Stanford School of Medicine

Surgical Pathology Criteria

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Squamous Cell Carcinoma of the Bladder


  • Carcinoma of the bladder with pure squamous differentiation

Diagnostic Criteria

  • WHO and most investigators require pure squamous differentiation for this diagnosis
    • AFIP requires 80%
    • If any component of urothelial differentiation is present, designate as urothelial carcinoma with squamous differentiation
      • It is not clear that there is any clinical outcome difference to this distinction between pure and partial squamous differentiation (Ehdaie 2012)
  • Squamous differentiation requires any of the following
    • Individual cell keratinization
    • Keratin pearls
    • Intercellular bridges
  • May be accompanied by adjacent bland squamous metaplasia
    • It is not clear what role this plays as a precursor
  • High grade squamous carcinoma may be impossible to distinguish from high grade urothelial carcinoma as differentiation is lost

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 10/28/12

Supplemental studies


  • Squamous differentated cells reported to be CK14 positive, CD20 negative and urothelial cells the reverse
    • We have not used immunohistochemistry for this distinction
    • Both are p63 positive

Differential Diagnosis

  • Squamous cell carcinoma is distinguished from squamous metaplasia by cytologic atypia and invasion

Grading / Staging


  • Typically graded as poor, moderate, well
    • No data to support significance of grading
    • Poorly differentiated squamous carcinoma may be impossible to distinguish from high grade urothelial carcinoma


  • Same as urothelial carcinoma


  • Pure squamous carcinoma is most common in areas of exposure to Schistosoma hematobium
  • Most cases in other regions are associated with spinal cord injuries, indwelling catheters, lithiasis, chronic infection
    • Most of these cases show partial squamous differentiation
  • Evidence is conflicting but it appears thta both have a worse prognosis than usual urothelial carcinoma

Classification / Lists

Flat Lesions of the Urinary Bladder

Papillary Lesions of the Urinary Bladder

Subtypes of High Grade Urothelial Carcinoma

Inverted Lesions of the Urinary Bladder

Glandular Lesions of the Urinary Bladder


  • Murphy WM, Grignon DJ, Perlman EJ. Tumors of the Kidney, Bladder and Related Urinary Structures, Atlas of Tumor Pathology, AFIP Fourth Series, Fascicle 1, 2004
  • Eble JN, Sauter G, Epstein JI, Sesterhenn IA eds. World Health Organization Classification of Tumors. Pathology and genetics of tumors of the Urinary System and Male Genital Organs. IARC Press: Lyon 2004.
  • Rogers CG, Palapattu GS, Shariat SF, Karakiewicz PI, Bastian PJ, Lotan Y, Gupta A, Vazina A, Gilad A, Sagalowsky AI, Lerner SP, Schoenberg MP. Clinical outcomes following radical cystectomy for primary nontransitional cell carcinoma of the bladder compared to transitional cell carcinoma of the bladder. J Urol. 2006 Jun;175(6):2048-53;
  • Black PC, Brown GA, Dinney CP. The impact of variant histology on the outcome of bladder cancer treated with curative intent. Urol Oncol. 2009 Jan-Feb;27(1):3-7.
  • Abol-Enein H, Kava BR, Carmack AJ. Nonurothelial cancer of the bladder. Urology. 2007 Jan;69(1 Suppl):93-104.
  • Lopez-Beltran A, Cheng L. Histologic variants of urothelial carcinoma: differential diagnosis and clinical implications. Hum Pathol. 2006 Nov;37(11):1371-88.
  • Ehdaie B, Maschino A, Shariat SF, Rioja J, Hamilton RJ, Lowrance WT, Poon SA, Al-Ahmadie HA, Herr HW. Comparative outcomes of pure squamous cell carcinoma and urothelial carcinoma with squamous differentiation in patients treated wit radical cystectomy. J Urol. 2012 Jan;187(1):74-9.
  • Shanks JH, Iczkowski KA. Divergent differentiation in urothelial carcinoma and other bladder cancer subtypes with selected mimics. Histopathology. 2009
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