Incidental finding in urine cytology in a patient with chronic renal disease.

An incidental finding in urine smears from a patient with a presumptive diagnosis of an IgA mesangial nephropathy is presented. A possible example of the potential value of urine cytology in functional renal disorders. We report a case of an incidental finding in urine cytology from a patient with a presumptive diagnosis of an IgA mesangial glomerulonephritis, previously diagnosed as atypical urothelial cells.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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 for urine cytology in upper tract urothelial specimens: A comparative analysis with biopsy and surgical resection.

INTRODUCTION: The Paris System (TPS) has recently been used in classification of urinary tract cytological specimens. Upper urinary tract (UUT) specimens are cytologically challenging. The utility of TPS was investigated in evaluating UUT specimens and its correlation with subsequent histological follow-up. METHOD: From 2014 to 2017, 324 cytology cases of UUT from 179 patients were retrieved. Concurrent or subsequent biopsy or resection within a 2-month period was available in 125 cases from 74 patients. RESULT: None of the cases with a cytology of low-grade urothelial neoplasm was found to have a high-grade urothelial carcinoma (HGUC) on biopsy. Among the 19 atypical urothelial cells (AUC) cytology cases, the histology is heterogeneous (seven benign, one atypia, five low-grade lesion, and six HGUC). The risk of HGUC for each cytological diagnostic category are 0% for non-diagnostic/unsatisfactory, 6% for negative for HGUC, 27.3% for AUC, 0% for low-grade urothelial neoplasm, 48% for suspicious for HGUC and 95% for positive HGUC. When we considered cytology cases with suspicious or positive for HGUC interpretations as positive, the performance of TPS in predicting high grade urothelial carcinoma on histology had values of: 78.6% sensitivity, 86% specificity, 80.5% positive predictive value and 84.5% negative predictive value. CONCLUSION: More than one-third of the UUT cytological cases were classified as AUC and approximately 1/15 as suspicious or positive for HGUC. Based on UUT cytology specimens, the risk of malignancy of each cytological diagnostic category of TPS was comparable to those reported in the literature. The use of TPS in evaluating UUT cytology specimens was specific and sensitive in identifying patients with HGUC by histology.

Application of The Paris System to atypical urine cytology samples: correlation with histology and UroVysion® FISH.

OBJECTIVES: To evaluate whether atypical urine cytology cases may be stratified more objectively using The Paris System (TPS) and whether reclassified cases correlate with histology and UroVysion® results. METHODS: Atypical urine cytology cases subjected to UroVysion® testing over a period of 6 years were reviewed. Each case was reclassified according to TPS and correlated with histology and UroVysion® results. RESULTS: A total of 91 cases were identified; 70.3% were reclassified as 'negative for high-grade urothelial carcinoma (HGUC)' and 14.3% as 'atypical urothelial cells (AUC)'. The histological correlation was available in 45 cases. In the 'negative for HGUC' category, 67.9% had no histological evidence of malignancy, but 17.9% were diagnosed as HGUC. In the 'AUC' category, histology revealed urothelial carcinoma in 70% of the cases (of these, 71.4% were high grade). There was no histological evidence of malignancy in 30% of cases; notably, all of which were from patients under surveillance. The sensitivity and specificity of UroVysion® were 85.7% and 33.3% in the 'AUC' group and 62.5% and 100% in the 'negative for HGUC' group. CONCLUSIONS: The Paris System is an objective template for reporting urine cytology specimens, and is particularly useful in identifying HGUC cases and refining the category of 'AUC'.

Diagnostic terminology for urinary cytology reports including the new subcategories 'atypical urothelial cells of undetermined significance' (AUC-US) and 'cannot exclude high grade' (AUC-H).

