High-Grade Urothelial Carcinoma on Urine Cytology Resembling Umbrella Cells

2017 ◽  
Vol 62 (1) ◽  
pp. 62-67 ◽  
Author(s):  
Andrew A. Renshaw ◽  
Edwin W. Gould
Keyword(s):  
Urothelial Carcinoma ◽  
Malignant Cell ◽  
Urine Cytology ◽  
Low Grade ◽  
High Grade ◽  
Malignant Cells ◽  
Abundant Cytoplasm ◽  
Abnormal Cells ◽  
Rare Cells ◽  
Umbrella Cells

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.

Umbrella Cells Mimicking Focal High-Grade Urothelial Carcinoma in Low-Grade Papillary Urothelial Carcinoma

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S121-S121
Author(s):  
Muhammad Masood Hassan ◽  
Tammey Naab ◽  
Ali Afsari
Keyword(s):  
Urothelial Carcinoma ◽  
Proliferation Index ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Prostate Hyperplasia ◽  
History Of ◽  
Papillary Urothelial Carcinoma ◽  
Artery Disease ◽  
Umbrella Cells

Abstract Objectives Low-grade papillary urothelial carcinoma (LGUC) has overall a preserved orderly appearance, minimal variability in architecture, and lack of significant cytologic atypia and mitotic activity without pleomorphism. A total of 53.8% of LGUC cases recur with 18.3% progression to high-grade UC. Even focal HGUC in LGUC can be a harbinger of progression. Accurate pathological interpretation is paramount in predicting recurrence and determining treatment. Methods A 63-year-old male with a past medical history of coronary artery disease, benign prostate hyperplasia, and obesity was referred to urology with a chief complaint of chronic hematuria. Cystoscopy with transurethral resection of bladder tumor was performed, which revealed mainly LGUC with focal high-grade-appearing UC. Results Histologic sections revealed papillary architecture with fused fronds, low-grade nuclear atypia, and scattered mitoses comprising 95% of the tissue submitted. No muscular wall invasion by carcinoma was seen. However, in one section, collections of large cells with well-defined cytoplasmic borders, multinucleation, and rare nuclear grooves were identified. The morphology raised the suspicion of a focal HGUC. Diffuse expression of CK20 and low Ki-67 proliferation index (1%) favored umbrella cells. Conclusion Our case reinforces the fact that sectioning can reveal foci, suspicious for HGUC, especially in urothelium. However, proper interpretation of morphology combined with the help of immunohistochemistry aids in accurate diagnosis, which is critical in determining proper clinical management of the patient.

Comparative Evaluation of ProEx C and ImmunoCyt/uCyt Assays in Atypical Urine Cytology

2014 ◽  
Vol 138 (9) ◽  
pp. 1215-1222 ◽  
Author(s):  
Maria E. Vergara-Lluri ◽  
Eugenia Hu ◽  
Jian-Yu Rao ◽  
Mary Levin ◽  
Sophia K. Apple ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Topoisomerase Ii ◽  
High Sensitivity ◽  
Urine Cytology ◽  
Urothelial Cell ◽  
Low Grade ◽  
Nuclear Staining ◽  
High Grade ◽  
Surgical Biopsy ◽  
Papillary Urothelial Carcinoma

Context.—Detection of urothelial carcinoma by urine cytology can be challenging. Recently, ProEx C has been studied as a marker to improve detection of urothelial carcinoma. ProEx C is an assay targeting expression of topoisomerase II-α and the minichromosome maintenance protein-2 and is used to assist in diagnoses of gynecologic specimens. Objective.—To evaluate the utility of ProEx C and uCyt in atypical urine cytology. Design.—Sixty-eight specimens with a diagnosis of atypical urine cytology, concurrent uCyt testing, and surgical biopsy follow-up were included. Slides were restained with ProEx C. ProEx C was recorded as positive when nuclear staining was seen in at least one morphologically atypical urothelial cell. The uCyt was scored as positive if at least one morphologically atypical urothelial cell showed positive fluorescence staining. Thirteen cases (19%) had benign histologic diagnoses, 18 (26%) had low-grade papillary urothelial carcinoma, and 37 (54%) had high-grade urothelial carcinoma. Results.—The overall sensitivity was 85% for ProEx C, 85% for uCyt, and 93% for the combination of the 2 assays. The overall specificity was 69% for ProEx C, 31% for uCyt, and 23% for the combination of the 2 tests. In predicting high-grade urothelial carcinoma, sensitivity was 92% for ProEx C, 86% for uCyt, and 92% for both tests. In predicting low-grade papillary urothelial carcinoma, sensitivity was best with the combination of the 2 tests at 94%. Conclusion.—ProEx C has superior specificity to uCyt. The combination of the 2 tests yielded high sensitivity not only for high-grade urothelial carcinoma but also for low-grade papillary urothelial carcinoma.

