Sessile Serrated Adenoma (SSA) vs. Traditional Serrated Adenoma (TSA)

Abstract

The morphologic distinction between various serrated polyps of the colorectum may be challenging. The distinction between sessile serrated adenoma (SSA) and traditional serrated adenoma (TSA) may be difficult using currently available criteria mostly based on cytologic characteristics. We have evaluated 66 serrated polyps including 29 SSA, 18 TSA, and 19 hyperplastic polyps for overall shape of the polyps, architectural features of individual crypts, the presence of eosinophilic cytoplasm, size and distribution of the proliferation and maturation zones, as well as Ki-67 and CK20 expression. The extent of the expression of CK20 and Ki-67 could not distinguish between the 3 types of serrated polyps, but the distribution of their expression was very helpful and differences were statistically significant. The distribution of Ki-67+ cells was the single most helpful distinguishing feature of the serrated polyp type (P<0.0001, chi test). Hyperplastic polyps had regular, symmetric, and increased Ki-67 expression. SSA had irregular, asymmetric, and highly variable expression of Ki-67. TSA had low Ki-67 expression, which was limited to "ectopic crypts" and admixed tubular adenomalike areas. In serrated polyps, ectopic crypt formation (ECF) defined by the presence of ectopic crypts with their bases not seated adjacent to the muscularis mucosae was nearly exclusive to TSA and was found in all cases, while the presence of cytologic atypia and eosinophilia of the cytoplasm were characteristic, but not limited to TSA. No evidence of ECF, but nevertheless abnormal distribution of proliferation zone was characteristic of SSA, whereas HP had neither. The presence of the ECF defines TSA in a more rigorous fashion than previous diagnostic criteria and also explains the biologic basis of exuberant protuberant growth associated with TSA and the lack of such growth in SSA. Recognition of this phenomenon may also help in exploring the genetic and molecular basis for differences between SSA and TSA, because these architectural abnormalities may well be a reflection of abnormalities in genetically programmed mucosal development.

A clinicopathological and molecular analysis of 200 traditional serrated adenomas

“…Ki67 and cytokeratin 20 predominantly showed the pattern described by Torlakovic et al, with a high Ki67 index in the ectopic crypt formations and basal crypts but very limited in the typical surface cells and the opposite pattern with cytokeratin 20. 13 The Ki67 index was high in essentially all areas of dysplasia or early carcinoma. A proportion of ordinary and advanced traditional serrated adenomas, particularly BRAF mutant cases, showed an aberrant cytokeratin 7 and cytokeratin 20 immunophenotype.…”

“…3,7,[11][12][13] All polyps displayed at least two of the following three features: (1) typical cytology, (2) slit-like epithelial serrations, and (3) ectopic crypt formations, with at least one feature evident in 450% of the polyps (Figures 1a and b).…”

“…7 Since then, a diverse range of polyps including sessile serrated adenoma, sessile serrated adenoma with dysplasia, and tubulovillous adenoma with prominent serration have been misclassified as traditional serrated adenomas. 11 Publications by Torlakovic et al 12,13 in 2003 and 2008 improved diagnostic reproducibility by characterizing the sessile serrated adenoma and identifying key features of the traditional serrated adenoma, in particular ectopic crypt formations. The fourth edition of the WHO Classification of Tumors of the Digestive Tract emphasizes protuberant and villiform growth patterns and ectopic crypt formations in the diagnosis of the traditional serrated adenoma.…”

“…Many pathologists consider the typical eosinophilic cell of the traditional serrated adenoma to be inherently dysplastic, yet these cells are not morphologically atypical, do not display mitotic activity, and show absent or minimal proliferative activity by Ki67 staining. 11,13 Moreover, a subset of traditional serrated adenomas develop discrete areas of morphologically overt dysplasia. [14][15][16] How to classify these advanced traditional serrated adenomas and how to separate them from ordinary traditional serrated adenomas in routine practice has been inadequately addressed.…”

“…Whereas some probably arise de novo, many appear to arise in a precursor polyp, especially microvesicular hyperplastic polyps or sessile serrated adenomas. 13,[16][17][18] The traditional serrated adenoma also shows more molecular heterogeneity than most other polyps. The frequency of BRAF and KRAS mutation and CpG island methylator phenotype high versus CpG island methylator phenotype low or negative is variable in the literature, unusual for a polyp that, above issues aside, is morphologically fairly uniform.…”