OBJECTIVE: We studied whether atypical, non-superficial urothelial cells (AUC) could be separated into new subcategories including AUC 'of undetermined significance' (AUC-US) and 'cannot exclude high grade'' (AUC-H) in order to help to standardize urine cytopathology reports, as it is widely accepted in the Bethesda system for gynaecological cytopathology. METHODS: We investigated whether AUC-US and AUC-H, defined by distinctive cytological criteria, might be separated with statistical significance according to actual diagnosis and follow-up data. A series of 534 cyto-histological comparisons taken in 139 patients, including 221 AUC at various steps of their clinical history was studied. There were 513 (96.1%) postcystoscopy and 469 (87.8%) ThinPrep® liquid-based specimens (95.9% and 89.1% of AUC cases, respectively). Patients viewed between 1999 and 2011 had histological control in a 0- to 6-months delay and were followed-up during an additional 5.9 ± 9.2 (0- to 56-) months period. RESULTS: The 221 AUC represented 0.8-2% of the specimens viewed during the study period. Among AUC-H cases, 70 out of 185 (37.8%) matched with high-grade lesions, compared with 3 of 38 (8.3%) of AUC-US cases (P = 0.0003). Conservatively treated patients with AUC-H more frequently developed high-grade lesions than those with AUC-US (54.1% versus 16.7%, P = 0.0007) with a 17.6-months mean delay. Nuclear hyperchromasia, a nuclear to cytoplasm (N/C) ratio > 0.7 and the combination of both were the more informative diagnostic criteria, all with P < 0.01. CONCLUSION: We conclude that the new subcategories could help to standardize urine cytopathology reports and contribute to the patient's management, provided it is validated by multicentric studies.

Diagnostic Accuracy of the Second Edition of the Paris System for Reporting High-Grade Urothelial Carcinoma in Urinary Cytology.

BACKGROUND: Urinary cytology, a non-invasive screening tool, is essential for detecting high-grade urothelial neoplasms. The Paris System (TPS) standardizes reporting practices to improve diagnostic accuracy. TPS 2.0, introduced in 2022, categorizes samples into six diagnostic groups, emphasizing high-grade urothelial carcinoma (HGUC). MATERIALS AND METHODS: This retrospective study analyzed urine cytology samples from June 2023 to May 2024, correlating with histopathology when available. Samples were classified under TPS 2.0 categories, and statistical metrics including sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated for three groups based on malignancy criteria. RESULTS: Out of 180 samples, the distribution was ND (3.9%), NHGUC (65.6%), AUC (10%), SHGUC (11.7%), and HGUC (8.9%). Histopathological correlation was available for 30.6% of cases. risk of malignancy values were: ND (33.3%), negative for HGUC (29.4%), AUC (66.7%), suspicious for HGUC (94.1%), and HGUC (100%). Group A showed the highest sensitivity (86.49%) and diagnostic accuracy (84.62%), while group C had 100% specificity and PPV. CONCLUSION: The study confirms TPS 2.0's efficacy in improving diagnostic accuracy for HGUC, with high specificity and sensitivity. Compared to TPS 1.0, TPS 2.0 offers clearer diagnostic criteria, enhancing clinical decision-making and patient outcomes. The findings support the continued use of TPS 2.0 in clinical practice, ensuring reliable identification of HGUC.

An Artificial Intelligence-assisted Diagnostic System Improves Upper Urine Tract Cytology Diagnosis.

