria, but occurred throughout the colorectum, and compared them with SSPs and MVHPs. Fifty nondysplastic serrated polyps (6 SSPs, 31 study polyps, and 13 MVHPs) were evaluated for Ki-67, O6-methylguanine methyltransferase, MUC2, and MUC5AC expression, and also their BRAF and KRAS mutational status. The study polyps and SSPs were similar; 52% and 50% expressed MUC5AC, and 87% and 100% harbored BRAF mutations, respectively, compared with 15% and 46% of MVHPs (P < or = 0.05, all comparisons). O6-methylguanine methyltransferase expression in the study polyps (29%) was intermediate between that of SSPs (83%, P=0.02) and MVHPs (15%, P=0.04). We conclude that the pathologic and molecular features of diminutive, distally located nondysplastic serrated polyps are often indistinguishable from proximally located SSPs, although convincing evidence linking the former to appreciable colorectal cancer risk is entirely lacking. Thus, we propose that, at present, the term "sessile serrated polyp" be restricted to large (> or = 1 cm), proximally located polyps with a presumed biologic risk, until prospective data regarding the natural history of small, distal lesions are available.

Mucin core protein expression in serrated polyps of the large intestine

“…In fact, as noted in Table 1, several histologic factors can be commonly observed between microvesicular HPs and SSAs. This result is consistent with a previous report by Chung et al [13].…”

“…In that framework, "architectural dysplasia" rather than "cytological dysplasia" was the hallmark for the diagnosis of SSA. The significant features distinguishing SSAs from HPs are horizontally and/or laterally branched crypts, basal crypt dilation, exaggerated luminal serration in the lower crypts, increased mucin production, superficial mitoses, cytological atypia in the upper crypts, and an increased epithelial-tostromal ratio [5,9,13]. In the present study, we diagnosed SSAs and HPs on the basis of these morphological features.…”

“…1d) [13]. We compared the following histological features between SSAs and microvesicular HPs (Table 1) [5,9,13]: (1) horizontally and/or laterally branched crypts (upper crypts/lower crypts); (2) basal crypt dilation; (3) exaggerated luminal serration in the lower crypts; (4) increased mucin production; (5) superficial mitoses; (6) mild cytological atypia in the upper crypts, specifically characterized by enlarged vesicular nuclei with prominent nucleoli; and (7) increased epithelial-stromal ratio (>50%). In cases of disagreement regarding histological classification, the two observers reviewed the slice together until a common consensus was obtained.…”

Serrated and non-serrated polyps of the colorectum: their prevalence in an unselected case series and correlation ofBRAFmutation analysis with the diagnosis of sessile serrated adenoma

“…This finding is in keeping with the hypothesis that some MVHPs can progress along the MSI pathway and develop into SSAs 1 3. However, the proportion of MVHPs with BRAF mutation in our study is lower than that reported by others 1 2 10. This could be because we were able to classify correctly a high proportion of serrated polyps with BRAF mutation as SSAs rather than MVHPs.…”

The serrated pathway of colorectal carcinogenesis

“…It is well accepted that a proportion of proximal SSAs will advance to cancer; however, these lesions and the histologically similar MVHPs may also arise in the distal colon. For this reason, Chung et al [52] recently suggested that only proximal serrated polyps that are larger than 1 cm be classifi ed as an SSA to increase the specifi city of predicting clinical signifi cance. The subclassifi cation of HPs into MPHPs, GCHPs, and MVHPs has been restricted to the research setting.…”