Urine cytology is still a mainstay in non-invasive diagnostic evaluation of urothelial carcinoma (UC), and indeed for the diagnosis of high-grade urothelial carcinoma (HGUC). Although useful, the conventional urine cytology has been plagued by lack of interpretive uniformity and lack of standardized diagnostic criteria, which has contributed to variability in reporting and consequently clinical management. To overcome these limitations, the Paris System for Reporting Urinary Cytology (TPS) was developed to create absolute diagnostic categories and criteria with particular focus on identifying HGUC due to its vast clinical importance. TPS implementation has led to outstanding improvement in reproducibility and accuracy of reporting of urine cytology. Several recent studies have reported the diagnostic utility of TPS in HGUC detection with increased accuracy. For instance, Daoud et al. (2024) [1] noted that the application of TPS in Bahrain significantly enhanced the sensitivity and specificity of urine cytology for HGUC, showing its role in screening and early detection. Similarly, Singh et al. (2024) [2] compared the second edition of TPS and found an outstanding improvement in diagnostic accuracy and interobserver concordance, particularly in uncertainty reduction in equivocal categories such as "atypical urothelial cells." TPS not only standardizes morphologic criteria—like increased nuclear-to-cytoplasmic (N/C) ratio, hyperchromasia, and abnormal nuclear membranes—but also lends itself to a formal system that allows for more consistent clinical decision-making. McIntire et al. (2019) [4] provided digital image analysis results in favor of a more precise N/C ratio cutoff (<0.7) as a sensitive predictor for HGUC. Furthermore, TPS application is not restricted to lower urinary tract specimens, as demonstrated by Zheng et al. (2018) [5], who demonstrated increased correlation between cytological features and histopathological confirmation in upper tract urothelial samples. Apart from improving diagnostic precision, TPS has also improved the predictability of indeterminate categories and reduced interobserver variation. Bakkar et al. (2019) [3] reported evidence of enhanced predictability performance and concordance between observers following the implementation of TPS. Ancillary techniques, including fluorescence in situ hybridization (FISH), have also been integrated side by side with TPS to provide optimal diagnostic yield in challenging cases, as documented by Vlajnic et al. (2020) [6]. Such developments not only increase the solidity of TPS diagnostics but also further improve cytological classification, especially when handling borderline or atypical specimens. More recently, studies like Miyai et al. (2024) [7] and Nguyen et al. (2021) [8] have centered on looking at alterations within the TPS categories themselves. Practicality has been challenged in relation to splitting "suspicious for HGUC" and "positive for HGUC" categories, and some have suggested merger to make reporting easier and reduce diagnostic uncertainty. These issues are testaments to the dynamic nature of TPS and to the continuing need for its reevaluation based on new information and clinical experience. Together, the redefinition of urine cytology in the TPS context represents a paradigm for the urothelial carcinoma diagnostic approach. The system's focus on morphologic distinction, diagnostic reliability, and clinical utility provides legitimacy for its ongoing application and refinement as a gold standard for urinary cytology.

This retrospective diagnostic analysis was performed in a tertiary care pathology lab from January 2022 through December 2023. It aimed at re-evaluating the diagnostic usefulness of urine cytology and assessing the utility of the Paris System for Reporting Urinary Cytology (TPS) for identifying high-grade urothelial carcinoma (HGUC). Institutional ethical approval was obtained for the study, and all procedures conformed to standards as laid down in the Declaration of Helsinki. Sample Inclusion and Selection 320 urine cytology samples were obtained from cytopathology archives. These comprised both voided and instrumented urine specimens sent in for hematuria evaluation or follow-up of previously diagnosed urothelial carcinoma. Inclusion criteria consisted of adult patients (≥18 years) with urine cytology samples having corresponding histopathological follow-up within three months of cytological examination. Excluded were cases of insufficient cellularity or without clinical or histologic correlation, leaving a final cohort of 268 evaluable cases. Cytological Assessment with the Paris System All cytology smears were independently examined by two practicing cytopathologists who were unaware of the ultimate histopathological results. The re-evaluation was made in compliance with the Paris System's criteria emphasizing identification of important morphological features like nuclear-to-cytoplasmic ratio, chromatin pattern, nuclear borders, and nucleoli presence. The cases were classified into routine TPS diagnostic categories: Non-Diagnostic, Negative for High-Grade Urothelial Carcinoma, Atypical Urothelial Cells, Suspicious for High-Grade Urothelial Carcinoma, and High-Grade Urothelial Carcinoma. Interobserver differences were addressed by consensus discussion. Histopathological Correlation Histological diagnoses, derived from cystoscopic biopsies or resection specimens, were used as reference gold standards for diagnostic validation. Final histopathology reports were categorized into benign, low-grade urothelial carcinoma, or high-grade urothelial carcinoma. The agreement between cytological and histological results was evaluated to ascertain the diagnostic accuracy of urine cytology and the effectiveness of TPS in HGUC detection. Statistical Analysis Statistical analysis was carried out using SPSS version 25.0. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall diagnostic accuracy were computed for both conventional cytology and TPS-based reporting. Cohen's kappa coefficient was used to determine interobserver agreement. A p-value of less than 0.05 was used as statistically significant. Quality Control and Reproducibility Measures In order to ensure reproducibility and reduce bias, cytopathologists also went through a calibration session based on TPS criteria before the start of the study. A random sample of 50 cases was re-examined after a three-month period in order to determine intra-observer variability. Quality assurance measures were also continued during the study, including consistency in slide preparation and ongoing audit of staining protocols. This organized approach enabled a thorough re-evaluation of urine cytology performance with the Paris System, thus enabling more precise determination of its diagnostic contribution towards detecting HGUC.

