Evaluating artificial intelligence-enhanced digital urine cytology for bladder cancer diagnosis.

BACKGROUND: This study evaluated the diagnostic effectiveness of the AIxURO platform, an artificial intelligence-based tool, to support urine cytology for bladder cancer management, which typically requires experienced cytopathologists and substantial diagnosis time. METHODS: One cytopathologist and two cytotechnologists reviewed 116 urine cytology slides and corresponding whole-slide images (WSIs) from urology patients. They used three diagnostic modalities: microscopy, WSI review, and AIxURO, per The Paris System for Reporting Urinary Cytology (TPS) criteria. Performance metrics, including TPS-guided and binary diagnosis, inter- and intraobserver agreement, and screening time, were compared across all methods and reviewers. RESULTS: AIxURO improved diagnostic accuracy by increasing sensitivity (from 25.0%-30.6% to 63.9%), positive predictive value (PPV; from 21.6%-24.3% to 31.1%), and negative predictive value (NPV; from 91.3%-91.6% to 95.3%) for atypical urothelial cell (AUC) cases. For suspicious for high-grade urothelial carcinoma (SHGUC) cases, it improved sensitivity (from 15.2%-27.3% to 33.3%), PPV (from 31.3%-47.4% to 61.1%), and NPV (from 91.6%-92.7% to 93.3%). Binary diagnoses exhibited an improvement in sensitivity (from 77.8%-82.2% to 90.0%) and NPV (from 91.7%-93.4% to 95.8%). Interobserver agreement across all methods showed moderate consistency (κ = 0.57-0.61), with the cytopathologist demonstrating higher intraobserver agreement than the two cytotechnologists across the methods (κ = 0.75-0.88). AIxURO significantly reduced screening time by 52.3%-83.2% from microscopy and 43.6%-86.7% from WSI review across all reviewers. Screening-positive (AUC+) cases required more time than negative cases across all methods and reviewers. CONCLUSIONS: AIxURO demonstrates the potential to improve both sensitivity and efficiency in bladder cancer diagnostics via urine cytology. Its integration into the cytopathological screening workflow could markedly decrease screening times, which would improve overall diagnostic processes.

Machine learning assisted microfluidics dual fluorescence flow cytometry for detecting bladder tumor cells based on morphological characteristic parameters.

BACKGROUND: Bladder cancer (BC) is the most common malignant tumor and has become a major public health problem, leading the causes of death worldwide. The detection of BC cells is of great significance for clinical diagnosis and disease treatment. Urinary cytology based liquid biopsy remains high specificity for early diagnosis of BC, however, it still requires microscopy examination which heavily relies on manual operations. It is imperative to investigate the potential of automated and indiscriminate cell differentiation technology to enhance the sensitivity and efficiency of urine cytology. RESULTS: Here, we developed a machine learning algorithm empowered dual-fluorescence flow cytometry platform (µ-FCM) for urinary cytology analysis. A phenotype characteristic parameter (CP) which correlated with the size of the cell and nucleus was defined to achieve the differentiation of the BC cells and uroepithelial cells with high throughput and high accuracy. Based on CP analysis, SV-HUC-1 cells were almost differentiated from EJ cells and effectively reduced the overlap with 5637 cells. To further differentiate SV-HUC-1 cells and 5637 cells, support vector machine (SVM) machine learning algorithm was optimized to assist data analysis with the highest accuracies of 84.7 % for cell differentiation including the specificity of 91.0 % and the sensitivity of 75.0 %. Furthermore, the false positive rate (FPR) compensation enabled the detection rates of rare BC cells predicted by the well-trained SVM model were close to the true proportions with the recognition error in 0.4 % for the tumor cells. SIGNIFICANCE: As a proof of concept, the developed µ-FCM system successfully demonstrates the capacity to identify the distribution of exfoliated cells in real urine samples. This system underscores the significance of integrating AI with microfluidics to perform high-throughput phenotyping of exfoliated cells, offering a pathway toward scalable, efficient, and automatic microfluidic systems in the fields of both biosensing and in vitro diagnosis of BC.

