Traditional serrated adenoma of the colorectum: Evolving concepts in histological classification and terminology

Traditional serrated adenoma (TSA) is the least common of the currently recognized serrated colorectal polyps and, thus, elucidating its pathogenesis, spectrum of morphological features and biological risk has been challenging. Most TSAs harbour either KRAS or BRAF mutations and may progress to adenocarcinoma via distinct carcinogenic pathways. TSAs with KRAS mutation are more commonly located in the distal colorectum, whereas BRAF-mutant TSAs typically arise proximal to the transverse colon, may be associated with a background sessile serrated lesion and represent putative precursors of biologically aggressive BRAF-mutant, mismatch repair-proficient colorectal carcinomas. This review summarizes the evolution of the concept of TSA as a distinct pathological entity and its relationship to other neoplasms within the serrated neoplastic pathway. The molecular and histopathological characteristics of TSAs are outlined, with particular emphasis on the classification of lesions with mixed morphology, including those associated with non-dysplastic serrated components and those showing progression to severe dysplasia, with the hope of improving their recognition. Although further studies are required to validate the proposed terminology, consistent classification of these lesions is essential to improve recognition and to advance understanding of this uncommon pathway to colorectal carcinoma.