Diagnosis Of High-grade Urothelial Carcinoma Research Articles

Reclassification of Urinary Cytology according to the Paris System for Reporting Urinary Cytology Correlation with Histological Diagnosis

Introduction: The Paris System for Reporting Urinary Cytology (TPS) was designed to provide precise diagnostic criteria when evaluating urine cytology and standardize the terminology used in reporting. In our study, we have aimed to determine the effect of TPS on the diagnostic performance of urine cytology, its impact on establishing appropriate risk stratification, and its effectiveness in the diagnosis and follow-up of the patients. Methods: We reevaluated 200 liquid-based urine cytologies with available histological diagnoses reported between 2015 and 2021 according to TPS criteria and compared them with the original cytological diagnoses. Area under the curve, sensitivity, specificity, and diagnostic accuracy of both methods were calculated and statistically analyzed to determine the diagnostic performance of the original reporting and TPS. Results: The sensitivity, specificity, positive predictive, negative predictive, and diagnostic accuracy rates of TPS were 60%, 99.3%, 97.2%, 97.2%, 85.7%, and 87.2%, respectively. In TPS, the risk of malignancy for negative for high-grade urothelial carcinoma, atypical urothelial cells, suspicious for high-grade urothelial carcinoma, and high-grade urothelial carcinoma (HGUC) is 3.5%, 20.9%, 60.8%, 97.2%, respectively. In the original reporting, the corresponding risks were 13.4%, 15%, 52%, 100%, respectively. A statistically significant difference was observed between diagnostic criteria of original cytology and TPS (p = 0.001). When the original reporting was compared with the TPS, the discriminative power of TPS in the diagnosis of HGUC was significantly higher (p < 0.001). Conclusions: The use of TPS provided a more accurate risk stratification of patients. The diagnostic performance of urine cytology was improved, especially for 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.

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. 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 3months. The second cohort was 36 HGUC cases with negative histology on concurrent biopsies and within 3months. The number of high-grade cells (HGCs) meeting the TPS qualitative criteria were counted under the light microscope driven in a grid-like manner. 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. 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.

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.

Abstract 5414: Automated detection of high-grade urothelial carcinoma from urine cytology slides using attention-based deep learning

Abstract Urine cytology has long been an effective and non-invasive test for the detection of bladder urothelial carcinomas (UC) routinely performed in cases of unexplained hematuria or for monitoring patients with UC. In cytopathology practice, urine cytology specimens are examined manually with a light microscope to identify morphologic features associated with different diagnostic categories based on the Paris System (TPS) for Reporting Urinary Cytology. Specifically, the diagnosis of high-grade urothelial carcinoma (HGUC) requires the identification of &amp;gt; 5-10 cells with a nuclear/cytoplasm ratio of 0.7 or greater and hyperchromasia together with coarse chromatin or irregular nuclear membranes. However, the task of identifying HGUC involves a substantial degree of manual review and is often associated with intra-and inter-observer variability. To address this, we have designed an accurate and efficient deep learning system capable of automatically distinguishing between HGUC and non-HGUC using digitized cytology slides. Our model has been developed using a retrospective cohort of 158 digitized urine ThinPrep cytology slides consisting of HGUC (n=98) and negative for HGUC (n=60). The model was then prospectively validated on a cohort of 105 urine cytology slides that were also independently reviewed prospectively in a blinded manner by a cytopathologist and cytotechnologist. Our system uses Otsu’s method for automatic image thresholding followed by dividing images into non-overlapping tiles of 500 × 500 pixels at the highest magnification. Subsequently, we use a pre-trained ResNet50 model to extract features which are used for training our attention-based multiple instance learning framework. For the training task, our retrospective cohort (158 slides) has been divided into 10 different splits each consisting of training (70%), validation (15%), and testing (15%) sets. The training and validation sets were used for the model training and optimalization, respectively, while the testing set was used for assessing the performance. This process yielded 10 different models with an average Area Under the ROC Curve (AUC) of 0.80 in the testing set. The best performing model had an AUC of 0.90 and an accuracy of 0.88. This model was subsequently validated prospectively in an independent testing cohort with 105 slides. In the prospective testing cohort, the model was able to accurately distinguish between HGUC and non-HGUC with an AUC of 0.83, accuracy of 0.76, sensitivity of 0.89, and specificity of 0.62. Additionally, our system can detect slide regions with high attention score for HGUC which are enriched in atypical urothelial cells. These findings show that our system can be utilized to assist cytopathologists in assessing urine cytology slides and to detect regions with high-diagnostic relevance for further assessment which is expected to reduce the time needed for manual review. Citation Format: Mohamed Omar, David Kim, Luigi Marchionni, Momin T. Siddiqui. Automated detection of high-grade urothelial carcinoma from urine cytology slides using attention-based deep learning. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5414.

