Virus-associated neoplasms of the nasopharynx and sinonasal tract: diagnostic problems

A significant fraction of nasopharyngeal and sinonasal tumors are associated with Epstein-Barr virus (EBV) or human papillomavirus (HPV). Nasopharyngeal carcinoma (NPC) and extranodal NK/T-cell lymphoma harbor EBV in practically all cases, although a small proportion of cases of the former harbor HPV. Sinonasal inverted papillomas harbor HPV in about 25% of cases. Sinonasal squamous cell carcinomas harbor transcriptionally active HPV in about 20% of cases, and limited data suggest that this subset has a better prognosis than the HPV-negative subset. This review addresses the diagnostic issues of the EBV-associated tumors. Difficulties in diagnosis of NPC may be encountered when there are prominent crush artifacts, many admixed lymphoid cells masking the neoplastic cells, or numerous interspersed granulomas, whereas benign cellular components (epithelial crypts and germinal centers) and reactive lymphoid hyperplasia can potentially be mistaken for NPC. Immunostaining for pan-cytokeratin and/or in situ hybridization for EBER can help in confirming or refuting a diagnosis of NPC. The main diagnostic problem of extranodal NK/T-cell lymphoma is recognition of the neoplastic nature of those examples predominated by small cells or showing a mixture of cells. The identification of a destructive infiltrate (dense expansile infiltrate; angiocentric growth) and definite cytologic atypia (clear cells; many medium-sized cells) would favor a diagnosis of lymphoma, which can be supported by immunohistochemistry (most commonly CD3+, CD5-, CD56+) and in situ hybridization for EBER. In conclusion, among nasopharyngeal and sinonasal neoplasms, demonstration of EBV may aid in diagnosis, particularly NPC and extranodal NK/T-cell lymphoma. Demonstration of HPV does not have a role yet in diagnosis, although this may change in the future.