Diagnostic accuracy of upper tract urothelial carcinoma using biopsy, urinary cytology, and nephroureterectomy specimens: A tertiary cancer center experience.

OBJECTIVES: We studied the diagnostic accuracy and discordance of upper tract urothelial carcinoma (UTUC) by comparing biopsy and urinary cytology with matched nephroureterectomy specimens. METHODS: Sixty-nine patients with UTUC without neoadjuvant treatment were retrospectively identified who had matched biopsy and nephroureterectomy specimens. Twenty patients had concurrent upper tract cytology. H&E and cytology slides were re-reviewed. Statistical analysis was performed. RESULTS: Patients included 48 men and 21 women with a mean age of 69 years. A concordant grade between biopsy and surgical specimen was present in 49 (71%) patients. The mean size of biopsy specimens in the discordant group was significantly smaller than that in the concordant group. Invasion was evaluated in 48 biopsy cases that had adequate subepithelial tissue, and 33 of them were diagnosed with concordant invasion status. Mean tumor size in both tumor grade and invasion discordant groups was significantly larger than that in the concordant group. High-grade urothelial carcinoma was detected in 84% of cases using urinary cytology. CONCLUSIONS: Our study demonstrates the diagnostic challenges of UTUC on small biopsy specimens. Biopsy specimen size and tumor size are significantly associated with the diagnostic discordance. Upper tract cytology showed high diagnostic accuracy and should be complementary to the biopsy.

[Urinary cytology for the detection of urothelial lesions]. / Rôle de la cytologie urinaire dans le dépistage des lésions urothéliales.

Urine cytology is a long-used technique for the detection of high grade neoplastic urothelial lesions. Since 2016, «The Paris System¼ classification has revolutionized this field by introducing a standardized terminology widely adopted by cytopathologists and urologists. In this article, we explain this classification and discuss its impact on the clinical management of patients with urothelial lesions, as well as its role in the secondary prevention of these lesions.

La cytologie urinaire est une technique utilisée depuis longtemps dans la détection des lésions urothéliales tumorales de haut grade. Depuis 2016, la classification «The Paris System¼ a révolutionné ce domaine en introduisant une terminologie standardisée largement adoptée par les cytopathologistes et les urologues. Dans cet article, nous expliquons cette classification et discutons de son impact sur la prise en charge clinique des lésions urothéliales, ainsi que son rôle dans la prévention secondaire de ces lésions.

Utility of the Paris System in Urine Cytology for Improved Screening of High-Grade Urothelial Carcinoma in Bahrain.

BACKGROUND: Urothelial carcinoma, a prevalent and aggressive urological malignancy, necessitates early detection for improved prognosis. Urine cytology serves as a cost-effective screening tool, but inconsistencies in reporting due to the lack of standardized criteria limit its efficacy. The Paris System for reporting urinary cytology (TPS) was introduced to address this issue, aiming to improve diagnostic accuracy. This retrospective study investigates the effectiveness of urine cytology in detecting high-grade urothelial carcinoma (HGUC) using TPS classification, specifically focusing on atypical urothelial cells (AUC) categorized as TPS-III and suspicious for high-grade urothelial carcinoma (SHGUC) categorized as TPS-IV. METHODS: We reviewed 470 urine cytology samples collected over two years at a tertiary healthcare center in Bahrain. All samples were re-evaluated using TPS classification by two independent consultant cytopathologists blinded to the original cytology report. The analysis included only samples categorized as TPS-III or TPS-IV with corresponding histopathology reports from confirmatory biopsies performed within four months of urine collection. Biopsy results were categorized as either benign/low-grade urothelial carcinoma (non-HGUC) or malignant (HGUC). The positive predictive value (PPV) of urine cytology for HGUC detection was calculated for both TPS-III and TPS-IV categories. Statistical significance was assessed using Fisher's exact test. RESULTS: Among the 470 urine cytology samples, 40 (8.5%) were classified as TPS-III or TPS-IV. Within this subset, 16 patients underwent confirmatory biopsies. Histopathological analysis revealed HGUC in 12 (75%) patients and non-HGUC (benign or low-grade) in 4 (25%) patients. The PPV of TPS-III for HGUC was 50%, while TPS-IV demonstrated a higher PPV of 90%. However, the difference between these values was not statistically significant (p = 0.25). This study explored the utility of TPS classification in urine cytology for HGUC detection. While SHGUC (TPS-IV) exhibited a numerically higher PPV compared to AUC (TPS-III), the lack of statistical significance necessitates further investigation. Our findings highlight the potential of TPS to improve the accuracy of urine cytology. TPS implementation has been shown to reduce the number of inconclusive "atypical" diagnoses, leading to more targeted investigations. CONCLUSION: Our study suggests that SHGUC (TPS-IV) within TPS classification framework might hold promise as a more specific indicator for HGUC compared to AUC (TPS-III). However, further research with larger cohorts is necessary to definitively establish the clinical significance of this observation. This investigation paves the way for future studies exploring the potential of TPS, particularly the SHGUC category, as a reliable screening tool for HGUC, potentially leading to earlier diagnoses and improved patient outcomes.

