Non‐conventional dysplasia in inflammatory bowel disease is more frequently associated with advanced neoplasia and aneuploidy than conventional dysplasia

Abstract

Conclusions: Non-conventional morphological patterns of dysplasia are not uncommon in IBD, detected in 33% of the patients. The higher frequencies of advanced neoplasia (HGD or CRC) and aneuploidy in non-conventional dysplasia, in particular CCD, hypermucinous and GCD variants, suggest that they may have a higher malignant potential than conventional dysplasia or sporadic tubular adenomas, and thus need complete removal and/or careful follow-up.Greater than 40% of non-conventional dysplasia presented as a flat/invisible lesion, suggesting that IBD patients may benefit from random biopsy sampling in addition to targeted biopsies. The majority of nonconventional subtypes appear to develop via the chromosomal instability pathway, whereas an alternative serrated pathway may be responsible for the development of at least a subset of SSL-like and TSA-like dysplasias.

Non-conventional dysplastic subtypes in inflammatory bowel disease: a review of their diagnostic characteristics and potential clinical implications

“…In support of this argument, we recently reported that nonconventional dysplasia (38%) is more frequently associated with advanced neoplasia than conventional dysplasia (19%) (p < .001) [38]. Notably, non-conventional dysplasia with low-grade morphology had a significantly higher rate of aneuploidy (46%) than low-grade conventional dysplasia (8%, p = .002) or sporadic adenomas (9%, p = .037).…”

“…It is predominantly found in UC patients (86%) who often have a concurrent history of PSC (29%). Although the majority of hypermucinous dysplastic lesions have a polypoid endoscopic appearance with a mean size of 2.1 cm [38], up to 42% are endoscopically invisible or flat (unpublished results). Hypermucinous dysplasia shows a predilection for the left colon (57%).…”

“…Although pathologists have a good grasp of the morphologic criteria of conventional dysplasia, several unfamiliar morphologic patterns of dysplasia (collectively known as "non-conventional" dysplasia) have been recently described in IBD. There are at least seven subtypes, including (1) hypermucinous dysplasia; (2) crypt cell dysplasia; (3) dysplasia with increased Paneth cell differentiation; (4) goblet cell deficient dysplasia; (5) SSL-like dysplasia; (6) TSA-like dysplasia; and (7) serrated dysplasia NOS [38,[41][42][43]. Although their clinicopathologic and molecular features are not fully characterized, in part due to the rarity of these subtypes and the likelihood that they are under-recognized, the recognition of these non-conventional subtypes is becoming increasingly important, as they often present as invisible/flat lesions, and at least some of them appear to have a higher malignant potential than conventional dysplasia or sporadic adenomas.…”

“…Morphologically, hypermucinous dysplasia most often demonstrates a tubulovillous/villous architecture lined by tall, prominent mucinous cells representing > 50% of the lesion (Fig. 3A, B) [38,41,43]. Although low-grade dysplastic features are usually present in crypts, the degree of atypia tends to decrease towards the surface epithelium due to prominent mucinous differentiation, so one must be careful not to miss hypermucinous dysplasia when evaluating superficial fragments with hypermucinous features but without significant nuclear atypia (Fig.…”

“…There is evidence that IBD-related invisible/flat dysplasia may have different molecular features compared with visible/ polypoid dysplasia. For instance, the frequency of large-scale chromosomal alterations resulting in aneuploidy as detected by DNA flow cytometry is significantly higher in invisible/flat dysplasia (41% for invisible/flat LGD and 93% for invisible/flat HGD) [37] than in low-grade conventional dysplasia (8%) or sporadic adenomas (9%) [38]. Likewise, using next-generation sequencing, Wanders et al [39] reported that IBD-related dysplastic lesions that are often invisible or flat have more DNA copy number alterations (average number of gains and losses of 4.3 and 3.2, respectively) than sporadic adenomas (1.5 and 0.5, respectively).…”