title: Causes of false-negative for high-grade urothelial carcinoma in urine cytology.
abstract: BACKGROUND
  The Paris System for classifying urine cytology emphasizes identification of high-grade urothelial carcinoma (HGUC). The causes of false-negative urine cytologies (UC) within this system are not well described.
  
  
  METHODS
  We identified 660 cases between 2005 and 2013 with both UC and subsequent cystoscopic biopsies. UC were classified as either Negative for HGUC or "Abnormal" ("Atypical", "Suspicious", and "Malignant"). Apparent false-negative cases were reviewed in a nonblinded fashion by two cytopathologists and two subspecialized genitourinary pathologists.
  
  
  RESULTS
  A total of 199 of the 660 cases (30%) were histologically diagnosed as HGUC. The UC were "Abnormal" in 170/199 cases (sensitivity/specificity of 86%/71%). Twenty four apparent false negative cases were available for retrospective review. Five of 24 (21%) cystoscopic biopsies were found not to be HGUC on review (one false positive and four low-grade urothelial carcinoma (LGUC on review). Of the remaining 19 UC, 7 (29%) cytology samples were found to be truly negative on review, 11 (46%) were found to be Atypical, and 1 (4%) suspicious. Of the 12 UC that were at least "Atypical" with histologic HGUC on review: six misses (half) were attributed to obscuring inflammation/blood, four to poor preservation, eight to paucity of abnormal cells, and 1 case to interpretive error; many cases demonstrated overlapping reasons.
  
  
  CONCLUSIONS
  About one fifth of apparent false negative diagnoses for HGUC can be because of overdiagnosis of HGUC by surgical pathologists. If poor preservation or obscured samples are called nondiagnostic, the sensitivity/specificity of UC for HGUC can be as high as 94%/71%. Diagn. Cytopathol. 2016;44:994-999. © 2016 Wiley Periodicals, Inc.
authors: Department of Pathology, University of Massachusetts Memorial Health Care, 1 Innovation Dr, Biotech 3, Worcester, Massachusetts.
authors: Paul J
authors: PJ
authors: Lee
authors: Department of Pathology, University of Massachusetts Memorial Health Care, 1 Innovation Dr, Biotech 3, Worcester, Massachusetts.
authors: Christopher L
authors: CL
authors: Owens
authors: Department of Pathology, University of Massachusetts Memorial Health Care, 1 Innovation Dr, Biotech 3, Worcester, Massachusetts.
authors: Marie Y
authors: MY
authors: Lithgow
authors: Department of Pathology, University of Massachusetts Memorial Health Care, 1 Innovation Dr, Biotech 3, Worcester, Massachusetts.
authors: Zhong
authors: Z
authors: Jiang
authors: Department of Pathology, University of Massachusetts Memorial Health Care, 1 Innovation Dr, Biotech 3, Worcester, Massachusetts.
authors: Andrew H
authors: AH
authors: Fischer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000473:pathology* / Q000652:urine; D003581:Cytodiagnosis / Q000592:standards / Q000706:statistics & numerical data; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014556:Urine / Q000166:cytology*; D014571:Urologic Neoplasms / Q000473:pathology* / Q000652:urine; D019459:Urothelium / Q000473:pathology*
keywords: Paris classification; false negative; fluorescence in situ hybridization; high-grade urothelial carcinoma; urine cytology