Non-Conventional Dysplasia in Patients With Inflammatory Bowel Disease and Colorectal Adenocarcinoma

Introduction: Patients with inflammatory bowel disease (IBD) face increased risk of colorectal cancer (CRC). While the characteristics of conventional dysplastic precursor lesions are well known, several atypical patterns of non-conventional (NC) lesions have been recently described in IBD. Others have shown that NC lesions are more likely than conventional dysplasia to be aneuploid and develop CRC. We aimed to assess the incidence of antecedent NC lesions in patients with IBD who developed CRC. Methods: A case-cohort study was performed to include patients with a diagnosis of IBD with or without CRC at a single large referral center who underwent at least 2 surveillance endoscopic procedures between 1/1/2007 and 5/31/2023. Relevant demographic, clinical, endoscopic, and histologic data were abstracted, including location and number of dysplastic lesions predating diagnosis of CRC. Non-conventional lesions included serrated change, indefinite for dysplasia, and hyperplastic lesions as documented in pathology reports. A Cox model with Prentice weights for case-cohort design was used to estimate the effect of number of lesions (square-root transformed) on the risk of CRC. Results: In total, 87 patients with IBD and CRC and 200 patients with IBD without CRC were identified. Of the cases (36.8% female, median age 50.6 years at first surveillance endoscopy), a majority had ulcerative colitis (59.8%) with extensive colitis being the most common type (88.5%). Fifteen (28.8%) had backwash ileitis and 25 (28.7%) had primary sclerosing cholangitis. Six (6.9%) had documented dysplasia prior to the start of the study period with indefinite for dysplasia being the most common baseline lesion morphology (50%). For the endpoint of CRC, most had surgical resection (88.5%) with most common locations being rectosigmoid (44.8%) and right (41.4%) colon. At the time of CRC diagnosis, a median of 3 (IQR 1, 5) NC lesions were identified per subject. Both conventional (HR 1.78, 95% CI 1.05-3.01) and NC (HR 1.91, 95% CI 1.35-2.71) lesions were associated with increased risk of CRC. There is no significant evidence (P=0.85) that the risk is different between these 2 classes of lesions (Table 1). Conclusion: Both conventional and NC lesions seem to be associated with increased risk of CRC. This highlights the importance of recognizing NC lesions in patients with IBD. Further studies to compare rates of NC lesions to conventional dysplasia prior to a diagnosis of CRC and assess incidence of CRC in longitudinal cohorts are needed. Table 1. - Patient characteristics Control (subcohort) (N = 200) Case (outside subcohort) (N = 87) P value Age at first surveillance endoscopic procedure 0.0021 Median (Q1, Q3) 42.6 (29.5, 56.8) 50.6 (35.7, 64.2) Sex 0.0932 Male 105 (52.5%) 55 (63.2%) Female 95 (47.5%) 32 (36.8%) Vital status < 0.0012 Alive 188 (94.0%) 68 (78.2%) Deceased 12 (6.0%) 19 (21.8%) Years of surveillance 0.131 Median (Q1, Q3) 5.2 (1.8, 8.9) 6.8 (3.0, 9.6) Total number of surveillance endoscopic procedures <0.0011 Median (Q1, Q3) 3.0 (2.0, 5.0) 4.0 (3.0, 7.0) 1Kruskal-Wallis rank sum test.2Pearson's Chi-squared test.