Nonconventional colorectal dysplasia is less prevalent and has a more limited morphologic spectrum in patients...

Colorectal dysplasia in inflammatory bowel disease (IBD) includes conventional and diverse nonconventional morphologic patterns, the latter of which are often endoscopically invisible or flat and are associated with an increased risk of advanced neoplasia. However, the prevalence and significance of nonconventional dysplasia in patients without IBD remain unclear. We analyzed 669 sporadic colorectal dysplastic lesions from 211 patients without IBD or syndromic polyposis, including 103 patients with colorectal cancer (CRC) (293 dysplastic lesions) and 108 without CRC (376 dysplastic lesions). Sporadic lesions were also compared with 317 dysplastic lesions from 168 patients with IBD. In the sporadic cohort, conventional dysplasia predominated (89%), whereas 11% were nonconventional, most commonly Paneth cell-rich dysplasia (9%). Goblet cell-deficient (1%) and hypermucinous (0.4%) patterns were rare, and no cases of basal crypt dysplasia, crypt cell dysplasia, or serrated dysplasia not otherwise specified were identified. Most sporadic lesions were tubular (93%), low-grade (95%), polypoid (97%), and right-sided (60%). Compared with lesions in the non-CRC group, those in the CRC group were more frequently nonconventional (14% vs. 9%, p = 0.045), larger (mean: 1.0 vs. 0.7 cm, p < 0.001), and more likely to show tubulovillous/villous architecture (10% vs. 5%, p = 0.016), high-grade dysplasia (HGD; 10% vs. 2%, p < 0.001), and invisible gross appearance (2% vs. 0%, p = 0.023). When compared with IBD-associated lesions, sporadic lesions occurred at an older age (mean: 61 vs. 53 years, p < 0.001) and showed significantly lower rates of nonconventional morphology (11% vs. 25%, p < 0.001), HGD (5% vs. 16%, p < 0.001), invisible/flat appearance (3% vs. 24%, p < 0.001), and left-sided location (39% vs. 48%, p = 0.006). In conclusion, although nonconventional dysplasia is not exclusive to IBD, several patterns, including hypermucinous, goblet cell-deficient, and basal crypt dysplasias, are rare or absent in patients without IBD. Although their low prevalence suggests that these patterns are unlikely to be major contributors to CRC risk in patients without IBD, a potential association with an increased risk of concurrent or subsequent CRC cannot be excluded, given the paucity of random colonic biopsies in this population.