Cyto-histo correlation and false-negative urine: Before and after the Paris system for reporting urinary cytology.

The impact of implementing the Paris system (TPS) on the rate of discrepant cases in the negative for high-grade urothelial carcinoma (NHGUC) category that had a subsequent diagnosis of high-grade urothelial carcinoma (HGUC) on histology is not well studied. We adopted TPS in May 2019. We searched discrepant cases with negative urine cytology 2017-2019 in our cyto-histo correlation database. The urine cytology and follow-up biopsy/resection were reviewed by a cytopathologist who also did Genitourinary (GU) Pathology subspecialty sign-out. Voided urine and instrumented urine were included in this study. There were total of 70 discrepant cases with negative cytology interpretation but HGUC on the subsequent biopsy or resected specimen. Following the TPS criteria, the rate of discrepant negative cytology cases increased from 6 cases between January 2017 and May 2019 to 64 cases after May 2019 when we adopted TPS. There were 2 discrepant negative cases in 2017, 3 cases in 2018, and 65 cases in 2019. Out of 65 cases in 2019, 64 cases were identified after May 2019. Additional 55 urine cytology slides were reviewed according to the TPS criteria, of which, the diagnoses remained unchanged in 45 (82%) cases and 10 (19%) cases were reassigned to either atypical or suspicious categories. The discrepancy was noted more on the instrumented urine and the upper tract urine. However, the false-negative rate rose faster in voided urine and lower tract urine. The risk of HGUC with the category of NHGUC was 0.03% in 2017, 0.05% in 2018, and 1.06% in 2019 at our institution. The increase in false-negative rate could not be attributed to a single cytopathologist. After adopting TPS for reporting urine cytology, there was an increase in HGUC from negative urine cytology which was subsequently confirmed on histology as cases of HGUC. The quality control of negative urines could be important monitoring the process when implementing TPS.

Pleural fluid metastasis of plasmacytoid urothelial carcinoma in comparison to micropapillary and conventional high-grade urothelial carcinoma: Cytologic and immuonohistochemical findings.

Plasmacytoid urothelial carcinoma (PUC) is a rare but clinically aggressive variant of high-grade urothelial carcinoma (HGUC). Cytological features include single plasmacytoid neoplastic cells with N:C ratio around 0.5, eccentric nuclei, nuclear hyperchromasia, irregular nuclear membrane, and vacuolated cytoplasm. Micropapillary urothelial carcinoma (MPUC) is another clinically aggressive variant of HGUC that shares some overlapping features of PUC. The diagnosis of these two aggressive variants in pleural effusions can be challenging due to features mimicking adenocarcinoma, unusual immunochemistry profile, and confusion with differential diagnoses, especially when pertinent clinical information is unavailable. We present report on one case each of pleural fluid metastasis of PUC and MPUC respectively, and compare the findings with that of a metastatic conventional HGUC originally thought to be metastatic adenocarcinoma. The diagnosis of PUC was confirmed with immunohistochemical studies showing expression for cytokeratin, GATA-3, uroplakin II, and CD138, diminished or loss of E-cadherin membranous expression, negative expression for p63, p53, Epicam-BerEP4, Epicam-MOC31, and p120. The diagnosis of MPUC was confirmed with immunostain profile similar to that of PUC except positive stain for E-cadherin, p120, and p53. The diagnosis of HGUC was confirmed with immunohistochemical studies showing expression for cytokeratin, GATA-3, uroplakin II, p63, Epicam-BerEP4 (focal weak), and Epicam-MOC31. Our cases of metastatic urothelial carcinoma showed features mimicking adenocarcinoma and others, especially the MPUC and HGUC were diagnosed without prior tissue diagnosis of urothelial carcinoma. This report emphasizes the cytohistological and immunohistochemical details of urothelial carcinoma involving effusion fluid and discusses potential pitfalls in diagnosis.

