title: Atypical nephrogenic metaplasia of the urinary tract: a precursor lesion?
abstract: BACKGROUND
  Nephrogenic metaplasia with cytologic atypia (atypical nephrogenic metaplasia) is occasionally encountered and its biologic potential is uncertain.
  
  
  METHODS
  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 (34betaE12), cytokeratin 7, cytokeratin 20, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), p53, and MIB-1 were performed in 9 cases.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. lcheng@iupui.edu
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: J C
authors.initials: JC
authors.lastname: Cheville
authors.forename: T J
authors.initials: TJ
authors.lastname: Sebo
authors.forename: J N
authors.initials: JN
authors.lastname: Eble
authors.forename: D G
authors.initials: DG
authors.lastname: Bostwick
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002272:Carcinoembryonic Antigen / Q000032:analysis; D004247:DNA / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D018396:Mucin-1 / Q000032:analysis; D011003:Ploidies; D011230:Precancerous Conditions / Q000175:diagnosis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014551:Urinary Tract / Q000737:chemistry / Q000473:pathology*; D014571:Urologic Neoplasms / Q000175:diagnosis* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D018396:Mucin-1; D016159:Tumor Suppressor Protein p53; D007633:Keratins; D004247:DNA