Intermediate serrated polyp as an intermediate lesion of hyperplastic polyp and sessile serrated polyp/adenoma in terms of morphological and molecular features.

Although a hyperplastic polyp (HP) shares morphological and molecular features with a sessile serrated adenoma/polyp (SSA/P), HPs and SSA/Ps are considered nonneoplastic and neoplastic epithelial polyps, respectively. Because HPs and SSA/Ps cover the morphological spectrum, we hypothesized that an intermediate serrated polyp (ISP) might exist between an HP and an SSA/P in terms of both morphological and molecular aspects. An ISP was defined as a serrated lesion that carries distorted crypts (columnar crypt dilation, irregularly branching crypts, or horizontally arranged basal crypts) in less than 3 consecutive crypts. We analyzed HPs (microvesicular, n = 16, and goblet cell-rich, n = 28), ISPs (n = 44), and SSA/Ps (n = 26) for their methylation status of 8 CpG island methylator phenotype panel markers and mutation status of KRAS/BRAF. The number of methylated markers and BRAF mutation frequency increased in the order of HP, ISP, and SSA/P. Microvesicular HPs and goblet cell-rich HPs are distinct from each other, based on the high frequency of BRAF and KRAS mutation, respectively, but are not different in the number of methylated panel markers. Proximally located microvesicular HPs and ISPs were higher in the number of methylated markers but lower in the frequency of BRAF mutation than distally located ones. However, SSA/Ps did not show any difference in the number of methylated markers and the frequency of BRAF mutation between proximally and distally located lesions. Our findings that serrated polyps, intermediate between HPs and SSA/Ps in terms of morphological features, display molecular alterations intermediate between those of HPs and SSA/Ps suggest the presence of ISPs between HPs and SSA/Ps.