Background: In urothelial carcinoma (UCA), squamous differentiation (SqD) occurs mainly in high-grade UCA with invasion. Therefore, we sought to determine the frequency of dysplastic squamous cells (DSC) in urine specimens obtained from patients with high-grade UCA asking if DSC could serve as a surrogate marker for high-grade UCA. Design: We searched for cases with a histologic diagnosis of high-grade UCA and available concurrent cytology, yielding 93 surgical specimens (including 71 biopsies, 12 cystectomies, 5 nephrectomies, 4 ureterectomies, and 1 urethrectomy) from 68 patients with 98 urine cytology samples. Both cytology and histologic specimens were evaluated for the presence of any SqD on histology and the presence of DSC on cytology besides urothelial cells. Results: Forty-three of 68 patients (63%) had a cytologic diagnosis of ‘positive/suspicious’. Twenty-one patients (30%) had surgical specimens that showed SqD. Seventeen patients had urine cytology specimens showing DSC (25%). Thirteen of these 17 patients showed DSC with concurrent malignant urothelial cells, while 4 patients displayed only isolated DSC. Conclusion: SqD is common in patients with high-grade UCA. DSC were detected in a subset of specimens from patients with high-grade UCA. In some instances, isolated DSC on cytology may represent the only evidence of an unsampled high-grade malignancy.

Eble JN, Sauter G, Epstein JI, Sesterhenn IA: Pathology and Genetics of Tumors of the Urinary System and Male Genital Organs. Lyon, IARC Press, 2004.
Rosai J: Ackerman’s Surgical Pathology, ed 8. St Louis, Mosby Press, 1996.
Weidner N, Cote RJ, Suster S, Weiss LM: Modern Surgical Pathology, ed 1. Philadelphia, Saunders, 2003.
Veeramachaneni R, Nordberg ML, Shi R, Herrera GA, Turbat-Herrera EA: Evaluation of fluorescence in situ hybridization as an ancillary tool to urine cytology in diagnosing urothelial carcinoma. Diagn Cytopathol 2003;28:301–307.
Bubendorf L, Grilli B, Sauter G, Mihatsch MJ, Gasser TC, Dalquen P: Multiprobe fish for enhanced detection of bladder cancer in voided urine specimens and bladder washings. Am J Clin Pathol 2001;116:79–86.
Tannenbaum M: Squamous cell carcinoma and urothelial tumor of bladder. Urology 1976;7:529–530.
Lopez-Beltran A, Martin J, Garcia J, Toro M: Squamous and glandular differentiation in urothelial bladder carcinomas. Histopathology, histochemistry and immunohistochemical expression of carcinoembryonic antigen. Histol Histopathol 1988;3:63–68.
Sakamoto N, Tsuneyoshi M, Enjoji M: Urinary bladder carcinoma with a neoplastic squamous component: a mapping study of 31 cases. Histopathology 1992;21:135–141.
Billis A, Schenka AA, Ramos CC, Carneiro LT, Araujo V: Squamous and/or glandular differentiation in urothelial carcinoma: prevalence and significance in transurethral resections of the bladder. Int Urol Nephrol 2001;33:631–633.
Scosyrev E, Yao J, Messing E: Urothelial carcinoma versus squamous cell carcinoma of bladder: is survival different with stage adjustment? Urology 2009;73:822–827.
Jankovic Velickovic L, Dolicanin Z, Hattori T, Pesic I, Djordjevic B, Stojanovic M, Stankovic J, Visnic M, Stefanovic V: Divergent squamous differentiation in upper urothelial carcinoma – comparative clinicopathological and molecular study. Pathol Oncol Res 2011;17:535–539.
Erdemir F, Tunc M, Ozcan F, Parlaktas BS, Uluocak N, Kilicaslan I, Gokce O: The effect of squamous and/or glandular differentiation on recurrence, progression and survival in urothelial carcinoma of bladder. Int Urol Nephrol 2007;39:803–807.
Honma I, Masumori N, Sato E, Takayanagi A, Takahashi A, Itoh N, Tamagawa M, Sato MA, Tsukamoto T: Local recurrence after radical cystectomy for invasive bladder cancer: an analysis of predictive factors. Urology 2004;64:744–748.
Martin JE, Jenkins BJ, Zuk RJ, Blandy JP, Baithun SI: Clinical importance of squamous metaplasia in invasive transitional cell carcinoma of the bladder. J Clin Pathol 1989;42:250–253.
Bastacky S, Ibrahim S, Wilczynski SP, Murphy WM: The accuracy of urinary cytology in daily practice. Cancer 1999;87:118–128.
Beyer-Boon ME, de Voogt HJ, van der Velde EA, Brussee JA, Schaberg A: The efficacy of urinary cytology in the detection of urothelial tumours. Sensitivity and specificity of urinary cytology. Urol Res 1978;6:3–12.
Demay RM: The Art and Science of Cytopathology. Chicago, ASCP Press, 1996.
Curry JL, Wojcik EM: The effects of the current World Health Organization/International Society of Urologic Pathologists bladder neoplasm classification system on urine cytology results. Cancer 2002;96:140–145.
Owens CL, Ali SZ: Atypical squamous cells in exfoliative urinary cytology: clinicopathologic correlates. Diagn Cytopathol 2005;33:394–398.
Hattori M, Nishimura Y, Toyonaga M, Kakinuma H, Matsumoto K, Ohbu M: Cytological significance of abnormal squamous cells in urinary cytology. Diagn Cytopathol 2011, E-pub ahead of print.
Lopez-Beltran A, Requena MJ, Alvarez-Kindelan J, Quintero A, Blanca AM, Montironi R: Squamous differentiation in primary urothelial carcinoma of the urinary tract as seen by Mac387 immunohistochemistry. J Clin Pathol 2007;60:332–335.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.