scholarly journals Paris System Has A Higher Cytohistologic Correlation And Reproducibility Than Traditional Urine Cytology Method

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S94-S94
Author(s):  
R P Mendoza ◽  
T Haidary ◽  
R Gupta
Keyword(s):  
Urothelial Carcinoma ◽  
Traditional Method ◽  
Urine Cytology ◽  
Low Grade ◽  
High Grade ◽  
Cytologic Diagnosis ◽  
Histologic Diagnosis ◽  
Negative Results ◽  
The Mean ◽  
Cytology Result

Abstract Introduction/Objective The major limitation of urine cytology is the lack of consensus regarding the terminology and diagnostic criteria that should be used for urothelial atypia. The main goal of the newly proposed Paris System for Reporting Urine Cytology is to concentrate primarily on the detection of high grade urothelial carcinoma while minimizing the detection of low grade lesions. This study aimed to apply the criteria and categories of the Paris system in retrospectively collected urine cytology specimens and assess histologic correlation and reproducibility. Methods Two senior pathologists independently reviewed retrospectively collected urine cytology specimens strictly following the Paris system criteria for categorization. Cytologic diagnosis were compared with previous cytology result and histologic diagnosis. Results A total of 67 patients were included in the study. The mean age is 65.8 years (36-89 years), majority were males (73.1%) and African American (89.6%). Urine cytology using traditional method showed mostly atypical results (58.2%), followed by reactive (26.9%), high-grade urothelial carcinoma (11.9%) and suspicious (3.0%). On the other hand, the Paris system had more negative results (62.7%), followed by atypical (19.4%), high-grade urothelial carcinoma (11.9%) and lastly suspicious (6.0%). All of negative cases (18 out of 18) and majority of HGUC cases (7 out of 8) were concordant between the two cytology methods. Traditional urine cytology method only yielded 71.4% histologic concordance, while 100% Paris system results were concordant with bladder histology. Majority of the atypical cases using traditional method were converted to negative, and a few atypical cases were converted to suspicious and high-grade. All results using Paris system were concordant between two general pathologists. Conclusion Using the Paris system in analyzing urine cytology resulted to higher cytohistologic concordance than traditional method. Majority of atypical cases from traditional method were converted to more definitive categories. The cytopathologic analyses from two general pathologists applying the criteria of Paris system had superior reproducibility. Applying the Paris system, therefore, can significantly improve the performance of urine cytopathology.

scholarly journals Application of the Paris Reporting System for Urine Cytology: The Three-Year Experience of a Single Tertiary Care Institute in Thailand

2022 ◽  
pp. 1-8
Author(s):  
Bantita Phruttinarakorn ◽  
Sirithep Plumworasawat ◽  
Jitchai Kayankarnnavee ◽  
Jirasit Lualon ◽  
Atcharaporn Pongtippan
Keyword(s):  
Urothelial Carcinoma ◽  
Predictive Value ◽  
Diagnostic Category ◽  
Malignant Neoplasm ◽  
Urine Cytology ◽  
Malignant Neoplasms ◽  
Low Grade ◽  
High Grade ◽  
Sensitivity Specificity