[What contribution can make artificial intelligence to urinary cytology?] / Quel apport de l'intelligence artificielle en cytologie urinaire ?

Urinary cytology using the Paris system is still the method of choice for screening high-grade urothelial carcinomas. However, the use of the objective criteria described in this terminology shows a lack of inter- and intra-observer reproducibility. Moreover, if its sensitivity is excellent on instrumented urine, it remains insufficient on voided urine samples. Urinary cytology appears to be an excellent model for the application of artificial intelligence to improve performance, since the objective criteria of the Paris system are defined at cellular level, and the resulting diagnostic approach is presented in a highly "algorithmic" way. Nevertheless, there is no commercially available morphological diagnostic aid, and very few predictive devices are still undergoing clinical validation. The analysis of different systems using artificial intelligence in urinary cytology rises clear prospects for mutual contributions.

Voided urine cytology is a useful tool predicting non-muscle-invasive bladder cancer risk before surgery.

OBJECTIVE: To determine the accuracy of voided urinary cytology (VUC) in predicting of non-muscle-invasive bladder cancer (NMIBC) risk stratification before surgery. METHODS: We prospectively collected data from all patients diagnosed with bladder cancer in our institution over 2 years. We have analyzed VUC accuracy of positive and suspicious VUC in the detection of high-risk tumors and negative and atypical VUC in the detection of low-risk tumors. To test this accuracy, we assessed sensitivity, specificity, positive (PPV) and negative predictive values (NPV), diagnostic odds ratio (DOR), and generated ROC curves (receiver operating characteristic curve). RESULTS: With 224 patients included, the positive VUC subcategory showed a specificity of 92.4% (95%CI: 83.2%-97.5%) and a PPV of 91.4 (95%CI: 81%-97.1%). DOR in this subgroup was 6.81. In the suspicious VUC, specificity was 90.9% (95%CI: 81.3%-96.6%), PPV was 88% (95%CI: 75.7%-95.5%) and DOR was 4.23. Combined analysis of positive and suspicious cytologies for detecting high-risk NMIBC showed a sensitivity of 65% (95%CI: 57.3%-73.2%) and a DOR of 9.51. Negative VUC showed high specificity in detecting low-risk (93.2% [95%CI: 87.9%-96.7%]) and a DOR of 6.90 (95%CI: 3.07-15.46). Atypical VUC was the least accurate and had rather low specificity and predictive values. CONCLUSIONS: VUC appears to be a good, inexpensive and easily available method to determine risk stratification before surgery. This can be useful in daily practice to determine which patients should receive a single instillation of MMC and to prioritize patients more likely to have a high- risk tumor.

Urine-Based Biomarker Test Uromonitor® in the Detection and Disease Monitoring of Non-Muscle-Invasive Bladder Cancer-A Systematic Review and Meta-Analysis of Diagnostic Test Performance.

