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

Abstract

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 < 0.001). Most lesions were low-grade (87%) at diagnosis, but goblet cell deficient dysplasia (31%) more often showed high-grade dysplasia (HGD) than 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 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.

The Significance of Flat/Invisible Dysplasia and Nonconventional Dysplastic Subtypes in Inflammatory Bowel Disease: A Review of Their Morphologic, Clinicopathologic, and Molecular Characteristics

“…6A). 38,41,43,44 Another common histologic feature includes eosinophilic luminal secretion (Fig. 6B).…”

“…38,44 Up to 65% of these lesions can present as flat/invisible dysplasia, but when endoscopically visible, they often have a polypoid appearance with a mean size of 1.7 to 1.9 cm. 38,44 It is more likely to be associated with conventional dysplasia (74%) than hypermucinous (43%) and crypt cell (48%) dysplasias (P = 0.044). 44 Similar to hypermucinous and crypt cell dysplasias, goblet cell deficient dysplasia may be another marker of increased risk for advanced neoplasia.…”

“…Although pathologists have become very familiar with the morphologic criteria of conventional dysplasia, several underrecognized morphologic patterns of epithelial dysplasia are known to occur in IBD and have been the recent focus of new investigations. 38,[41][42][43][44] These novel forms are collectively known as "nonconventional" dysplasia and include at least the following 7 subtypes:…”

“…38,44 Although it is not uncommonly associated with conventional dysplasia, hypermucinous dysplasia may be the only dysplastic subtype identified in up to 57%. 44 Histologically, hypermucinous dysplasia is defined by the presence of tall, prominent mucinous cells representing > 50% of the lesion (Fig. 3).…”

“…42 Greater than half of these lesions (52%) can occur as isolated dysplastic lesions without association with conventional dysplasia. 44 Similar to hypermucinous dysplasia, increasing evidence suggests that crypt cell dysplasia likely represents at least highrisk LGD, if not already HGD. In favor of this, we previously reported that all 14 crypt cell dysplastic lesions from 7 IBD patients demonstrated aneuploidy.…”