Pathology of serrated colorectal lesions Adrian C Bateman Correspondence to Dr Adrian C Bateman, Department of Cellular Pathology, University Hospital Southampton NHS Foundation Trust, MP002, Level E, South Block, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK; adrian.bateman@uhs.nhs.uk Received 8 January 2014 Accepted 14 January 2014 Published Online First 21 February 2014 To cite: Bateman AC. J Clin Pathol 2014;67:865–874. ABSTRACT The concept of serrated colorectal neoplasia has become recognised as a key process in the development of colorectal cancer (CRC) and an important alternative pathway to malignancy compared with the long- established ‘adenoma-carcinoma’ sequence. Increasing recognition of the morphological spectrum of serrated lesions has occurred in parallel with elucidation of the distinct molecular genetic characteristics of progression from normal mucosa, via the ‘serrated pathway’, to CRC. Some of these lesions can be difficult to identify at colonoscopy. Challenges for pathologists include the requirement for accurate recognition of the forms of serrated lesions that are associated with a significant risk of malignant progression and therefore the need for widely disseminated reproducible criteria for their diagnosis. Alongside this process, pathologists and endoscopists need to formulate clear guidelines for the management of patients with these lesions, particularly with respect to the optimal follow-up intervals. This review provides practical guidance for the recognition of these lesions by pathologists, a discussion of ‘serrated adenocarcinoma’ and an insight into the distinct molecular genetic alterations that are seen in this spectrum of lesions in comparison to those that characterise the classic ‘adenoma-carcinoma’ sequence. INTRODUCTION Until relatively recently the only serrated (‘saw tooth’) colorectal lesion that many diagnostic histo- pathologists were aware of was the hyperplastic polyp. The term ‘serrated polyp’ was first used in 1990 by Longacre and Fernoglio-Preiser to describe a newly recognised form of colorectal polyp that showed features of a conventional adenoma and a hyperplastic polyp. This lesion subsequently became known as the ‘traditional’ serrated adenoma (TSA). 1 Torlakovic and Snover later iden- tified subtle differences between sporadically occur- ring hyperplastic polyps and the polyps found in the condition initially known as ‘hyperplastic polyposis’. These polyps showed a constellation of features that were distinct from both sporadic hyperplastic polyps and TSAs, and this led to the recognition of the ‘sessile serrated lesion’ (SSL). 2 SSLs can of course occur sporadically as well as in the setting of polyposis. Jass later demonstrated that SSLs were associated with a distinct molecular pathway to colorectal cancer (CRC). 3 Jass high- lighted the biological importance of these ‘hyper- plastic polyp-like’ lesions that were more commonly found within the right colon, were usually sessile and relatively large (often 10 mm or more in diameter) but that did not show features of dysplasia as seen in ‘classical’ adenomas. 4 As a result of these and other studies, a spectrum of colorectal polyps exhibiting a partially or wholly serrated architecture is now recognised (table 1). Some of these lesions show no dysplasia of any rec- ognisable form while others show ‘dysmaturation’ that is now recognised by at least some pathologists as a subtle form of dysplasia. Finally, some serrated lesions show ‘conventional’ dysplasia, as is already widely recognised by histopathologists as an inte- gral feature of ‘classical’ colorectal adenomas. These areas of ‘conventional’ dysplasia may be low grade or high grade in nature and in the setting of serrated colorectal polyps, and are usually present within one or more areas of the polyp, combined with other areas that do not show ‘conventional’ dysplasia. This heterogeneous appearance has led to use of the term ‘mixed polyp’ by some groups. During the process of recognition of the serrated colorectal polyp ‘spectrum’, several names have been used to describe some of these lesions and this has led to terminological confusion. The key skill for the diagnostic histopathologist is the ability to recognise that some colorectal lesions that would probably previously have been called ‘hyperplastic polyps’, with the implication that they are not asso- ciated with a significant increase in CRC risk, may in fact represent one of the forms of colorectal polyp that can progress to malignancy. The ability of histopathologists to differentiate accurately between types of serrated lesion is most pertinent during the differentiation between SSLs and hyperplastic polyps, as SSLs are the lesions that may not show conventional dysplasia, yet are asso- ciated with an increased risk of progression to CRC. CRC arising in association with serrated polyps most often shows histological features that are not distinguishable from those of CRC arising in associ- ation with ‘classical’ adenomas. Alternatively, it may show a range of morphological appearances that are characteristic of ‘serrated adenocarcin- oma’. 7 The molecular alterations occurring during progression to CRC along the ‘serrated pathway’ are distinct to those occurring within the classical ‘adenoma-carcinoma sequence’, and there is evi- dence that this progression occurs more quickly within the ‘serrated pathway’. 5 THE SPECTRUM OF SERRATED LESIONS Hyperplastic polyp Hyperplastic polyps are very commonly encoun- tered by all pathologists who report colorectal lesions. They occur at all sites within the large intestine—although they are most common within the distal colon and rectum—and are classically less than 10 mm in size. They share some histological features with SSLs, for example, a serrated architec- ture. Three morphological variants exist—microve- sicular, goblet cell and mucin-poor ( figure 1). Very few pathologists will use this subclassification Editor’s choice Scan to access more free content Bateman AC. J Clin Pathol 2014;67:865–874. doi:10.1136/jclinpath-2014-202175 865 Review group.bmj.com on October 21, 2017 - Published by http://jcp.bmj.com/ Downloaded from