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Introduction: Compared to urothelial carcinomas (UCs), the cytomorphology of renal cell carcinomas (RCCs) is underdescribed. This study aims to investigate whether UCs and RCCS of the upper urinary tract can be differentiated cytologically, and to identify distinguishing cytomorphological features., Methodology: Consecutive urine cytology specimens with atypical/C3, suspicious/C4 or malignant/C5 diagnoses matched with a nephrectomy or ureterectomy specimen with UC or RCC over a 15-year period were reviewed for cellularity, architecture, background composition and cytomorphologic features., Results: Totally 132 specimens were retrieved, comprising 24 RCCs and 108 UCs. Clear cell RCC (CCRCC) (n = 18) was the most common RCC. Urine cytology specimens from UC showed a trend of higher cellularity (p = 0.071) against RCC and was significant in subgroup analysis with CCRCC (p < .001). Epithelial structures in sheets, tubules, and papillae were exclusive in specimens of UC (p < .05). For background features, squamous cells were more common for RCC (p = .006) including CCRCC (p = .003), whereas polymorphs (p = .011) and necrotic material (p = .010) were associated with UC. Average nuclear size was larger and nuclear size variation (p < .001) and nuclear-cytoplasmic ratio (p = .001) were greater in UC (p = .001) than RCC. Comparing RCC to high-grade UCs only, nuclear-cytoplasmic ratio maintained statistical significance (p = .006) while average nuclear size showed a trend (p = .063)., Conclusion: A clean background free of tumor necrosis and polymorphs, and the lack of complex tumor fragments favors RCC. UCs also display larger nuclear size, higher nuclear size variation and nuclear-cytoplasmic ratio. These cytomorphological features with corroboration of clinical/radiological findings, can aid in raising a diagnosis of RCC., (© 2024 The Author(s). Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Background: To compare predictive value of MCM5 to urinary cytology (UC) for the primary diagnosis of bladder cancer (BCa)., Methods: We prospectively enrolled 91 patients who presented macroscopic hematuria or persistent lower urinary tract symptoms at our institution. Single voided mid-stream urine specimens were collected for UC and MCM5 (ADXBLADDER; Arquer Diagnostics Ltd, Sunderland, United Kingdom) assessment. Cystoscopy was used as confirmatory test, and positive cases underwent transurethral resection of bladder tumor with histopathological evaluation., Results: Forty cases (43.9%) showed a positive cystoscopy for BCa. Histology was obtained in 37 cases: 16 (43.2%) high-grade (HG) and 21 (56.8%) low-grade (LG) transitional cell carcinoma (TCC). UC had a sensitivity of 62.5%, specificity of 86.3%, PPV of 78.1% and NPV of 74.6%. Sensitivity, specificity, PPV and NPV of MCM5 were 60.0%, 88.2%, 80.0% and 73.8%, respectively. According to tumor grade, MCM5 and UC showed a sensitivity of 47.6% and 52.4% in LG, and 87.5% and 75.0%, respectively, in HG TCC. False-positive rates were 11.8% and 13.7% of negative cases for BCa with MCM5 and UC test, whereas false-negative results were found in 40.0% and 37.5% of BCa cases, respectively. The combination of the two tests showed a sensitivity of 71.4% in LG, and 93.8% in HG TCC., Conclusion: In the present analysis, MCM5 showed lower sensitivity than UC in predicting BCa primary diagnosis. According to tumor grade, MCM5 showed a higher sensitivity in the detection of HG BCa compared to UC, although values were not significantly different., (© 2020 Wiley Periodicals LLC.)

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.)