BACKGROUND/AIM: To evaluate efficacy of the AIxURO system, a deep learning-based artificial intelligence (AI) tool, in enhancing the accuracy and reliability of urine cytology for diagnosing upper urinary tract cancers. MATERIALS AND METHODS: One hundred and eighty-five cytology samples of upper urine tract were collected and categorized according to The Paris System for Reporting Urinary Cytology (TPS), yielding 168 negative for High-Grade Urothelial Carcinoma (NHGUC), 14 atypical urothelial cells (AUC), 2 suspicious for high-grade urothelial carcinoma (SHGUC), and 1 high-grade urothelial carcinoma (HGUC). The AIxURO system, trained on annotated cytology images, was employed to analyze these samples. Independent assessments by a cytotechnologist and a cytopathologist were conducted to validate the initial AIxURO assessment. RESULTS: AIxURO identified discrepancies in 37 of the 185 cases, resulting in a 20% discrepancy rate. The cytotechnologist achieved an accuracy of 85% for NHGUC and 21.4% for AUC, whereas the cytopathologist attained accuracies of 95% for NHGUC and 85.7% for AUC. The cytotechnologist exhibited overcall rates of roughly 15% and undercall rates of greater than 50%, while the cytopathologist showed profoundly lower miscall rates from both undercall and overcall. AIxURO significantly enhanced diagnostic accuracy and consistency, particularly in complex cases involving atypical cells. CONCLUSION: AIxURO can improve the accuracy and reliability of cytology diagnosis for upper urine tract urothelial carcinomas by providing precise detection on atypical urothelial cells and reducing subjectivity in assessments. The integration of AIxURO into clinical practice can significantly ameliorate diagnostic outcomes, highlighting the synergistic potential of AI technology and human expertise in cytology.

Utility of Image Morphometry in the Atypical Urothelial Cells and High-Grade Urothelial Carcinoma Categories of the Paris System for Reporting Urinary Cytology.

Introduction: Urinary cytology (UrCy) is highly sensitive to diagnosing high-grade urothelial carcinoma (HGUC) but cannot predict muscularis propria invasion. Further, the atypical urothelial cell category (AUC) may have variable outcomes. Image morphometry (IM) may be a valuable adjunct technique in this setting. Hence, we evaluated IM in the AUC and HGUC categories to improve the diagnostic performance. Materials and Methods: The following six nuclear parameters were evaluated by IM on 3150 cells: nucleo-cytoplasmic (N:C) ratio, nuclear area, diameter, perimeter, standard deviation of the nuclear area (SDNA; pleomorphism) and integrated density (ID; nuclear chromasia), using the ImageJ software, in three cohorts based on the histopathology outcome: 20 cases of AUC - benign non-neoplastic outcome (AUC-B); 22 cases of HGUC Muscle invasive (HGUC-MI) and 21 cases of HGUC non-muscle invasive (HGUC-MF). Results: A retrospective analysis of urine cytology. The patient's ages ranged from 36 to 85 years, with a mean age of 60.6. The male-to-female ratio was 5.4:1. A total of 20 cases of AUC-B and 43 cases of HGUC were selected for IM analysis. HGUC cases had higher nuclear parameters than AUC-B, and HGUC-MI had higher SDNA, ID, diameter, and area than HGUC-MF. SDNA and ID predict muscularis propria invasion in HGUC. Conclusions: Image morphometry successfully differentiates HGUC cases from benign non-neoplastic ones and might help to identify muscularis propria invasion in HGUC using a combination of nuclear parameters.

Utility of UroVysion Fluorescence in situ Hybridization in Improving the Diagnostic Performance of Urine Cytology.

INTRODUCTION: The atypical urothelial cell (AUC) category in The Paris System (TPS) in urine cytology (UrCy) is a challenging area. This study aimed to evaluate the UroVysion fluorescence in situ hybridization (U-FISH) assay in predicting the outcome of AUC. Additionally, we explored the association of abnormal U-FISH results in high-grade urothelial carcinoma (HGUC) concerning muscularis propria invasion (MPI). METHODS: This is a retrospective study, and U-FISH was done on archived Papanicolaou-stained smears. Four cohorts were included: non-neoplastic AUC (AUC-NN), neoplastic AUC (AUC-N), muscle-invasive HGUC (HGUC-MI), and muscle-free HGUC (HGUC-MF) outcome on histopathology (HPE) and with clinical follow-up of 12-29 months. U-FISH was evaluated for diagnostic purposes, and MPI and tumor stage prediction by urine FISH score (UFS; high vs. low) based on copy number gain of chromosomes (Chr). RESULTS: U-FISH was performed on 70 cases (20 AUC-NN, 20 AUC-N, 15 HGUC-MI, and 15 HGUC-MF) and was successful in 58/70 (82.85%) cases. All UC cases showed polysomy of ≥2Chr, and all the AUC-NN cases reported non-neoplastic on HPE were negative for U-FISH. U-FISH picked up all carcinoma cases in the AUC-N cohort. Chr 3 polysomy was statistically significant in differentiating HGUC-MI from HGUC-MF and low-grade urothelial carcinoma cases. Chr 3 signals with a cut-off of 6 signals could identify MPI with a sensitivity of 80.95% and specificity of 41.94%. The UFS of the HGUC-MI group was significantly higher than HGUC-MF. CONCLUSIONS: U-FISH successfully identified all cases of AUC with neoplastic outcomes. In the HGUC group, there was a difference in cases with and without MPI, which requires further confirmation in a larger prospective cohort.