The Paris System for reporting urinary cytology improves the negative predictive value of high-grade urothelial carcinoma

BackgroundThe Paris System (TPS) for reporting urinary cytology differs from conventional systems (CS) in that it focuses on the diagnosis of high-grade urothelial carcinoma (HGUC). This study investigated the impact of TPS implementation on the diagnostic accuracy of HGUC by comparing it with our institutional CS.MethodsA total of 649 patients who underwent transurethral resection of bladder tumor (TURBT) between January 2009 and December 2020 were included in this study. Our institution adopted TPS to report urinary cytology in February 2020. The diagnostic accuracy of HGUC in preoperative urinary cytology was compared with the presence or absence of HGUC in resected specimens of TURBT before and after TPS implementation.ResultsAfter implementing TPS in urinary cytology, 89 patients were reviewed and compared with 560 patients whose urinary cytology was diagnosed by CS. TPS and CS for detecting HGUC had 56.0% and 58.2% sensitivity, 97.8% and 91.2% specificity, and 93.3% and 87.9% positive predictive values, respectively. There were no significant differences between TPS and CS in terms of sensitivity, specificity, and positive predictive value for HGUC (P = 0.83, 0.21, 1.00). On the other hand, the negative predictive value for HGUC using TPS was 80.0%, which was significantly higher than that of CS (66.4%, P = 0.04) The multivariate logistic regression analysis indicated that not using TPS was one of the independent predictive factors associated with false-negative results for HGUC (odds ratio, 2.26; 95% confidence interval, 1.08–4.77; P = 0.03).ConclusionIn instances where urinary cytology is reported as negative for HGUC by TPS, there is a low probability of HGUC, indicating that TPS has a potential diagnostic benefit.

Urine cytology findings in patients with biopsy-confirmed urothelial carcinoma in situ with plasmacytoid features.

Urine cytology is an important screening tool in the diagnosis of high-grade urothelial carcinoma. Diagnosis in urine samples follows criteria outlined by The Paris System for Reporting Urinary Cytology (TPS). However, cytologic characteristics of the recently described urothelial carcinoma in situ with plasmacytoid features (P-CIS) have not been described, and it is unknown whether they conform to TPS criteria for high-grade urothelial carcinoma. This study was aimed at better characterizing possibly unique cytologic features of P-CIS. The authors collected urine cytology specimens from patients with subsequent bladder biopsy-proven P-CIS. Specimens were re-reviewed according to the TPS criteria. The proposed cytologic features of P-CIS (eccentric, enlarged, and hyperchromatic nuclei) were evaluated; this included the reproducibility of 3 cytopathologists for the proposed cytologic features. Seventy-four urine specimens from 18 patients with P-CIS-diagnosed bladder biopsies were identified. The TPS diagnoses of the 74 urine cytology specimens were as follows: negative for high-grade urothelial carcinoma (n = 26), atypical urothelial cells (n = 26), suspicious for high-grade urothelial carcinoma (n = 12), and high-grade urothelial carcinoma (n = 10). Only 7 urine specimens met the proposed cytologic criteria for P-CIS, and they had TPS diagnoses of negative for high-grade urothelial carcinoma (n = 1), atypical urothelial cells (n = 3), and high-grade urothelial carcinoma (n = 3). The κ interobserver agreement ranged from poor to fair. The features of P-CIS on urine cytology are subtle and infrequently reproducible and often do not meet the TPS criteria for diagnosis as high-grade urothelial carcinoma. In specimens that do not meet TPS criteria for high-grade urothelial carcinoma, P-CIS cytology in isolation would be best classified as atypical urothelial cells.

