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

Patients with inflammatory bowel disease are at significantly increased risk of dysplasia and colorectal cancer (CRC). The early detection, histologic grading, and removal of dysplasia plays a critical role in preventing the development of CRC. With advances in endoscopic visualization and resection techniques, colectomy is no longer recommended to manage dysplasia, unless surveillance colonoscopy detects flat/invisible dysplasia (either high-grade dysplasia or multifocal low-grade dysplasia) or an endoscopically unresectable lesion. Although there are numerous review articles and book chapters on the morphologic criteria of conventional (intestinal type) dysplasia, the most well-recognized form of dysplasia, at least 7 distinct nonconventional morphologic patterns of epithelial dysplasia have been recently described in inflammatory bowel disease. Most practicing pathologists are not familiar with these nonconventional subtypes and thus, may even overlook some of these dysplastic lesions as benign or reactive. However, the recognition of these subtypes is important, as some of them appear to have a high risk of developing advanced neoplasia (high-grade dysplasia or CRC) and often show molecular alterations characteristic of advanced neoplasia. This review briefly describes the morphologic criteria of conventional dysplasia but predominantly focuses on all 7 nonconventional subtypes as well as our understanding of their clinicopathologic and molecular features that can assist in their risk stratification.