A comparison between conventional and the Paris systems of reporting urinary cytopathology with a literature update.

INTRODUCTION: Owing to certain inherent limitations of earlier reporting systems, "The Paris System for Reporting Urinary Cytology (TPS)" was implemented in 2015 to standardize reporting urine cytology with more stringent cytomorphologic criteria. We share our post-TPS experience, comparing it with the conventional system (CS). AIM: To assess and compare the cyto-histopathologic/cystoscopic agreement between the conventional and the Paris systems (CS and TPS) for reporting urine cytology. MATERIALS AND METHODS: It is a cross-sectional study involving urine samples from 170 patients divided into two groups (CS and TPS). Of the 170 cases, 85 were reported according to the CS, and 85 were reported according to TPS with all the relevant clinical, radiologic, and cystoscopic findings. Using the kappa statistics, both groups were statistically analyzed for sensitivity, specificity, predictive values, and agreement. RESULTS: The sensitivity and specificity for high-grade urothelial carcinoma (HGUC) as per TPS were 83.33% and 94.59%, respectively, while they were 73.47% and 80.56% for the conventional system. The agreement for HGUC with TPS was 87.06% with a kappa value of 0.7416, while it was 76.5% with a kappa value of 0.53 for the CS. Implementing the TPS minimized usage of the atypical urothelial cells (AUC) category, increasing the clarity in detecting HGUC. CONCLUSION: TPS provides better agreement with histopathology than the CS for diagnosing HGUC, which is attributable to stringent TPS criteria that prompt cytopathologists to look more diligently for morphologic and numeric criteria.

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.

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

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The Paris System for reporting urinary cytology in daily practice with emphasis on ancillary testing by multiprobe FISH.

AIMS: The Paris System (TPS) was introduced in the diagnostic routine with the goal to simplify and standardise diagnostic reporting of urinary cytology. The diagnostic categories of TPS are based on defined cytological criteria, with a focus on high-grade urothelial carcinoma (HGUC). While the categories 'negative for HGUC (NHGUC)' and 'HGUC' are straightforward, the categories 'atypical urothelial cells (AUC)' and 'suspicious of HGUC (SHGUC)' remain inconclusive. In this study, we evaluated the feasibility of TPS in daily practice with special emphasis on ancillary fluorescence in situ hybridisation (FISH) testing in the setting of TPS categories. METHODS: In a 19-month period, TPS was prospectively applied in the routine diagnostic setting on 3900 urinary cytology cases comprising bladder and upper urinary tract washings and voided urine specimens. Additionally, we analysed the results of the FISH assay UroVysion prospectively performed on a cohort of 128 cases enriched for AUC and SHGUC categories. RESULTS: The most frequently reported category was NHGUC (n=3496, 89.7%), followed by AUC (n=178, 4.6%), HGUC (n=155, 4%), SHGUC (n=61, 1.6%), low-grade urothelial neoplasia (n=6, 0.1%) and other malignancies (n=4, 0.1%). In the FISH cohort, 40/90 (44%) cases within the AUC category were FISH positive, consistent with urothelial neoplasia. In the SHGUC category, 16/21 (76%) cases were FISH positive. CONCLUSIONS: When prospectively applying TPS in urinary cytology, inconclusive atypia accounts only for a small subset of cases. FISH additionally improves the stratification between reactive and malignant cells in the indeterminate AUC and SHGUC categories.

