Colorectal serrated lesions are characterized by a sawtooth or stellate architecture [1]. This category of lesions includes different entities, with peculiar morphological, molecular and clinical features, namely hyperplastic polyps (HPs), sessile serrated lesions (SSLs), and traditional serrated adenomas (TSAs). HPs are further divided into two categories: microvesicular (MVHPs) and goblet cell-rich HPs (GCHPs) [1], [2]. A subset of colorectal serrated lesions harbors dysplasia. In particular, SSLs can show adenomatous dysplasia, similar to that seen in conventional adenomas; serrated dysplasia, with crowded glands composed of cells with eosinophilic cytoplasm, markedly atypical round nuclei and numerous mitoses; or the so called “minimal deviation dysplasia”, characterized by subtle cytological and architectural atypia and often by the loss of MLH1 expression [1], [3]. Similarly, TSAs, charactered by slit-like serrations and ectopic crypts, may also have areas of overt dysplasia, which is described as either conventional, or serrated type [4].

MVHPs and SSLs typically present BRAF activating mutations. Moreover, some SSLs, especially the ones located in the right colon, can show extensive methylation of CpG islands, with the consequent inactivation of different genes [5]. In some SSL with dysplasia (in particular, of the “minimal deviation” type), the silencing of MLH1 gene in the dysplastic component, through the hypermethylation of its promoter, is associated with loss of expression of MLH1 and PMS2 proteins and with the impairment of the DNA mismatch repair system (MMR), resulting in microsatellite instability (MSI) [6]. On the other hand, GCHPs and TSAs are known to have KRAS activating mutations [7], [8]; these lesions are not associated with DNA hypermethylation, with the possible exception of right-sided TSA, which may present BRAF mutations and genomic hypermethylation, but usually without MLH1 inactivation [9].

Among dysplastic serrated lesions of the colon and rectum, some show mixed histological features, having a serrated and a conventional adenomatous component. According to the 2019 World Health Organization (WHO) classification, SSL and TSA with areas of conventional adenomatous dysplasia are not classified as mixed lesions, but as SSL or TSA with dysplasia [1]. However, in some cases the adenomatous component may not have arisen in the context of the serrated lesion, but may be an independent lesion, arisen de novo. Thus, certain SSLs or TSAs with conventional type dysplasia may actually represent collision lesions, as demonstrated by Bettington et al. through BRAF mutational analysis [10].

The aim of this study was to analyze a series of dysplastic serrated lesions (in particular, of conventional type) using immunohistochemistry and molecular methods in order to evaluate the presence of concordance between the dysplastic and the non-dysplastic component. Among the dysplastic serrated lesions we considered, some were identified as SSL with dysplasia, according to the last edition of WHO classification, while others were identified as mixed lesions, comprising a hyperplastic polyp and a conventional adenomatous component. In this way, we could assess whether adenomatous dysplasia had developed in the serrated lesion, or whether it represented a distinct lesion that had fused with the serrated polyp.