Serrated tubulovillous adenoma of the large intestine

Mark Bettington, Neal Walker, Christophe Rosty, Ian Brown, Andrew Clouston, Diane McKeone, Sally-Ann Pearson, Kerenaftali Klein, Barbara Leggett, Vicki Whitehall

Most colorectal polyps are readily classified, but a subset of tubulovillous adenomas (TVA) with prominent serrated architecture cause diagnostic confusion. We aimed to 1) identify histological features that separate serrated TVAs from both conventional TVAs and traditional serrated adenomas (TSA) and 2) perform a clinicopathological and molecular analysis to determine if the serrated TVA has unique features. We collected 48 serrated TVAs, 50 conventional TVAs and 66 BRAF wild-type TSAs for analysis. For each polyp we performed a clinicopathological assessment, BRAF and KRAS mutation profiling, CpG island methylator phenotype status, MGMT methylation and immunohistochemical assessment of seven markers (MLH1, p16, p53, β-catenin, Ki67, CK7 and CK20). We found that serrated TVAs can be reliably diagnosed and have features distinct from both conventional TVAs and TSAs. Compared to conventional TVAs, serrated TVAs are larger, more often proximal, more histologically advanced, show more CpG island methylation and more frequent KRAS mutation. Compared to TSAs, they are more often proximal, show less CpG island methylation, more frequent MGMT methylation and more frequent nuclear staining for β-catenin. The serrated TVA can be reliably diagnosed and has unique features. It represents a precursor of KRAS mutated, microsatellite stable colorectal carcinoma. This article is protected by copyright. All rights reserved.