Optimal urine-based diagnostic tests (UBDT) minimize unnecessary follow-up cystoscopies in patients with non-muscle-invasive bladder-cancer (NMIBC), while accurately detecting high-grade bladder-cancer without false-negative results. Such UBDTs have not been comprehensively described upon a broad, validated dataset, resulting in cautious guideline recommendations. Uromonitor®, a urine-based DNA-assay detecting hotspot alterations in TERT, FGFR3, and KRAS, shows promising initial results. However, a systematic review merging all available data is lacking. Studies investigating the diagnostic performance of Uromonitor® in NMIBC until November 2023 were identified in PubMed, Embase, Web-of-Science, Cochrane, Scopus, and medRxiv databases. Within aggregated analyses, test performance and area under the curve/AUC were calculated. This project fully implemented the PRISMA statement. Four qualifying studies comprised a total of 1190 urinary tests (bladder-cancer prevalence: 14.9%). Based on comprehensive analyses, sensitivity, specificity, positive-predictive value/PPV, negative-predictive value/NPV, and test accuracy of Uromonitor® were 80.2%, 96.9%, 82.1%, 96.6%, and 94.5%, respectively, with an AUC of 0.886 (95%-CI: 0.851-0.921). In a meta-analysis of two studies comparing test performance with urinary cytology, Uromonitor® significantly outperformed urinary cytology in sensitivity, PPV, and test accuracy, while no significant differences were observed for specificity and NPV. This systematic review supports the use of Uromonitor® considering its favorable diagnostic performance. In a cohort of 1000 patients with a bladder-cancer prevalence of ~15%, this UBDT would avert 825 unnecessary cystoscopies (true-negatives) while missing 30 bladder-cancer cases (false-negatives). Due to currently limited aggregated data from only four studies with heterogeneous quality, confirmatory studies are needed.

[The Paris System, 2022 edition: What is new?] / La version 2022 du Système de Paris : quoi de neuf ?

The second version of the Paris System for reporting urine cytology was published in 2022. It follows the first version of 2016, which was very successful and widely adopted by many cytopathologists from different countries. Thus, numerous publications using the Paris System have made possible to refine the criteria as well as discussing the limits. The diagnostic accuracy of urinary cytology is high for detection of high-grade urothelial carcinoma, but not for low-grade carcinoma where there are few cytological abnormalities. So, the chapter individualizing low-grade urothelial neoplasms was deleted; the latter were included in the category "negative for high-grade urothelial carcinoma". Indeed, the risk of malignancy is replaced by the risk of high-grade urothelial carcinoma. A new chapter has been devoted to urothelial tumors of the upper tract. Finally, the pitfalls linked to cellular degeneration are discussed for each category. The risk of high-grade malignancy associated with each category will help communication with the clinician and help patient care.

Urinary tract cytology showing variant morphology and divergent differentiation.

Urothelial carcinoma represents a diverse group of tumours with distinct histologic subtypes, each exhibiting unique cytomorphologic features, architectural growth patterns, and/or well-developed aberrant differentiation. In fact, there are more than 13 subtypes of urothelial carcinoma recognized in the 2022 WHO classification of tumours in the urinary tract. The identification of these subtypes is crucial for an accurate diagnosis of urothelial carcinoma, and many have important clinical implications. Variant/divergent features may coexist with conventional high-grade urothelial carcinoma (HGUC) or present with 100% variant morphology. In urinary tract cytology (UTC), urothelial carcinoma can display divergent differentiation, such as squamous, glandular, or small cell carcinoma differentiation. The use of cell block preparations and immunohistochemistry with available residual urine can enhance diagnostic accuracy. On the other hand, identifying urothelial carcinoma variants, including nested, micropapillary, and plasmacytoid subtypes, poses significant challenges in UTC. Many cases of these variants are only detected retrospectively after variant histology has been established from resection specimens. Moreover, some variants exhibit features inconsistent with the diagnostic criteria for HGUC according to the Paris System for Reporting Urinary Tract Cytology. Nevertheless, the rarity of pure variant morphology and the occurrence of some false negatives for these variant cases are essential to maintain the specificity of UTC overall. This review covers the histology, cytomorphology, and important clinical aspects observed in urothelial carcinoma exhibiting divergent differentiation and various urothelial carcinoma variants detected in UTC.

