Urothelial carcinoma with prominent squamous differentiation in the setting of neurogenic bladder: role of human papillomavirus infection

Mod Pathol. 2012 Nov;25(11):1534-42. doi: 10.1038/modpathol.2012.112. Epub 2012 Jul 6.


Squamous cell carcinomas of the urinary bladder are rare in the Western world; the majority of cases are reported in countries endemic to Schistosoma parasitic infections. Unlike squamous tumors of the uterine cervix or oropharynx, the human papillomavirus (HPV) is not commonly associated with bladder squamous cell carcinomas. We report on two cases of HPV-positive urothelial carcinomas of the urinary bladder with extensive squamous differentiation showing the typical basaloid, poorly differentiated morphology of HPV-associated tumors. These occurred in patients with neurogenic bladders who had long-standing histories of self-catheterization with tumors that tested positive for HPV by in situ hybridization. A retrospective review of our institutional database revealed four additional patients with bladder tumors showing squamous differentiation arising in the setting of neurogenic bladder. Review of these cases showed the more common well-differentiated keratinizing appearance of squamous cell carcinomas of the bladder. These tumors showed only patchy positivity for p16 immunohistochemical stain (not the diffuse strong staining seen in HPV-positive tumors), and the one tested case was negative for HPV by in situ hybridization. HPV infection and neurogenic bladder have been independently associated with increased risk of developing carcinoma in the urinary bladder; however, this is the first report of squamous tumors arising in the setting of concurrent neurogenic bladder and HPV infection. The morphology of these tumors is similar to that of other high-risk HPV-associated squamous carcinomas with a basaloid, poorly differentiated appearance and little to no keratin formation.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Biomarkers, Tumor / analysis
  • Carcinoma, Squamous Cell / chemistry
  • Carcinoma, Squamous Cell / etiology*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Carcinoma, Squamous Cell / virology
  • Cell Differentiation*
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis
  • DNA, Viral / analysis
  • Female
  • Human Papillomavirus DNA Tests
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Middle Aged
  • Papillomaviridae / genetics*
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / diagnosis
  • Papillomavirus Infections / virology
  • Risk Factors
  • Urinary Bladder / chemistry
  • Urinary Bladder / pathology*
  • Urinary Bladder / virology
  • Urinary Bladder Neoplasms / chemistry
  • Urinary Bladder Neoplasms / etiology*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy
  • Urinary Bladder Neoplasms / virology
  • Urinary Bladder, Neurogenic / therapy*
  • Urinary Catheterization / adverse effects*
  • Urothelium / chemistry
  • Urothelium / pathology*


  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral