Traditional serrated adenoma: an overview of pathology and emphasis on molecular pathogenesis

Abstract

ObjectiveTo provide an overview of the pathology and molecular pathogenesis of traditional serrated adenomas (TSA).DesignDescribe the morphology and molecules that play a role in their pathogenesis.ResultsThese exuberant polypoid lesions are typified by tall cells with deeply eosinophilic cytoplasm, elongated nuclei bearing delicate chromatin, ectopic crypt foci, deep clefting of the lining mucosa and an overall resemblance to small bowel mucosa.Broadly, TSAs arise via three mechanisms. They may beBRAFmutated and CpG island methylator phenotype (CIMP)-high: right sided, mediated through a microvesicular hyperplastic polyp or a sessile serrated adenoma, may also haveRNF43mutations and result in microsatellite stable (MSS) colorectal cancers (CRC). The second pathway that is mutually exclusive of the first is mediated throughKRASmutation with CIMP-low TSAs. These are left-sided TSAs, are not associated with another serrated polyp and result in MSS CRC. These TSAs also haveRSPO3,RNF43andp53mutations together with aberrant nuclear localisation of β-catenin. Third, there is a smaller group of TSAs that areBRAFandKRASwild type and arise by as yet unknown molecular events. All TSAs show retention of mismatch repair proteins.ConclusionThese are characteristic unusual polyps with a complex molecular landscape.