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Objective: Recently, the nuclear area has attracted attention as a morphological parameter to differentiate high‐grade urothelial carcinoma (HGUC) cells from benign reactive cells. The nuclear long diameter (NLD) strongly correlates with the nuclear area and is easy to subjectively estimate. Therefore, this study examined the usefulness of the NLD‐to‐neutrophil diameter ratio for detecting HGUC cells in urine cytology. Methods: This study included 29, 26 and 18 patients with HGUC, glomerular disease and urolithiasis respectively. An image analysis system was used to measure the NLD of HGUC and benign reactive cells (reactive renal tubular cells and reactive urothelial cells) and the neutrophil diameter that appeared in the voided urine in these cases. The NLD index was calculated using the NLD‐to‐neutrophil diameter ratio. We subsequently compared HGUC and benign reactive cells with respect to NLD and NLD indices. In addition, the HGUC cell group and benign reactive cell group were compared by selecting the five cells with the largest NLD and NLD index on each slide. Results: The NLD and NLD indices of HGUC cells were significantly higher than those of benign reactive cells in all cells and in the five cells with the largest NLD and NLD indices. The cut‐off value of the NLD index for detecting HGUC cells was 1.25 in all cells and 1.80 in the five cells with the largest NLD index. Conclusions: The NLD index is a useful parameter that can be introduced into routine microscopic examinations to differentiate HGUC cells from benign reactive cells. [ABSTRACT FROM AUTHOR]

The nested subtype of urothelial carcinoma (NS-UC), a rare and aggressive bladder cancer, mimics benign bladder lesions but behaves like high-grade urothelial carcinomas. The author reported a rare case of NS-UC, initially presenting with inguinal lymph node metastasis. The tumor cells of NS-UC exhibit minimal cellular atypia, forming small nests, while the tumor cells of lymph node metastatic carcinoma show greater cellular atypia with diverse structures. Immunohistochemistry is helpful in determining the origin of lymph node metastatic carcinoma. NS-UC often presents morphologically similar to benign lesions, which should be given sufficient attention. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC). Methods A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared. Results There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant (P＜0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant (P＜0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusions: 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. This retrospective study of 223 consecutive upper urinary tract cytology specimens from 137 patients revealed that adaptation of The Paris System for Reporting Urine Cytology improved the accuracy of selective upper urinary tract cytology in predicting histologic high‐grade urothelial carcinoma, which was unaffected by the application of contrast reagents. The current data indicate the usefulness of this system for upper urinary tract cytology in routine clinical settings. [ABSTRACT FROM AUTHOR]

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

Background: Bladder diverticula are herniations of bladder urothelium and mucosa through the muscularis propria. The reported incidence of neoplasia arising in bladder diverticula is widely variable. The authors' objective was to study the characteristics and sensitivity of urine cytology in these patients with emphasis on primary intradiverticular bladder cancer (IDBC). Methods: A 17‐year, retrospective review of all resected bladder diverticula associated with bladder carcinoma was performed. Cases that had complete diverticular resections and preresection urine samples were included in this study. The cases were divided into either primary IDBC or primary extradiverticular bladder cancer (EDBC). Demographic data and urine cytology characteristics were recorded, and sensitivity was calculated. For IDBC, a comparison between voided and cystoscopic urines was done for cases that had both collection methods performed. Results: Of 70 patients with IDBC, 47 patients had urine cytology results that were either positive for high grade‐urothelial carcinoma (HG‐UC) or suspicious for HG‐UC. The sensitivity for HG‐UC in IDBC samples was 80%, compared with 82% in EDBC samples (p >.05). Also, 28 patients in the IDBC group had both voided and cystoscopic urine samples for comparisons; in seven patients, the voided urine sample yielded a more definitive diagnosis; in 10 patients, the cystoscopic urine sample yielded a more definitive diagnosis; and, in 11 patients, both samples were equally diagnostic (p >.05). Conclusions: The characteristics and sensitivity of urine cytology in bladder diverticula were investigated in association with neoplasia, with an emphasis on primary intradiverticular bladder cancer. The results indicated that urine cytology remains a reliable screening and diagnostic test for detecting IDBC, with sensitivity similar to that for detecting EDBC, and no significant difference was noted between voided and cystoscopic samples. The characteristics and sensitivity of urine cytology in bladder diverticula were investigated in association with neoplasia, with an emphasis on primary intradiverticular bladder cancer (BC). The results indicated that urine cytology remains a reliable screening and diagnostic test for detecting intradiverticular BC, with sensitivity similar to that for detecting extradiverticular BC, and no significant difference was noted between voided and cytoscopic samples. [ABSTRACT FROM AUTHOR]

Objective: The Paris System for Reporting Urinary Cytology considered the nuclear‐to‐cytoplasmic (N:C) ratio as the most important cytomorphological feature for detecting high‐grade urothelial carcinoma (HGUC) cells. Few quantitative studies have been conducted on other features although quantitative studies on the N:C ratio have been reported. Therefore, this study quantitatively analysed important cytomorphological features in distinguishing benign reactive cells from HGUC cells. Methods: We analysed 2866 cells from the urine of 52 patients. A digital image analyser was used to quantitatively measure the nuclear area, cell area, N:C ratio, and nuclear roundness for HGUC cells and benign reactive cells. Additionally, the diagnostic value of quantitative cytomorphological criteria in HGUC cells was evaluated by the receiver operating characteristic curve. Results: The area under the curve for the prediction of HGUC cells for all cells and the top five cells was in the following order: nuclear area (0.920 and 0.992, respectively), N:C ratio (0.849 and 0.977), cell area (0.781 and 0.920), and nuclear roundness (0.624 and 0.605). The best cutoff value of the N:C ratio to differentiate HGUC cells from benign reactive cells was 0.438, and using the N:C ratio of 0.702, the positive predictive value obtained was 100%. Conclusions: Our study indicated that nuclear area is a more important cytomorphological criterion than the N:C ratio for HGUC cell detection. Moreover, extracted data of the top five cells were more valuable than the data of all cells, which can be helpful in the routine practice and future criteria definition in urine cytology. [ABSTRACT FROM AUTHOR]

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

Abstract Background The 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. Methods A 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. Results After 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). Conclusion In 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.