Urinary Cytology in the Diagnosis of Bladder Cancer

The examination of urine is an ancient medical procedure dating back thousands of years. Microscopic examination of cells in the urine is being done since the invention of microscope. Presently the cytological examination of urine or other fluid samples from the urinary tract is a routine non-invasive diagnostic procedure to detect cancer of the urinary tract, especially in patients with painless haematuria. It is also used in the follow-up of patients previously treated for bladder cancer to detect recurrence or a new primary. It is a highly specific method for the diagnosis of invasive and in situ urothelial carcinoma and high-grade papillary carcinoma. However, it is unreliable for the detection of low-grade papillary neoplasms. Malignant cytomorphological characteristics of the exfoliated cells in urine or bladder washing can facilitate the diagnosis of bladder cancer. The Paris System (TPS) Working Group has proposed. The Paris System (TPS) authorities have proposed a standard reporting stem which includes specified diagnostic categories and cytomorphologic criteria for diagnosis of High-grade Urothelial Carcinoma (HGUC).

Effect of the Paris system for reporting urinary cytology with histologic follow-up.

The Paris system (TPS) for Reporting Urinary Cytology provides a standardized reporting system whose main focus is the diagnosis of high-grade urothelial carcinoma (HGUC). We conducted a study to see the impact of The Paris System on our cytologic diagnoses with associated histology. We reviewed our pathology database regarding urinary specimens in the year before implementation of The Paris System and the year after. We gathered the data regarding cytologic diagnosis and concurrent/subsequent histology. Over a 1-year period from 2016-2017, 486 urine cytology specimens were identified before implementation of The Paris System and diagnosed as follows: 83% benign/negative, 10% atypical, 2% suspicious, 5% HGUC, 0.2% low grade urothelial neoplasm (LGUN), and 0.2% unsatisfactory. Over a next 1-year period from 2017 to 2018, 602 specimens used TPS and diagnosed as follows: 85% negative for HGUC, 6% atypical, 3% suspicious, 4% HGUC, 0.17% LGUN, and 2% unsatisfactory. Although, not listed as a standardized category in The Paris System, our institution used "Negative for high-grade, cannot rule out low-grade urothelial neoplasm (NHL)" as a subcategory of Negative for HGUC. 4% of the cases fell into this category. Focusing on the Atypical category before TPS, histology was available in 15/49 (31%) cases. Of these, 40% had HGUC. Regarding the Atypical category after TPS, histology was available in 21/36 (58%) cases. Of these, 52% were HGUC. For the NHL category, concurrent histology was available in 13/26 (50%) cases. Of these, 67% were low grade urothelial neoplasms. Our study showed that TPS lowered the rate of Atypical from 10% to 6%. After the implementation of TPS, Atypical corresponded to a higher rate of high-grade urothelial carcinoma. Also, the NHL subcategory had a high positive predictive value for diagnosing low grade urothelial neoplasms.

Should "suspicious for high-grade urothelial carcinoma" and "positive for high-grade urothelial carcinoma" remain separate categories?

The Paris System (TPS) for Reporting Urinary Cytology aims to standardize urine cytology reporting. Per TPS, the diagnosis of "suspicious for high-grade urothelial carcinoma (SHGUC)" is applied in cases that have few urothelial cells with severe atypia but are quantitatively insufficient for a diagnosis of "high-grade urothelial carcinoma (HGUC)." In our study, we compared the diagnostic accuracy and risk of malignancy (ROM) of these 2 categories to assess whether they could be combined in clinical practice to perhaps improve overall interobserver variability. All urine specimens with a diagnosis of either SHGUC or HGUC from January 2016 to July 2019 were retrieved from the pathology database of 2 large academic institutions. Only cases with follow-up biopsies within 6 months were included. One hundred eighty-nine cases met the study criteria. Of these, 122 had a cytologic diagnosis of SHGUC, and 67 had a diagnosis of HGUC. Ninety-five (78%) cases from the SHGUC group and 64 (96%) cases from the HGUC group had biopsy-proven HGUC. The majority of cases with discordance had a history of treatment with either intravesical bacillus Calmette-Guérin or mitomycin. The difference in the rate of biopsy-proven HGUC between the SHGUC category and the HGUC category (95/122 vs 64/67, respectively) was statistically significant (P < .001). The difference in ROM between SHGUC and HGUC was statistically significant in our study cohort. Intravesical chemotherapy was frequently observed in negative biopsy cases in both groups. Our preliminary findings suggest that the 2 TPS categories should remain separate.

