Suspicious For High-grade Urothelial Carcinoma Research Articles

[Practical application of the Paris system for reporting urinary cytology].

Objective: To validate the diagnostic performance of the Paris system for reporting urinary cytology (TPS). Methods: A total of 7 046 urine cytology samples from 3 402 patients collected in the Department of Pathology, Beijing Hospital, China from January 2020 to January 2022 were analyzed. 488 patients had a biopsy or resection specimen during the follow-up period of 6 months. The sensitivity, specificity, risk of malignancy (ROM) and risk of high-grade malignancy (ROHM) of the TPS were evaluated using histological diagnosis as the golden standard. Results: Among the 7 046 samples, high-grade urothelial carcinoma (HGUC) accounted for 5.7% (399/7 046), suspicious for high-grade urothelial carcinoma (SHGUC) for 3.2% (227/7 046), atypical urothelial cells (AUC) for 8.4% (593/7 046), and negative for high-grade urothelial carcinoma (NHGUC) for 72.9% (5 139/7 046) including low-grade urothelial neoplasm (LGUN) for 0.8% (59/7 046) and insufficient samples for 9.8% (688/7 046). 488 patients had a bladder biopsy or resection in the follow-up of six months, including 314 males and 174 females, aged 27 to 92 years (average, 66 years). The ROHM of TPS was 94.7% in HGUC, 83.3% in SHGUC, 41.3% in AUC and 18.8% in NHGUC. The sensitivity and specificity of urine cytology were 70.1% (169/241) and 97.0% (162/167), respectively. The negative predictive value of NHGUC was 69.2% (162/234). Conclusions: The study has shown that TPS classification has high sensitivity and specificity, high ROHM for HGUC and SHGUC, and high negative predictive value for NHGUC. The application of TPS reporting system can better interpret the clinical significance of cytology samples, improve the accuracy of urine cytopathology and ensure continuous diagnostic consistency.

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

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. 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. 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 highlightthe 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. 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.

Implementation of The Paris System for Reporting Urine Cytology improves diagnostic accuracy of selective upper urinary tract cytology.

The Paris System for Reporting Urine Cytology (TPS) recommends diagnostic criteria for urinary tract cytology, focusing primarily on the detection of high-grade urothelial carcinoma (HGUC) in the lower urinary tract. The second edition of TPS (TPS 2.0), published in 2022, extends these recommendations to the upper urinary tract (UUT); however, there is a lack of comprehensive data on this subject. In total, 223 consecutive UUT cytology specimens from 137 patients were retrieved and reclassified according to TPS 2.0 criteria and were compared with the original diagnosis based on the conventional system (CS). Histologic follow-up within a 3-month period was conducted for 43 patients. Histologic follow-up revealed 30 HGUCs, five low-grade urothelial carcinomas (LGUCs), and eight nonneoplastic fibrotic tissues. The risk of high-grade malignancy for each TPS diagnostic category was 16.7% for nondiagnostic/unsatisfactory, 2.3% for negative for HGUC (NHGUC), 42.1% for atypical urothelial cells, 50.0% for suspicious for HGUC (SHGUC), and 81.8% for HGUC. In all five cases of histologically diagnosed LGUC, the cytologic diagnosis was NHGUC. When SHGUC/HGUC was considered positive, the diagnostic accuracy of TPS had 63% sensitivity, 95% specificity, a 90% negative predictive value, and a 79% positive predictive value, which were better than those of CS. In addition, the TPS indices did not differ significantly between the specimens obtained before and after the application of contrast reagents. TPS implementation improved the accuracy of UUT cytology in predicting histologic HGUC, which was unaffected by the application of contrast reagents. These data indicate the usefulness of TPS for UUT cytology in routine clinical settings.

Correlation between urine cytology results on the day after overnight continuous saline irrigation following transurethral resection of bladder tumor and bladder tumor recurrence.

To investigate the relationship between urine cytology results after overnight continuous saline irrigation (OCSI) following transurethral resection of bladder tumor (TURBT) and bladder tumor recurrence in non-muscle invasive bladder cancer (NMIBC). A retrospective study was conducted on patients diagnosed with NMIBC between 2016 and 2020 after undergoing TURBT at our hospital. All patients received OCSI following TURBT and had urine cytology test at postoperative 1 day. Urine cytology was classified into three groups: Negative, low-grade urothelial neoplasm (LGUN)+atypical urothelial cells (AUC), and suspicious for high-grade urothelial carcinoma (SHGUC)+high-grade urothelial carcinoma (HGUC). Recurrence-free survival (RFS) in each group was compared using the Kaplan-Meier method. Univariable and multivariable Cox regression analyses were performed to evaluate independent prognostic factors. A total of 172 patients were included in this study. Based on urine cytology group (after OCSI), RFS did not reach the median value in the Negative group. In the LGUN+AUC group, the median RFS was 615.00 days. In the SHGUC+HGUC group, the median RFS was 377.00 days. In survival analysis, the Negative group had a longer RFS than the SHGUC+HGUC group (p=0.013). However, Cox regression analysis showed that SHGUC+HGUC was not an independent prognostic factor for recurrence. Urine cytology results after OCSI following TURBT in NMIBC were associated with bladder tumor recurrence. Specifically, SHGUC or HGUC in urine cytology after OCSI showed earlier recurrence than negative cases. However, further research is needed to accurately determine whether it is an independent prognostic factor.

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

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. 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. 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. 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).

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

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. 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. 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. 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.

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. 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. 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%). 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 Category of the Johns Hopkins Template Has Higher Risk of Malignancy than the Paris System but the Paris System Is More Applicable for Suspicious Category

Introduction: The aim of this study was to compare performance of individual categories between the Johns Hopkins template and the Paris system for reporting urinary cytology. Methods: Medical records of patients with bladder biopsy and relevant cytology slides were obtained from archived material. Slides were reclassified according to Johns Hopkins template and the Paris system. Results were compared to histological diagnoses. Results: BD SurePath preparations from 205 cases with biopsy follow-up (118 benign, 5 dysplasia, 23 low, and 59 malignant urothelial carcinoma [UC]) were reviewed. There were 2 inadequate specimens in each system. According to the Johns Hopkins template, there were 96 (46.8%) no urothelial atypia or malignancy, 37 (18%) atypical urothelial cells of uncertain significance (AUC-US), 21 (10.2%) atypical urothelial cells, cannot exclude high-grade urothelial carcinoma (HGUC), 38 (18.5%) HGUC, and 11 (5.4%) low-grade urothelial carcinoma (LGUC). The Paris system categorized 111 (54.1%) negative for high-grade urothelial carcinoma, 29 (14.1%) atypical urothelial cells (AUCs), 25 (12.2%) suspicious for HGUC (SHGUC), 36 (17.6%) HGUC, and 2 (1%) LGUC. The Johns Hopkins template had a sensitivity of 95.6%, specificity of 73.6%, positive predictive value of 61.5%, negative predictive value of 96.3, with an overall diagnostic accuracy of 79.8%. The Paris System had a sensitivity of 93.6%, specificity of 77.9%, positive predictive value of 65.6%, negative predictive value of 96.5, with an overall diagnostic accuracy of 82.8%. The risk of malignancy (ROM) for atypical category (AUC-US/AUC) in the Johns Hopkins template was 43.2%, while it has been 24.1% for the Paris System. The ROM for suspicious category was 47.6% and 68.0%, respectively. There were statistically significant differences between negative and atypical, suspicious, and HGUC categories in each system (p < 0.0001). Conclusions: Discrete negative or benign urine cytology had the same sensitivity and specificity between two systems. Although atypical category was associated with a higher ROM with the Hopkins template, the ROM for the suspicious category yielded better result with the Paris system.

ThinPrep® imaging system-assisted vs manual screening of urinary cytology slides in the detection of the "suspicious for high-grade urothelial carcinoma" category.

The ThinPrep® Imaging System (TIS) is a Food and Drug Administration-approved review system for cervical cytopathology, where it has been shown to increase performance over manually reviewed slides. Application of the TIS to urinary cytology has only been reported in a single study, in 2013. We aimed to compare the agreement of two cytotechnologists' and a pathologist's manual screening (dots) with the fields of view (FOVs) selected by the TIS. We also aimed to track cases in which the TIS could identify missed abnormals and reduce the false-negative fraction. Electronically marked TIS fields (EMTFs) suspicious for high-grade urothelial carcinoma (SHGUC) were controlled by follow-up cystoscopy and histology, where available. A total of 826 consecutive specimens were studied. Of those, 94 (11.4%) were unreadable by the TIS. There were 710 possible comparisons, of which 380 (53.5%) received no dot after manual screening. Of the 330 remaining slides, 149 (45.1%) had at least one dot matching with the TIS FOVs. After TIS reading, EMTFs were noted in 13 of 636 (2.0%) negative cytology cases. Surveillance showed that 3/13 (23.1%, 0.4% of the 710 possible comparisons) of those cases matched with high grade urothelial carcinoma (HGUC), whereas 6/13 (46.1%, 0.8% of the 710 possible comparisons) had negative follow-up at 24 months, and 4/13 (30.8%) were lost for follow-up. The TIS increases the detection rate of SHGUC cells, potentially leading to a slight decrease in the false-negative fraction, but at the expense of a slight but larger increase in the number of false-positive cases. These findings stress the importance of a careful approach to the evaluation of the FOVs.

The Paris system classification for urinary cytology in patients under bacillus Calmette-Guerin treatment.

The role of urinary cytology as a diagnostic test for the detection and surveillance of urothelial cancer is crucial. Intravesical bacillus Calmette-Guerin (BCG) is the appropriate therapeutic strategy for patients with high-grade urothelial carcinoma (HGCU) or in situ carcinoma. We investigate how applicable is the Paris System for reporting urinary cytology (TPS) and how accurate is urinary cytology, in patients who undergo intravesical BCG instillations. Our study contains urine samples from patients during the period January 1, 2017 to December 31, 2019. The inclusion criteria were patients with history of urothelial bladder carcinoma who had been treated with intravesical BCG instillation and cytology was followed by histology. We report our results and estimate the risk of high-grade malignancy (ROHM) for each TPS category and cytology accuracy. Four hundred thirty-eight samples corresponding to 146 patients fulfilled the criteria to be included in the study. There were 2 inadequate, 118 negative for high-grade urothelial carcinoma (NHGUC), 14 atypical urothelial cells (AUC), 6 suspicious for high-grade urothelial carcinoma (SHGUC), and 6 cases HGUC. Corresponding histology assessment has shown that the ROHM amounted to 0 for inadequate, 3.4% for NHGUC, 57% for AUC, 100% for SHGUC and HGUC. Sensitivity was 50%, specificity 100%, PPV 100%, NPV 91%, and accuracy 91.7%, considering inadequate, NHGUC and AUC as negative and SHGUC and HGUC as positive result. However, considering AUC a positive result, the accuracy parameters were different; sensitivity 83.3%, specificity 95%, PPV 76.9%, NPV 96.67%, and accuracy 93%. The Paris system for reporting urinary cytology can be safely applied to patients during follow-up after BCG intravesical administration.

The Paris System for Reporting Urinary Cytology: A Meta-Analysis.

The Paris System (TPS) for Reporting Urinary Cytology is a standardized, evidence-based reporting system, comprising seven diagnostic categories: nondiagnostic, negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells (AUC), suspicious for high-grade urothelial carcinoma (SHGUC), HGUC, low-grade urothelial neoplasm (LGUN), and other malignancies. This study aimed to calculate the pooled risk of high-grade malignancy (ROHM) of each category and demonstrate the diagnostic accuracy of urine cytology reported with TPS. Four databases (PubMed, Embase, Scopus, Web of Science) were searched. Specific inclusion and exclusion criteria were applied, while data were extracted and analyzed both qualitatively and quantitatively. The pooled ROHM was 17.70% for the nondiagnostic category (95% CI, 0.0650; 0.3997), 13.04% for the NHGUC (95% CI, 0.0932; 0.1796), 38.65% for the AUC (95% CI, 0.3042; 0.4759), 12.45% for the LGUN (95% CI, 0.0431; 0.3101), 76.89 for the SHGUC (95% CI, 0.7063; 0.8216), and 91.79% for the HGUC and other malignancies (95% CI, 0.8722; 0.9482). A summary ROC curve was created and the Area Under the Curve (AUC) was 0.849, while the pooled sensitivity was 0.669 (95% CI, 0.589; 0.741) and false-positive rate was 0.101 (95% CI, 0.063; 0.158). In addition, the pooled DOR of the included studies was 21.258 (95% CI, 14.336; 31.522). TPS assigns each sample into a diagnostic category linked with a specific ROHM, guiding clinical management.