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. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV)-positive urinary tract carcinomas (UTCas) have distinct morphology and molecular features with potential treatment implications. Cytomorphologic analysis of these tumors on urine cytology specimens has not yet been reported. The authors evaluated the cytomorphologic findings of HPV-positive UTCa on urine cytology using The Paris System for Reporting Urinary Cytology (TPS) criteria., Methods: HPV-positive cases were identified by a retrospective review of surgical specimens that had UTCa confirmed by HPV in situ hybridization. Cases that had concurrent urine cytology were reviewed using TPS. Cytomorphologic features of high-grade urothelial carcinoma (HGUC) were evaluated as well as the presence of atypical squamous cells (ASCs) and basaloid features., Results: Sixteen cytology specimens from eight patients with HPV-positive UTCa were included. On original diagnosis, none of the cytology specimens were suggested to be HPV-associated. TPS diagnostic criteria identified eight cases with at least atypical findings, including five HGUC cases, one case that was suspicious for HGUC, and two atypical urothelial cases. Common cytomorphologic features included basaloid clusters (six of eight cases; 75%) and ASCs (four of eight cases; 50%) that matched the corresponding surgical specimens. Most cases exhibited urothelial cell hyperchromasia (seven of eight cases; 88%), and hypochromasia was a frequently observed variant (four of eight cases; 50%), either alone or in addition to hyperchromasia., Conclusions: HPV-positive UTCa can be identified reliably as HGUC by using TPS criteria; however, these cases may not be recognized as HPV-associated. The presence of basaloid cells or ASCs can help suggest screening for HPV in urine specimens. Larger scale studies are warranted to validate cytomorphologic differences and determine the impact of HPV infection on clinical outcomes for patients with UTCa., (© 2024 The Author(s). Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

The Paris System for Reporting Urine Cytology (TPS) is remarkable for its high predictive value in the detection of high-grade urothelial carcinoma, especially of the bladder. However, universal compliance with TPS-recommended threshold for atypical call rates (15%) and TPS performance in the rarer upper tract urothelial carcinomas (UTUC) are challenging. UTUC diagnosis is compounded by instrumentation artifacts, degenerative changes superimposed on an ambiguous cytology, difficult-to-access location, lack of specific standardized criteria, and a limited number of UTUC-focused studies. We reviewed TPS-applied studies published since 2022, noting up to 50%, exceeding the suggested 15% threshold for atypia. Our examination of ancillary tests for UTUC explored novel approaches including DNA methylation analysis, the detection of overexpressed tumor-linked messenger RNAs, and immunohistochemistry on markers such as CK17. Preliminary evidence from our review suggests that ancillary tests display superior performance over cytology, including in voided samples and low-grade urothelial carcinoma. Importantly, voided samples obviate the risks of ureterorenoscopy. Finally, we explored the future opportunities offered by artificial intelligence and machine learning for a more objective application of TPS criteria on urine samples., (Copyright © 2024 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

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., (© 2024 S. Karger AG, Basel.)

High-grade urothelial carcinoma either non- Schistosoma (NS-UBC) or Schistosoma (S-UBC)-associated is the tenth cause of death worldwide and represents a serious therapeutic problem. Evaluation of the immmunohistochemical expression of tumor necrosis factor-alpha (TNFα), epidermal growth factor receptor (EGFR), programmed cell death protein-1 (PDL1), estrogen receptor-alpha (ERα) and UroplakinIII, in the high-grade in NS-UBC and S-UBC as potential prognostic and therapeutic targets analyzed through estimation of area percentage, optical density and international pathological scoring system for each marker. Sixty high grade urothelial carcinoma cases were enrolled in the study (30 cases of NS-UBC and 30 cases of S-UBC). The cases were immunohistochemically-assessed for TNFα, EGFR, PDL1, ERα and Uroplakin III expression. In S-UBC, parasite load was also evaluated for correlation with the immunohistochemical markers' expression in S-UBC. The area percentage of immune-expression of TNFα and EGFR was higher in S-UBC compared to NS-UBC. On the other hand, the NS-UBC displayed statistically-higher expression of PDL1 and uroplakinIII (p-value <0.001). ERα revealed higher, yet, non-significant expressions in S-UBC compared to NS-UBC (p-value =0.459). PDL1 expression showed the most superior record regarding area percentage (64.6± 34.5). Regarding optical density, TNF-α showed the highest transmittance expression (2.4 ± 0.9). EGFR positively correlated with PDL1 in S-UBC (r= 0.578, p-value =0.001) whereas in NS-UBC, TNFα and PDL1 (r=0.382, p-value=0.037) had positive correlation. Schistosoma eggs in tissues oppose uroplakin III expression and trigger immunomodulation via PDL1. Due to lower UroplakinIII expression, S-UBC is supposed to have a poorer prognosis. Hormonal therapy is not hypothesized due to a very minimal ERα expression in both NS-UBC and S-UBC. Regarding immunotherapy, anti-TNF-α is suggested for S-UBC whilst in NS-UBC, blockading PDL1 might be useful. Targeted EGFR therapy seems to carry emphasized outcomes in S-UBC. Correlations encourage combined immune therapy in NS-UBC; nevertheless, in S-UBC, combined anti-EGFR and PDL1 seem to be of benefit. • Uroplakin III showed minimal expression in S-UBC indicating poor prognosis. • The weak expression of ER does not support hormonal therapy in both S-UBC and NS-UBC. • Anti-TNF is recommended in S-UBC. • Blockage of the PD-1/PDL1 pathway is suggested be efficient in NS-UBC. [ABSTRACT FROM AUTHOR]