We analyzed a total of 268 urine cytology samples using the Paris System for Reporting Urinary Cytology (TPS), and we had histopathological follow-up data for every single case. Out of these samples, 112 were confirmed as high-grade urothelial carcinoma (HGUC), 46 as low-grade urothelial carcinoma (LGUC), and 110 were identified as benign or reactive urothelial conditions based on histopathology. The average age of the patients was 62.4 years, ranging from 35 to 87 years, with a male-to-female ratio of about 2.3:1. The application of TPS criteria really improved the diagnostic clarity when assessing HGUC. When we categorized the cytology results under TPS, we found that 28 cases (10.4%) were Non-Diagnostic, 72 (26.8%) were Negative for HGUC, 64 (23.9%) were classified as Atypical Urothelial Cells (AUC), 38 (14.2%) were Suspicious for HGUC (SHGUC), and 66 (24.6%) were Positive for HGUC (HGUC). To evaluate the diagnostic performance of TPS, we compared the cytological findings with the histopathological outcomes. TPS showed a sensitivity of 84.8% and a specificity of 91.3% for detecting HGUC, with a positive predictive value (PPV) of 89.4% and a negative predictive value (NPV) of 87.1%. In contrast, the conventional cytology results recorded before implementing TPS had a lower sensitivity of 71.4% and a specificity of 81.6%. When it came to interobserver agreement using TPS criteria, we found it to be quite substantial, with a Cohen’s kappa coefficient of 0.78, compared to 0.61 under the previous reporting format. Table 1: Distribution of Cytological Diagnoses Based on the Paris System TPS Diagnostic Category Number of Cases (n=268) Percentage (%) Non-Diagnostic 28 10.4 Negative for HGUC 72 26.8 Atypical Urothelial Cells (AUC) 64 23.9 Suspicious for HGUC (SHGUC) 38 14.2 Positive for HGUC (HGUC) 66 24.6 Table 2: Diagnostic Performance of Urine Cytology Before and After Paris System Implementation Diagnostic Metric Conventional Cytology Paris System Cytology Sensitivity (%) 71.4 84.8 Specificity (%) 81.6 91.3 Positive Predictive Value (%) 76.2 89.4 Negative Predictive Value (%) 78.9 87.1 Overall Accuracy (%) 76.1 88.4 Interobserver Agreement (Kappa) 0.61 0.78 We analyzed a total of 268 urine cytology samples using the Paris System for Reporting Urinary Cytology (TPS), and we had histopathological follow-up data for every single case. Out of these samples, 112 were confirmed as high-grade urothelial carcinoma (HGUC), 46 as low-grade urothelial carcinoma (LGUC), and 110 were identified as benign or reactive urothelial conditions based on histopathology. The average age of the patients was 62.4 years, ranging from 35 to 87 years, with a male-to-female ratio of about 2.3:1. The application of TPS criteria really improved the diagnostic clarity when assessing HGUC. When we categorized the cytology results under TPS, we found that 28 cases (10.4%) were Non-Diagnostic, 72 (26.8%) were Negative for HGUC, 64 (23.9%) were classified as Atypical Urothelial Cells (AUC), 38 (14.2%) were Suspicious for HGUC (SHGUC), and 66 (24.6%) were Positive for HGUC (HGUC). To evaluate the diagnostic performance of TPS, we compared the cytological findings with the histopathological outcomes. TPS showed a sensitivity of 84.8% and a specificity of 91.3% for detecting HGUC, with a positive predictive value (PPV) of 89.4% and a negative predictive value (NPV) of 87.1%. In contrast, the conventional cytology results recorded before implementing TPS had a lower sensitivity of 71.4% and a specificity of 81.6%. When it came to interobserver agreement using TPS criteria, we found it to be quite substantial, with a Cohen’s kappa coefficient of 0.78, compared to 0.61 under the previous reporting format. Table 1: Distribution of Cytological Diagnoses Based on the Paris System TPS Diagnostic Category Number of Cases (n=268) Percentage (%) Non-Diagnostic 28 10.4 Negative for HGUC 72 26.8 Atypical Urothelial Cells (AUC) 64 23.9 Suspicious for HGUC (SHGUC) 38 14.2 Positive for HGUC (HGUC) 66 24.6 Table 2: Diagnostic Performance of Urine Cytology Before and After Paris System Implementation Diagnostic Metric Conventional Cytology Paris System Cytology Sensitivity (%) 71.4 84.8 Specificity (%) 81.6 91.3 Positive Predictive Value (%) 76.2 89.4 Negative Predictive Value (%) 78.9 87.1 Overall Accuracy (%) 76.1 88.4 Interobserver Agreement (Kappa) 0.61 0.78 These findings highlight how effective the Paris System is in improving both the accuracy of diagnoses and the consistency among different observers in urine cytology, especially when it comes to identifying high-grade urothelial carcinoma. The increased sensitivity and specificity it offers really emphasize its importance in everyday cytopathological assessments and in making decisions about patient care.

