1 AJCP / Original article Am J Clin Pathol 2021;XX:1-6 DOI: 10.1093/ajcp/aqaa254 © American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com “Indeterminate” UroVysion Fluorescence In Situ Hybridization Results Clinical Implications of Diagnostic Terminology Jing Xu, MD, PhD,* Danielle E. Westfall, MD,* and Jean R. Lopategui, MD From the Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Key Words: UroVysion; Molecular diagnostics; Urinary tract neoplasm Am J Clin Pathol 2021;XX:1–6 DOI: 10.1093/AJCP/AQAA254 ABSTRACT Objectives: UroVysion cases with one to three abnormal cells that do not meet the threshold for positivity may be better classifed as “indeterminate.” The aim of this study is to determine the incidence and clinical signifcance of these indeterminate UroVysion results. Methods: The UroVysion fuorescence in situ hybridization (FISH) results over a 4-year period in our institution were retrospectively analyzed. Follow-up of the initial UroVysion cases, including urine cytology or bladder biopsy performed within 12 months of the initial diagnosis of the result, was obtained from pathology reports. Results: A signifcant fraction (178 of 1,907, 9.3%) of the UroVysion cases had indeterminate results. Overall, the subsequent malignancy rate of the group with indeterminate UroVysion results (14 of 59, 23.7%) was higher than the group with normal results (48 of 319, 15.0%), although the difference was not signifcant (P = .124). For patients without a history of urinary tract neoplasm, the subsequent malignancy rate in the group with indeterminate results (7 of 18, 38.9%) was signifcantly higher than the group with normal results (16 of 103, 15.5%) (P = .044). Conclusions: Our results support that indeterminate UroVysion FISH result may warrant closer clinical follow-up in patients without a history of urinary tract neoplasm. We suggest reporting these cases as “aneusomy of undetermined signifcance.” Bladder cancer is one of the most common cancers in the United States, with an estimated 81,400 new cases and 17,980 deaths from bladder cancer in 2020. 1 Initial diag- nosis and monitoring for recurrence of bladder cancer are mainly accomplished by cystoscopy combined with urine cytology. 2 Cytology has a high specificity for the detection of bladder cancer (72%-93%) but a rather low sensitivity (28%-100%; mean, 48%), especially for the detection of low-grade cancers in which the sensitivity may reach as low as 17%. 3-8 An atypical cytology result may confound the clinical decision-making process further. Certain treatment modalities employed in the treatment of bladder cancer, such as Bacillus Calmette-Guérin, mitomycin, or radiation, may also cause reactive morphologic changes in cells that further complicate the diagnosis of recurrent carcinoma. Recent research has focused on urine tumor markers. While several of these markers are approved by the US Food and Drug Administration (FDA) and many have a high sensi- tivity, few attain the high specificity of urine cytology. 6,9,10 One such ancillary technique for the detection of bladder carcinoma is the fluorescence in situ hybridization (FISH) test, UroVysion (Abbott/Vysis). UroVysion is an FDA-approved, four-target, multicolor interphase FISH probe set approved for use on voided urine specimens for monitoring patients with bladder cancer (2001) as well as Key Points • Of the UroVysion cases in our institution, 9.3% had indeterminate results. • In patients with a history of urinary tract malignancy, there was no signifcant difference in the subsequent malignancy rate between cases with indeterminate UroVysion results and normal results. • In patients without a history of urinary tract malignancy, cases with indeterminate UroVysion results were more likely to develop malignancy compared with those with normal results. Downloaded from https://academic.oup.com/ajcp/advance-article/doi/10.1093/ajcp/aqaa254/6161213 by guest on 08 April 2021