Human papillomavirus-related multiphenotypic sinonasal carcinoma: An emerging tumor type with a unique microscopic appearance and a paradoxical clinical behaviour

Human papillomavirus (HPV) is well established as a causative factor in most squamous cell carcinomas of the oropharynx (OPSCC). Indeed, a growing awareness over the past two decades that HPV-OPSCC is a distinct form of head and neck cancer has had a profound impact on diagnostic and clinical practices. The sinonasal tract is a second anatomic “hot spot” for HPV-related head and neck carcinomas, but certain pathologic features and the clinical behavior of HPV-related carcinomas at this site remain unclear. The enigmatic nature of HPV-positive sinonasal carcinomas is especially true for an emerging form recently designated as HPV-related multiphenotypic sinonasal carcinoma (HMSC). HMSC has come to the attention of the pathology community largely owing to its highly unusual microscopic appearance: it exhibits mixed salivary gland (e.g. adenoid cystic carcinoma) and squamous differentiation. At the same time, HMSC is largely unknown by the clinical community despite an unexpected clinical behavior that could affect therapy. HMSC is characterized by high grade histologic features, locally destructive growth, advanced T stage, and a propensity for local recurrence; and yet it appears to have little potential for metastatic spread or lethal behavior. This review will describe the unique pathologic features of HMSC, discuss its distinction from adenoid cystic carcinoma and squamous cell carcinoma, and draw attention to a behavior that departs from the expected clinical course of most high grade carcinomas of the head and neck.