<b><i>Introduction:</i></b> Urothelial carcinoma is one of the most common human cancers, both in Thailand and worldwide. Urine cytology is a screening tool used to detect urothelial carcinoma. The Paris System for Reporting Urinary Cytology (TPSRUC) was first published in 2016 to standardize the procedures, reporting, and management of urothelial carcinoma. Diagnostic categories include negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells (AUCs), suspicious for HGUC (SHGUC), HGUC, low-grade urothelial neoplasm, and other malignancies. <b><i>Material and Methods:</i></b> In a retrospective review, urine cytology specimens from 2016 to 2019 were reevaluated using the TPSRUC. The risk of high-grade malignant neoplasm (ROHM) for each diagnostic category was calculated. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of prediction of high-grade malignant neoplasms were evaluated for cases with histological follow-up specimens. <b><i>Results:</i></b> In total, 2,178 urine cytology specimens were evaluated, of which 456 cases had follow-up histological specimens. The ROHM in each diagnostic category was as follows: NHGUC, 17.4%; AUC, 49.9%; SHGUC, 81.2%; HGUC, 91.3%; and other malignant neoplasms, 87.5%. The sensitivity, specificity, PPV, NPV, and accuracy for high-grade malignant neoplasm prediction were 63%, 92.8%, 89%, 73.1%, and 78.5% when AUC was included as malignant in the comparison and 82.6%, 74.7%, 75.1%, 82.3%, and 78.5% when AUC was not considered malignant. <b><i>Conclusions:</i></b> TPSRUC provides reliable results that are reproducible by different interpreters and is a helpful tool for the detection of HGUC.

scholarly journals Differential expression of NF-κB heterodimer RelA/p50 in human urothelial carcinoma

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5563 ◽  
Author(s):  
Sankari Durairajan ◽  
Charles Emmanuel Jebaraj Walter ◽  
Mary Divya Samuel ◽  
Dinesh Palani ◽  
Dicky John Davis G ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Disease Progression ◽  
Differential Expression ◽  
Malignant Cell ◽  
Immunohistochemical Localization ◽  
Low Grade ◽  
High Grade ◽  
Cytoplasmic Expression ◽  
Over Expression ◽  
Muscle Invasion

Background Urothelial carcinoma (UC) is the fifth most common malignancy that accounts for 5% of all cancers. Diagnostic markers that predict UC progressions are inadequate. NF-κB contributes towards disease progression upon constitutive activation in many solid tumors. The nuclear localization of NF-κB indicates increased transcriptional activity while cytoplasmic localization indicates the inactive protein repository that can be utilized readily by a malignant cell. This study delineates the nuclear and cytoplasmic differential expression of NF-κB heterodimers in UC progression. Methods The involvement of the NF-κB proteins in UC was analyzed in silico using cytoscape. The expression of NF-κB heterodimers was analyzed by immunohistochemistry. Results PINA4MS app in cytoscape revealed over expression of RelA and suppression of NF-κB1 (p50 precursor) in UC whereas the expression of NF-κB target proteins remained unhindered. Immunohistochemical localization showed nuclear RelA/p50 in low grade UC whereas in high grade only RelA expression was observed. Conversely, cytoplasmic expression of RelA/p50 remained extensive across high and low grade UC tissues (p < 0.005). RelA nuclear and cytoplasmic expression (p < 0.005) was directly proportional to the disease progression. In our study, some of the high-grade UC tissues with squamous differentiation and muscle invasion had extensive nuclear p50 localization. The phenomenon of RelA/p50 expression seen increased in low-grade UC than high grade UC might be due to their interaction with other members of NF-κB family of proteins. Thus, NF-κB RelA/p50 differential expression may play a unique role in UC pathogenesis and can serve as a biomarker for diagnosis.

Utility of Urine Cytology in Genitourinary Lesions and Implication of Paris System in the Diagnosis of Urothelial Carcinoma - Five Years of Experience from a Tertiary Care Centre at North Karnataka

2021 ◽  
Vol 8 (02) ◽  
pp. 58-63
Author(s):  
Ranjana Shashidhar Ranade ◽  
Netra Prakash Kori ◽  
Vidisha Sharatchandra Athanikar
Keyword(s):  
Diagnostic Accuracy ◽  
Urothelial Carcinoma ◽  
Predictive Accuracy ◽  
Tertiary Care ◽  
Urine Cytology ◽  
Low Grade ◽  
High Grade ◽  
Tertiary Care Centre ◽  
Screening And Surveillance ◽  
Reporting Systems

