Expression of p16 in Sinonasal Undifferentiated Carcinoma (SNUC) Without Associated Human Papillomavirus (HPV)

Sinonasal undifferentiated carcinoma (SNUC) is an uncommon and highly aggressive neoplasm of the paranasal sinuses and nasal cavity. Its undifferentiated histologic appearance often requires immunohistochemical studies to distinguish it from other high-grade neoplasms. Due to the rarity of SNUC, its immunohistochemical staining profile has been incompletely characterized, and little work has been done on its expression of the markers for human papillomavirus (HPV). Our objective is to expand our knowledge of its immunophenotype and its association with HPV in order to define markers with mechanistic potential in the disease process, or of possible therapeutic importance. A total of five patients (one woman and four men) with SNUC, ranging in age from 26 to 75 years (mean 56.8 years) were compared to five patients (five men) with poorly differentiated squamous cell carcinoma (PDSCC), ranging in age from 53 to 75 years (mean 62.2 years). PDSCC was chosen as a control, given its well-reported immunohistochemical profile and negativity for HPV markers. The immunohistochemical panel included: CK7, CK19, EMA, NSE, chromogranin, p53, CK5/6, p63, CK14, S100, HMB-45, desmin, muscle specific actin, and CD45. Additionally, tests for p16, EBV, and HPV (subtypes 6, 11 16, 18) were performed. The diagnosis of SNUC was confirmed in all cases by histology and immunohistochemical stains. An interesting finding of strong diffuse positivity for p16 was noted in all SNUC cases, compared to only two of five PDSCC that were positive for p16. HPV DNA was not detected in any SNUC cases or any cases of PDSCC. All SNUC cases demonstrated over expression of p16 in the absence of HPV DNA expression. This may represent residual epithelial p16 staining, which is normally present in the sinonasal tract. Due to the rarity of SNUC, more cases will need to be evaluated to confirm the absence of HPV DNA.