Background: The Paris System for Reporting Urinary Cytology (TPS) uses hyperchromasia as major diagnostic criterion for high‐grade urothelial carcinoma (HGUC). The purpose of the study was to evaluate cases that were diagnosed as HGUC by TPS and determine whether there are different chromatin distribution patterns (ie, subsets). Methods: Digital image annotations were performed on microscopic images of HGUC urine specimens with surgical biopsy/resection follow‐up. Median gray values were generated for each cell. Neutrophils (polymorphonuclear leukocyte [PMN]) were also enumerated in each case to serve as an internal control. A HGUC/PMN ratio was generated for each case, and the cases were distributed. Results: Sixty‐nine HGUC cases yielded 2660 cells, including 2078 HGUC (30.1 cells/case) and 582 PMNs (8.4 cells/case). The average median gray value of an HGUC was 50.6 and of a PMN was 36.8 (P <.0001). Eight of 69 cases (11.6%) contained nuclei that, on average, were darker than or as dark as a PMN (extremely dark, ie, "India ink"). Fifty‐one of 69 cases (74.0%) contained nuclei that, on average, were slightly brighter than a PMN (hyperchromatic). Ten of 69 cases (14.5%) contained nuclei that, on average, were much brighter than a PMN (hypochromatic). Within a single case, all cases showed heterogeneity with the hypochromatic cases showing the most dramatic effect. Conclusions: Digital image analysis reveals that there are large variations in chromasia between cases including a subset of cases with hypochromasia and another with extremely dark or "India ink" nuclei. There was much heterogeneity of chromasia seen within a single sample. In The Paris System for Reporting Urinary Cytology, hyperchromasia is a major diagnostic criterion for high‐grade urothelial carcinoma. Digital image analysis reveals that there are large variations in chromasia between cases, including a subset of cases with hypochromasia and another with extremely dark or "India ink" nuclei. [ABSTRACT FROM AUTHOR]

Background: The 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.Methods: A 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.Results: After 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).Conclusion: In 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. [ABSTRACT FROM AUTHOR]

Introduction: Bladder cancer is among the most common malignant neoplasms in the world. Transurethral resection of bladder tumor (TURBT) is considered the standard procedure for diagnosis, staging, and risk classification of bladder tumors. Lymphovascular invasion (LVI) is considered a poor prognostic factor. Its assessment of TURBT is very important for risk stratification and decision-making for further treatment. The purpose of our clinical study is to attempt to predict/assess the correlation between LVI and various preoperative (age, gender, history of smoking, hematuria, urine cytology, and hydronephrosis/hydroureteronephrosis), intraoperative (tumor number, size, and appearance - sessile/ pedunculated) and histopathological (tumor histology, grading, and muscle invasion) factors., Methodology: In this prospective study, 75 patients with bladder tumors underwent TURBT (standard monopolar TURBT with 1.5% glycine as irrigation solution) in the Department of Urology at Sri Venkateswara Institute of Medical Sciences (SVIMS), Tirupati between October 2021 and March 2023. Histopathological examination (HPE) reports were looked for the presence or absence of LVI. Accordingly, patients were divided into two groups, i.e., those with LVI and those without LVI. Various preoperative and intraoperative variables were analyzed for each subject in both groups. Statistically significant variables occurring in those patients with LVI compared to those without LVI were considered predictors of LVI in bladder tumors.  Results: Sixteen patients out of 75 (21.33%) had LVI on their histopathology examination. The mean age was 68.19 years in the group with LVI and 64.14 years in the group without LVI. A total of 60 men (80%) and 15 women (20%) were included in our study. Thirteen men (21.7%) and three women (20%) were found to have LVI. We observed a significant association between the appearance of the tumor and LVI. Fifty-four subjects in our study had sessile tumors. Fifteen out of them (27.8%) had LVI, while only one out of 21 patients (4.8%) with pedunculated tumors had LVI (p-value=0.028). 30% of subjects who had high-grade tumors on HPE also had LVI. On the contrary, only one of 25 patients (4%) with low-grade tumors had LVI (p-value=0.010). Our study also showed a significant association between muscle invasion and LVI. Thirty-four (45.3%) and 41 (54.7%) patients had muscle-invasive and non-muscle-invasive tumors, respectively. While 12 (35.3%) patients with muscle-invasive tumors had LVI, only four (9.8%) patients with non-muscle-invasive tumors showed LVI (p-value=0.007)., Conclusion: We observed that LVI of bladder tumors at first TURBT is significantly associated with tumor grade, tumor appearance, and depth of invasion of the tumor. Though statistically not significant, we further observed that LVI was more commonly found in smokers, patients with hematuria, and larger tumor sizes. We conclude that these factors can be used as reliable predictors of LVI of bladder tumors at their first TURBT., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee of Sri Venkateswara Institute of Medical Sciences issued approval 1218. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nallabothula et al.)

Acute esophageal necrosis is a rare syndrome with endoscopic findings of a diffuse circumferential pattern of black mucosa. Although underlying pathogenesis is unclear, it is known to have associations with malignancy. We present a rare case of a patient with a history of metastatic urothelial carcinoma who was found to have acute esophageal necrosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Lin et al.)

Objective: In The Paris System for Reporting Urinary Cytology (TPS), the important cytomorphological features for diagnosing high‐grade urothelial carcinoma (HGUC) are a nuclear‐to‐cytoplasmic (N:C) ratio exceeding 0.7, hyperchromasia, coarse chromatin, and irregular nuclear borders. However, quantitative cytomorphological assessments of HGUC cells using SurePath slides are rare. Therefore, we evaluated HGUC cells on SurePath slides quantitatively using a digital image analysis system and compared these data with ThinPrep data. Methods: The same urine samples were divided into two aliquots and used to prepare SurePath and ThinPrep slides. We used ImageJ to measure the N:C ratio, hyperchromasia, and irregular nuclear borders for HGUC cells on SurePath and ThinPrep slides. Results: The total number of analysed HGUC cells on SurePath slides was 981, versus 889 on ThinPrep slides. Hyperchromasia and irregular nuclear borders were significantly more severe on SurePath than on ThinPrep slides. Conversely, the N:C ratio did not differ between the methods. Additionally, HGUC cells with N:C ratios exceeding 0.7 were present on almost all slides for both methods. Conclusions: Our data indicated the reasonableness of using the N:C ratio as the major criterion for TPS on both SurePath and ThinPrep slides, and an N:C ratio cut‐off of 0.7 as suitable for identifying HGUC cells. However, the severity of hyperchromasia and irregular nuclear borders differed between the processing methods. Our study indicated the reasonableness of using the N:C ratio as the major criterion for The Paris System for Reporting Urinary Cytology on both SurePath and ThinPrep slides. However, the severity of hyperchromasia and irregular nuclear borders differed between the processing methods. [ABSTRACT FROM AUTHOR]

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. • The current accuracy of urine cytology in Japan is not high. • Statistical analysis was used to examine the cellular features of HGUC. • The results revealed 7 validated cellular features. • This study facilitates high accuracy diagnosis of HGUC in routine cytology practice. [ABSTRACT FROM AUTHOR]

