Accuracy of grading of urothelial carcinoma on urine cytology: An analysis of interobserver and intraobserver agreement (original) (raw)

The Utility of Fluorescence in Situ Hybridization for Early Detection of Bladder Urothelial Carcinoma in Comparison with Urine Cytology

Life Science Journal

]UroVysion is a multitarget multicolor florescent in situ hybridization (FISH) probe set combining 4 probes in single probe that detects aneuploidy of chromosomes 3, 7, and 17 and loss of the 9p21 locus in exfoliated urine cells, our study investigated the role of UroVysion in predicting tumor recurrence in patients with free cystoscopy and –ve cytology and detecting new cases of urothelial carcinoma of the bladder in patients complaining of hematuria with high risk of malignancy. Material and Methods: our study conducted on 46 patients, group A: 30 patients with history of superficial urothelial carcinoma and16 patients complaining of gross heamaturia subdivided after cystoscopy into group B) 8 patients with 1ry urothelial carcinoma and group C)8 patients with cystitis. All patients were subjected to voided urine cytology and UroVysion before cystoscopy ± biopsy. Follow up of group A and one case of group C with +ve UroVysion was done for 18 months. Results: The mean age of patient...

Performance of Urinary Markers for Detection of Upper Tract Urothelial Carcinoma: Is Upper Tract Urine More Accurate than Urine from the Bladder?

Disease markers, 2018

To assess the performance of urine markers determined in urine samples from the bladder compared to samples collected from the upper urinary tract (UUT) for diagnosis of UUT urothelial carcinoma (UC). The study comprised 758 urine samples either collected from the bladder ( = 373) or UUT ( = 385). All patients underwent urethrocystoscopy and UUT imaging or ureterorenoscopy. Cytology, fluorescence in situ hybridization (FISH), immunocytology (uCyt+), and nuclear matrix protein 22 (NMP22) were performed. UUT UC was diagnosed in 59 patients (19.1%) (UUT urine) and 27 patients (7.2%) (bladder-derived urine). For UUT-derived samples, sensitivities for cytology, FISH, NMP22, and uCyt+ were 74.6, 79.0, 100.0, and 100.0, while specificities were 66.6, 50.7, 5.9, and 66.7%, respectively. In bladder-derived samples, sensitivities were 59.3, 52.9, 62.5, and 50.0% whereas specificities were 82.9, 85.0, 31.3, and 69.8%. In UUT-derived samples, concomitant bladder cancer led to increased false-po...

Is urinary tract cytology still useful for diagnosis of bladder carcinomas? A large series of 592 bladder washings using a five-category classification of different cytological diagnoses

Cytopathology, 2007

Is urinary tract cytology still useful for diagnosis of bladder carcinomas? A large series of 592 bladder washings using a five-category classification of different cytological diagnoses Background: The aim of this study was to estimate the efficiency of a recent five-category urinary cytological classification. Methods: A total of 592 bladder washings were fixed immediately with Saccomanno's fixative. All samples were centrifuged in a Hettich cyto-centrifuge. For each sample, the reference standard was the histology when a lesion was present at the time of cystoscopy. A five-category cytological classification was used: negative, suspicious of low (S-Lg) or high (S-Hg) grade neoplasia and consistent with low (Lg) or high (Hg) grade neoplasia. Results: For cytological diagnoses of S-Lg and Lg, sensitivity was 37% and specificity was 95% for the histological diagnosis of low-grade non-invasive urothelial papillary tumour (Lg-UPT), which included papillary urothelial neoplasm of low malignant potential and low-grade urothelial carcinoma. For cytological diagnosis of S-Hg and Hg, sensitivity was 44% for high-grade non-invasive urothelial papillary carcinoma (Hg-UPC), 70% for carcinoma in situ (CIS) and 81% for invasive carcinoma (T1 and higher). Specificity was 99% in each case. Cytological diagnosis of S-Hg or Hg was not found for Lg-UPT (0/59) and no cytological diagnosis of S-Lg or Lg was found for invasive carcinoma, but was seen for Hg-UPC in 10% (3/28) and for CIS in 6% (3/50) of cases. Conclusion: Despite the absence of international consensus, the recent five-category cytological classification for urine is accurate for current urological practice.

Comparison of urinary cytology and fluorescence in situ hybridization in the detection of urothelial neoplasia: An analysis of discordant results

Diagnostic Cytopathology, 2018

Background: We examine the performance of cytology and FISH in the detection of urothelial carcinoma (UC), and explore the reasons for discrepant results, and potential clinical implications. Methods: Urine samples from 89 patients were prospectively collected for simultaneous cytology and UroVysion FISH, and results correlated with concurrent biopsies and/or clinical or histologic follow-up data. Corresponding tissue biopsies, where available, were also evaluated by FISH. Results: Sensitivity and specificity of cytology and FISH for the detection of UC was 54.8% and 92% and 50% and 88%, respectively. Only one of seven false-positive urinary FISH results proved to be an "anticipatory positive" on extended follow-up. Five of eight (62.5%) high grade (HG) carcinomas with false-negative urinary FISH, were negative due to the absence/paucity of FISH-detectable changes in the tumor cells. In atypical cytology cases, the FISH result did not assist in identifying UC. There was no significant difference between an atypical cytology result and a positive FISH result, with respect to the identification of patients with UC. Conclusions: We found urinary cytology to be more sensitivity and specific than FISH in the detection of UC, though the difference was not statistically significant. Up to 24% of HG UCs are FISH negative due to an absence of FISH-detectable abnormalities in the tumor cells. Paucity of neoplastic cells in the urine also contributes to false-negative FISH results in both HG and low grade tumors. Negative urinary FISH cannot be taken alone as indicating the absence of significant disease in patients with atypical cytology.

