Serrated lesions in Inflammatory Bowel Disease
Magali Svrcek, H-ECCO Member
In addition to the “classical” pathway of colorectal carcinogenesis, involving development of cancer from an adenomatous precursor lesion, an alternative pathway, the serrated pathway, is now recognised to exist, and it is estimated that approximately 30% of colorectal cancers (CRC) arise via this alternative pathway . In the last WHO classification, serrated polyps were classified as (i) hyperplastic polyps (HP), (ii) sessile serrated adenoma/polyps (SSA/P), with or without dysplasia, and (iii) traditional serrated adenomas (TSA). The possibility of a serrated pathway has also been suggested in colorectal carcinoma complicating Inflammatory Bowel Disease (IBD) [2–4]. Little is known concerning immunohistochemical and molecular features of serrated lesions in IBD: Data are limited to small series of patients or case reports and findings are controversial due to the rarity of the cases. However, the clinical, pathological and biological characteristics of serrated polyps in patients with IBD do seem to resemble those of their sporadic counterparts.
Most serrated lesions observed in IBD are HP (96% in Shen’s series), almost all of the remainder being SSA/P. TSA seems to be exceptional . The majority of these serrated lesions are observed in the left colon and rectum, in areas involved by the IBD, and more than 50% are detected endoscopically . Dysplasia in SSA/P in IBD patients may not resemble conventional adenomatous dysplasia, which is typically characterised by elongated, penicillate, pseudo-stratified nuclei, with mitosis. Indeed, “serrated” dysplasia, first described in 2010 in the WHO classification, is characterised instead by round or oval and vesicular nuclei. However, some SSA/P may contain foci of conventional dysplasia.
In the two most important literature series in which the 2010 WHO criteria for classification of sporadic serrated lesions were applied, the diagnostic inter-observer reproducibility was relatively good: Kappa = 0.63  and nearly 100% . However, in these two series, the pathologists were experts in gastrointestinal pathology.
The incidence of serrated lesions in IBD seems to be very low. One of the most important recent series (from one large North American centre) retrospectively identified 78 serrated polyps among 6,602 IBD patients undergoing surveillance colonoscopies between 2000 and 2013 , representing an incidence of 1.2%. Serrated polyps negative for dysplasia, which are morphologically similar to SSA/P, are more common in women and are mostly right sided, whereas serrated polyps with low-grade dysplasia or indefinite for dysplasia are more common in males and more commonly left sided [3, 5].
From a molecular point of view, the majority of serrated polyps negative for dysplasia have mutations in BRAF, whereas few serrated polyps with low-grade dysplasia and no serrated polyps indefinite for dysplasia have BRAF mutations. In contrast, KRAS mutations are the most common mutations in serrated polyps positive for low-grade dysplasia and serrated polyps indefinite for dysplasia, but are only seen in a minority of serrated polyps negative for dysplasia.
Serrated lesions arising in the setting of IBD can be multiple and resemble the entity described as “hyperplastic/serrated polyposis syndrome” [2, 6]. The seven patients reported in these two series had a moderate to severe pancolitis, evolving for more than 10 years, and had more than 20 polyps. Morphologically, the serrated lesions were a combination of HP and SSA/P in all cases with, in addition, TSA and “conventional” adenomas in two and three patients respectively.
Besides serrated lesions, “serrated epithelial changes” (or SEC) have been described as a histological finding in longstanding colitis. According to some authors, these epithelial changes with a serrated architecture could be synonymous with hyperplastic-like mucosal change and flat serrated change. They are characterised, from a morphological point of view, by glands with distorted architecture (in contrast to HP) and by crypts which are no longer perpendicular to the muscularis mucosae and which do not necessarily reach the muscularis mucosae. Serration of the epithelium and enlarged goblet cells both extend to the base of the crypts . However, publications mentioning these lesions do not systematically show images or systematically detail the pathological criteria used for the diagnosis of SEC. Therefore, it is difficult to recognise them and to compare various studies . The significance of SEC and their relationship to dysplasia in IBD patients are not clearly understood. Some publications suggest an association between SEC and dysplasia in IBD patients [7, 8]. However, further controlled studies are needed to determine whether SEC are a precancerous lesion in IBD patients and whether the presence of SEC warrants revision of IBD surveillance protocols.
The risk of progression of serrated lesions in IBD is not clear. It is worth noting that two of the three patients with multiple serrated lesions in one study had a synchronous CRC (one adenocarcinoma developing from an SSA/P and one mucinous carcinoma from a TSA) . Patients with HP in a setting of IBD seem to have a very low risk of developing a conventional neoplastic lesion (flat dysplasia or CRC), and should not need a higher frequency of surveillance . In the study by Ko et al., rates of prevalent neoplasia associated with serrated polyps with low-grade dysplasia, indefinite for dysplasia and no dysplasia were 76%, 39% and 11% respectively . In the same study, the actuarial 10-year rates of development of advanced neoplasia (high-grade dysplasia and carcinoma) in patients with serrated polyps with low-grade dysplasia, indefinite for dysplasia and negative for dysplasia were 17%, 8% and 0% respectively. Therefore, these authors felt it reasonable to conclude that a diagnosis of low-grade dysplasia or indefinite for dysplasia in an IBD-associated serrated polyp warrants clinical caution and careful follow-up, in contrast to non-dysplastic serrated lesions (though the level of evidence is low). Overall, however, the question of the appropriate surveillance strategy in patients with serrated lesions in IBD remains open.
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