The Paris System for Reporting Urinary Cytology (TPS) was developed for standardization purposes and it placed an emphasis on screening for high-grade urothelial carcinoma (HGUC). Since then, it has shown to reduce atypia rates and better correlate with surgical specimens. The aim of this study was to calculate the negative predictive value (NPV) of urinary cytology for detecting HGUC using TPS and compare these data to our recently published pre-TPS cohort. As a screening test, it is imperative that TPS has a high NPV. A search of our institution's pathology database for the term "negative for HGUC" from January 1, 2016, to December 31, 2017, was conducted. A true negative was defined as a patient with at least 1 subsequent negative urine cytology/surgical biopsy specimen or the patient being clinically negative for 6 months. NPV rates were calculated based on the data obtained. The cohort consisted of 2960 urine cytology specimens from 1894 patients. A total of 99 false negatives were identified, generating a NPV of 96.7% (2861/2960). This NPV is identical to our previously published pre-TPS cohort (years 2012-2013; NPV: 96.7%). The clinical indication most effected NPV, with a history of urothelial carcinoma with a NPV of 93.9% followed by hematuria at 98.9%. The atypia rate in years 2012-2013 was 8.2% and in 2016-2017 it was 5.7% (P < 0.001). We demonstrate that TPS did not alter the NPV for detecting HGUC compared to our pre-TPS cohort. We believe that TPS is an effective reporting system for screening HGUC in urinary cytology. • The overall negative predictive value (NPV) was 96.7% (same as pre-TPS). • Patient with a history of urothelial carcin.oma had a NPV of 93.9% followed by hematuria at 98.9% • Voided urine had the highest NPV of 98.9%, followed by washing at 96.6% and brushing 81.3%. • The atypia rate in years 2012-2013 was 8.2% and in 2016-2017 it was 5.7% (P < 0.001). [ABSTRACT FROM AUTHOR]

The Paris System for Reporting Urinary Cytology (TPS) was first published in 2016 to standardize reporting and placed a specific emphasis on high-grade urothelial carcinoma (HGUC). The urinary tract is anatomically divided into the upper tract (UT) and the lower tract (LT). A major morphologic criterion in TPS for HGUC defines the nuclear-to-cytoplasmic (N/C) ratio as ≥ 0.7. In this study, we evaluated N/C ratios of HGUC arising from UT and LT urine specimens, to ascertain differences due to location. Digital annotations of whole slide scanned images were performed and enumerated. The cohort consisted of 59 ThinPrep specimens from 52 patients. The majority of the tumors were located in LT (39 of 59, 66.1%). A total of 590 cells were analyzed (10 cells per case). In UT, the average N/C was 0.58 and LT the average was 0.54 (P < 0.001). The average nuclear area for UT was 126.3 and for LT was 158.2 μm2 (P = 0.01). The average cytoplasmic area for UT was 219.1 μm2 and for LT was 296.2 μm2 (P < 0.001). The average cellular circumference for UT was 59.4 μm and for LT was 66.1 μm (P < 0.001). We found that UT HGUCs have higher N/C ratios, smaller cell circumference, smaller nuclei, and less cytoplasm compared with LT. When UT was divided into renal pelvis and ureter, no statistical difference was identified. • Morphologic analysis of upper tract high grade urothelial carcinoma. • Morphologic analysis of lower tract high grade urothelial carcinoma. • Comparison of morphology based on location of primary. [ABSTRACT FROM AUTHOR]

The Paris System (TPS) for reporting urine cytology was developed for standardization of diagnosis focusing on the detection of high-grade urothelial carcinoma (HGUC). Probably the most challenging task for TPS is to provide criteria for the atypical urothelial cell (AUC) category. The TPS criteria for AUC include increased nuclear/cytoplasmic (N/C) ratio (>0.5) and 1 of the 3 minor criteria including nuclear hyperchromasia (NH), coarse chromatin (CC) and irregular nuclear membrane (INM). We evaluated TPS-AUC diagnostic value and investigated whether other morphologic parameters can improve its criteria. Urine samples with diagnoses of AUC collected during a 6-month period were re-reviewed. Data captured included N/C ratio >0.5, NH, CC, INM, and 2 additional criteria including enlarged nuclear size (ENS) and the presence of nucleolus (N). ENS was considered when the nucleus was 2 times larger than the urothelial cell or 3 times larger than lymphocyte. By applying the TPS-AUC criteria, the rate of atypia diagnosis reduced in comparison to Pre-TPS (9% versus 13%, P = 0.02). Among the AUC minor criteria, NH was the best criterion with the highest interobserver agreement (IOA) and correlation with HGUC (k = 0.342, r = 0.61, P < 0.001) and strong PPV (93.6%). ENS had the highest PPV (95.8%) and, after NH, had the highest IOA and correlation with HGUC (k = 0.29, r = 0.52, P < 0.001). TPS improves the diagnostic value of urine cytology, particularly in cases with atypia. ENS is a strong criterion for increasing the diagnostic value of AUC and potentially can improve TPS performance as a minor criterion. • We studied the performance of the Paris system for urine cytology with a focus on AUC (Atypical Urothelial Cell) category. • TPS AUC criteria for cases with AUC diagnosis and available biopsy follow up were reevaluated by three cytopathologists. • By applying TPS AUC criteria, the rate of the inconclusive diagnosis of "atypia" was reduced in comparison to Pre-TPS atypical diagnosis rate (9% vs. 13 %, P: 0.02). • The rate of TPS-NHGUC increased in comparison to Pre-TPS negative for malignancy rate (86% vs. 80%, P: 0.007). However, the rate of HGUC in follows up biopsies did not change (60% and 55 %, P: 0.66). • Among the AUC minor criteria, Nuclear Hyperchromasia (NH) was the best criterion with the highest Interobserver agreement (IA) and correlation with HGUC (k: 0.342, r: 0.61, P < 0.001) and strong PPV (93.5%). • Enlarged nuclear size (ENS) had the highest PPV among the all studied parameters (95.8%), and after NH, had the highest IA and correlation with HGUC (k: 0.29, r: 0.52, P < 0.001) in comparison to other AUC minor criteria including coarse chromatin and irregular nuclear membrane. • ENS is a strong criterion for increasing the diagnostic value of AUC and potentially can improve TPS performance as a minor criterion. [ABSTRACT FROM AUTHOR]

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., (© 2024 Wiley Periodicals LLC.)