Implementation of the Paris System for Reporting Urinary Cytology (TPS) has had a profound impact on the diagnostic sensitivity of urine cytology, especially for identifying high-grade urothelial carcinoma (HGUC). In the current study, use of TPS showed higher sensitivity (84.8%) and specificity (91.3%) than conventional cytology, which had sensitivity of 71.4% and specificity of 81.6%. This significant improvement corresponds to the system's standardized morphological parameters, with emphasis on high nuclear-to-cytoplasmic ratio, irregularities in chromatin, and nuclear borders—features that are well known to be related to HGUC. These findings concur with the increase in international literature attestating the clinical significance of TPS. Zhao et al. (2024) [9], working in the practical context of a cancer hospital, observed that the Paris System cut down significantly on the number of equivocal diagnoses but enhanced the diagnosis of HGUC, demonstrating its relevance in high-volume oncologic centers. Khajir et al. (2024) [10] also presented high histopathological correlation in upper tract urothelial samples with the second edition of TPS, attesting to its utility across varied anatomical sites and specimen types. The rise in diagnostic precision and decrease in ambiguity our study observed is in line with Farahani et al. (2024) [11] systematic review and meta-analysis, which concluded that application of TPS improves sensitivity and interobserver agreement considerably compared to non-standardized cytological reporting. These findings further add strength to the argument for international implementation of TPS as a standardized diagnostic system for urinary cytology. Notably, the intermediate groups—specifically "Atypical Urothelial Cells" (AUC) and "Suspicious for High-Grade Urothelial Carcinoma" (SHGUC)—remain of critical importance in clinical triage. In our population, a significant percentage of histologically verified HGUC cases (18 out of 112) were initially reported as AUC, and 34 as SHGUC. Although the AUC category is necessarily heterogeneous, our data indicate that patients within this category need close follow-up and, where indicated, the use of adjunctive diagnostic modalities. Celik and Kavas (2023) [13] pointed out that although the Johns Hopkins template might label as higher-risk for malignancy those atypical cases, the Paris System offers more distinction and reproducibility in the suspicious category, consistent with our experience that SHGUC is highly correlated with proven malignancy. Additionally, our findings demonstrated an interobserver agreement (kappa = 0.78) higher than what has been seen with traditional cytology, highlighting TPS's ability to normalize diagnostic interpretation among various observers. This aligns with reports from Rohra et al. (2021) [14], who also noted increased diagnostic uniformity with the implementation of TPS in a large institutional trial with histologic follow-up. Rai et al. (2019) [15] also reported that TPS decreases subjective interpretation and improves diagnostic consistency among pathologists, thus favoring more consistent clinical decision-making. Pastorello et al. (2021) [12], in their extensive review of the TPS literature, highlighted its two-fold purpose of enhancing the diagnostic yield as well as the clinical significance of cytologic evidence. This is corroborated by our study, especially by the evident stratification within the "Positive for HGUC" group that had a high correlation (50 of 66 cases) with histologically proven high-grade lesions. Such diagnostic accuracy is crucial in streamlining patient management by avoiding unnecessary biopsies on benign conditions and by ensuring early treatment of malignant ones. Overall, the use of the Paris System in our study not only enhanced diagnostic accuracy but also decreased the number of indeterminate reports and improved interobserver agreement. These results are consistent with those reported in studies in other countries within diverse clinical and geographic environments, corroborating the increasing view that TPS is a significant improvement in urinary cytology. The efficiency of the system in stratifying risk, increasing reproducibility, and correlating cytologic findings to histopathology cements its position as an important tool in the early detection and surveillance of HGUC.

In conclusion, the Paris System for Reporting Urinary Cytology really boosts the accuracy and reliability of urine cytology when it comes to spotting high-grade urothelial carcinoma. By laying out clear morphological criteria and structured reporting categories, this system cuts down on diagnostic confusion and enhances agreement among different observers. Our research shows a strong alignment between cytological interpretations and histopathological results, especially in the “Suspicious” and “Positive” categories, confirming that the Paris System is a dependable tool for early detection and effective clinical triage of urothelial cancers. Given its demonstrated clinical benefits and its fit with global research, the Paris System should be the go-to framework for urinary cytological assessments in both everyday practice and specialized oncology settings.

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