Background: Cytological examination of voided urine (VU) can reliably diagnose high-grade urothelial carcinoma (HGUC) of the lower urinary tract, but its value in the diagnosis of upper tract HGUC (UTHGUC) is less well-established. To clarify the utility of VU in the setting of UTHGUC, we examined urinary specimens from patients with UTHGUC on follow-up surgical pathology., Methods: 52 VU specimens (47 patients) with subsequent biopsy-proven UTHGUC were identified over a 12-year period; 32 had a corresponding upper tract urinary washing (UW) specimen. Patients with concurrent bladder HGUC were excluded. The diagnoses of VU specimens were tabulated and compared to those of UW specimens., Results: Three UW specimens had a less severe diagnosis, 8 had the same diagnosis, and 21 had a more severe diagnosis than the corresponding VU specimen from the same patient. Significantly more UW specimens demonstrated high-risk features as compared with VU specimens (P = .003). In specimens with atypia, a definitive diagnosis of HGUC was made significantly more often on UW vs. VU specimens (P = .003)., Conclusions: Among patients with confirmed UTHGUC, 50% of preceding VU specimens demonstrated high-grade features compared to almost 90% of UW specimens. Though VU cytology shows atypia in the majority of cases, it performs inferiorly to UW for the detection of UTHGUC. Diagn. Cytopathol. 2017;45:700-704. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Aims and Objective: To build up an artificial neural network (ANN) model in the diagnosis of urothelial cell carcinoma (UCC) in urine cytology smears., Material and Methods: We randomly selected a total of 115 urine cytology samples, out of which 59 were histopathology proven UCC cases and remaining 56 were benign cases from routine cytology samples. All the carcinoma cases were proven on histopathology. Image morphometric analysis was performed on Papanicolaou's stained smears to study nuclear area, diameter, perimeter, standard deviation of nuclear area, and integrated gray density. Detailed cytological features were also studied in each case by two independent observers and were semi-quantitatively graded. The back propagation ANN model was designed as 17-11-3 with the help of heuristic search. The cases were randomly partitioned as training, validation, and testing sets by the program. There were 79 cases for training set, 18 cases for validation set and 18 cases for test set., Result: In the training set, ANN was able to diagnose all the malignant and benign cases. In the test set, all the benign and malignant cases were diagnosed correctly. However, one of the low grade cases was diagnosed as high grade UCC by ANN model., Conclusions: We successfully built an ANN model in urine from the visual and morphometric data to identify the benign and malignant cases. In addition, the system can also identify the low grade and high grade UCC cases., (© 2015 Wiley Periodicals, Inc.)

Background: This prospective study compares urine NMP22 immunoassay and cytomorphology for detecting recurrent urothelial carcinoma (UC) of the bladder and correlates between NMP22 levels and grade, multiplicity, and size of the tumor. We aimed refining the use of NMP22 test in the management of UC at our institution., Methods: Urine specimens, collected prior to a cystoscopic biopsy either from patients with a history of bladder cancer (n = 50) or from controls (n = 15) were studied. Cytology and NMP22 results were compared with subsequent biopsies and performance characteristics were measured., Results: Overall sensitivity and specificity of cytology was 62.5% and 87.5%, respectively while NMP22 had a sensitivity of 85.4% and specificity of 76.5%. NMP22 was superior to cytology for detecting low-grade UC (82.6% vs. 54.5%) and in terms of NPV (65% vs. 44.4%) while cytology reached 100% detection rate for high-grade UC. And, the sensitivity of 98% was achieved when NMP22 was combined with atypical cytology. Optimal performance of NMP22 has been detected around the reference value of 6.4 U/ml. The mean NMP22 values in control and study groups were 2.5 U/ml and 36 U/ml, respectively. The mean NMP22 value was 20.9 U/ml in low-grade UC and 53.2 U/ml in high-grade category., Conclusions: The NMP22 values displayed higher sensitivity for low-grade UC while cytology was highly sensitive and spesific in detection of high-grade UC. Combining urine NMP22 assay with atypical cytology improved sensitivity for detection of recurrent UC. The inclusion of the adjunctive NMP22 test in monitoring protocols for low-grade UC in combination with cytology for high-grade UC could enable clinicians to decrease the frequency of follow-up cystoscopies., (© 2014 Wiley Periodicals, Inc.)

Cystoscopic urine obtained before the resection of low-grade urothelial carcinoma (LGUC), with adequate cytological sampling of the tumor, frequently revealed the presence of three-dimensional cell groups with disordered nuclei and cellular discohesion (3DDD). 936 cystoscopic urine specimens were categorized into five groups: Group 1 (80 specimens) with biopsy-proven LGUC within 6 months of cytologic examination, Group 2 (23 specimens) with biopsy proven LGUC within 6 to 36 months of cytologic examination, Group 3 (527 specimens) with a history of LGUC but no tumor for a period of greater than 3 years, Group 4 (300 specimens) with no association with LGUC, and Group 5 (6 specimens) with urinary lithiasis. Specimens with scant cellularity accounted for 20% of those in Group 1. For 3DDD in detecting LGUC in adequate cystoscopic urine, the sensitivity was 70%, specificity was 94%. Two- or three-dimensional cell groups with ordered nuclei and/or cellular non-discohesion were often seen in specimens from Groups 4 or 5. The 3DDD was present in a significant number of cases with concurrent negative cystoscopic findings but also positive LGUC in ensuing follow-up. In these cases, 3DDD with or without tumor identified at concurrent cystoscopy were found to be morphologically similar. Furthermore, the presence of 3DDD in 8% of Group 3 likely represents urothelial dysplasia that is not cystoscopically detectable. The high specificity and sensitivity of 3DDD is demonstrated. These findings are consistent with the decreased cell adhesion and disordered nuclear arrangement of low grade urothelial neoplasia., (© 2013 Wiley Periodicals, Inc.)