Background: Urothelial carcinoma, a prevalent and aggressive urological malignancy, necessitates early detection for improved prognosis. Urine cytology serves as a cost-effective screening tool, but inconsistencies in reporting due to the lack of standardized criteria limit its efficacy. The Paris System for reporting urinary cytology (TPS) was introduced to address this issue, aiming to improve diagnostic accuracy. This retrospective study investigates the effectiveness of urine cytology in detecting high-grade urothelial carcinoma (HGUC) using TPS classification, specifically focusing on atypical urothelial cells (AUC) categorized as TPS-III and suspicious for high-grade urothelial carcinoma (SHGUC) categorized as TPS-IV., Methods: We reviewed 470 urine cytology samples collected over two years at a tertiary healthcare center in Bahrain. All samples were re-evaluated using TPS classification by two independent consultant cytopathologists blinded to the original cytology report. The analysis included only samples categorized as TPS-III or TPS-IV with corresponding histopathology reports from confirmatory biopsies performed within four months of urine collection. Biopsy results were categorized as either benign/low-grade urothelial carcinoma (non-HGUC) or malignant (HGUC). The positive predictive value (PPV) of urine cytology for HGUC detection was calculated for both TPS-III and TPS-IV categories. Statistical significance was assessed using Fisher's exact test., Results: Among the 470 urine cytology samples, 40 (8.5%) were classified as TPS-III or TPS-IV. Within this subset, 16 patients underwent confirmatory biopsies. Histopathological analysis revealed HGUC in 12 (75%) patients and non-HGUC (benign or low-grade) in 4 (25%) patients. The PPV of TPS-III for HGUC was 50%, while TPS-IV demonstrated a higher PPV of 90%. However, the difference between these values was not statistically significant (p = 0.25). This study explored the utility of TPS classification in urine cytology for HGUC detection. While SHGUC (TPS-IV) exhibited a numerically higher PPV compared to AUC (TPS-III), the lack of statistical significance necessitates further investigation. Our findings highlight the potential of TPS to improve the accuracy of urine cytology. TPS implementation has been shown to reduce the number of inconclusive "atypical" diagnoses, leading to more targeted investigations., Conclusion: Our study suggests that SHGUC (TPS-IV) within TPS classification framework might hold promise as a more specific indicator for HGUC compared to AUC (TPS-III). However, further research with larger cohorts is necessary to definitively establish the clinical significance of this observation. This investigation paves the way for future studies exploring the potential of TPS, particularly the SHGUC category, as a reliable screening tool for HGUC, potentially leading to earlier diagnoses and improved patient outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Mahmoud Daoud et al.)

Introduction: Urine cytology is an indispensable test for detecting high-grade urothelial carcinoma (HGUC); however, the distinction between HGUC cells and morphologically similar benign atypical cells poses clinical challenges. In this study, we performed double immunostaining for p53 and vimentin to establish a diagnostic method to accurately distinguish HGUC cells from benign atypical cells., Methods: This study included 41 cases of HGUC, 11 of urolithiasis, and 22 of glomerular disease diagnosed histopathologically or clinically. After preparing urine cytology specimens from voided urine samples, p53 immunostaining was performed, and the p53-positive intensity and p53 positivity rate were calculated. Subsequently, vimentin immunostaining was performed on the same specimens to calculate the rate of vimentin positivity., Results: The HGUC cell group had a mean p53-positive intensity of 2.40, a mean p53 positivity rate of 73.2%, and a mean vimentin positivity rate of 5.1%. In contrast, the mean p53-positive intensity, p53 positivity rate, and vimentin positivity rate were 1.63, 36.7%, and 66.2%, respectively, in the benign atypical cell group. There were significant differences between the two groups for each parameter. Moreover, two multiple logistic regression models combining the results of these three parameters exhibited higher sensitivity and specificity than solely assessing the p53-positive intensity, positivity rate, and vimentin positivity rate., Conclusion: Since double immunostaining with p53 and vimentin distinguishes HGUC cells from benign atypical cells, it could be to improve the diagnostic accuracy of urine cytology., (© 2024 S. Karger AG, Basel.)

BACKGROUND: Urinary tract cytology (UTCy) is used for screening urothelial carcinoma (UC) and it must have a high negative predictive value (NPV) to be an effective test. To the authors’ knowledge, the literature regarding the NPV of UTCy provides little information regarding the risk of malignancy, especially for patients with high-grade urothelial carcinoma (HGUC). METHODS: Patients with negative UTCy specimens were identified in the pathology files at the study institution for the years 2012 through 2013. Cases were deemed true-negative cases if there was at least 1 subsequent negative specimen or negative clinical follow-up within 6 months of the index case. False-negative cases were defined as HGUC or carcinoma in situ by surgical biopsy and/or any UTCy with suspicious for HGUC or HGUC follow-up. RESULTS: A total of 2614 UTCy specimens from 2089 patients were identified. There was a disease prevalence of 6.5%. There were 87 false-negative results for HGUC, which corresponded to an overall NPV of 96.7%. When categorized by clinical indication, hematuria resulted in the highest NPV of 99.5% followed by other indications (97.7%) and a history of UC (90.1%). When categorized by the specimen type, voided urine specimens were found to have the highest NPV of 98.7% followed by other indications (96.9%) and washing specimens (96.2%). Of the 717 patients with a history of UC, the NPV was lower for washing specimens (89.8%) than for voided urine specimens (96.2%). When including either low-grade urothelial carcinoma or HGUC as a positive follow-up, the NPV dropped to 93.3% from 96.7% (HGUC only). The sensitivity of the diagnostic category of atypical urothelial cells or higher was 93.0%. CONCLUSIONS: Overall, UTCy appears to have a good NPV and a high sensitivity for HGUC. The clinical indication had a greater impact on NPV compared with the specimen type. [ABSTRACT FROM AUTHOR]

