Lymphoepithelial carcinoma of the parotid gland: a unique example showing p16 immunoreactivity

Lymphoepithelial carcinoma (LEC) shows characteristic histology of nesting growth of tumor cells with unclear differentiation against the lymphoid stroma background. Although rare in salivary glands, it has previously been recognized as a type of undifferentiated carcinoma but is currently clearly defined as an independent disease separate from undifferentiated carcinoma. We report a case of LEC that developed in the parotid gland and was immunohistochemically positive for p16, which suggested the causative involvement of human papillomavirus (HPV). The patient was a 38-year-old Japanese male aware of mass formation in the left parotid area for 8 years. Parotidectomy was performed and there have been no signs of recurrence or metastasis for 18 month post-operation. The tumor was histologically typical except for Epstein-Barr virus (EBV)-encoded small RNA (EBER)-negative in situ hybridization (ISH), but p16-positivity by immunohistochemistry, and also frequent contact with extended and expanded pre-existing ductal structures. Although usually strongly associated with EBV infection, the tumor could be regarded to have eventually reached completion as a LEC lesion associated with HPV infection possibly through the pathway shared with squamous cell carcinoma. EBER-ISH remains the most promising index for confirming diagnosis of LEC, but EBV-negative result alone should not prevent diagnosis of LEC.