Hypermucinous, Goblet Cell Deficient, and Crypt Cell Dysplasias in Inflammatory Bowel Disease are Often Associated with Flat/Invisible Endoscopic Appearance and Advanced Neoplasia on Follow-Up.

BACKGROUND AND AIMS 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 more attention, but there is limited information regarding their clinicopathologic features and clinical outcomes. METHODS 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 7 different institutions and analyzed. RESULTS 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 50%) nuclear overexpression or null staining pattern, including 4 (33%) of 12 hypermucinous, 2 (29%) of 7 goblet cell deficient, and 8 (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). CONCLUSIONS Hypermucinous, goblet cell deficient, and crypt cell dysplasias have distinct clinicopathologic features but appear to have a similar high risk of association with advanced neoplasia (HGD or adenocarcinoma). Greater 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.