Flat intraurothelial lesions of the urinary bladder-do hyperplasia, dysplasia, and atypia of unknown significance need to exist as diagnostic entities? and how to handle in routine clinical practice

Mod Pathol. 2022 Oct;35(10):1296-1305. doi: 10.1038/s41379-022-01087-7. Epub 2022 Apr 25.


Classification of the putative flat preneoplastic and neoplastic lesions of the urothelium with features subthreshold for urothelial carcinoma in situ remains a challenging, indeed, vexing problem in diagnostic surgical pathology. This area, subtending lesions including flat urothelial hyperplasia, urothelial dysplasia, and atypia of unknown significance, has struggled under evolving classifications, changing criteria, and limited clinical actionability, all confounded by the recognized lack of diagnostic reproducibility. Herein, we review the state of the literature around these lesions, reviewing contemporary criteria and definitions, assessing the arguments in favor and against of retaining hyperplasia, dysplasia, and atypia of unknown significance as diagnostic entities. We clarify the intent of the original definitions for dysplasia as a lesion felt to be clearly neoplastic but with morphologic features that fall short of the threshold of urothelial carcinoma in situ. While several pathologists, including some experts in the field, conflate the term dysplasia with urothelial atypia of unknown significance, the latter is defined as a descriptive diagnosis term to express diagnostic uncertainty of a lesion of whether it is clearly reactive or neoplastic. Both molecular studies and clinical needs are considered, as we outline our approach on diagnosing each of these lesions in clinical practice. Recommendations are made to guide consistency and interoperability in future scholarship, and the place of these lesions in context of evolving trends in the field is considered.

Publication types

  • Review

MeSH terms

  • Carcinoma in Situ* / diagnosis
  • Carcinoma in Situ* / pathology
  • Carcinoma, Transitional Cell* / pathology
  • Humans
  • Hyperplasia / diagnosis
  • Hyperplasia / pathology
  • Precancerous Conditions* / diagnosis
  • Precancerous Conditions* / pathology
  • Reproducibility of Results
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms* / diagnosis
  • Urinary Bladder Neoplasms* / pathology
  • Urothelium / pathology