Long-standing inflammatory bowel disease (IBD) increases the risk of dysplasia and colorectal cancer (CRC), particularly in patients with extensive disease or coexisting primary sclerosing cholangitis (PSC). Several non-conventional dysplasia subtypes have been identified. Hypermucinous dysplasia was first formally proposed in 2020, and it arises predominantly in patients with long-standing ulcerative colitis, frequently in extensive disease and concomitant PSC. Histologically, hypermucinous dysplasia is characterized by a tubulovillous or villous architecture lined by tall, prominent, mucin-rich epithelial cells comprising more than 50% of the lesion, with minimal-to-mild cytologic atypia. Although often classified as low-grade dysplasia according to previously established criteria, hypermucinous dysplasia is disproportionately associated with advanced neoplasia, including high-grade dysplasia and CRC, and frequently coexists with both conventional and other non-conventional dysplasias. Molecular alterations commonly include aneuploidy and occasional TP53 mutation. Emerging evidence suggests that non-dysplastic, mucin-rich epithelial proliferation, such as hypermucinous mucosa and foveolar metaplasia, may represent putative precursor lesions within a broader metaplasia–dysplasia sequence. This review provides the first comprehensive synthesis focusing exclusively on hypermucinous dysplasia, highlighting the consistency in histopathologic definitions, proposed precursor lesions, clinicopathological associations, molecular features, and diagnostic reproducibility. Increased awareness of hypermucinous dysplasia is essential for accurate diagnosis, risk stratification, high-risk IBD population screening, and optimal management of patients with IBD.
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2026 The Author(s). Journal of Digestive Diseases published by Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.
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