Urine cytology is a proven and widely used screening tool for the detection of urothelial carcinoma. However, morphologic features of polyomavirus infected cells, characterized by nuclear inclusions (decoy cells) are a known source of diagnostic confusion with malignancy. Fluorescence in situ hybridization (FISH) is now routinely used to support the cytological diagnosis of urothelial carcinoma and monitor for recurrence. We sought to determine whether polyomavirus infection could result in positive FISH results (aneuploidy). This study deals with retrospective study of 100 polyomavirus-infected urine samples from patients with no history of urothelial carcinoma or organ transplantation. All cases were stained with Papanicolaou and acid hematoxylin stain. One slide from each sample was de-stained and FISH was performed using chromosome enumeration probes 3, 7, 17, and locus-specific probe 9p21. Adequate cells for FISH analysis (25 cells) were present in 81 cases; 19 cases were insufficient due to loss of cells during de-staining and FISH preparation process. All polyomavirus-infected cells (decoy cells) exhibited a normal chromosome pattern. Four cases were FISH positive, but there were no positive decoy cells. Decoy cells did not exhibit aneuploidy by FISH. The presence of decoy cells does not exclude the possibility of concurrent urothelial carcinoma. Acid hematoxylin stain appeared to supplement the Papanicolou stain in identifying and confirming the presence of polyomavirus infection., (Copyright © 2013 Wiley Periodicals, Inc.)

The urine fluorescence in situ hybridization (FISH) assay (UroVysion™), with the current scoring criteria, has a higher sensitivity than routine cytopathology but a lower specificity. Among 215 urine FISH tests we performed, 45 had associated histopathology and clinical follow up. In this study, a cell with four signals for each probe was classified as a uniform tetraploid cell (UTC); a presumed reparative cell which is currently classified as an abnormal cell in the FDA approved assay. By using the existing criteria, the tests were scored as positive or negative before and after exclusion of the UTCs. Before the exclusion, 24 positive, 13 negative, seven false positive, and one false negative result were obtained with 96% sensitivity and 65% specificity. After the exclusion, the results changed to 22 positive, 19 negative, one false positive, and three false negatives resulting in a 88% sensitivity of 88% and a 95% specificity; a significant improvement in the specificity. We conclude that exclusion of the UTCs as abnormal cells would result in a more solid performance of the FISH assay., (Copyright © 2011 Wiley Periodicals, Inc.)

The objective of this study is to evaluate the role of micronuclei (MN) in identifying the atypical urothelial cells urinary cytology. This is a retrospective study of a total of 30 cases of urine samples. Of these, 15 cases were selected where the initial diagnosis was atypical urothelial cell and later turned out as malignant cells on follow-up histopathology. The rest of the 15 cases were reported as normal urothelial cells. The number of MN in 1,000 urothelial cells was counted in all the cases and was expressed as percentage. All the cases diagnosed as atypical urothelial cells show the presence of MN. The mean number of MN was 2.53 ± 0.99%. No MN was noted in any of the normal urothelial cells in control cases. The Student's t-test of MN scoring was highly significant (P < 0.000) in test (atypical urothelial cells) versus control group (benign urothelial cells). MN is an important biomarker of malignancy. Micronuclear score in atypical urothelial cells in urine cytology smears may help in proper diagnosis of the case., (© 2010 Wiley-Liss, Inc.)

The usefulness of urine cytology combined with NMP22 was evaluated for the primary diagnosis of urothelial carcinoma. Of 53 clinically suspected patients, histopathological diagnoses were low-grade urothelial carcinoma (25), high-grade urothelial carcinoma (13), and inflammatory lesions (15). Cytology was positive in 25 and negative in 14 patients. Fourteen of 25 low-grade urothelial carcinoma and 11/13 high-grade urothelial carcinoma were diagnosed correctly on urine cytology. Atypical cells seen in 14 patients were categorized as inconclusive for malignancy. The overall sensitivity of urine cytology was 65.8%, whereas specificity was 100%. NMP22 was positive in 33 patients. Of these 30, 18 low-grade and 12 high-grade lesions were true positive. Of the 20 NMP22, eight negative cases were false-negative. Ten of 15 with negative histopathology were also negative for NMP22, three were false-positive, and two showed erratic results. Nine of 14 cases with atypical urine cytology were positive for NMP22. Eight of these showed low-grade carcinoma on histopathology. The sensitivity of BladderChek NMP22 test was 79%, whereas specificity was 80%. NMP22 BladderChek test is a useful adjunct to urine cytology in atypical and low-grade carcinoma., (© 2009 Wiley-Liss, Inc.)

