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Sessile Serrated Lesions in Inflammatory Bowel Disease: Hidden Players in Colitis-Associated Colorectal Cancer?
Roberto de Sire1,2, Diletta De Deo1,3, Miriana Mercurio1,3
1Endoscopy Unit, Gastroenterology Department, Humanitas Research Hospital IRCCS, 20089 Rozzano, Italy.
Abstract:
Sessile serrated lesions (SSLs) are well-known precursors of colorectal cancer in the general population, but their role in inflammatory bowel disease (IBD) is less clear. This narrative review summarizes what is known about the prevalence, molecular features, endoscopic detection, malignant potential, and management of SSLs in patients with IBD, highlighting where evidence supports action nowadays and where prospective studies are urgently needed. IBD-associated colorectal cancer has long been considered a consequence of the inflammation-dysplasia-carcinoma sequence, distinct from the conventional adenoma-carcinoma pathway. Increasing evidence, however, suggests that the serrated pathway, typically characterized by SSLs and traditional serrated adenomas (TSAs), may also contribute to IBD-related oncogenesis. This review synthesizes histopathological, molecular, endoscopic, and clinical data on SSLs in patients with IBD, with contextual reference to TSAs, sessile serrated lesions with dysplasia, and serrated epithelial change only when relevant to their interpretation or risk stratification. SSLs are now more frequently identified in IBD surveillance, especially in ulcerative colitis and the proximal colon, although prevalence estimates remain heterogeneous due to evolving definitions and significant interobserver variability. Molecular studies indicate that IBD-associated serrated lesions often harbor BRAF mutations but display a lower CpG island methylator phenotype than their sporadic counterparts, suggesting an inflammation-modified biology. While most hyperplastic polyps and non-dysplastic SSLs appear to pose limited neoplastic risk, dysplastic serrated lesions carry a markedly higher likelihood of synchronous or metachronous advanced neoplasia. Advances in high-definition endoscopy and chromoendoscopy improve the detection of these subtle, mucus-capped, flat lesions, while endoscopic resection is nowadays feasible in expert hands. Future priorities should include prospective multicenter cohorts integrating molecular profiling to refine surveillance strategies.
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