Improved Detection of Urothelial Carcinomas with Fluorescence Immunocytochemistry (uCyt+ Assay) and Urinary Cytology: Results of a French Prospective Multicenter Study

Laboratory Investigation, 2003

The aim of the study was to assess the sensitivity and specificity of fluorescence immunocytochemistry (uCytϩ assay) as combined with urinary cytology for detection of primary and recurrent urothelial carcinomas. We analyzed 694 urinary samples from 236 new symptomatic patients and 458 patients followed after transurethral resection (TUR) for bladder tumor. Lesions suspicious for cancer at cystoscopy were sampled by biopsies or TUR. Sensitivity and specificity of tests were calculated using cystoscopy and histopathology, whether or not combined as gold standards. In new symptomatic patients, sensitivity of uCytϩ was 40%, 88.2%, and 76.7%, whereas that of urinary cytology was 30%, 70.6%, and 83.3%, respectively, in G1, G2, and G3 tumors. In follow-up cases, sensitivity of uCytϩ was 61.9%, 66.7%, and 76.9%, whereas that of urinary cytology was 38.1%, 58.3%, and 64.1%, respectively, in G1, G2, and G3 tumors. The combination of uCytϩ and urinary cytology significantly increased mean sensitivity in newly diagnosed cases (86.4% versus 71.2% with urinary cytology only, p Ͻ 0.05), as well as in patients followed after TUR (79.3% versus 55.2%, p Ͻ 0.001). Specificity of uCytϩ and urinary cytology was identical in new patients (83.3%) and was 81.9% and 86.2%, respectively, in patients followed after TUR. In patients with negative cystoscopy, positive uCytϩ tests had a strong predictive value for tumor recurrence at 1 year (47.0% versus 11.9% in patients with negative assay, p Ͻ 0.01). We conclude that combining uCytϩ with urinary cytology improves the detection of urothelial carcinomas as well in patients with symptoms suggesting bladder cancer as in those followed after treatment.

Modified UroVysion scoring criteria increase the urothelial carcinoma detection rate in cases of equivocal urinary cytology

Histopathology, 2011

Modified UroVysion scoring criteria increase the urothelial carcinoma detection rate in cases of equivocal urinary cytology Aims: UroVysion Ò is a four-target fluorescence in situ hybridization technique for the detection of urothelial carcinoma (UC) in urinary cytology. The aim of this retrospective study was to investigate the UC detection rate of a modified UroVysion test in patients with equivocal urinary cytology. The modification comprised the addition of a cytological prescreening technique and different evaluation criteria. Methods and results: Thin-layer slides were prepared from the residual urine samples of 82 patients with equivocal urinary cytology, prestained and prescreened to confirm the presence of atypical urothelial cells. The same slides were used for the UroVysion test, and scored according to different evaluation criteria. The results were compared with the outcomes of cystoscopic and histological findings. UroVysion detected 68% of the UCs when the manufacturer's evaluation criteria were applied. In cases of altered evaluation criteria, the sensitivity increased to 81% when at least one copy number change of a probe target was considered to be a positive test result. The specificity only decreased from 84% to 82%. Conclusions: Our data suggest that the sensitivity of the UroVysion test can be increased by the addition of a cytological pre-screening technique prior to the UroVysion test and a modification of the UroVysion evaluation criteria.

A Novel Urine-Based Assay for Bladder Cancer Diagnosis: Multi-Institutional Validation Study

European Urology Focus, 2016

Background: CellDetect is a unique histochemical stain enabling color and morphological discrimination between malignant and benign cells based on differences in metabolic signature. Objective: The objective of the present study was to validate the performance of this assay in a controlled, blinded, multicenter study. Design, setting, and participants: The study, conducted in nine hospitals, included patients with documented history of bladder cancer, monitored for urothelial carcinoma (UCC) or scheduled for bladder cancer surgery. Outcome measurements and statistical analysis: Cystoscopy and/or biopsy were used as a reference standard to determine sensitivity and specificity. Smears were stained by CellDetect and interpreted by two cytologists blinded to the patient's final diagnosis. The findings were compared with those of standard urine cytology and BTA stat. Results and limitations: Two hundred and seventeen voided urine specimens were included. Ninety-six (44%) were positive by histology and 121 (56%) were negative by either cystoscopy or histology. The overall sensitivity of CellDetect was 84%. Notably, the sensitivity for detecting lowgrade nonmuscle-invasive bladder cancer tumors was greater than this of BTA stat (78% vs 54%) and more than twofold higher compared with standard cytology (33%, p 0.05). The specificity was 84% in patients undergoing routine surveillance by cystoscopy. At a median follow-up of 9 mo, 21% of the patients with positive CellDetect and negative reference standard developed UCC, which was significantly higher compared with the 5% of the true negative cases. Limitations include the lack of instrumental urine samples and the lack of patients with nongenitourinary cancers in the study population. Conclusions: This study validates the performance of CellDetect as a urine-based assay to identify UCC in patients with history of bladder cancer. The high sensitivity was maintained across all cancer grades and stages without compromising the assay specificity. Further studies are required to test whether this novel stain can be incorporated in routine bladder cancer surveillance as a noninvasive alternative to cystoscopy. Patient summary: Surveillance of bladder cancer requires frequent invasive procedures. In the present study, we validate the ability of a novel biomarker to accurately identify early-stage tumors in urine specimens for the noninvasive monitoring of patients with history of bladder cancer.