Letter to the Editor

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The Routine Use of Urine Cytology in Initial Assessment in a One Stop. Hematuria Clinic: ... cytology and 124 patients had abnormal urine cytology; of the 83 ...
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Saudi J Kidney Dis Transpl 2013;24(5):1009-1011 © 2013 Saudi Center for Organ Transplantation

Saudi Journal of Kidney Diseases and Transplantation

Letter to the Editor The Routine Use of Urine Cytology in Initial Assessment in a One Stop Hematuria Clinic: The Controversy Continues, but can it be Resolved? To the Editor, The value of urine cytology in the initial assessment of hematuria is debatable.1 Interpretation of cytology is observer-dependent, and its sensitivity and specificity vary by collection method and tumor grade.2 False-negative test results are generally attributed to an inability to sample some lesions, e.g. voided urine specimens may not contain shed neoplastic cells, or to difficulties in diagnosing some entities, e.g. low-grade cancers cytologically resemble non-neoplastic urothelium.3 We conducted this study to evaluate the clinical value and cost-effectiveness of routine urine cytology in a one-stop hematuria clinic. Five hundred consecutive patients who attended the one-stop hematuria clinic, with either microscopic or macroscopic hematuria, between January 2008 and December 2008, were studied retrospectively. The investigations included urine cytology, upper tract imaging (intravenous pyelogram and ultrasound scan for macroscopic hematuria or ultrasound scan

and KUB for microscopic hematuria) and flexible cystoscopy. All abnormal results, including malignant cells, suspicious cells and atypical cells, were considered positive. In the study group, 190 patients presented with dipstick-positive hematuria and 210 patients presented with macroscopic hematuria. The median age was 63 years (range, 18–96 years). Five hundred samples of urine were sent for cytology and 124 patients had abnormal urine cytology; of the 83 patients found to have cancer, 62 patients had bladder cancer on flexible cystoscopy, four patients had upper urinary tract cancer diagnosed radiologically and a further nine patients had renal cancer diagnosed radiologically. There were also seven patients with prostate cancer detected either clinically or chemically in patients with an elevated prostate-specific antigen. The remaining 42 patients with abnormal cytology were not found to have cancer on further investigations (Table 1). The estimated total cost for routine urine cytology was £20,000 based on an estimated laboratory cost of £40

Table 1. Analysis of 42 patients with an abnormal result and benign disease. Benign disease Number Polycystic kidney disease 1 Angiomyolipoma 1 Chronic pyelonephritis 1 Renal calculi 12 Ureteric calculi 2 Ureteric stricture 1 Bladder outflow obstruction 23 Colovesical fistula 1

Present age 0.2% 0.2% 0.2% 2.4% 0.4% 0.2% 4.6% 0.2%

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per sample. This did not include the cost of additional investigations and consultations needed to exclude malignancy. Non-malignant transitional cells can show marked variation in size and shape, being multinucleated and polyploid, and can frequently exhibit nuclear and cytoplasmic degenerative changes that can mimic malignancy.4 The paradox of urine cytology is that pleomorphic cells with enlarged hyperchromatic nuclei containing prominent nucleoli can be benign while malignant cells may appear less abnormal.4 Urine cytology lacks sensitivity for low- and intermediate-grade superficial tumors, which constitute the majority of transitional cell carcinomas. Most reported sensitivities for lowgrade tumors are in the region of 30–60%.5 Specificity is higher, but it is not possible to localize cancer based on urine cytology alone. Reactive changes due to stones, infection, inflammation, intravesical therapy and instrumentation, as well as papillary clusters, are responsible for most false diagnoses. In our study, 33.9% of the patients had a benign cause of their hematuria. The majority of these cases was due to urinary calculus or bladder outflow obstruction. Thus, we emphasize the importance of giving clinical information (including instrumentation, previous treatment and the method of urine collection) to enable the cytopathologist to report with greater accuracy. A review of 17 published series showed that, at worst, the false-negative rates for urine cytology were more than 50% for primary bladder cancer, and averaged nearly 75% for superficial low-grade disease.6 An important diagnostic principle is that the higher the grade of the tumor, the more accurate the diagnosis.6 A positive test requires further investigation, which may be invasive and/or involve radiation exposure to localize or rule out malignancy. These investigations may also cause unnecessary anxiety and morbidity to the patients. Furthermore, performing urine cytology on all patients has significant financial and manpower implications.7 In order to reduce the number of unnecessary urine cytology requests, we recommend using the American Urological Association (AUA)

Letter to the Editor

criteria to identify patients with a high risk of having urothelial tumors. The AUA Best Practice Policy on microcopic hematuria recommends cytology only in patients with risk factors for transitional cell carcinoma prior urological history.8 These risk factors include history of smoking, analgesic abuse or cyclophosphamide use; occupational exposure to chemicals or dyes; age older than 40 years; history of gross hematuria, irritative voiding symptoms, urinary tract infection or pelvic irradiation; and prior urological history. Despite the limitations, urine cytology remains very useful in the monitoring of patients with high-grade, superficial, urothelial carcinoma, where sensitivity and specificity are high.5 Acknowledgment The authors would like to thank Mr. D. Byrant, Specialty Registrar in the Northern Deanery, for his contribution in the data collection. Dr. Nourdin Kadi1, Dr. Edwin Lim1, Dr. Pravin Menezes2 1

Urology Department, Derby Royal Hospital, Derby, Midland, 2Urology Department, Sunderland Royal Hospital, Sunderland, Tyne and Wear, England E-mail: [email protected] References 1.

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Hofland CA, Mariani AJ. Is cytology required for a hematuria evaluation? J Urol 2004;171: 324-6. Rosenthal DL, Raab SS. Cytologic Detection of Urothelial Lesions. New York, NY: SpringerVerlag; 2005. Geisinger KR, Stanley MW, Raab SS, et al. Urinary tract cytology. In: Geisinger KR, Stanley MW, Raab SS, et al, eds. Modern Cytopathology. Philadelphia, PA: Saunders; 2003. p. 213-56. Viswanath S, Zelhof B, Ho E, Sethia K, Mills R. Is routine urine cytology useful in the

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Letter to the Editor

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hematuria clinic? Ann R Coll Surg Engl 2008; 90:153-5. Soloway MS. International consultation on bladder tumours. Urology 2005;66:20-1. 40-1. Wiener HG, Vooijs GP, van't Hof-Grootenboer B. Accuracy of urinary cytology in the diagnosis of primary and recurrent bladder cancer. Acta Cytol 1993;37:163-9.

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Nabi G, Greene DR, O'Donnell M. How important is urinary cytology in the diagnosis of urological malignancies? Eur Urol 2003;43: 632-6. Hofland CA, Mariani AJ. Is cytology required for a hematuria evaluation? J Urology 2004; 71:324-6.