Sinonasal undifferentiated carcinoma: immunohistochemical profile and lack of EBV association

The role of Epstein-Barr virus (EBV) in the development of sinonasal undifferentiated carcinoma (SNUC) remains unresolved. Reports of EBV-positivity in SNUC may reflect inclusion of lymphoepithelioma-like carcinomas within this group. In addition, SNUC have been incompletely characterized immunohistochemically, and their undifferentiated appearance often requires such ancillary studies to aid in their distinction from other high-grade neoplasms. To address these two issues, 25 cases of SNUC diagnosed between the years 1983 and 1999 were selected from our files. EBER in situ hybridization (ISH) was performed on the paraffin-embedded tissue by using 3H-labeled EBER-1 RNA probes. Neoplasms with sufficient tissue (22 of 25) were evaluated immunohistochemically for Ki-67, p53, chromogranin, synaptophysin, placental alkaline phosphatase (PLAP), CD99, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), neuron-specific enolase (NSE), and latent membrane protein-1 (LMP-1). The median patient age was 58 years (range, 20-81 years), with a male-to-female ratio of approximately 3:1. The most common tumor location was the nasal cavity (18 cases), followed by the ethmoid and maxillary sinuses. Median survival was 18 months. All 25 tumors were negative for EBER-I by ISH. Ki-67 was negative in one case, 1+ in nine, 2+ in six, 3+ in five, and 4+ in one. P53 was negative in nine, 1+ in five, 2+ in two, 3+ in none, and 4+ in six. CD99 expression was strongly positive in 3 of 22 (14%) and completely negative in the remainder. Variably intense focal staining for EMA was present in 4 of 22 (18%). NSE faintly stained 4 of 22 (18%). Chromogranin, synaptophysin, PLAP, CEA, and LMP-1 were negative (0 of 22). Our results suggest that EBV does not play a role in the development of SNUC. Strict histologic criteria are necessary to avoid confusion with lymphoepithelioma-like carcinoma or other high-grade malignancies in this region. The finding of occasional CD99-positive cases adds SNUC to the growing list of CD99-positive neoplasms.