Cytologic evaluation of upper urinary tract specimens: An institutional retrospective study using The Paris System for Reporting Urine Cytology second edition with histopathologic follow-up.

OBJECTIVE: Cytologic evaluation of the upper urinary tract (UUT) can be challenging due to instrumentation artefacts. This study retrospectively reviewed UUT specimens using The Paris System for Reporting Urinary Cytopathology, second edition (TPS 2.0), compared it with the original reporting system (ORS) and correlated it with histopathologic follow-up. METHODS: An institutional database was reviewed for the UUT biopsy/resection histopathologic specimens, and we included 52 UUT cytology specimens pertinent to these cases in the study. These specimens were blindly reviewed and reclassified using TPS 2.0. The correlation between TPS 2.0, ORS and histopathologic follow-up was assessed. RESULTS: The UUT cytology specimens corresponded to 21 (40.4%) high-grade urothelial carcinoma (HGUC), 27 (51.9%) low-grade urothelial carcinoma (LGUC) and 4 (7.7%) benign cases on follow-up. For HGGC cases, the associated TPS categories included unsatisfactory (n = 1, 4.8%), negative for HGUC (NHGUC; n = 3, 14.3%), atypical urothelial cells (AUC; n = 6, 28.6%), suspicious for HGUC (SHGUC; n = 3, 14.3%) and HGUC (n = 8, 38.1%), while ORS categorised the specimens as unsatisfactory (n = 1, 4.8%), negative for malignant cells (NFMC; n = 3, 14.3%), AUC (n = 5, 23.8%), low-grade urothelial carcinoma (LGUC; n = 0, 0%), SHGUC (n = 5, 23.8%) and HGUC (n = 7, 33.3%). The risks of high-grade malignancy among cytologic categories were similar between ORS and TPS (p > 0.05). The majority of LGUC were classified as AUC similarly by ORS and TPS (55.6% vs. 59.3%). CONCLUSIONS: Our study demonstrated comparable performance between TPS 2.0 and ORS for UUT cytology specimens. Cytological diagnosis of UUT specimens remains challenging, especially for LGUC.

Methylation Analysis of Urinary Sample in Non-Muscle-Invasive Bladder Carcinoma: Frequency and Management of Invalid Result.

BACKGROUND: Numerous studies showed that methylation analysis represents a newly developed urinary marker based on DNA methylation changes in a panel of genomic biomarkers and it could represent a valid tool in terms of the diagnosis and prediction of high-grade urothelial carcinoma recurrences. One of the limits of the use of this new molecular method during a follow-up is represented by the number of invalid tests in routine practice. METHOD: A total of 782 patients with a diagnosis of non-muscle-invasive high-grade carcinoma (NMIBC) was studied. The Bladder EpiCheck test (BE) was performed together with cytology in all cases within 1 year after the end of treatment. In 402 patients, the urinary samples were voided urine (UV), while, in 380 cases, the samples were collected after bladder washing (IU). For all the patients with invalid BE results, a second BE test was performed following the instructions for use that indicated the test should be repeated with a new urinary sample in the case of an invalid result. RESULTS: Analyzing the two different groups (UV and IU), we found the invalid BE results seemed to be not related to urinary samples (p = 0.13 Fisher's exact test), suggesting that the collection method was not relevant in order to reduce the number of invalid tests. CONCLUSIONS: In the follow-up for NMIBC, for patients for whom a BE test is planned, a combined approach of cytology and a methylation test is recommended in order to repeat the BE test with an invalid result only in those cases with a cytological diagnosis of atypical urothelial cells (AUC) suspicious for high-grade urothelial carcinoma (SHGUC) and high-grade urothelial carcinoma (HGUC).

Are we on track for diagnosing high-grade urothelial carcinoma with a minimum quantity of five malignant cells in lower tract specimens? Critical analysis of The Paris System Quantitation Criteria.

BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) has gained universal acceptance as the standard for reporting urine cytology requiring at least 5-10 malignant cells to diagnose high-grade urothelial carcinoma (HGUC) in lower and upper urinary tract specimens, respectively. These quantitation criteria are still subject to discussion, and this study specifically aims to validate the quantitation criterion of HGUC in lower urinary tract. DESIGN: The authors reviewed two cohorts of lower urinary tract cases. The first cohort consisted of 100 liquid-based ThinPrep slides with the diagnosis of HGUC having positive histology on concurrent or follow-up biopsies within 3 months. The second cohort was 36 HGUC cases with negative histology on concurrent biopsies and within 3 months. The number of high-grade cells (HGCs) meeting the TPS qualitative criteria were counted under the light microscope driven in a grid-like manner. RESULTS: The first 100 urine samples showed five cases (5.0%) with three HGCs, three cases (3.0%) had four HGCs, five cases (5.0%) showed five HGCs, and 25 cases (25.0%) had between 6-10 HGCs. The risk of high-grade malignancy (ROHM) in cases with five or more HGCs was 100%, whereas those with three HGCs was 60.0%. The second cohort of HGUC was considered "positive" despite a negative histology. CONCLUSION: This study confirms that quantitation is an essential key to diagnose HGUC. The current TPS criterion of a minimum of five malignant cells in lower tract is robust with a ROHM of 100%. Diagnosing HGUC with less than five HGCs runs the risk of lowering the ROHM.

Diagnosis of Low-Grade Urothelial Neoplasm in the Era of the Second Edition of the Paris System for Reporting Urinary Cytology.

BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) is considered the gold standard when it comes to diagnostic classifications of urine specimens. Its second edition brought some important changes, including the abolition of the diagnostic category of "low-grade urothelial neoplasm (LGUN)", acknowledging the inability of cytology to reliably discern low-grade urothelial lesions. METHODS: In this retrospective study, we assessed the validity of this change, studying the cytological diagnoses of histologically diagnosed low-grade urothelial carcinomas during a three-year period. Moreover, we correlated the sum of the urinary cytology diagnoses of this period with the histological diagnoses, whenever available. RESULTS: Although all the cytological diagnoses of LGUN were concordant with the histological diagnoses, most low-grade urothelial carcinomas were misdiagnosed cytologically. Subsequently, the positive predictive value (PPV) of urinary cytology for the diagnosis of LGUN was 100%, while the sensitivity was only 21.7%. Following the cyto-histopathological correlation of the sum of the urinary cytology cases, the sensitivity of urinary cytology for the diagnosis of high-grade urothelial carcinoma (HGUC) was demonstrated to be 90.1%, the specificity 70.8%, the positive predictive value (PPV) 60.3%, the negative predictive value (NPV) 93.6% and the overall accuracy 77.2%, while for LGUN, the values were 21.7%, 97.2%, 87.5%, 58.6% and 61.9%, respectively. Risk of high-grade malignancy was 0% for the non-diagnostic (ND), 4.8% for the non-high-grade urothelial carcinoma (NHGUC), 33.3% for the atypical urothelial cells (AUCs), 65% for the suspicious for high-grade urothelial carcinoma (SHGUC), 100% for the HGUC and 12.5% for the LGUN diagnostic categories. CONCLUSIONS: This study validates the incorporation of the LGUN in the NHGUC diagnostic category in the second edition of TPS. Moreover, it proves the ability of urinary cytology to safely diagnose HGUC and stresses the pivotal role of its diagnosis.

Utility and performance of cell blocks in urine cytology: Experience at three teaching hospitals.

