A review of the performance of urinary cytology with a focus on atypia, upper tract and updates on novel ancillary testing

J Am Soc Cytopathol. 2025 Jan-Feb;14(1):23-35. doi: 10.1016/j.jasc.2024.09.001. Epub 2024 Sep 19.

Abstract

The Paris System for Reporting Urine Cytology (TPS) is remarkable for its high predictive value in the detection of high-grade urothelial carcinoma, especially of the bladder. However, universal compliance with TPS-recommended threshold for atypical call rates (15%) and TPS performance in the rarer upper tract urothelial carcinomas (UTUC) are challenging. UTUC diagnosis is compounded by instrumentation artifacts, degenerative changes superimposed on an ambiguous cytology, difficult-to-access location, lack of specific standardized criteria, and a limited number of UTUC-focused studies. We reviewed TPS-applied studies published since 2022, noting up to 50%, exceeding the suggested 15% threshold for atypia. Our examination of ancillary tests for UTUC explored novel approaches including DNA methylation analysis, the detection of overexpressed tumor-linked messenger RNAs, and immunohistochemistry on markers such as CK17. Preliminary evidence from our review suggests that ancillary tests display superior performance over cytology, including in voided samples and low-grade urothelial carcinoma. Importantly, voided samples obviate the risks of ureterorenoscopy. Finally, we explored the future opportunities offered by artificial intelligence and machine learning for a more objective application of TPS criteria on urine samples.

Keywords: Artificial intelligence and machine learning; High-grade urothelial carcinoma; Low-grade urothelial carcinoma; The Paris System; Upper tract urothelial carcinoma; Urothelial carcinoma.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor* / urine
  • Carcinoma, Transitional Cell / diagnosis
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / urine
  • Cytodiagnosis / methods
  • DNA Methylation
  • Humans
  • Immunohistochemistry / methods
  • Urinalysis / methods
  • Urinary Bladder Neoplasms / diagnosis
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / urine
  • Urine / cytology
  • Urologic Neoplasms* / diagnosis
  • Urologic Neoplasms* / pathology
  • Urologic Neoplasms* / urine
  • Urothelium / pathology

Substances

  • Biomarkers, Tumor