BACKGROUND Urine cytology when combined with cystoscopy remains a gold standard in screening and surveillance of urothelial carcinoma. Paris system for reporting urine cytology (PSRUC) gives seven well defined diagnostic criteria. We aimed to analyse utility of urine cytology in patients with urogenital symptoms, compare existing institutional system (EIS) with PSRUC and assess the performance of both reporting systems in predicting subsequent high-grade urothelial carcinoma on histopathology. METHODS A five year retrospective study included a total of 146 urine samples from 74 patients. Each case was assigned a category according to both EIS and PSRUC system. After cyto-histological correlation, sensitivity, specificity and diagnostic accuracy of urine cytology in detecting malignancy using PSRUC and EIS were determined. Performance of urine cytology in predicting subsequent high grade urothelial carcinoma (HGUC) was assessed for both reporting systems. RESULTS PSRUC resulted in reduction in number of cases assigned to atypical category (10.5 % vs. 3.4 %) and increase in low grade carcinomas assigned to NGUC category (66 % vs. 100 %). Positive predictive value (PPV) for predicting subsequent high grade urothelial carcinoma for HGUC and SHGUC category remained the same (100 %). Sensitivity (66.67 % vs. 55.5 %), specificity (100 % vs. 85.71 %) and diagnostic accuracy (81 % vs. 68.75 %) was improved with application of PSRUC when compared to EIS. Two cases of genitourinary tuberculosis were diagnosed. CONCLUSIONS PSRUC improves predictive accuracy of subsequent high-grade urothelial carcinoma on histopathology and it ensures uniformity in reporting. Judicious use of urine cytology might aid in early diagnosis of infectious conditions like tuberculosis. KEYWORDS PSRUC, Urine Cytology, High Grade Urothelial Carcinoma

scholarly journals Expression of Semaphorin 3A in Malignant and Normal Bladder Tissue: Immunohistochemistry Staining and Morphometric Evaluation

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 109
Author(s):  
Ilan Bejar ◽  
Jacob Rubinstein ◽  
Jacob Bejar ◽  
Edmond Sabo ◽  
Hilla K Sheffer ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Carcinoma In Situ ◽  
Urothelial Cancer ◽  
Basal Layer ◽  
Low Grade ◽  
High Grade ◽  
Bladder Tissue ◽  
Normal Bladder ◽  
Normal Bladder Tissue

Introduction: Our previous studies showed elevated levels of Semaphorin3a (Sema3A) in the urine of patients with urothelial cancer compared to healthy patients. The aim of this study was to analyze the extent of Sema3A expression in normal and malignant urothelial tissue using immune-staining microscopic and morphometric analysis. Materials and Methods: Fifty-seven paraffin-embedded bladder samples were retrieved from our pathology archive and analyzed: 14 samples of normal urothelium, 21 samples containing low-grade urothelial carcinoma, 13 samples of patients with high-grade urothelial carcinoma, 7 samples containing muscle invasive urothelial carcinoma, and 2 samples with pure urothelial carcinoma in situ. All samples were immunostained with anti Sema3A antibodies. The area of tissue stained with Sema3A and its intensity were analyzed using computerized morphometry and compared between the samples’ groups. Results: In normal bladder tissue, very light Sema3A staining was demonstrated on the mucosal basal layer and completely disappeared on the apical layer. In low-grade tumor samples, cells in the basal layer of the mucosa were also lightly stained with Sema3A, but Seama3A expression intensified upon moving apically, reaching its highest level on apical cells exfoliating to the urine. In high grade urothelial tumors, Seama3A staining was intense in the entire thickness of the mucosa. In samples containing carcinoma in situ, staining intensity was high and homogenous in all the neoplastic cells. Conclusions: Sema3A may be serve as a potential non-invasive marker of urothelial cancer.

High-grade Urothelial Carcinoma with Malignant Melanocytic Differentiation

2021 ◽  
pp. 106689692110004
Author(s):  
Hongzhi Xu ◽  
Elizabeth M. Genega ◽  
Liyan Zhuang ◽  
Ming Zhou
Keyword(s):  
Urothelial Carcinoma ◽  
Bladder Wall ◽  
Minor Component ◽  
Asian Woman ◽  
High Grade ◽  
Therapeutic Implications ◽  
Divergent Differentiation ◽  
Rare Cells ◽  
A Minor ◽  
Melanocytic Differentiation

