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

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.