Serrated neoplasia pathway

Epithelial serration, namely the saw-toothed outline derived from infolded epithelial tufts in the Lieberkühn's crypt, typically features hyperplastic polyps of the large bowel as a result of inhibition of the apoptotic homeostatic control. Dysplasia can affect the serrated epithelium of hyperplastic polyps, featuring right-sided colonic neoplastic polyps, the serrated adenomas. Whereas the diagnosis of sessile serrated adenomas is based mainly on architectural dysplasia, cytologic and nuclear dysplasia define traditional (polypoid) serrated adenomas. In mixed serrated polyps, both tubular or tubulo-villous and serrated adenomatous tissue can be seen, indicating the fusion of the classical adenoma-carcinoma sequence with the serrated pathway. Activating mutation of the BRAF gene is the triggering event, and the CpG islands methylator phenotype is the molecular genetic mechanism driving serrated tumorigenesis. Serrated adenomas are potentially evolving neoplastic lesions, maximally in hyperplastic polyposis, and need to be histologically classified and appropriately managed.