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BACKGROUND. Undifferentiated carcinoma of the salivary glands is a rare disease, the incidence of which is highest among the Inuit of Greenland and North America. It was demonstrated to be closely related to Epstein- Barr virus (EBV) infection. However, the relation of EBV to this tumor has not been studied to any great extent here in Taiwan because of the small number of cases. METHODS. Twelve cases of undifferentiated carcinoma of the salivary glands from the period 1977-1996 were retrieved from the cancer registry at National Taiwan University Hospital. The clinical data were analyzed retrospectively based on the medical records. Eleven formalin fixed, paraffin embedded tissue sections were used for in situ hybridization with an antisense probe complementary to EBV-encoded RNA 1 (EBER1). RESULTS. Ten of 12 tumors originated from the parotid gland and 2 from the submandibular gland. The patients' ages ranged from 22 to 63 years, with an average of 38.1 years. One patient was lost to follow-up, 2 patients died of metastatic disease, and the remaining 9 patients were all alive and disease free at last follow-up. The actuarial 5-year survival rate was 79.8%. In situ hybridization demonstrated EBER1 in 9 of the undifferentiated carcinomas with lymphoid stroma, but EBER1 was not demonstrated in the other 2 tumors without lymphoid stroma. CONCLUSIONS. Undifferentiated carcinoma with lymphoid stroma of the major salivary glands is closely associated with EBV. The mainstay of treatment is surgery and postoperative radiotherapy. The outcomes in this series were good except for two elderly patients who died of rapid and progressive distant metastases.

BACKGROUND Undifferentiated carcinomas of the major salivary glands are rare malignant neoplasms of the head and neck region, and patients with these lesions have a poor prognosis. Patients with lymphoepithelial carcinoma (LEC), a specific subtype of undifferentiated carcinoma, however, have a better prognosis, and LEC seems to differ from large cell undifferentiated carcinoma (LCUC) clinically. METHODS Sixteen patients with LEC and 12 patients with LCUC were retrieved from the records of 295 patients who had malignancies of the major salivary glands. A retrospective study on clinical manifestations, treatments, long-term outcomes, and an association with Epstein–Barr virus (EBV) by EBV-encoded small RNA-1 in situ hybridization was conducted to identify their differences. RESULTS The median patient age was 44.5 years in the LEC group and 56 years in the LCUC group. At the time of presentation, patients with LCUC had a history of rapid-growing tumor and more advanced locoregional disease (Stage IV in 75% of patients with LCUC compared with 13% of patients with LEC). All 16 patients with LEC underwent curative surgery and radiotherapy, and their 5-year survival rate was 85.6%. In the LCUC group, only 7 patients were eligible to undergo radical surgery and receive radiotherapy, and their 2-year survival rate was only 36%. Age > 50 years was associated with a significantly worse prognosis for patients with LCUC. Neck metastasis and tumor size > 6 cm tended to be poor prognostic factors. Tumors were positive for harboring the EBV genome in all 16 LEC samples but in none of the LCUC samples. CONCLUSIONS The clinicopathologic features of LEC and LCUC of the major salivary glands were different. LEC was associated with EBV, and patients with LEC had a much better prognosis compared with the prognosis for patients with LCUC. Therefore, LEC should be put in an independent group and should not be included in the same category as undifferentiated carcinomas of the salivary gland. Cancer 2004. © 2004 American Cancer Society.

BACKGROUND Nasopharyngeal carcinoma (NPC) is a highly metastatic carcinoma whose consistent association with Epstein–Barr virus (EBV) has been established. Latent membrane protein 1 (LMP1), an EBV membrane protein expressed in latent infection, is considered to be the EBV oncoprotein. Matrix metalloproteinase 9 (MMP9), one of the MMP families, degrades Type IV collagen, a major component of extracellular matrix and is believed to be crucial for cancer invasion and metastasis. Although MMP9 is reported to be expressed in a variety of cancers, no reports concerning NPC have been published to date to the authors' knowledge. Recently, the authors have shown that LMP1 induces MMP9 in vitro cell line, which suggests the possibility of a mechanism in which LMP1 of EBV contributes to the metastasis and tumorigenesis of NPC by the induction of MMP9. METHODS The expressions of LMP1 and MMP9 were immunohistochemically examined in 38 NPC sections, and the relation of these proteins were statistically analyzed. The authors also analyzed the associations of these proteins with clinical features. RESULTS Both LMP1 and MMP9 proteins were predominantly immunolocalized in cancer nests. The expression of MMP9 showed a significant positive correlation with the expression of LMP1 (r = 0.75; P < 0.0001). Also, the expression of MMP9 correlated with lymph node metastasis (P = 0.0004). CONCLUSIONS The results suggest that the induction of MMP9 by LMP1 contributes to the metastatic potential of NPC. Cancer 2000;89:715–23. © 2000 American Cancer Society.