Basal crypt dysplasia in inflammatory bowel disease: morphological quandaries, p53 immunohistochemistry and...

Basal crypt dysplasia (BCD) is among the most diagnostically challenging of the non-conventional dysplasia subtypes that arise in the setting of longstanding inflammatory bowel disease (IBD). Its defining characteristic, cytological atypia restricted to the basal compartment of the crypt with a deceptively bland surface epithelium, is contrary to the classical dictum that dysplasia invariably involves the luminal surface. Hence, BCD is frequently under-recognised, misclassified as regenerative change, or dismissed as indefinite for dysplasia, resulting in potentially serious clinical consequences given the established association with synchronous and metachronous advanced neoplasia. p53 immunohistochemistry exploits the early and disproportionate accumulation of p53 mutations in colitis-associated carcinogenesis and has emerged as an invaluable ancillary tool in this specific context. Aberrant or mutant p53 expression: either diffuse strong nuclear overexpression reflecting missense mutation or complete absence of staining reflecting a null/truncating mutation, confined to basal crypts provide objective diagnostic support for dysplasia and supplements morphological assessment. This review examines the molecular and biological rationale underpinning p53 alterations in IBD-related neoplasia briefly, the histopathological definition and clinicopathological significance of BCD, the patterns and diagnostic interpretation of p53 immunostaining, and a practical approach for the pathologist in routine practice. The limitations of p53 immunohistochemistry and the emerging role of complementary biomarkers, most notably SATB2, are critically appraised. Finally, the review addresses some of the controversies and reproducibility studies on BCD in IBD.