P1188Sessile serrated lesions in inflammatory bowel disease: Do they behave differently? A retrospective comparative analysis

Abstract Background It is uncertain if sessile serrated lesions (SSLs) in patients with inflammatory bowel disease (IBD) represent coincidental sporadic lesions or a distinct biological entity. Molecular studies suggest SSLs in IBD are more frequently KRAS mutated, contrasting with the BRAF driven pathway typical of sporadic SSLs.¹,² More recent data supports a distinct clinicopathologic and molecular profile,3 the understanding of which is critical for optimising surveillance strategies. Methods Colonic serrated lesions from St. Mark’s Hospital pathology database (2014–2022) were reviewed and classified as SSL or dysplastic SSL (SSL-D) and stratified by disease background: IBD, serrated polyposis syndrome (SPS) or sporadic. Cases with overlapping conditions or indeterminate features were excluded. Lesion size, location, patient demographics and IBD subtype and extent were compared. Ethical approval was obtained for this study. Results IBD group: 224 SSLs were identified (200 SSL, 24 SSL-D; dysplasia rate 10.7%). 132 out of 157 patients had ulcerative colitis. No significant differences were seen in lesion location, size or IBD related factors between SSL and SSL-D (Table 1). Median cumulative inflammatory burden for SSL-D was 3.58. SSL-Ds did not show a significant right-sided predominance. SSL-Ds were more frequent in older patients (median 69 vs 60 yrs, p = 0.006). Sporadic group: 5304 SSLs (5030 SSL, 274 SSL-D; dysplasia rate 5.2%) were identified. SSL-Ds were predominantly right-sided and more frequent in older patients (median 68 vs 61 yrs; p 0.001). SPS group: 4554 SSLs (3662 SSL, 82 SSL-D; dysplasia rate 2.2%) were identified. SSL-Ds were also mainly right-sided and more frequent in older patients (median 64 vs 41 yrs; p 0.001). The proportion of low to high grade dysplasia was similar across groups (p = 0.32), but dysplasia rates were significantly higher in IBD (p 0.000001). SSL-Ds occured throughout the IBD colon, lacking the right-sided predominance seen in sporadic or SPS cases (IBD p = 0.3; Sporadic p = 0.001; SPS p = 0.007). Demographically, groups were similar with no significant age difference (p = 0.058). Conclusion SSLs in IBD show a significantly higher dysplasia rate than those in SPS or sporadic cases, despite similar demographic and morphologic features. SSL-Ds in IBD were more likely to be found throughout the colon compared with the typical right sided dominance seen in SPS and sporadic cases. Traditional risk factors for advanced neoplasia, including disease duration and extent, did not distinguish dysplastic from non-dysplastic SSLs in IBD, although small numbers of SSL-D may underestimate significant findings. Further clinical and molecular investigation is needed to clarify the unexpectedly high dysplasia rate in IBD associated SSLs. References: 1. Singhi AD, Waters KM, Makhoul EP, et al. Targeted next-generation sequencing supports serrated epithelial change as an early precursor to inflammatory bowel disease-associated colorectal neoplasia. Hum Pathol. 2021;112:9-19. doi:10.1016/j.humpath.2021.03.002 2. Waters KM, Singhi AD, Montgomery EA. Exploring the spectrum of serrated epithelium encountered in inflammatory bowel disease. Hum Pathol. 2023;132:126-134. doi:10.1016/j.humpath.2022.06.018 3. Balajthy Z, Almási S, Lantos T, et al. Whole-Exome Sequencing Analysis of Inflammatory Bowel Disease-Associated Serrated Dysplasia. Int J Mol Sci. 2025;26(12):5704. Published 2025 Jun 13. doi:10.3390/ijms26125704 Conflict of interest: Dr. Renshaw, Sara: No conflict of interest Latchford, Andrew: No conflict of interest Panchall, Lajja: No conflict of interest Dhillon, Angad: No conflict of interest Thomas-Gibson, Siwan: No conflict of interest Powell, Nick: No conflict of interest Wilson, Ana: No conflict of interest