Objectives: Urine cytology has a high sensitivity in morphological recognition of high‐grade urothelial carcinoma (HGUC) as compared to low‐grade urothelial neoplasms. The Paris system (TPS) was designed to standardise the reporting of HGUC on urine cytology. We evaluated the diagnostic efficacy of urine cytology in routine practice with the cytohistological correlation and application of TPS. Methods: A retrospective review of urine cytology reported from 2014 to 2015 was carried out with cytohistological correlation, wherever available. The cases were also recategorised according to TPS with the calculation of malignancy risk of all categories. Results: More than 4000 specimens from 1396 patients were evaluated. Histopathology was available in 244 cases. Urine cytology had a sensitivity of 70.5%, specificity of 78.4%, with an overall diagnostic accuracy of 71.7%. The urine cytology when categorised by TPS had 0.9% unsatisfactory cases, 75.9% negative for HGUC, 8.5% atypical urothelial cells, 0.2% suspicious for HGUC, 14.1% HGUC and 0.4% cases of other malignancies. The risk of HGUC with each category of negative for HGUC, atypical, suspicious for HGUC, HGUC and other malignancy was 11.6%, 12.3%, 33.3%, 58.8% and 80%, respectively. Conclusion: Urine cytology continues to show high diagnostic accuracy for the detection of urothelial carcinoma with a relatively high sensitivity for HGUC. TPS for reporting urine cytology defines specific criteria for diagnosing atypical and HGUC but increases the cases in the atypical category. [ABSTRACT FROM AUTHOR]

Abstract Urinary tract cytology is a common diagnostic test used in the initial work up of bladder cancer. Since its inception as an utilizable diagnostic technique by Dr. Papanicolaou in 1945, urinary cytology has proven to be a cheap, easily obtained, and accurate method in the detection of high-grade urothelial carcinoma. Despite readily agreed upon features of high-grade urothelial carcinoma, a reproducible, universally accepted reporting method has not been attained. The Paris System for Reporting Urinary Cytology was developed to bring about a standardized reporting system with specific diagnostic categories and clear cytomorphologic criteria for the reliable diagnosis of high-grade urothelial carcinoma. This paper sets out to review the utility of urinary cytology, the current understanding of urothelial carcinoma, and the diagnostic categories of The Paris System. We finish with a review of the current literature regarding implementation of The Paris System. [ABSTRACT FROM AUTHOR]

Objectives: The Paris System for Reporting Urinary Cytology (TPS) is designed to standardize the criteria and terminology used in urinary tract cytology reporting. The aim of this study was to evaluate the impact of implementing TPS and to analyze the correlation with follow-up biopsies in order to assess its reproducibility.Methods: Urinary tract cytology specimens with follow-up biopsies over a 2-year period were reviewed and reclassified according to TPS criteria. Surgical follow-up diagnoses were correlated with the initial cytology diagnoses and TPS interpretations, and the results were compared.Results: Applying TPS in comparison to our previous reporting system resulted in fewer cases in the atypia category (11.8% vs 24.2%) and higher specificity, accuracy, and predictive value. We observed acceptable interobserver agreement in diagnostic categories of this reporting system.Conclusions: TPS improves the overall performance of urinary tract cytology by standardizing the criteria and terminology. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Human polyomaviruses (PyV) are ubiquitous, remaining predominantly inactive hence asymptomatic in the healthy, immunocompetent population. BK and JC PyV potentially infect pan-urinary tract epithelial cells. With reactivation, PyV disrupt cell cycling mechanisms, facilitating viral replication leading to cell necrosis, exfoliation, and, infrequently, carcinogenesis. Exfoliated PyV-infected cells pose diagnostic pitfalls, hence they are termed “decoy cells” as they may mimic high-grade urothelial carcinoma cells. BK polyomavirus-associated-nephropathy (BKVAN) is an inflammatory disease causing interstitial fibrosis with tubular atrophy in renal transplant recipients, increasing risk of graft loss. BKVAN is confirmed by renal biopsy, and managed by immunosuppression modulation. As voided urine may provide pan-reno-urinary tract sampling, cytopathology may serve a critical diagnostic purpose coupled with decoy cell quantification and indirect BK PyV load gauging. Thus, identification of decoy cells and differentiation from high-grade urothelial carcinoma cells, and degenerated, benign urothelial cells, is clinically essential. PyV virology and pathobiology in the context of renal transplantation, immuno-suppression and BKVAN, and, decoy cell cytomorphology and cytopreparation with commentary are highlighted. Decoy cell overall characteristics : variable degeneration; cytomegaly; comet-like shapes; angular cytoplasmic extensions; eccentric, polar nuclear placements; moderate anisocytosis; typically single cells with high N:C ratios. Cytoplasmic features : moderate-abundance; granular, blue-gray monochromatism. Nuclear features : karyomegaly; haphazardly-scattered chromatin densities; smudged, homogeneous, basophilic ground glass masses displacing chromatin alongside inner periphery of regular, symmetrical nuclear envelopes. Background features : granular cellular debris; inflammatory cells; intact and lyzed erythrocytes. Decoy cells lack coarse chromatin as in high-grade urothelial carcinoma cells. Benign urothelial cells exhibit low N:C ratios with fine chromatin distribution and euchromasia. [ABSTRACT FROM AUTHOR]

Introduction The ability to consistently diagnose low-grade urothelial carcinoma (LGUC) in urinary tract cytology (UTCy) specimens remains controversial, as the reported sensitivity of UTCy in the detection of LGUC is as low as 10%. To determine whether a consistent cytologic diagnosis of LGUC is possible, we assessed the presence and frequency of previously described cytomorphologic features of LGUC in UTCy from patients with LGUC and a negative control group. Materials and methods Biopsy-proven cases of LGUC from June 1, 2010 to January 31, 2014 were identified; UTCy obtained within 3 months prior to biopsy composed the study group (n = 98). The negative control group consisted of UTCy obtained from patients with negative cystoscopy and biopsy (n = 53). All specimens were masked and reviewed in random order to evaluate 17 cytomorphologic parameters. Results Univariate statistical analyses demonstrated that the prevalence of paired cells, clumpy chromatin, and cytoplasmic homogeneity was higher in the study group; however, multivariate analysis did not show these features as significant predictors of LGUC. Conclusions No cytomorphologic feature was statistically significant in the LGUC group versus the negative control group. The presence of 3-dimensional papillary structures with fibrovascular cores is diagnostic of LGUC, but it is only seen in a small minority (2 of 98) cases. Our results reemphasize the fact that urinary tract cytology has a low sensitivity for the diagnosis of LGUC and suggest that, instead of striving to detect LGUC in urine specimens, we should concentrate on the clinically relevant goal of urine cytology—the detection of high-grade lesions. [ABSTRACT FROM AUTHOR]

