Increased Risk of Non-conventional and Invisible Dysplasias in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Disease

Background and Aims Patients with primary sclerosing cholangitis and inflammatory bowel disease [termed PSC-IBD] have a higher risk of developing colorectal neoplasia than those with IBD alone. The mechanism by which concomitant PSC increases the risk of colorectal neoplasia remains unknown. Seven distinct non-conventional dysplastic subtypes have been recently described in IBD, including crypt cell dysplasia, hypermucinous dysplasia, goblet cell-deficient dysplasia, dysplasia with increased Paneth cell differentiation [DPD], sessile serrated lesion [SSL]-like dysplasia, traditional serrated adenoma [TSA]-like dysplasia, and serrated dysplasia, not otherwise specified [NOS]. Despite the lack of high-grade morphological features, crypt cell, hypermucinous, and goblet cell-deficient dysplasias often show molecular features characteristic of advanced neoplasia [i.e. aneuploidy and KRAS mutations] and are more frequently associated with advanced neoplasia than conventional dysplasia on follow-up. We aimed to characterise clinicopathological features of dysplasia found in PSC-IBD patients. Methods A cohort of 173 PSC-IBD patients were analysed. All dysplastic lesions were subtyped as either conventional or non-conventional dysplasia. The clinicopathological features of PSC-IBD patients with neoplasia were also compared with those of non-PSC IBD patients with neoplasia. Results There were 109 [63%] men and 64 [37%] women, with a mean age of 26 years at IBD diagnosis and a long history of IBD [mean duration: 14 years]. Ulcerative colitis was the most common IBD subtype [80%], and the majority of patients [92%] had a history of pancolitis. A total of 153 dysplastic lesions were detected in 54 [31%] patients, 35 [65%] of whom had multifocal dysplasia. One additional patient presented with colorectal cancer [CRC] without a history of dysplasia. Dysplasia was often non-conventional [n = 93; 61%], endoscopically/grossly invisible [n = 101; 66%], and right/proximal-sided [n = 90; 59%]. All seven non-conventional subtypes were identified, including 46 [30%] crypt cell dysplasia, 23 [15%] hypermucinous dysplasia, 12 [8%] goblet cell-deficient dysplasia, seven [5%] DPD, three [2%] TSA-like dysplasia, one [1%] SSL-like dysplasia, and one [1%] serrated dysplasia NOS. Follow-up information was available for 86 lesions, of which 32 [37%] were associated with subsequent detection of advanced neoplasia [high-grade dysplasia or CRC] within a mean follow-up time of 55 months. PSC-IBD patients with neoplasia were more likely to have pancolitis [98%, p = 0.039] and a longer IBD duration [mean: 17 years, p = 0.021] than those without neoplasia [89% and 12 years, respectively]. When compared with a cohort of non-PSC IBD patients with neoplasia, the PSC-IBD group with neoplasia was more often associated with non-conventional [61%, p <0.001], invisible [66%, p <0.001], and right/proximal-sided [59%, p = 0.045] dysplasias [vs 25%, 21%, and 47%, respectively, for the non-PSC IBD group]. The rate of advanced neoplasia was nearly 2-fold higher in the PSC-IBD group [37%] compared with the non-PSC IBD group [22%] [p = 0.035]. Conclusions Nearly a third of PSC-IBD patients developed dysplasia, which is often associated with non-conventional dysplastic features, invisible endoscopic/gross appearance, right/proximal-sided colon, multifocality, and advanced neoplasia on follow-up. These findings underscore the importance of recognising these non-conventional subtypes by practising pathologists and the need for careful and frequent endoscopic surveillance, with random biopsies, in PSC-IBD patients.

Automated summary

Nearly a third of PSC-IBD patients developed dysplasia, which is often associated with non-conventional dysplastic features, invisible endoscopic/gross appearance, right/proximal-sided colon, multifocality, and advanced neoplasia on follow-up.