Original article
Evidence-based adequacy criteria for urinary bladder barbotage cytology

https://doi.org/10.1016/j.jasc.2014.09.206Get rights and content

Introduction

Adequacy criteria are well established in some areas of cytopathology to prevent false negative diagnoses. To date, no such criteria have been proposed and validated for urinary tract specimens. Our aim was to determine a cellularity cutoff point that significantly affects the sensitivity of detecting high-grade or in situ urothelial carcinoma (HGUC or UCIS) in bladder barbotage/washing specimens.

Materials and methods

Bladder barbotage specimens collected in liquid-based media were selected. Specimens diagnosed as “positive for HGUC” (with histologic confirmation) composed the study group, with negative cases as control specimens. Samples were serially diluted and ThinPrep slides of decreasing cellularity were made and reviewed for diagnosis and cellularity. In a retrospective validation study, we identified cases with a “negative for malignancy” bladder barbotage/washing and a surgical pathology diagnosis of UCIS or HGUC (ie, false negative cytology). Cellularity was assessed.

Results

A distinct difference in sensitivity was noted at a cutoff point of 2644 (20 per 10 high-power fields) urothelial cells. Sensitivities increased for atypical or higher (68.3% versus 100%) and HGUC (43.3% versus 88.0%) after application of this cutoff point with high statistical significance (P = 0.001 and 0.0001, respectively). For the retrospective review, cases below the cutoff point were reclassified as unsatisfactory, and sensitivity rose from 76.3% to 84.8% (P = 0.0027).

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 high-power fields) well-visualized, well-preserved urothelial cells to increase the positive predictive value of this test.

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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