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.

Analysis of the Cytomorphological Features in Atypical Urine Specimens following Application of The Paris System for Reporting Urinary Cytology.

BACKGROUND: This study investigates the use of The Paris System (TPS) for Reporting Urinary Cytopathology and examines the performance of individual and combined morphological features in atypical urine cytologies. METHODS: We reviewed 118 atypical cytologies with subsequent bladder biopsies for the presence of several morphological features and reclassified them into Paris System categories. The sensitivity and specificity of individual and combined features were calculated along with the risk of malignancy. RESULTS: An elevated nuclear-to-cytoplasmic ratio was only predictive of malignancy if seen in single cells, while irregular nuclear borders, hyperchromasia, and coarse granular chromatin were predictive in single cells and in groups. Identification of coarse chromatin alone yielded a malignancy risk comparable to 2-feature combinations. The use of TPS criteria identified the specimens at a higher risk of malignancy. CONCLUSION: Our findings support the use of TPS criteria, suggesting that the presence of coarse chromatin is more specific than other individual features, and confirming that cytologic atypia is more worrisome in single cells than in groups.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Improved diagnostic precision of urine cytology by implementation of The Paris System and the use of cell blocks.

BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) published in 2016 provides a standardized approach to evaluating urine cytology. In the authors' practice, a TPS-like approach was adopted in 2012 using similarly defined cytologic criteria and correlating cystoscopic findings, and they also began incorporating the use of cell block (CB) material. The objective of the current study was to assess whether this TPS-like approach with the use of CB, as well as direct implementation of TPS, improved the diagnostic value of urine cytology. METHODS: In total, 188 consecutive urine cytology specimens from 2010 through 2016 that had concurrent or subsequent histologic specimens available were retrospectively analyzed for diagnostic correlation. Urine cytology performance was compared between the periods 2010 to 2012 (pre-TPS-like), 2013 to 2016 (TPS-like), and after TPS reclassification, including blind review by a cytopathologist. The contribution of available CB material to final diagnoses also was assessed. RESULTS: Both the TPS-like approach and TPS reclassification resulted in significantly lowering the rate of atypical urothelial cells (AUC) diagnosis from 48%, to 21%, to 9% (from pre-TPS, to TPS-like, to after TPS reclassification, respectively; P < 0.01) while increasing the positive predictive value of an AUC diagnosis for high-grade urothelial carcinoma from 21%, to 43%, to 83%, respectively. The use of CBs contributed to a definitive final diagnosis in 24 of 36 cases (66.7%). CONCLUSIONS: In support of the new TPS recommendations, the application of stringent "TPS-like" and TPS criteria improves the value of an AUC diagnosis for clinicians and patients by lowering the AUC rate and increasing the positive predictive value of AUC for high-grade urothelial carcinoma. CBs can be used to help resolve problematic cases for more definitive diagnostic categorization.

Utility of the Paris System in Reporting Urine Cytology.

OBJECTIVE: To find out the utility of The Paris System (TPS) in reporting urine cytology and to compare it with the reporting system currently used in our laboratory. STUDY DESIGN: This retrospective study was undertaken over a period of 1 year during which slides of all the urine specimens sent for cytological examination were retrieved from our laboratory filling system. They were blindly reviewed and reclassified according to TPS. Surgical follow-up was obtained from the uropathology services of our department. RESULTS: A total of 176 cases were meticulously reviewed. The mean age of the patients was 52 years, and 71% of cases presented with hematuria. Histopathological follow-up was available in 34 cases. Reporting by TPS detected 13.0% high-grade urothelial carcinoma (HGUC) and 5.1% atypical urothelial cells versus 7.3 and 11.9% by the current reporting system, respectively. The sensitivity and diagnostic accuracy for detecting HGUC of TPS were higher than those of our reporting system. CONCLUSION: TPS has increased the rate of detection of HGUC and reduced the rate of reporting "atypical" urothelial cells. TPS has also standardized the diagnostic criteria, thereby bringing uniformity and reproducibility into the system of reporting for urine cytology.

