title: Clinical significance of negative and equivocal urinary bladder cytology alone and in combination with DNA image analysis and cystoscopy.
abstract: BACKGROUND
  We evaluated the individual and combined ability of cytology (CYT), image analysis (IA), and cystoscopy (CYSTO) to predict the presence of transitional cell carcinoma (TCC) at 6 months of follow-up in patients with or without a prior history of urothelial carcinoma and negative (NEG) or equivocal (atypical or suspicious) urinary CYT.
  
  
  METHODS
  Fifty-one patients (43 with prior TCC) provided 57 urinary samples that were evaluated by CYT and DNA IA. Forty-nine patients were evaluated by CYSTO. Disease status was reassessed at 6 months by a combination of clinical, CYSTO, CYT, and histologic follow-up.
  
  
  RESULTS
  At 6 months' follow-up, the incidence of recurrence for patients with diploid, broad diploid, or aneuploid DNA histograms was 38%, 73%, and 100%, respectively. In the same group of patients, 43% of patients with NEG and "atypical" CYT recurred compared with 83.3% of patients with "suspicious" CYT. The predictive value (PV) of a positive (+) CYSTO evaluation was 100%; however, a NEG CYSTO examination was correct in only 73% of cases. Sensitivities of CYT, IA, and CYSTO to predict recurrence were 54%, 59%, and 62.5%, respectively, whereas the combined sensitivity of all three modalities was 72%. The +PV of combined CYT and IA in patients with prior TCC was 90% with aneuploidy 100% specific for malignancy; the NEG PV of combined CYT, IA, and CYSTO was 70%. CYT, IA, and CYSTO were highly significant in predicting recurrence (P = 0.0017, P = 0.0026, and P = 0.0002, respectively) whereas tumor grade and degree of invasiveness as assessed on initial biopsy were not significant. However, 11% of patients recurred between 6 months to 1 year who had NEG CYT, NEG CYSTO, and NEG IA.
  
  
  CONCLUSIONS
  Diagnostic accuracy increases in patients with NEG or equivocal CYT if supplemented by DNA IA and CYSTO. In patients with no history of TCC, equivocal urine CYT and/or abnormal DNA IA can occur after chemotherapy, radiation therapy, or viral infection. In these patients, the combined approach together with accurate history is essential for correct diagnosis. For the small subpopulation of patients who recur but demonstrate no abnormalities on combined testing, more sensitive diagnostic tests, such as chromosomal abnormalities by in situ hybridization, need to be developed.
authors.affiliation: Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Katz
authors.forename: P A
authors.initials: PA
authors.lastname: Sinkre
authors.forename: H H
authors.initials: HH
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Kidd
authors.forename: D
authors.initials: D
authors.lastname: Johnston
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000473:pathology*; D003558:Cystoscopy; D004273:DNA, Neoplasm / Q000032:analysis*; D018572:Disease-Free Survival; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011003:Ploidies; D011237:Predictive Value of Tests; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*; D014556:Urine / Q000166:cytology
chemical_list: D004273:DNA, Neoplasm