Histologic mimics of urothelial carcinoma

Semin Diagn Pathol. 2026 Mar;43(2):150993. doi: 10.1016/j.semdp.2026.150993. Epub 2026 Jan 29.

Abstract

Conventional urothelial carcinoma in its invasive form has a relatively nonspecific morphologic description, frequently described as nests of epithelial cells containing hyperchromatic and pleomorphic nuclei, with readily identified mitotic figures, and moderate amounts of eosinophilic cytoplasm, infiltrating as irregular nests, single cells or solid sheets. The presence of a noninvasive papillary or flat component (urothelial carcinoma in situ), combined with the clinical presentation of a urinary bladder mass, typically helps to make the diagnosis. However, morphologic mimics of urothelial carcinoma are not uncommon and they can mimic both invasive and noninvasive forms, range from benign to malignant, and therefore pose significant diagnostic pitfalls that have profound effect on a patient's treatment planning and prognostic implications. Herein, we discuss some of the diagnostic mimickers of urothelial carcinoma and the clinical, immunohistochemical and molecular approaches that can prove useful for making the correct diagnosis. We highlight both the most common and the most difficult diagnostic dilemmas and pitfalls that we have seen in our clinical practice.

Keywords: Ancillary testing; Histologic mimics; Pitfalls; Urothelial carcinoma.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / analysis
  • Carcinoma, Transitional Cell* / diagnosis
  • Carcinoma, Transitional Cell* / pathology
  • Diagnosis, Differential
  • Humans
  • Urinary Bladder Neoplasms* / diagnosis
  • Urinary Bladder Neoplasms* / pathology
  • Urothelium* / pathology

Substances

  • Biomarkers, Tumor