Iatrogenic changes in the urinary tract

Antonio Lopez-Beltran, Gladell P. Paner, Rodolfo Montironi, Maria R. Raspollini, Liang Cheng

Research output: Contribution to journalReview article

11 Scopus citations


A handful of therapeutic procedures are used to treat malignancies of the urinary tract, most frequently intravesical immunotherapy or chemotherapy, but also neoadjuvant systemic chemotherapy. These treatment modalities produce morphological changes in the urothelium that can be mistaken for carcinoma; in particular, these therapies frequently mimic urothelial carcinoma in situ (CIS) urothelial dysplasia or true invasive neoplasia. Drugs such as mitomycin C used after transurethral resection of bladder tumour to reduce recurrences, bacillus Calmette–Guérin (BCG) intravesical immunotherapy to treat high-risk non-muscle-invasive bladder cancer and urothelial CIS and platin-based systemic chemotherapy to improve postcystectomy disease-specific survival are examples of therapy-related atypia seen in the urinary tract. To complicate the pathologist's life, a number of systemic drugs in use to treat other diseases, such cyclophosphamide, used to treat some autoimmune disorders or certain haematological malignancies or, in the case of anaesthetics, ketamine, used increasingly as an illegal recreational drug, may produce similarly relevant atypical changes in the urothelium, and therefore need to be differentiated from intraepithelial neoplasia. Other less frequent procedures, such as photodynamic and laser therapy or the newer gene therapy to treat urothelial neoplasia, remain experimental. An immunohistochemical approach to reactive urothelium versus carcinoma in situ using p53, cytokeratin 20 and CD44 is also valid in the post-therapy setting. The pathologist should be aware of these novelties, as he or she plays a crucial role in evaluating treatment efficacy, but at the same time needs to avoid misdiagnosing secondary atypia as intraepithelial neoplasia.

Original languageEnglish (US)
Pages (from-to)10-25
Number of pages16
Issue number1
StatePublished - Jan 1 2017


  • atypia
  • bladder flat lesions
  • chemotherapy
  • immunotherapy
  • radiation therapy
  • urothelium

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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    Lopez-Beltran, A., Paner, G. P., Montironi, R., Raspollini, M. R., & Cheng, L. (2017). Iatrogenic changes in the urinary tract. Histopathology, 70(1), 10-25. https://doi.org/10.1111/his.13090