There is a strong association Protein Tyrosine Kinase inhibitor between squamous cell carcinoma

of the anus and high-risk subtypes of HPV, most notably HPV-16 and HPV-18 (2). Infection with HIV is a prominent risk factor for the development of squamous cell carcinoma of the anus, and the prevalence of anal cancer in patients with HIV infection is significantly higher than that of the general population (3). In contrast Inhibitors,research,lifescience,medical to squamous cell carcinoma, small cell carcinoma of the anal canal is extremely rare. A recent study that collected data from population-based registries covering approximately 83% of the U.S. population identified only 210 cases of small cell carcinoma of the anus between 1998 and 2003 (4). While small cell carcinomas of the head and neck and the Inhibitors,research,lifescience,medical cervix have known associations with HPV (5,6), the relationship between HPV and small cell carcinoma of the anus is largely undefined to date. There is data, however, to suggest that a relationship between these entities may exist. A recent study by Cimino-Mathews et al. aimed to determine the prevalence of high-risk HPV (including HPV-16 and HPV-18) in the tumors of 16 patients with small cell Inhibitors,research,lifescience,medical carcinoma of the anus (n=5) or rectum (n=11) at Johns Hopkins University. The investigators found that 100% of tumors in both the anus and rectum were strongly positive for high-risk Inhibitors,research,lifescience,medical HPV by immunohistochemistry

(using nuclear and cytoplasmic p16 as a surrogate marker) and that 100% of the anal tumors and 82% of the rectal tumors were positive for high-risk HPV by in situ hybridization (7). These results suggest that HPV infection is a component of the pathogenesis of small cell carcinoma of the anus. In addition to the cases identified in the Johns Hopkins study, five Inhibitors,research,lifescience,medical individual case reports of small cell carcinoma of the anus have been published within the English language literature to date (Table 1) (8-12). Notably, ours is the first report of a patient with

small cell carcinoma of the anus in the setting of previously identified squamous dysplasia and/or CIS, although there is one additional case report of a patient with Rutecarpine neuroendocrine carcinoma of the anus with associated squamous intraepithelial neoplasia and molecular studies positive for HPV-18 (13). Our patient’s clinical course, in conjunction with the data from Cimino-Mathews et al., suggest that, in a similar manner to that of squamous cell carcinoma, small cell carcinoma of the anus may develop linearly from squamous dysplasia and CIS. Table 1 Individual case reports of patients with small cell carcinoma of the anal canal While the relationship between HIV and squamous cell carcinoma of the anus is well established, the role of HIV infection in the pathogenesis of small cell carcinoma of the anus is unclear.