Original articleEvidence-based adequacy criteria for urinary bladder barbotage cytology
Introduction
Urinary tract cytology (UTC) is widely used for the evaluation of hematuria, irritative voiding symptoms, and in the follow-up of urothelial carcinoma (UC).1 The continued use of UTC in the detection of UC, despite numerous proposed alternatives (BTA [Bladder tumor antigen] STAT and BTA TRAK [Polymedco, Courtlandt Manor, NY], Nuclear Matrix Protein/NMP22 [Matritech Inc., Newton, MA], Immunocytology/ImmunoCyte/uCyt+ [Diagnocure, Sainte-Foy, Quebec, Canada], and others2), is due to its high specificity, ranging from 78% to 100%.3 Nonetheless, the reported sensitivity of UTC for the detection of UC is low, especially in studies including low-grade UCs, for which reported detection rates can be as low as 10%.3 Even for high-grade UC (HGUC), the reported sensitivity of UTC ranges from 38% to 100%.3, 4, 5 This large variation in reported sensitivities of UTC in the detection of HGUC is most likely related to multiple factors, including the diagnostic criteria used for the grading of UC on histologic evaluation,6 the type of specimen used (voided urine, bladder barbotage, etc),7 cytopreparatory method, the experience and skill of the interpreter, and the quality of the sample. The quality of the specimen can affect the sensitivity of UTC and may be, at least in part, responsible for its low sensitivity in the detection of HGUCs reported in some studies. However, the impact of the quality of the specimen on the performance of UTC cannot be assessed in the absence of quantifiable adequacy criteria. Unfortunately, such adequacy criteria have not been defined to date.
The aim of this study was to determine what constitutes an adequate bladder washing/barbotage specimen. To reach this goal, we determined the minimum cellularity that allows a cytologic diagnosis to be rendered by using a 2-step approach. In the first step, we serially diluted residual bladder barbotage specimens known to be positive for malignancy to determine the minimum cellularity at which the cytologic preparation could still be diagnosed as abnormal (atypical urothelial cells [AUC] and above). In the second step of this study, we used the cellularity criteria determined in the first step to retrospectively assess the impact on the sensitivity in a large cohort of previously diagnosed bladder barbotage specimens. To our knowledge, this is the first evidence-based study to determine adequacy criteria for bladder washing/barbotage cytology.
Section snippets
Prospective determination of adequacy criteria
Nineteen bladder barbotage specimens were selected for the study. Cases were selected based on the cytologic diagnosis, the availability of residual material, and adequate histologic follow-up. The study group was composed of 10 consecutive specimens diagnosed as “positive for HGUC” that had histologic confirmation as either HGUC or UC in situ (UCIS). The control group consisted of 9 consecutive cases diagnosed as negative for UC or diagnosed as atypical or suspicious with reactive or low-grade
Results
Of a total of 85 UC slides, 19 (22.4%) received a consensus diagnosis of “negative,” 15 (17.6%) of AUC, 3 (3.5%) of suspicious for HGUC, and 48 (56.5%) of positive for HGUC. To achieve a consensus diagnosis, 23 of 85 had to be reviewed over a multiheaded microscope and discussed. In the remaining 62 cases, there was 3-way agreement in 32 cases, 4-way agreement in 21, and 5-way agreement in 9. Table 1 outlines the sensitivity of the consensus diagnosis of both AUC or higher (AUC+) and HGUC.
The
Discussion
In this study, we found that a cutoff value of 20 urothelial cells per 10 hpfs showed a statistically significant increase in sensitivity for the cytologic diagnosis of UC in both phases of our study—the prospective dilutional study and the retrospective review. This suggests that an adequate bladder barbotage specimen should have ≥20 urothelial cells per 10 hpfs when processed by the ThinPrep method. The applicability of this cellularity threshold to other urinary cytopreparatory methods
Conclusions
Our results indicate that, in the absence of atypical or malignant cells, an adequate bladder barbotage specimen should have a minimum of 2644 (20 per 10 hpfs) well-visualized, well-preserved urothelial cells to increase the sensitivity of this test.
Funding sources
No specific funding was disclose.
Conflict of interest disclosures
The authors made no disclosures.
Acknowledgments
The authors thank Elizabeth Sheil and Maria Vivo for their technical expertise in preparing the study material.
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