The pathology of serrated colorectal neoplasia: practical answers for common questions

In the past 10-15 years, recognition and considerable understanding of much of the so-called 'serrated pathway' of colorectal neoplasia has emerged, although much remains to be discovered. Key elements appear to be a propensity for the elderly, females more than males, and right colon; precursor lesions with serrations; and frequent BRAF mutations, hypermethylation (particularly involving the MHL1 promoter), and resultant dysfunctional DNA mismatch repair and microsatellite instability (MSI) of the colorectal adenocarcinomas. For the anatomic pathologist, this has created challenges in sometimes having to morphologically subdivide once-comfortable hyperplastic polyps into hyperplastic polyps and 'sessile serrated adenoma/polyps' (SSA/Ps), learn to distinguish these from 'traditional' serrated adenomas, and learn to recognize biologically progressing forms of SSA/Ps known as 'sessile serrated adenoma with cytological dysplasia'. The goal of this article is to highlight for the practicing anatomic pathologist the current status of our understanding of serrated colorectal neoplasms from a practical perspective.