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.

Consensus statement on the pathology of IgG4-related disease.

IgG4-related disease is a newly recognized fibro-inflammatory condition characterized by several features: a tendency to form tumefactive lesions in multiple sites; a characteristic histopathological appearance; and-often but not always-elevated serum IgG4 concentrations. An international symposium on IgG4-related disease was held in Boston, MA, on 4-7 October 2011. The organizing committee comprising 35 IgG4-related disease experts from Japan, Korea, Hong Kong, the United Kingdom, Germany, Italy, Holland, Canada, and the United States, including the clinicians, pathologists, radiologists, and basic scientists. This group represents broad subspecialty expertise in pathology, rheumatology, gastroenterology, allergy, immunology, nephrology, pulmonary medicine, oncology, ophthalmology, and surgery. The histopathology of IgG4-related disease was a specific focus of the international symposium. The primary purpose of this statement is to provide practicing pathologists with a set of guidelines for the diagnosis of IgG4-related disease. The diagnosis of IgG4-related disease rests on the combined presence of the characteristic histopathological appearance and increased numbers of IgG4⁺ plasma cells. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. We propose a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy. Tissue IgG4 counts and IgG4:IgG ratios are secondary in importance. The guidelines proposed in this statement do not supplant careful clinicopathological correlation and sound clinical judgment. As the spectrum of this disease continues to expand, we advocate the use of strict criteria for accepting newly proposed entities or sites as components of the IgG4-related disease spectrum.