Several different types of non-conventional dysplasia have been recently described in inflammatory bowel disease [IBD]. Hypermucinous, goblet cell-deficient and crypt cell dysplasias have received most attention, but there is limited information regarding their clinicopathological features and clinical outcomes. A total of 126 cases of hypermucinous [n = 55], goblet cell-deficient [n = 26] and crypt cell [n = 45] dysplasias from 97 IBD patients were collected from seven different institutions and analysed. The cohort included 62 [64%] men and 35 [36%] women with a mean age of 49 years [range: 20–78]. The majority of affected patients had longstanding IBD [mean duration: 18 years]. Nineteen [20%] patients had a concurrent history of primary sclerosing cholangitis. As a group, non-conventional dysplasia was predominantly found in patients with ulcerative colitis [UC] [n = 68; 70%] and occurred in the left colon [n = 80; 63%]; however, hypermucinous dysplasia [57%] was the least frequently associated with UC compared with goblet cell-deficient [74%] and crypt cell [89%] dysplasias [p = 0.016]. Fifty [52%] patients had a history of conventional dysplasia, detected in the same colonic segment as non-conventional dysplasia at a rate of 33%. Goblet cell-deficient dysplasia [74%] was more frequently associated with conventional dysplasia than hypermucinous [43%] and crypt cell [48%] dysplasias [p = 0.044]. While hypermucinous dysplasia often had a polypoid appearance [58%], crypt cell [96%] and goblet cell-deficient [65%] dysplasias were more likely to present as flat/invisible lesions [p < 0.001]. Most lesions were low-grade [87%] at diagnosis, but goblet cell-deficient dysplasia [31%] more often showed high-grade dysplasia [HGD] compared with hypermucinous [15%] and crypt cell [0%] dysplasias [p = 0.003]. Hypermucinous dysplasia usually demonstrated a tubulovillous/villous architecture [76%], whereas goblet cell-deficient dysplasia was predominantly tubular [92%]. A flat architecture was exclusively associated with crypt cell dysplasia [100%] [p < 0.001]. Immunohistochemical stain results for p53 were available for 33 lesions; 14 [42%] showed strong [3+] and patchy [10–50%] to diffuse [>50%] nuclear overexpression or null staining pattern, including four [33%] of 12 hypermucinous, two [29%] of seven goblet cell-deficient and eight [57%] of 14 crypt cell dysplastic lesions [p = 0.726]. Follow-up biopsies or resections were available for 92 low-grade lesions from 71 patients; 55 [60%] lesions, including 19 [49%] of 39 hypermucinous, 10 [59%] of 17 goblet cell-deficient and 26 [72%] of 36 crypt cell dysplastic lesions [p = 0.116], were associated with subsequent detection of HGD [n = 34; 37%] or adenocarcinoma [n = 21; 23%] at the site of previous biopsy or in the same colonic segment within a mean follow-up time of 12 months [range: <1–73]. Hypermucinous, goblet cell-deficient and crypt cell dysplasias have distinct clinicopathological features but appear to have a similar high risk of association with advanced neoplasia [HGD or adenocarcinoma]. More than half of the lesions [66%] presented as flat/invisible dysplasia, suggesting that IBD patients may benefit from random biopsy sampling in addition to targeted biopsies. Although not uncommonly associated with conventional dysplasia, non-conventional dysplasia may be the only dysplastic subtype identified in IBD patients. Therefore, it is important to recognize these non-conventional subtypes and recommend complete removal and/or careful examination and follow-up.

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. 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. 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]. 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.