Tuberculosis of the urinary tract is usually secondary to tuberculosis of the kidney. Multinucleated giant cell histiocytes, often with peripheral nuclei (Langhans' cells), may be identified. Acid-fast bacilli on smear or positive urine cultures confirm the diagnosis. Similar findings can also be seen in patients treated with Bacillus Calmette Guérin (BCG) for transitional cell carcinoma or after bladder surgery. Here, we present two cases showing epithelioid cell granulomas and multinucleated giant cells on urine cytology, and discuss the differentiating features on cytomorphology and their therapeutic implications., (© 2010 Wiley-Liss, Inc.)

Our purpose was to evaluate the feasibility of performing fluorescence in situ hybridization (FISH) on routine urine samples and to compare the relative sensitivities of urine cytology and FISH for detecting urothelial carcinoma. Light microscopy (LM) using cytologic evaluation and FISH were used to study 121 consecutive urine samples. A mixture of fluorescent probes to chromosomes 3, 7, 17, and the 9p21 locus were used for detection of numerical chromosomal abnormalities (UroVysion, Vysis/Abbott). Biopsy specimens from patients in the study were reviewed if available. FISH analysis was performed without knowledge of cytology or biopsy findings. The urine cytology of 121 samples was interpreted as 59 negative, 41 reactive, 16 atypical, 2 suspicious and 3 insufficient cells for diagnosis. 85 samples were successfully analyzed by FISH. Thirty-one of these showed chromosomal abnormalities and these samples were initially regarded on the original cytology reading as follows: 10 negative, 10 reactive, 9 atypical, and 2 suspicious. FISH demonstrated chromosomal abnormalities in a significant number of cases (67%) that were initially diagnosed as normal or reactive by LM. Twenty-five patients were identified who had biopsy-proven TCC and successful FISH. Thirteen of the 25 patients (52%) were abnormal by FISH (cytology: 2 suspicious, 6 atypical, 4 reactive, 1 negative). One patient was atypical by cytology with normal FISH results but had TCC on biopsy. Hyperdiploidy for chromosomes 3 (77%) and 7 (67%) were seen consistently. Multiple chromosomal abnormalities were seen in 67% of these cases. We conclude that FISH has a greater sensitivity in detecting urothelial carcinoma when coupled with urine cytology. It is not entirely clear at this time whether a positive FISH may indicate frank neoplastic urothelial transformation or merely be an indicator of unstable urothelium capable of or primed for malignant transformation thus detecting patients at significant risk. The use of FISH in conjunction with urine cytology can potentially reduce urothelial carcinoma morbidity and mortality by diagnosing these tumors earlier., (Copyright 2003 Wiley-Liss, Inc.)

The 1998 World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification of urothelial neoplasms introduced a category called papillary neoplasm of low malignant potential (LMP) and separated it from low-grade papillary urothelial carcinoma (LGPUC), which was thought to yield abnormal cells in cytology specimens. The objective of our study was to evaluate the effectiveness of urine cytology in diagnosing these lesions. Eighty-six paired transurethral surgical biopsy and corresponding urine cytology specimens representing the spectrum of urothelial papillary lesions were examined. Consensus diagnosis on each biopsy was made, and the distribution was as follows: 16 benign urothelium, 27 LMP, 28 LGPUC, and 15 high-grade papillary urothelial carcinoma (HGPUC). This was followed by a blinded independent review of the urine cytology specimens by three observers. Each cytology case was marked as negative, atypical, suspicious, or positive for malignant cells by using previously published cytologic criteria. When the negative and atypical diagnoses were grouped together as "benign" and the suspicious and malignant diagnoses as "malignant," the detection rate of "malignancy" of the lesions was as follows: LMP, 37%; LGPUC, 25%; and HGPUC, 53%. The false positive rate was 6%, and the positive predictive value (PPV) was 94%. Detection rates of cells that were at least "atypical" were as follows: LMP, 74%; LGPUC, 79%; and HGPUC, 100%. While most of the LMP and LGPUC cases yielded cells that were at least "atypical," there was no significant difference in the distribution of cytologic diagnoses for LMP and LGPUC cases (P > 0.05). Urine cytology in the context of the 1998 WHO/ISUP classification appears to be useful as a screening tool but does not appear to discriminate LMP effectively from LGPUC., (Copyright 2003 Wiley-Liss, Inc.)

