Anal canal neuroendocrine carcinoma associated with squamous intraepithelial neoplasia: a human papillomavirus 18-related lesion

Pathol Int. 2012 May;62(5):356-9. doi: 10.1111/j.1440-1827.2012.02800.x. Epub 2012 Mar 28.


Neuroendocrine carcinoma (NEC) of the anal canal is exceedingly rare and its histogenesis is poorly understood. We present a case of small-cell NEC of the anal canal in a 70-year-old woman. The NEC appeared as a submucosal tumor at the dentate line and was associated with squamous intraepithelial neoplasia (SIN). The NEC was positive for neuroendocrine markers including synaptophysin, chromogranin A and CD56, whereas the SIN component did not express any of these markers. Both components exhibited p16 overexpression. A PCR analysis revealed that both the SIN and NEC components were positive for human papillomavirus (HPV) 18 DNA. Our observations imply that SIN may be a precursor of anal canal NEC and that HPV18 may play an important role in the histogenesis of anal canal NEC, similar to its role in cervical NEC.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anus Neoplasms / metabolism
  • Anus Neoplasms / pathology*
  • Anus Neoplasms / virology
  • Biomarkers, Tumor / metabolism
  • Bone Neoplasms / secondary
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology*
  • Carcinoma in Situ / virology
  • Carcinoma, Neuroendocrine / metabolism
  • Carcinoma, Neuroendocrine / secondary*
  • Carcinoma, Neuroendocrine / virology
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / secondary*
  • Carcinoma, Squamous Cell / virology
  • DNA, Viral / genetics
  • Fatal Outcome
  • Female
  • HeLa Cells
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / isolation & purification*
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / secondary
  • Neoplasm Proteins / metabolism
  • Neoplasms, Multiple Primary
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / pathology*
  • Papillomavirus Infections / virology


  • Biomarkers, Tumor
  • DNA, Viral
  • Neoplasm Proteins