Sinonasal undifferentiated carcinoma,
olfactory neuroblastoma and
malignant melanoma of the sinonasal regions are included within the category of small round cell
tumors of the sinonasal region. It is difficult to diagnose these
tumors on the basis of light-microscopic features alone, but, in some instances, immunohistochemical staining evaluating
cytokeratin and
S-100 protein, for example, is of value. On the other hand, the sinonasal region is a significant site for Epstein-Barr-virus (EBV)-related
tumors, including
sinonasal undifferentiated carcinoma or
malignant lymphoma. Twenty-three sinonasal small round cell
tumors (SSRCT) comprising 5 sinonasal
undifferentiated carcinomas, 9
olfactory neuroblastomas and 9
malignant melanomas were evaluated for the presence of
EBV infection by in situ hybridization for EBV-encoded
RNA, combined with immunostaining for EBV-related
proteins (LMP-1 and EBNA2). Furthermore, 55 SSRCT comprising 37 sinonasal
undifferentiated carcinomas, 9
olfactory neuroblastomas, and 9
malignant melanomas were examined for the presence of cytokeratins (AE1/ AE3 and
CAM5.2),
S-100 protein and p53
protein using immunohistochemical staining. According to in situ hybridization for detecting EBV-encoded
RNA 1 (
EBER1), all of the sinonasal
undifferentiated carcinomas showed clear, intense hybridization signals localized 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 the
olfactory neuroblastomas revealed hybridization signals. Immunohistochemically, 4 out of 5 (80%) sinonasal
undifferentiated carcinomas were positive for LMP-1, whereas only 2 out 9 (22.2%)
malignant melanomas and no
olfactory neuroblastomas were positive. With regard to EBNA2, sinonasal
undifferentiated carcinomas,
malignant melanomas and
olfactory neuroblastomas were all negative. Out of 37 sinonasal
undifferentiated carcinomas 35 (94.6%) showed a diffuse positive immunoreaction for AE1/AE3, whereas neither
olfactory neuroblastoma nor
malignant melanoma revealed a positive reaction. All 9
malignant melanomas and 6 out of 9
olfactory neuroblastomas (75%) were positive for
S-100 protein, whereas only 6 cases of sinonasal
undifferentiated carcinomas (19.4%) were positive. As for p53
protein, 16 of 37 sinonasal
undifferentiated carcinomas (43.2%) were positive, whereas neither
olfactory neuroblastoma nor
malignant melanoma revealed any positive reaction. The above results suggest that
EBV infection is closely associated with sinonasal
undifferentiated carcinomas, and that some
malignant melanomas may also have a relationship with its
infection. For the differential diagnosis of SSRCT, it is important to evaluate
EBV infection along with immunohistochemical staining for cytokeratins and
S-100 protein. The overexpression of p53
protein was found to be related to the
oncogenesis of
sinonasal undifferentiated carcinoma; however, there was no association between its overexpression and
malignant melanoma or
olfactory neuroblastoma.