BACKGROUND: The use of cell block (CB) preparation is underused in urine cytology (UC) and varies among hospitals. In addition to confirming a diagnosis, CBs can be useful in cases of metastatic disease, diagnoses requiring immunohistochemical (IHC) staining, and for ancillary studies. The role of this study is to examine the performance of CBs for UC at three affiliated teaching hospitals. MATERIALS AND METHODS: A retrospective review of UC cases with a CB was conducted at a county hospital, Veterans Affairs hospital, and tertiary university-based hospital. For each specimen, patient demographics, specimen type, volume, original diagnosis, and IHC stains were recorded. Each case was reviewed for diagnosis based on ThinPrep alone, diagnosis based on ThinPrep and CB, utility of CB for diagnosis, and CB cellularity. RESULTS: A total of 250 UC specimens with CB from 186 patients was identified. Bladder washes were the most common (72.1%). IHC stains were performed on 17.2% of cases. On blinded review, CB preparation was deemed useful in 61.2% of cases, with the highest rate for suspicious for high-grade urothelial carcinoma (SHGUC) cases (87.0%). The diagnosis based on ThinPrep review changed with incorporation of CB in 13.2% of cases, with the highest rate for SHGUC cases (43.5%). CONCLUSIONS: The results demonstrate that use of CB in UC confirms the final diagnosis in more than one-half of cases and changes the diagnosis in a subset of cases. Use of CB was most helpful in the SHGUC category. Further evaluation of the types of cases in which CB are prepared is warranted.

Atypical urothelial cells classified according to the Paris System for Reporting Urinary Cytology: A 2-year experience with histological correlation from a Finnish tertiary care center-low rate and high risk of malignancy.

BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) was issued to shift the focus of urine cytology to high-grade lesions to increase the diagnostic accuracy of urine cytology. The aim of this study was to evaluate the power of TPS in the atypical urothelial cells (AUC) category with histological correlation and follow-up. METHODS: The data cohort consisted of 3741 voided urine samples collected during a 2-year period between January 2017 and December 2018. All samples were prospectively classified using TPS. This study focuses on the subset of 205 samples (5.5%) classified as AUC. All cytological and histological follow-up data were analyzed until 2019, and the time between each sampling was documented. RESULTS: Of the 205 AUC cases, cytohistological correlation was possible in 97 (47.3%) cases. Of these, 36 (12.7%) were benign in histology, 27 (13.2%) were low-grade urothelial carcinomas, and 34 (16.6%) were high-grade urothelial carcinomas. Overall, the risk of malignancy was 29.8% for all cases in the AUC category, and 62.9% in the histologically confirmed cases. The risk of high-grade malignancy was 16.6% in all the AUC category samples and 35.1% in the histological follow-up group. CONCLUSIONS: The performance of 5.5% AUC cases is considered good and within the limits proposed by TPS. TPS is widely accepted by cytotechnologists, cytopathologists, and clinicians; it improves communication and patient management.

Diagnostic value of Xpert® BC Detection, Bladder Epicheck®, Urovysion® FISH and cytology in the detection of upper urinary tract urothelial carcinoma.

PURPOSE: Following the current guidelines, diagnosis and staging for upper urinary tract tumours (UTUC) can be performed with Computed Tomography, urography, ureterorenoscopy (URS) and selective cytology. The aim of the study was to evaluate the performance of the Xpert®-BC-Detection and the Bladder-Epicheck®-test in the detection of UTUC and compare it with cytology and the Urovysion®-FISH test using histology and URS as gold standard. METHODS: A total of 97 analyses were collected through selective catheterization of the ureter before URS to test for cytology, Xpert®-BC-Detection, Bladder-Epicheck® and Urovysion®-FISH. Sensitivity, specificity, and predictive values were calculated using histology results/URS as reference. RESULTS: Overall sensitivity was 100% for Xpert®-BC-Detection, 41.9% for cytology, 64.5% for Bladder-Epicheck® and 87.1% for Urovysion®-FISH. The sensitivity of Xpert®-BC-Detection was 100% in both, LG and HG tumours, sensitivity of cytology increased from 30.8% in LG to 100% in HG, for Bladder-Epicheck® from 57.7% in LG to 100% in HG and of Urovysion®-FISH from 84.6% in LG to 100% in HG tumours. Specificity was 4.5% for Xpert®-BC-Detection, 93.9% for cytology, 78.8% for Bladder-Epicheck® and 81.8% for Urovysion®-FISH. PPV was 33% for Xpert®-BC-Detection, 76.5% for cytology, 58.8% for Bladder-Epicheck® and 69.2% for Urovysion®FISH. NPV was 100% for Xpert®-BC-Detection, 77.5% for cytology, 82.5% for Bladder-Epicheck® and 93.1% for Urovysion®FISH. CONCLUSION: Bladder-Epicheck® and Urovysion®FISH along with cytology could be a helpful ancillary method in the diagnosis and follow-up of UTUC while due to its low specificity Xpert®-BC Detection seems to be of limited usefulness.