Digital image analysis supports a nuclear-to-cytoplasmic ratio cutoff value of 0.5 for atypical urothelial cells.

BACKGROUND: An elevated nuclear-to-cytoplasmic (N:C) ratio of ≥0.5 is a required criterion for the diagnosis of atypical urothelial cells (AUC) in The Paris System for Reporting Urinary Cytology. METHODS: To validate the N:C ratio cutoff value and its predictive power for high-grade urothelial carcinoma (HGUC), the authors retrospectively reviewed the urinary tract cytology specimens of 15 cases of AUC with HGUC on follow-up (AUC-HGUC) and 33 cases of AUC without HGUC on follow-up (AUC-N-HGUC). The number of atypical cells in each case was recorded, and each atypical cell was photographed and digitally examined to calculate the nuclear size and N:C ratio. RESULTS: On average, the maximum N:C ratios of atypical cells were significantly different between the AUC-HGUC and AUC-N-HGUC cohorts (0.53 vs 0.43; P =.00009), whereas the maximum nuclear sizes of atypical cells (153.43 µM2 vs 201.47 µM2 ; P = .69) and the number of atypical cells per case (10.13 vs 7.88; P = .12) were not found to be significantly different. Receiver operating characteristic analysis demonstrated that the maximum N:C ratio alone had high discriminatory capacity (area under the curve, 79.19%; 95% confidence interval, 64.19%-94.19%). The optimal maximum N:C ratio threshold was 0.486, giving a sensitivity of 73.3% and a specificity of 84.8% for predicting HGUC on follow-up. CONCLUSIONS: The identification of AUC with an N:C ratio >0.486 has a high predictive power for HGUC on follow-up in AUC specimens. This justifies using the N:C ratio as a required criterion for the AUC category. Individual laboratories using different cytopreparation methods may require independent validation of the N:C ratio cutoff value. Cancer Cytopathol 2017;125:710-6. © 2017 American Cancer Society.

The diagnostic value of cytohistological urine analysis and cytokeratin 20 in malignant and atypical urothelial cells.

INTRODUCTION: To determine the ability of cytohistology and cytokeratin 20 (CK 20) expression in malignant and atypical cells (AUC) from urine to serve as a diagnostic tool for assessing urothelial carcinoma (UC). METHODS: Diagnoses from 55 urine cytological samples from 55 patients were analyzed and correlated with subsequent biopsy findings. A total of 50 archived urine slides from patients that received a cytological diagnosis and histological follow-up were selected for immunostaining with monoclonal CK 20 antibodies and elaborated by Z-test for proportions. RESULTS: The majority of all positive or atypical smears (24; 89%) were confirmed through histological analysis. The majority of urinary cytological diagnoses reported as negative (15; 54%) were also confirmed through biopsies. The overall sensitivity, specificity, PPV, and NPV were 65%, 83%, 89%, and 54%, respectively. All 13 smears cytologically determined to contain malignant cells, with subsequent biopsies confirming UC, exhibited strong positive staining with the CK 20 antibody. All cases evaluated as benign both cytologically and histologically had negative CK 20 staining. Of the 15 AUC cases with lesions confirmed through biopsies, 11 (73%) had atypical cells that stained positive for CK 20. DISCUSSION: Our results demonstrate the diagnostic value of urinary cytology and confirm CK 20 as an adjunct marker for the diagnosis of UC and for the triage of AUC.