Comparison of Diagnostic Performances of Urine Cytology Before and After the Use of The Paris System Criteria: An Institutional Experience from Turkey.

Background:Urine cytology remains to be the test of choice in the detection of high-grade urothelial carcinomas (HGUC) due to its favorable sensitivity. However, a significant rate of cases is reported under atypical/indeterminate categories, which result in a decrease in its specificity. Providing standardized cytologic criteria, one of the aims of The Paris System (TPS) is to reduce the use of indeterminate diagnoses and provide a higher predictive value in these categories.Aims:We compared the diagnostic performances of TPS and our original reporting system, and also investigated the interobserver reproducibility of the cytologic criteria used.Materials and Methods:A total of 386 urine samples were reviewed retrospectively. Original cytologic diagnoses have been made using similar cytologic features proposed by TPS. All slides were recategorized after the use of the cytologic criteria as described by TPS guideline.Results:After TPS, specificity of the test increased from 39.6% to 63.5, sensitivity decreased from 92.5% to 88.8%, and diagnostic accuracy increased from 63.6% to 75%. The use of negative category increased threefold. Frequencies of indeterminate categories of atypical urothelial cells (AUC) and suspicious for HGUC (SHGUC) decreased by 36% and 56.5%, respectively. A subsequent detection of HGUC after AUC and SHGUC categories increased by 38% and 64%, respectively. Interobserver agreement for TPS categorization was 39%.Conclusions:TPS improved diagnostic accuracy of urine cytology by reducing the use of indeterminate categories, and resulted in increase in their predictive value for subsequent diagnosis of HGUC. However, reproducibility of diagnostic categories seemed to be imperfect.

Methylation study of the Paris system for reporting urinary (TPS) categories

AimsBladder EpiCheck is one of several urinary tests studied to identify bladder tumours and analyses 15 methylation biomarkers determining bladder cancer presence on the basis of methylation profile.Methods374 patients diagnosed...

An institutional experience evaluating hTERT immunostaining in 100 consecutive ThinPrep urine specimens

Studies have shown that expression of human telomerase reverse transcriptase (hTERT) in mature urothelial cells indicates an increased risk of urothelial carcinoma. We evaluated the utility of immunocytochemistry with a commercially available anti-hTERT antibody (SCD-A7) in 100 consecutive urine cytology specimens using ThinPrep processing. ThinPrep slides prepared from 100 consecutive urine specimens were stained using anti-hTERT antibody (SCD-A7) after staining optimization had been successfully completed. Patient demographics, cytology diagnoses, histologic follow-up data, and anti-hTERT staining results were recorded. The cytology diagnoses included 7 cases of high-grade urothelial carcinoma (HGUC), 2 cases suspicious for HGUC (SHGUC), 24 cases of atypical urothelial cells (AUCs), and 67 cases negative for HGUC (NHGUC). Of 92 samples, 68 (74%) were positive and 24 (26%) were negative for anti-hTERT staining. Although 31 of 32 specimens (97%) with a diagnosis of AUCs and greater showed positive staining, 37 of 60 NHGUC cases (62%) were also positive for anti-hTERT. Although the HGUC and suspicious for HGUC cases were more likely to show strong staining (6 of 9; 67%), 7 AUC (32%) and 8 NHGUC (22%) cases also demonstrated strong staining. Eight samples (8%) were unsatisfactory for interpretation. Anti-hTERT staining of nonurothelial cells was seen in 77 of 92 samples (84%). Interpretation of anti-hTERT immunocytochemical staining of ThinPrep material is challenging owing to obscuring of nonurothelial cell staining and difficulty discerning individual urothelial cell cytomorphology when the cells are stained. The significance of the large number of anti-hTERT-positive but cytology-negative cases in our study is uncertain.