A new 7-point method facilitates accurate diagnosis of high-grade urothelial carcinoma in routine urinary cytology practice

This study was designed to identify the minimal and necessary cell morphologies to be considered for high-precision diagnosis of high-grade urothelial carcinoma (HGUC) in a routine urinary cytology practice. We included 338 urine cytology specimens from 11 medical facilities in Japan. Six experts evaluated these Papanicolaou-stained specimens using their own diagnostic criteria to categorize them within an initial 4-tiered classification system. Of the 338 cases, 70 HGUC and 32 benign cases (with a complete consensus diagnosis of 6 experts) were included for the analysis. Two of the cytologists evaluated the specimens for 20 specific cellular features. The results were analyzed using a contingency table and by discriminant analysis. Of the original 338 cases, 165 were originally diagnosed as HGUC, but only 70 (42.4%) were scored as malignant by all participating cytologists; of the 101 benign cases, only 32 (31.7%) were classified as such in all examinations. These specimens were re-evaluated by 6 experts using a panel of 20 specific cellular features used to distinguish between HGUC and benign diseases; tests of significance and discriminant analyses identified 7 critical features that were most useful for cytological diagnosis. Statistical analysis revealed that a focus on these 7 features led to a diagnosis of HGUC with a probability of over 95%. The accuracy of our presently used method to evaluate urinary cytology is not consistently high. This novel classification system, which focuses on 7 critical features, facilitates the high accurate diagnosis of HGUC in routine cytology practice.

Polyomavirus (BK) cytopathic effect in urine cytology is not associated with high risk of developing high-grade urothelial carcinoma

Polyomavirus cytopathic effect (BK-CPE) is classified as "negative for high-grade urothelial carcinoma" (NHGUC) in the Paris System for Reporting Urinary Cytology. However, polyomaviruses have been historically associated with tumor development and have been recently reported as an independent risk factor for renourinary carcinoma in transplant patients. The aim of the present study was to investigate the relationship between polyomavirus infection in the urinary tract and the subsequent risk of developing high-grade urothelial carcinoma (HGUC) in the general population. A retrospective case-control study was conducted to assess BK-CPE in all urinary cytology examinations performed from 2009 to 2011 for cases with an interpretation of NHGUC, NHGUC with BK, atypical urothelial cells (AUCs), or AUCs with BK. The endpoint of the present study was a diagnosis of HGUC on either bladder biopsy or urine cytology for those patients with subsequent follow-up data. A total of 252 cases with a urinary cytology interpretation of NHGUC, 234 with NHGUC + BK, 255 with AUCs, and 64 with AUCs + BK were identified. The surgical and cytological follow-up data showed that the overall risk of the development of HGUC for those with NHGUC, NHGUC + BK, AUCs, and AUCs + BK was 6.0%, 6.8%, 23.5%, and 12.5%, respectively. No statistically significant differences were found between the patients with NHGUC and those with NHGUC + BK. A statistically significant difference was found for patients with AUCs compared with patients with NHGUC + BK and those with AUCs + BK (P < 0.001). The presence of BK-CPE in urine cytology samples does not increase the overall risk of the development of HGUC. Our results support the recommendation from the Paris System for Reporting Urinary Cytology to place urine samples with BK-CPE in the NHGUC category.

Cytological features of micropapillary and plasmacytoid variants of urothelial carcinoma.