Urothelial carcinoma usually shows divergent differentiation and variant histology with squamous and glandular morphology being most common. In this report, we present a case of divergent malignant melanocytic differentiation in a high-grade urothelial carcinoma. A 98-year-old East Asian woman with an anterior bladder wall mass underwent resection, which revealed a high-grade poorly differentiated tumor. A minor component of high-grade papillary urothelial carcinoma and carcinoma in situ is also present. The majority of the tumor cells are morphologically and immunohistochemically consistent with melanoma, a minority of cells are positive for urothelial markers, and rare cells coexpress both melanocytic and urothelial markers. Cells that express melanocytic markers or urothelial markers are intimately admixed together. Taken together, a diagnosis of high-grade urothelial carcinoma with malignant melanocytic differentiation was rendered. This is the first report in the literature of malignant melanocytic differentiation in a high-grade urothelial carcinoma, a finding that may have important diagnostic and therapeutic implications.

scholarly journals CK20 and CK5/6 Immunohistochemical Staining of Urothelial Neoplasms: A Perspective

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Mohammed Akhtar ◽  
Sameera Rashid ◽  
Mohamed Ben Gashir ◽  
Noheir Mostafa Taha ◽  
Issam Al Bozom
Keyword(s):  
Mechanical Stability ◽  
Basal Layer ◽  
Low Grade ◽  
High Grade ◽  
Basal Cells ◽  
The Family ◽  
Prognostic Implications ◽  
Umbrella Cells ◽  
Proper Interpretation ◽  
Aggressive Clinical Behavior

Cytokeratins belong to the family of intermediate filaments. They are expressed in a highly specific manner in epithelial cells where they play a crucial role in the integrity and mechanical stability of the cells. Several types of cytokeratins have been described in normal as well as neoplastic urothelium. In the case of urothelial neoplasms expression of CK20 and CK5/6 has been shown in several studies to have diagnostic and prognostic implications. Thus, low-grade urothelial carcinoma manifests CK expression limited to the umbrella cells, while high-grade tumors usually have an expression in the entire thickness of the urothelium except for the basal layer. CK5/6 expression on the other hand is expressed in the basal cells in all low-grade and some high-grade urothelial carcinomas. Diffuse CK20 staining accompanied by loss of CK5/6-positive basal layer is usually associated with aggressive clinical behavior. Double staining of the slides for these cytokeratins may facilitate proper interpretation and correlation.

scholarly journals Interobserver reproducibility of The Paris System for Reporting Urinary Cytology

CytoJournal ◽  
2017 ◽  
Vol 14 ◽  
pp. 17 ◽  
Author(s):  
Theresa Long ◽  
Lester J. Layfield ◽  
Magda Esebua ◽  
Shellaine R. Frazier ◽  
D. Tamar Giorgadze ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Urinary Cytology ◽  
Low Grade ◽  
High Grade ◽  
Urothelial Cells ◽  
Urothelial Carcinomas ◽  
Absolute Agreement ◽  
Potential Impact ◽  
Urine Specimens

Background: The Paris System for Reporting Urinary Cytology represents a significant improvement in classification of urinary specimens. The system acknowledges the difficulty in cytologically diagnosing low-grade urothelial carcinomas and has developed categories to deal with this issue. The system uses six categories: unsatisfactory, negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells, suspicious for high-grade urothelial carcinoma, high-grade urothelial carcinoma, other malignancies and a seventh subcategory (low-grade urothelial neoplasm). Methods: Three hundred and fifty-seven urine specimens were independently reviewed by four cytopathologists unaware of the previous diagnoses. Each cytopathologist rendered a diagnosis according to the Paris System categories. Agreement was assessed using absolute agreement and weighted chance-corrected agreement (kappa). Disagreements were classified as low impact and high impact based on the potential impact of a misclassification on clinical management. Results: The average absolute agreement was 65% with an average expected agreement of 44%. The average chance-corrected agreement (kappa) was 0.32. Nine hundred and ninety-nine of 1902 comparisons between rater pairs were in agreement, but 12% of comparisons differed by two or more categories for the category NHGUC. Approximately 15% of the disagreements were classified as high clinical impact. Conclusions: Our findings indicated that the scheme recommended by the Paris System shows adequate precision for the category NHGUC, but the other categories demonstrated unacceptable interobserver variability. This low level of diagnostic precision may negatively impact the applicability of the Paris System for widespread clinical application.

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