Revisiting the distinct histomorphologic features of inflammatory bowel disease-associated neoplastic precursor lesions in the SCENIC and post-DALM Era

Distinct histomorphologic features of colitis-associated dysplasia (CAD) or neoplastic precursors in inflammatory bowel disease (IBD) have never been clearly identified. In this study, we tried to further explore the differentiating morphologic features of CAD by retrospectively reviewing the lesions that were clearly associated with carcinomas (carcinoma-related lesions) and by comparing between endoscopically nonpolypoid (non-adenoma-like) lesions and polypoid (adenoma-like) lesions and sporadic conventional adenomas found in the noncolitic mucosa and in patients without IBD. Our study results have revealed that (1) precursor lesions related to IBD-associated colorectal carcinomas were almost always nonpolypoid in macroscopic/endoscopic appearance; (2) nearly half of the carcinoma-related lesions and nonpolypoid lesions were similarly nonadenomatous (nonconventional) lesions, largely serrated type, with no or only mild/focal adenomatous dysplasia, and commonly had mixed adenomatous and nonadenomatous features; (3) carcinoma-related and nonpolypoid adenomatous dysplastic lesions frequently showed some peculiar histocytologic features that we observed and described for the first time, including mixed features of inflammatory pseudopolyps or granulation tissue, pleomorphic and disarrayed nuclei, micropapillary or hobnailing surface epithelial cells, and microvesicular or bubbling cytoplasm of dysplastic cells; and (4) polypoid lesions in the colitic mucosa were identical to sporadic adenomas in the noninflamed mucosa and in patients without IBD, and they lacked the aforementioned features. The seemingly distinctive morphologic characteristics that we proposed here, although still not absolutely specific or unique, can be used as the features of inclusion for identifying CAD on endoscopic biopsies when the endoscopy images are not readily available to pathologists and thus to alert clinicians for a closer follow-up.