BACKGROUND The interpretation of urothelial tissue fragments (UTF) in voided urine (VU) specimens is controversial. If UTF contain cytomorphologically atypical cells, the diagnosis often becomes more challenging. The authors previously analyzed the outcome of patients with benign-appearing UTF in 274 noninstrumented VU specimens. In this retrospective study, noninstrumented VU specimens containing UTF with atypical cytomorphological features (AUTF) were evaluated and compared with the previous results. METHODS The Johns Hopkins Hospital electronic pathology database was searched for VU cases containing UTF over a 5-year period. RESULTS A total of 170 noninstrumented VU specimens containing AUTF were identified. Twenty-four specimens had subsequent or coincidental surgical pathology specimens with the following overall rates of neoplasia: high-grade urothelial carcinoma: 8.8% (15 specimens), low-grade urothelial neoplasia: 1.2% (2 specimens), and prostate carcinoma invading the bladder: 0.6% (1 specimen). A total of 49 specimens (28.8%) were diagnosed with urolithiasis on follow-up. Twenty-five cases had follow-up cytology specimens, all of which were negative for malignancy. Of 72 cases without histopathologic, radiologic, or cytopathologic follow-up, 62 (86.1%) had a mean clinical follow-up of 22.5 months and 10 cases did not have clinical follow-up. CONCLUSIONS The presence of AUTF in noninstrumented VU is associated with low rates of urothelial neoplasia but a statistically higher risk of urothelial neoplasia than the presence of BUTF (10.0% vs 4.4%; P<.05). In particular, the rate of high-grade urothelial carcinoma is significantly higher in noninstrumented VU specimens containing AUTF than those containing BUTF (8.8% vs 0.7%; P<.0001). In addition, urolithiasis is associated with AUTF in a substantial percentage of noninstrumented VU specimens. Cancer (Cancer Cytopathol) 2015. © 2015 American Cancer Society. Cancer (Cancer Cytopathol) 2015;123:186-192. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Introduction The rate of atypical diagnoses in urine cytology can be high depending on the screening population. Unlike thyroid and cervical cytology, there is a lack of standardized criteria to stratify them into more clinically meaningful categories. Materials and methods A set of diagnostic criteria described by Johns Hopkins Hospital (JHH) provided a tool to divide atypical urine specimens into those that were low risk and those likely to be predictive of high-grade urothelial carcinoma (HGUC). In this study, the JHH template was applied to a cohort of atypical urine cytology specimens from the University of Chicago (U of C) to compare it to existing U of C terminology and determine whether it should be formally adopted. Results Sixty-eight percent of patients classified as atypical urothelial cells, favor high-grade lesion (AUC-H) were diagnosed with HGUC during the study. Correlation was noted between the JHH diagnostic categories and the U of C diagnostic categories, with 49% of patients reclassified as AUC-H being diagnosed with atypical urothelial cells, suspicious for neoplasia and 83% of cases of patients reclassified as atypical urothelial cells of unknown significance being diagnosed as atypical, urothelial cells. The JHH category of AUC-H had a higher positive predictive value for HGUC than the U of C category atypical urothelial cells, suspicious for neoplasm did (69% versus 58%, p = 0.0087). Unlike the JHH study, AUC-H showed higher correlation with HGUC in the hematuria group (90%) than in the surveillance group (66%). Conclusions JHH criteria demonstrated a higher rate of predicting HGUC than U of C diagnostic categories, supporting the adoption of these criteria at U of C. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: The Paris System (PS) has replaced the classical Papanicolaou System (PapS) in reporting urine cytology, due to its improved sensitivity and negative predictive value (NPV) without loss of specificity. Furthermore, it has enabled the risk of malignancy to be established in each cytological category. The aim of this study is to compare the Paris System with previous results and determine the changes in sensitivity, specificity, positive predictive value, NPV and risk of malignancy in our centre, MATERIALS AND METHODS: Evaluation of the diagnostic power of urine cytology by means of a retrospective cohort study, comparing two series of 400 cytological studies, one using the Papanicolaou System and the other the Paris System., Results: In the detection of high-grade urothelial carcinoma, Paris System has better specificity (93.82% PapS vs 98.64% PS; P=.001) and PPV (39.5% PapS vs 70.6% PS; P=.044) than Papanicolaou System, without changes in sensitivity (53.5% PapS vs 37.5% PS; P=.299) or NPV (96.4% PapS vs 94.8% PS; P=.183). The risk of malignancy for the atypical category increases from low to high levels (1.6% PapS vs 40.0% PS; P=.001); the other categories showed no significant statistical changes., Conclusion: The Paris System improves specificity and positive predictive value and establishes a better indication of risk of malignancy for each category, enabling specific clinical management in each case., (Copyright © 2022 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Urine cytology evaluation is an effective test in the detection of high-grade urothelial carcinoma (HGUC). While the guideline distinguishes the 2 categories: "positive for HGUC" (PHGUC) and "suspicious for HGUC" (SHGUC), the association between these categories with their subsequent follow-up biopsies remains unclear. This study aims to determine and compare the positive predictive value (PPV) of the specimens in PHGUC and SHGUC categories with their respective histologic diagnoses., Methods: During the period of 03/01/2008 to 07/31/2018, urine cytology cases diagnosed as PHGUC and SHGUC with subsequent bladder biopsy within 12 months were retrieved. All cases were correlated with first biopsy obtained during 12 months of cytology specimen. Biopsy result with HGUC, carcinoma in situ, or non-urothelial carcinoma diagnoses were considered as concordance., Results: 378 cases (229 SHGUC and 149 PHGUC) were identified from 263 patients. For the 229 SHGUC cases, the PPV was 72% (n = 166) and for the 149 PHGUC cases, the PPV was 85% (n = 127). While both categories have high PPV, they are statistically significant (p < 0.0001). Additionally, 33 cases were found to have low-grade urothelial carcinoma (LGUC), constituting a portion of discordant results., Conclusion: PHGUC and SHGUC categories are both associated with a high risk of malignancy, however, there is a statistically significant difference between them in our study, supporting the PSRUC guidelines of two separate categories. In instances when urine cytology is discordant with biopsy results, further investigation and clinical follow up is warranted. LGUC appears to remain a common pitfall especially in the suspicious category., (© 2020 Wiley Periodicals LLC.)