Impact of the Paris system for reporting urine cytopathology on predictive values of the equivocal diagnostic categories and interobserver agreement.

Background:The Paris System (TPS) acknowledges the need for more standardized terminology for reporting urine cytopathology results and minimizing the use of equivocal terms. We apply TPS diagnostic terminologies to assess interobserver agreement, compare TPS with the traditional method (TM) of reporting urine cytopathology, and evaluate the rate and positive predictive value (PPV) of each TPS diagnostic category. A survey is conducted at the end of the study.Materials and Methods:One hundred urine samples were reviewed independently by six cytopathologists. The diagnosis was rendered according to TPS categories: negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells (AUC), low-grade urothelial neoplasm (LGUN), suspicious for high-grade urothelial carcinoma (SHGUC), and high-grade urothelial carcinoma (HGUC). The agreement was assessed using kappa. Disagreements were classified as high and low impacts. Statistical analysis was performed.Results:Perfect consensus agreement was 31%, with an overall kappa of 0.362. Kappa by diagnostic category was 0.483, 0.178, 0.258, and 0.520 for NHGUC, AUC, SHGUC, and HGUC, respectively. Both TM and TPS showed 100% specificity and PPV. TPS showed 43% sensitivity (38% by TM) and 70% accuracy (66% by TM). Disagreements with high clinical impact were 27%. Of the 100 cases, 52 were concurrent biopsy-proven HGUC. The detection rate of biopsy-proven HGUC was 43% by TPS (57% by TM). The rate of NHGUC was 54% by TPS versus 26% by TM. AUC rate was 23% by TPS (44% by TM). The PPV of the AUC category by TPS was 61% versus 43% by TM. The survey showed 33% overall satisfaction.Conclusions:TPS shows adequate precision for NHGUC and HGUC, with low interobserver agreement for other categories. TPS significantly increased the clinical significance of AUC category. Refinement and widespread application of TPS diagnostic criteria may further improve interobserver agreement and the detection rate of HGUC.

Implementation of the Paris system versus institutional diagnosis in the performance of urinary cytology: A 5 years correlative study of 74 cases

Introduction: Urine cytology used for diagnosing high-grade urothelial carcinoma (HGUC), but plagued by low sensitivity and wide inter-observer variability mainly ascribed to the lack of an established template of reporting. We assessed the performance of urine cytology by comparing the Paris System with our current institutional system. This study is developed to identify the prevalence of various cytological categories and their association with a subsequent diagnosis of high-grade urothelial carcinoma. Materials and Methods: A total of seventy four urine cytological specimens were studied which have follow up biopsy with histological correlation was done to categorize: benign, atypical urothelial cells (AUCs), suspicious for high-grade urothelial carcinoma (SHGUC), and high-grade urothelial carcinoma (HGUC). Original cytological diagnoses were recorded. Results: Males outnumbered females with a mean age of 57.4 years (range 21-86) (46 M and 28 F) with no statistical significance among the age groups and between male and female genders. By applying TPS, number of cases assigned to AUC category are very few (7 cases out of 74 with 9.45. Using the TPS resulted in a higher number of low-grade carcinomas assigned to the benign rather than the AUC category. LGUN category includes all low grade urothelial neoplasms of urinary tract, such as LGUC and PUN of uncertain malignant potential. According to institute diagnosis categories for urine cytology, there were 2 cases shown negatives, 16 cases shown Atypical/suspicious, 21 cases shown LG papillomas, and 35 cases shown HGUC. In negative group; out of 2 cases, 2 cases were papilloma. In HGUC group, out of 35 cases, 27 cases were turned out to be HGUC with 77.14%. In HGUC group, out of 35 cases, 8 cases were turned out to be LGUP with 29.62%. Conclusion: The TPS seems to improve the performance of urine cytology by limiting the AUC category to cases that are more strongly associated with HGUC. This is the first inclusive a

Digital image analysis supports a nuclear-to-cytoplasmic ratio cutoff value below 0.7 for positive for high-grade urothelial carcinoma and suspicious for high-grade urothelial carcinoma in urine cytology specimens.

