• bladder;
  • nephrogenic metaplasia;
  • urinary tract;
  • atypia;
  • precursor;
  • urothelial carcinoma;
  • adenocarcinoma



Nephrogenic metaplasia with cytologic atypia (atypical nephrogenic metaplasia) is occasionally encountered and its biologic potential is uncertain.


The authors describe 18 cases of atypical nephrogenic metaplasia characterized by the presence of prominent cytologic atypia, including nuclear enlargement, nuclear hyperchromasia, and enlarged nucleoli. DNA ploidy analysis by digital image analysis and immunostaining for high-molecular-weight cytokeratin (34βE12), cytokeratin 7, cytokeratin 20, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), p53, and MIB-1 were performed in 9 cases.


The mean patient age was 62 years (median, 65 years; range, 39–84 years). The male-to-female ratio was 2.6:1. Two patients had a history of noninvasive papillary urothelial carcinoma. The typical clinical presentation was hematuria (8 patients) and voiding symptoms (5 patients). Cystoscopic findings were suspicious for neoplasm in 7 of 13 cases. The neoplastic cells were positive for high-molecular-weight cytokeratin, cytokeratin 7, and EMA, and were usually negative for cytokeratin 20 and CEA. p53 nuclear accumulation and increased MIB-1 labeling index were seen in 4 cases. DNA ploidy analysis showed aneuploid pattern in 2 of 9 cases. The mean patient follow-up was 3.5 years (range, 0.5–10.6 years); 2 patients had recurrent nephrogenic metaplasia, and the remainder were alive without recurrence or urothelial carcinoma.


Atypical nephrogenic metaplasia is benign; it occasionally displays substantial cytologic abnormalities of no apparent clinical significance. Awareness of the spectrum of cytologic changes within this entity is critical to prevent overdiagnosis of cancer and avoid unnecessary treatment. There is no direct evidence that links atypical nephrogenic metaplasia to cancer. Cancer 2000;88:853–61. © 2000 American Cancer Society.