Micropapillary and plasmacytoid variants of urothelial carcinoma (UC) exhibit very aggressive clinical behavior. To date, only a small number of cytology cases have been reported in either of these variants. Herein, we report 15 cases of UC with combined micropapillary and plasmacytoid features based on urine cytology. We performed a retrospective analysis of all patients with carcinoma of bladder with predominant plasmacytoid and micropapillary histology who had been seen from 2005 to 2017. A total of 15 cases (six cases of plasmacytoid variant and nine cases of micropapillary variant of bladder cancer) with urine specimen were evaluated. The cytomorphological features were compared between two histological variants. Fifteen urine cytology cases with the diagnosis of high-grade UC were investigated. The ratio man to women was 5:1 with a median age of 79 years (range: 72-90 years). Single-cell pattern, flat sheets, three-dimensional clusters, micropapillae, nuclear grade, cytoplasmic vacuoles, and necrosis, were evaluated in urine samples of micropapillary variant. The cytological features of plasmacytoid are characterized by large, discohesive, isolated tumor cells that have abundant, thick cytoplasm, and eccentrically located, hyperchromatic nuclei with coarse chromatin and inconspicuous nucleoli. It is important to recognize the cytological characteristics of these uncommon but aggressive entities to determine a precise diagnosis. Attention to morphological features, together with clinical history and appropriate immunohistochemical studies may be useful to urologist in pre-operative planning and may lead to a more aggressive surgical approach.

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

One year of experience using the Paris System for Reporting Urinary Cytology.

The Paris System for Reporting Urinary Cytology (TPS) was published in November 2015. It focuses on the diagnosis of high-grade urothelial carcinoma (HGUC) and provides criteria with which to define the category of atypical urothelial cells (AUC). The objective of the current study was to compare two 1-year consecutive periods before and after use of TPS. A total of 1634 and 1814 urine cytology cases, respectively, were analyzed before and after use of TPS. Histological diagnosis within 6 months was available for 330 and 299 cases, respectively. After use of TPS, the authors reported significantly fewer low-grade urothelial neoplasms (0.94% vs 1.84%; P<.05) and more cases that were suspicious for HGUC (2.09% vs 0.73%; P<.01) compared with before use of TPS. For the AUC category, there was no significant change in frequency noted for before versus after TPS (6.12% vs 5.18%), whereas the rate of detection of HGUC on histology significantly increased after TPS when compared with before TPS (49.02% vs 28.17%; P<.02). For the HGUC category, neither the frequency (4.69% vs 4.47%) nor the risk of malignancy (89.39% vs 91.04% with HGUC on histology) were found to be significantly different when comparing before and after use of TPS. In the authors' practice, TPS helped to better characterize the categories of AUC, low-grade urothelial neoplasm, and suspicious for HGUC, which were associated with a higher risk of HGUC compared with the authors' previous classification. Cancer Cytopathol 2018;126:430-6. © 2018 American Cancer Society.

Implementing The Paris System for Reporting Urinary Cytology results in a decrease in the rate of the "atypical" category and an increase in its prediction of subsequent high-grade urothelial carcinoma.

In the current study, the authors evaluated the impact of implementing The Paris System for Reporting Urinary Cytology (PSRUC) on the prevalence of various cytological categories and their association with a subsequent diagnosis of high-grade urothelial carcinoma (HGUC). A comparative study was conducted over the 6-month period before PSRUC implementation (2013), including 1653 patients and 2371 specimens versus a 6-month period after implementation of the PSRUC (2016), including 1478 patients and 2392 specimens. The following cytological categories were correlated with the subsequent biopsy result when available (355 cases): negative for HGUC (NHGUC), atypical urothelial cells (AUC), suspicious for HGUC, and HGUC. Although 18.6% of specimens were diagnosed as AUC in 2013, the percentage was 14.4% in 2016 (P < .0001). Concurrently, the prevalence of the "benign" category increased from 2013 to 2016 (75.4% vs 80%; P < .0001). After implementation of the PSRUC, there was no significant change noted with regard to the association between the categories of NHGUC, suspicious for HGUC, and HGUC and a subsequent HGUC biopsy diagnosis. However, the predictive value of an AUC diagnosis increased from 28.3% to 46.1% (P = .077). Most important, after the implementation of the PSRUC, there was a significant difference noted with regard to the predictive association for HGUC between the NHGUC and AUC groups (13.6% vs 46.1%; P = .003), a difference that was not found to be statistically significant before implementation of the PSRUC (18% vs 28.3%; P = .175). There was a much higher risk of HGUC conveyed by AUC cytology after implementation of the PSRUC, justifying more aggressive investigations of patients who receive an AUC diagnosis. Cancer Cytopathol 2018;126:207-14. © 2017 American Cancer Society.