Urinary cytology is sensitive and specific for diagnosing and screening high-grade urothelial carcinomas (HGUC). The Paris System (TPS) for urinary cytology was introduced in 2016 to standardize reporting. According to TPS diagnostic categories of HGUC and suspicious for HGUC (SHGUC), the average nuclear-to-cytoplasm (N:C) ratio of atypical cells should be ≥0.7. The objective of the current study was to measure the N:C ratio of urine cytology specimens with HGUC and SHGUC diagnoses and biopsy-proven HGUC follow-up. A cohort of 64 cases (HGUC, 49 cases; SHGUC, 15 cases) from 57 patients was constructed. Urine cytology slides were scanned into whole-slide digital images. The nuclear and cytoplasmic areas were enumerated by digital image analysis (DIA), and the N:C ratios were measured. In total, 640 cells were analyzed by DIA (HGUC, 490 cells; SHGUC, 150 cells). For HGUC and SHGUC, the average N:C ratios were 0.57 and 0.53, respectively. The maximum average N:C ratio was 0.73 for HGUC and 0.68 for SHGUC. HGUC had higher average N:C ratio (P < .001), higher average nuclear area (P < .001), higher average maximum N:C ratio (P = .005), and higher average maximum nuclear area (P = .006) compared with SHGUC. The N:C ratios for the HGUC (0.57) and SHGUC (0.53) categories are lower than those previously suggested in TPS. The authors advocate reducing the N:C ratio below the current threshold of 0.7.

Clinical follow up and the impact of the Paris system in the assessment of patients with atypical urine cytology.

Urinary cytology is routinely used in the diagnosis of urothelial neoplasms, with good sensitivity for high-grade urothelial carcinoma (HGUC) but less so for low-grade urothelial neoplasm (LGUN). There is significant interobserver and interinstitutional variability, especially for the atypical category. The Paris system for reporting urinary cytology (TPS) was introduced to better define the various categories, especially atypical cytology. We retrospectively reviewed 630 atypia of undetermined significance (AUS) cases and reclassified them based on TPS. In total, 501 cases previously reported as negative for malignancy had their medical records reviewed to serve as negative controls. Of 630 AUS cases, 299 (47.5%) were reclassified as negative for HGUC (NHGUC), 313 (49.7%) as atypical urothelial cells (AUCs) and 18 (2.9%) as suspicious for HGUC (SHGUC). Based on our institution's previous reporting system, the rate of underlying or subsequent HGUC was 2.8% for AUS, and 0% for negative. When AUS cases were reclassified under TPS, the rates were 1.5% for NHGUC, 4.8% for AUC, and 0% for SHGUC. Review of medical records showed that patients with AUS were more likely to be followed-up compared with those with negative urine cytology (77.8% compared with 54.3%), particularly those under the care of non-urologists. AUS diagnosis is associated with more patient follow up compared with NEG urine particularly among non-urologists. Reclassifying according to TPS results in significant reduction in the rate of AUS and thus unnecessary testing. This reduction however may be at the expense of slightly decreased detection rate of HGUC.

Impact of Implementing the Paris System for Reporting Urine Cytology in the Performance of Urine Cytology:  A Correlative Study of 124 Cases.

We assessed the performance of urine cytology using the Paris System for Reporting Urine Cytology (PSRUC) in comparison to our current system. In total, 124 specimens with histologic correlation were reviewed and assigned to the PSRUC categories: benign, atypical urothelial cells (AUCs), suspicious for high-grade urothelial carcinoma (SHGUC), and high-grade urothelial carcinoma (HGUC). Original cytological diagnoses were recorded. Fewer cases were given an AUC diagnosis using the PSRUC in comparison to the original diagnoses (26% vs 39%), while the association of AUCs with subsequent HGUC increased from 33% to 53% with the PSRUC. Using the PSRUC resulted in a higher number of low-grade carcinomas assigned to the benign (40%) rather than the AUC (22%) category. The performance of SHGUC/HGUC diagnoses was similar in both systems (predictive value = 94%). The PSRUC seems to improve the performance of urine cytology by limiting the AUC category to cases that are more strongly associated with HGUC.