We compared the ThinPrep (TP) technique to the cytospin (CS) preparation in the cytological diagnosis of urine by processing 79 specimens by these two techniques. Ten cases were positive for malignancy (six high grade (HG)/carcinoma in situ; four low grade (LG) transitional cell carcinomas (TCC)). Forty-eight cases were within normal limits (59%) and 21 cases had atypical cytological features (19%). The TP technique was better in terms of a cleaner background with fewer obscuring inflammatory cells and blood and with a more even distribution of cells. In general, the cytomorphology was comparable in both techniques. However, in cases with malignancy, CS was relatively superior in the cytomorphologic details; in TP, the diagnostic cells were mostly dispersed as single cells with loss of architectural features and were difficult to find. Artifactual empty spaces and air-drying were more frequently present in TP. In cases contaminated with squamous cells, the urothelial cells were difficult to find in TP. Screening time was comparable for both techniques. In conclusion, to avoid false-negative diagnosis, CS would be complementary to the TP technique in malignant cases and, in particular, those with low cellularity., (Copyright 2003 Wiley-Liss, Inc.)

Our study evaluated the BTA (bladder tumor antigen) stat test kit as a primary screening device for the detection of transitional-cell carcinoma (TCC) of the bladder, with direct comparison by voided urine cytology (VUC) on the same specimens. The unfixed voided urine of 100 patients with no history of bladder cancer who had signs and symptoms of dysuria, incontinence, and gross hematuria and microhematuria were tested using the one-step BTA stat test kit before processing via the cytospin technique for fluid cytological evaluation. The patients in the study were followed for up to 12 mo with repeated urine cytological testing, cystoscopy, and bladder biopsy when clinically indicated. Nineteen cases tested positive, and 81 cases tested negative on the BTA stat test. VUC diagnosed three cases as unequivocally positive for TCC, 93 cases as negative, and four cases in which unqualified atypical urothelial cells were noted. TCC was confirmed by cystoscopy and bladder biopsy in three of three cases diagnosed by VUC and in three of 19 cases that tested positive by the BTA stat test. These findings resulted in an 84% false-positive rate for the BTA stat test and no false-positive cases for VUC during the 12-mo follow-up period. The results indicate that the sensitivity and specificity of BTA stat test are comparable to those of VUC; however, owing to a relatively high false-positive rate, it can at best act as an adjunct to urine cytological study for bladder cancer screening.

This study compares urine nuclear matrix protein 22 (NMP22) immunoassay and conventional urine cytologic examination for detecting recurrent transitional-cell carcinoma (TCC) of the urinary bladder. One hundred twenty-eight urine specimens from 107 patients with a history of TCC of the urinary bladder were studied. NMP22 immunoassay and conventional cytologic examination were performed on each specimen. The NMP22 and cytology results were then compared with the results of subsequent cystoscopies/surgical biopsies performed over a 6-mo follow-up period. The sensitivity of urine cytologic study for predicting recurrent TCC was 60%, while the sensitivity of NMP22 assay was 47%. When both NMP22 assay results and the cytologic interpretation were positive for TCC, the positive predictive value of the combined tests was 74%. When both tests showed negative results, the negative predictive power was 81%. Our findings suggest that urine NMP22 assay may represent a useful diagnostic adjunct to conventional urine cytologic examination for the detection of recurrent TCC of the urinary bladder.

Routine urine cytology has been performed for 809 male patients presenting with symptoms due to prostatic hypertrophy. In 6.42% of the cases, bladder tumor was revealed incidentally diagnosed by urine cytology. Cystoscopy and bladder biopsies were performed to confirm malignancy. The age of these patients ranged from 48-84 years (mean 65.2) and they complained mainly of irritative bladder symptoms. It is therefore strongly indicated that all patients with prostatic disease should have routine cytological examination of urine sediments.

The diagnostic yield of cytology in histologically proven transitional-cell carcinoma (TCC) of the urinary bladder has been studied in 100 cases. Cytohistologic correlation rates were 20 percent, 61.7 percent, and 92.8 percent, respectively, for grade 1, 2, and 3 tumors. When further evaluated, G2 cases were segregated into 2 subcategories, G2a and G2b, based on histologic preservation of nuclear polarity, pleomorphism, and other cellular irregularities. Correlation rates were rather low for G2a cases (6/18, 33%) and high for G2b cases, (23/29; 79%). The prevalence of atypical cells was 2 (11.1%) cases in G2a and 16 (55.2%) cases in G2b. The results of this study confirm that cytology has an extremely varying diagnostic yield in urinary bladder TCC. Greater cell exfoliation, increased atypia, and a tendency to infiltration of G2b and G3 cases probably account for the higher diagnostic yield detected in these groups.