Background/aim: The Paris System (TPS) has recently been proposed as a method to standardize urinary cytology reporting. In this study, we evaluated the impact of implementing TPS compared to the traditional reporting system., Patients and Methods: In total, 299 urine samples were reclassified according to TPS. We examined correlations between cytological and histological diagnoses, and calculated probabilities for detecting high-grade urothelial carcinoma (HGUC)., Results: TPS resulted in a decrease in the proportion of cases diagnosed as atypical urothelial cell (AUC) (43% to 31%). Among the AUC cases, the proportion of histologically confirmed HGUC cases rose (75% to 80%), as did the proportion of low-grade urothelial neoplasms (57% to 71%). All probabilities for detecting HGUC significantly increased using TPS., Conclusion: TPS improved the diagnostic yield of urinary cytology. The implementation of TPS is expected to be a major step towards standardizing urinary cytology reporting and providing clear information to clinicians., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Recently, The Paris System for Reporting Urinary Cytology (TPS) has led to major changes in the approach to evaluate urine cytology and pattern of reporting. The aim of this study was to reclassify urine cytology reports with TPS in order to determine the frequency of abnormal results compared with the previous system; also, we performed cytohistological correlation in abnormal cytological results., Methods: In this study, the voided urine specimens from the patients referred to Shiraz University of Medical Sciences affiliated laboratories were retrieved and analyzed using the laboratory's electronic records system; slides prepared from the samples were reviewed by single cytopathologist blindly according to the proposed criteria of TPS., Results: Totally, 1842 urine cytology slides from 828 patients were blindly evaluated by TPS criteria and compared with routine urine cytology classification. Then, available cytohistological correlation was done on 99 abnormal urine cytological results from 58 patients. Among the 26 cytology slides with atypical urothelial cell (AUC) in the previous classification, eight (30.70%) slides were downgraded to negative results, and four (15.30%) were upgraded to higher groups. Therefore, through the reclassification of the slides with TPS, 46% of the AUC changed to other groups. Diagnostic accuracy of the TPS classified urine cytology was 78%, including 87.88% sensitivity, 27.27% specificity, 64.44% positive predictive value, and 60% negative predictive value., Conclusion: The findings of the present study confirmed the importance and utility of TPS regarding the reclassification of AUC to other groups and its high sensitivity for detecting high-grade urothelial carcinoma (HGUC)., (© 2020 Wiley Periodicals, Inc.)

Context: High-grade urothelial carcinoma (UC) cells have many appearances on urine cytology, but according to The Paris System, they can be easily distinguished from umbrella cells., Objective: We aimed to define the incidence and appearance of high-grade UC cells that resemble umbrella cells in Cytospin preparations on urine cytology., Results: Cytospin preparations from 331 cases with biopsy follow-up (230 benign/low-grade and 101 malignant [22 carcinoma in situ, 52 papillary, 19 invasive UC, 8 other] cases) were reviewed. A total of 18 cases with malignant cells resembling umbrella cells were identified (17.8% of the malignant cases) and were the only type of malignant cell in 3% of the cases. Two patterns were identified. Tumor cells were either identifiable by at least 20 abnormal cells which were large, had abundant cytoplasm but an elevated nuclear-to-cytoplasmic ratio, and markedly enlarged, round-to-elongated nucleoli, or else rare cells with abundant cytoplasm but obviously malignant nuclei. Cells without nucleoli or obviously malignant nuclei were not specific., Conclusions: Malignant cells resembling umbrella cells can be seen in up to 17% of urine cytology specimens., (© 2017 S. Karger AG, Basel.)

Introduction: The Paris System for classifying urine cytology emphasizes identification of high-grade urothelial carcinoma (HGUC). The causes of false-negative urine cytologies (UC) within this system are not well described., Material and Methods: We identified 660 cases between 2005 and 2013 with both UC and subsequent cystoscopic biopsies. UC were classified as either Negative for HGUC or "Abnormal" ("Atypical", "Suspicious", and "Malignant"). Apparent false-negative cases were reviewed in a nonblinded fashion by two cytopathologists and two subspecialized genitourinary pathologists., Results: A total of 199 of the 660 cases (30%) were histologically diagnosed as HGUC. The UC were "Abnormal" in 170/199 cases (sensitivity/specificity of 86%/71%). Twenty four apparent false negative cases were available for retrospective review. Five of 24 (21%) cystoscopic biopsies were found not to be HGUC on review (one false positive and four low-grade urothelial carcinoma (LGUC on review). Of the remaining 19 UC, 7 (29%) cytology samples were found to be truly negative on review, 11 (46%) were found to be Atypical, and 1 (4%) suspicious. Of the 12 UC that were at least "Atypical" with histologic HGUC on review: six misses (half) were attributed to obscuring inflammation/blood, four to poor preservation, eight to paucity of abnormal cells, and 1 case to interpretive error; many cases demonstrated overlapping reasons., Conclusion: About one fifth of apparent false negative diagnoses for HGUC can be because of overdiagnosis of HGUC by surgical pathologists. If poor preservation or obscured samples are called nondiagnostic, the sensitivity/specificity of UC for HGUC can be as high as 94%/71%. Diagn. Cytopathol. 2016;44:994-999. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Introduction: Urothelial carcinoma (UCC) of the bladder is the most common malignancy of the urinary tract. The performance of urine cytology (UCy) after radical cystectomy (RC) and urinary diversion is quite variable and there is no consensus regarding its role in post-treatment surveillance. The goal of this study is to retrospectively review the diagnostic value of positive (suspicious or positive for malignancy) diverted urine cytology (DUCy) in the detection of urinary tract recurrence of UCC., Materials and Methods: A retrospective 10-year (January 2005 to January 2015) computerized search for all DUCy specimens was conducted. All suspicious (Susp) or positive for malignant cells (PMC) ThinPrep cases were identified and retrospectively reviewed. Clinical, surgical, and pathological follow-up for patients with Susp or PMC UCy were tabulated and analyzed., Results: During the 10-year-period, 1,525 DUCy cases from 408 patients were identified. Of these, 25 cases (1.64%) from 10 patients were called either Susp (13; 0.85%) or PMC (12; 0.79%). The 25 DUCy cases occurred within a mean of 20 months post-RC. Out of 10 patients, 9 had a concurrent biopsy or a subsequent resection of the recurrent site. Of these 9 patients, 8 (89%) had subsequent biopsy or resection, which showed recurrent UCC. In 5/8 patients, positive DUCy was the very first manifestation of recurrence, which was subsequently confirmed by imaging or histology., Conclusion: It is our experience that patients with positive UCy after RC have a high likelihood of recurrent UCC and should be counseled and managed accordingly. Diagn. Cytopathol. 2016;44:975-979. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)