Filiform serrated adenoma is an unusual, less aggressive variant of traditional serrated adenoma

Abstract

Aims: Filiform serrated adenoma (SA) is an uncommon type of polyp that shows morphological features similar to traditional serrated adenoma (TSA). Unlike TSA, filiform SA is composed predominantly of prominent, thin, elongated filiform projections lined by neoplastic epithelium with a serrated contour. However, the molecular pathogenesis underlying filiform SA is unclear and its relationship with TSA has not been explored yet. The purpose of this study was to determine the clinicopathological and molecular characteristics of filiform SA in a cohort of Korean patients. Methods: Thirteen filiform SAs were evaluated for mutations of BRAF and KRAS genes, microsatellite instability (MSI), and promoter hypermethylation of hMLH1, MGMT, p16, MINT1, MINT2, MINT31 and the APC genes. The clinicopathological and molecular results were compared to results from previously published studies of left-sided TSAs among Koreans. Results: All but one filiform SAs were located in the left colon and showed low grade dysplasia. BRAF and KRAS mutations were observed in six (46.2%) and four (30.3%) filiform SAs, respectively. Hypermethylation of hMLH1 (using both Herman et al. and Park et al.), MGMT, p16, MINT1, MINT2, MINT31 and the APC gene was found in 30.3% and 7.7%, 38.5%, 15.4%, 53.8%, 46.2%, 38.5% and 15.4% of cases, respectively. Thirteen filiform SAs were MS stable and classified with a CpG island methylator phenotype (CIMP) of high in five, CIMP low in five and CIMP negative in three cases. Compared to TSAs in the left colon, methylation of hMLH1, APC, and MGMT was less frequent in cases of filiform SA, but the filiform SA sizes were larger. Conclusion: Our findings suggest that filiform SA may grow larger without acquisition of additional genetic alterations and can be categorised as a rare, less aggressive variant of TSA with unique morphology.