DNA methylation analysis in urinary samples: A useful method to predict the risk of neoplastic recurrence in patients with urothelial carcinoma of the bladder in the high-risk group.

BACKGROUND: Recently, it was reported that the Bladder EpiCheck test is likely to represent a valid tool in the diagnostic process of patients who have suspected bladder carcinoma, with some controversial management decisions because of the technical limitations of cytology. METHODS: Two hundred ninety patients with a diagnosis of nonmuscle-invasive bladder carcinoma who were admitted at the authors' department from March 2019 to December 2019 were treated and followed for 1 year. During follow-up, all patients were evaluated by voided urine cytology, white-light cystoscopy (according to European Association of Urology guidelines), and the Bladder EpiCheck test. RESULTS: The cytologic diagnoses of high-grade urothelial carcinoma (HGUC) and suspicious for HGUC were histologically confirmed in 5 of 20 patients (25%) who had quantitative Bladder EpiCheck scores (EpiScores) from 60 to 69, in 23 of 36 patients (64%) who had EpiScores from 70 to 79, and in 42 of 56 patients (75%) and 57 of 63 patients (90%) who had EpiScores between 80 and 89 and EpiScores >90, respectively. Of 48 patients who had a cytologic diagnosis of HGUC or suspicious for HGUC with EpiScores ≥60 and negative histology, 20 (42%) had a recurrence of HGUC, which was cytologically and histologically confirmed, at 6-12 months during follow-up. CONCLUSIONS: To the best of the authors' knowledge, this is the first study in which patients at high risk for HGUC were stratified using the Bladder EpiCheck EpiScore. The results validate this methylation analysis tool as a useful method for predicting recurrent HGUC during the follow-up of patients with nonmuscle-invasive bladder carcinoma.

Perceptions of Paris: an international survey in preparation for The Paris System for Reporting Urinary Cytology 2.0 (TPS 2.0).

INTRODUCTION: An international panel of experts in the field of urinary cytopathology conducted a survey, supported by the American Society of Cytopathology, to seek opinions, gather evidence, and identify practice patterns regarding urinary cytology before and after the introduction of The Paris System for Reporting Urinary Cytopathology (TPS). Results from this survey were utilized in the development of the second edition of TPS (TPS-2.0). MATERIALS AND METHODS: The study group, originally formed during the 2013 International Congress of Cytology, reconvened at the 2019 annual meeting of the American Society of Cytopathology. To prepare for the second edition of TPS, the group generated a survey that included 43 questions related to the taxonomy and practice of urinary cytology. RESULTS: A total of 523 participant responses were collected, and 451 from 54 countries passed a qualifying screen. Three hundred ninety-four participants provided information about their work settings. Eighty-two percent (218/266) of responding participants use TPS. One hundred sixty-eight people who responded on their urinary cytology atypia rates reported an average decrease from 21.6% to 16%. Over three fourths of participants felt that the same criteria should be used for upper and lower tract interpretations and for instrumented and voided samples. There were varied opinions on addressing atypical squamous cells and suggestions for an expanded discussion of the issue to be included in TPS 2.0. CONCLUSIONS: Results of the survey demonstrate strong support for TPS and show a decreased self-reported atypia rate in the laboratories using TPS. The majority of participants related that the criteria put forth for the reporting categories were user-friendly and applied with relative ease. The comment section of the survey included suggestions from the participants for further improvement of TPS. Results of this survey have been useful in fine-tuning and advancing TPS. They were considered along with recent literature to generate the second edition of TPS.