Noninvasive Diagnosis of High-Grade Urothelial Carcinoma in Urine by Raman Spectral Imaging.

The current gold standard for the diagnosis of bladder cancer is cystoscopy, which is invasive and painful for patients. Therefore, noninvasive urine cytology is usually used in the clinic as an adjunct to cystoscopy; however, it suffers from low sensitivity. Here, a novel noninvasive, label-free approach with high sensitivity for use with urine is presented. Coherent anti-Stokes Raman scattering imaging of urine sediments was used in the first step for fast preselection of urothelial cells, where high-grade urothelial cancer cells are characterized by alarge nucleus-to-cytoplasm ratio. In the second step, Raman spectral imaging of urothelial cells was performed. A supervised classifier was implemented to automatically differentiate normal and cancerous urothelial cells with 100% accuracy. In addition, the Raman spectra not only indicated the morphological changes that are identified by cytology with hematoxylin and eosin staining but also provided molecular resolution through the use of specific marker bands. The respective Raman marker bands directly show a decrease in the level of glycogen and an increase in the levels of fatty acids in cancer cells as compared to controls. These results pave the way for "spectral" cytology of urine using Raman microspectroscopy.

Improved risk stratification for patients with high-grade urothelial carcinoma following application of the Paris System for Reporting Urinary Cytology.

The Paris System for Reporting Urinary Cytology (TPS) requires 4 cytomorphologic criteria for a definitive diagnosis of high-grade urothelial carcinoma (HGUC) in urinary tract cytology (UTC) specimens: an elevated nuclear-to-cytoplasmic (N/C) ratio (at or above 0.7), markedly atypical nuclear borders, moderate to severe hyperchromasia, and coarse chromatin. However, malignant UTC specimens often contain degenerative changes, and this limits the number of malignant cells meeting all 4 TPS cytomorphologic criteria. One hundred twelve UTC specimens from patients with a subsequent diagnosis of HGUC were reviewed and reclassified according to TPS criteria. The presence of TPS cytomorphologic criteria for HGUC in each specimen was recorded, as was the proportion of atypical cells meeting all 4 criteria. The number of specimens definitively diagnosed as HGUC did not significantly change upon reclassification. However, approximately 40% of indeterminate specimens (21 of 51) were reclassified into a higher risk category. The most restrictive cytomorphologic criterion was an N/C ratio of 0.7 or higher (seen in 78% of specimens), and approximately half of specimens containing all 4 cytomorphologic criteria did not meet TPS's numerical criterion for HGUC (at least 5 malignant cells). In the majority of specimens qualifying for HGUC by TPS standards, only a small fraction of atypical cells (10%-20%) met all the criteria. When applied to malignant UTC specimens, TPS criteria improved specimen risk stratification by upgrading approximately 40% of indeterminate specimens into higher risk categories while not significantly changing the frequency of HGUC diagnoses. Cancer Cytopathol 2017;125:427-34. © 2017 American Cancer Society.

The Paris System for Reporting Urinary Cytology: The Quest to Develop a Standardized Terminology.

The main purpose of urine cytology is to detect high-grade urothelial carcinoma. With this principle in mind, The Paris System (TPS) Working Group, composed of cytopathologists, surgical pathologists, and urologists, has proposed and published a standardized reporting system that includes specific diagnostic categories and cytomorphologic criteria for the reliable diagnosis of high-grade urothelial carcinoma. This paper outlines the essential elements of TPS and the process that led to the formation and rationale of the reporting system. TPS Working Group, organized at the 2013 International Congress of Cytology, conceived a standardized platform on which to base cytologic interpretation of urine samples. The widespread dissemination of this approach to cytologic examination and reporting of urologic samples and the scheme's universal acceptance by pathologists and urologists is critical for its success. For urologists, understanding the diagnostic criteria, their clinical implications, and limitations of TPS is essential if they are to utilize urine cytology and noninvasive ancillary tests in a thoughtful and practical manner. This is the first international/inclusive attempt at standardizing urinary cytology. The success of TPS will depend on the pathology and urology communities working collectively to improve this seminal paradigm shift, and optimize the impact on patient care.