Evaluation of Epstein-Barr virus infection in sinonasal small round cell tumors

Sinonasal undifferentiated carcinoma, olfactory neuroblastoma and malignant melanoma of the sinonasal regions are included within the category of smal l round cell tumors of the sinonasal region. It is difficult to diagnose th ese tumors on the basis of light-microscopic features alone, but, in some i nstances, immunohistochemical staining evaluating cytokeratin and S-100 pro tein, for example, is of value. On the other hand, the sinonasal region is a significant site for Epstein-Barr-virus (EBV)-related tumors, including s inonasal undifferentiated carcinoma or malignant lymphoma. Twenty-three sin onasal small round cell tumors (SSRCT) comprising 5 sinonasal undifferentia ted carcinomas, 9 olfactory neuroblastomas and 9 malignant melanomas were e valuated for the presence of EBV infection by insitu hybridization for EBV- encoded RNA, combined with immunostaining for EBV-related proteins (LMP-1 a nd EBNA2). Furthermore, 55 SSRCT comprising 37 sinonasal undifferentiated c arcinomas, 9 olfactory neuroblastomas, and 9 malignant melanomas were exami ned for the presence of cytokeratins (AE1/ AE3 and CAM5.2), S-100 protein a nd p53 protein using immunohistochemical staining. According to insitu hybr idization for detecting EBV-encoded RNA 1 (EBER1), all of the sinonasal und ifferentiated carcinomas showed clear, intense hybridization signals locali zed over the nuclei of the tumor cells and, in 3 out of 9 (33.3%) malignant melanomas, hybridization signals were also recognized. However, none of th e olfactory neuroblastomas revealed hybridization signals. Immunohistochemi cally, 4 out of 5 (80%) sinonasal undifferentiated carcinomas were positive for LMP-1, whereas only 2 out 9 (22.2%) malignant melanomas and no olfacto ry neuroblastomas were positive. With regard to EBNA2, sinonasal undifferen tiated carcinomas, malignant melanomas and olfactory neuroblastomas were al l negative. Out of 37 sinonasal undifferentiated carcinomas 35 (94.6%) show ed a diffuse positive immunoreaction for AE1/AE3, whereas neither olfactory neuroblastoma nor malignant melanoma revealed a positive reaction. All 9 m alignant melanomas and 6 out of 9 olfactory neuroblastomas (75%) were posit ive for S-100 protein, whereas only 6 cases of sinonasal undifferentiated c arcinomas (19.4%) were positive. As for p53 protein, 16 of 37 sinonasal und ifferentiated carcinomas (43.2%) were positive, whereas neither olfactory n euroblastoma nor malignant melanoma revealed ally positive reaction. The ab ove results suggest that EBV infection is closely associated with sinonasal undifferentiated carcinomas, and that some malignant melanomas may also ha ve a relationship with its infection. For the differential diagnosis of SSR CT, it is important to evaluate EBV infection along with immunohistochemica l staining for cytokeratins and S-100 protein. The overexpression of p53 pr otein was found to be related to the oncogenesis of sinonasal undifferentia ted carcinoma; however, there was no association between its overexpression and malignant melanoma or olfactory neuroblastoma.