OBJECTIVE. Our purposewas to depict the characteristics of the global vasculatureof cervical lymphadenopathies and to clarify the efficiency of Doppler spectral analysis and power Doppler sonography in the differential diagnosis.SUBJECTS AND METHODS. Prospectively, 289 lymph nodelesionsunderwentDop pier flow studiesand were groupedas metastasis, lymphoma,tuberculosis, and benignlym phadenopathies. Sonographic assessmentsincluded vascular pattern and vascular density (presentedas vascularityindex) asrevealedby power Doppler sonography. Vascularresistive index and pulsatility index were assessed by at least three flow samplings. Values of both the highest and the lowest resistancewere analyzed. Vascularity index, resistive index, pulsatility index, nodal size, and age were correlated. RESULTS. Most benign lymphadenopathies (87%), tuberculous lymphadenopathies (72%),and lymphomas (7 1%) revealed an avascular or hilar vascular pattern. Vascular patterns of most metastaticlymphadenopathies(90%) were of spotted(26%). peripheral (I 1%). or mixed (53%) type. The vascularity indexes of metastatic lymphadenopathy (mean, 0. 176) and lymphoma (mean, 0.122) were significantly higher than those of tuberculous and benign lymphadenopathy (mean, 0.054 and 0.042, respectively). In vascular resistance studies, the highest pulsatility index andresistiveindex in metastaticlymphadenopathystatisticallyexceededthoseofbenign lymphad enopathy,whereasno difference was found in the lowest values.Negativecorrelation was found between the vascularity index of meta.static lesions and their lowest vascular resistance, and posi tive correlation wasfound betweenvascularityindex andnodal sizein benign lymphadenopathies. CONCLUSION.In additionto vascularresistanceassessed traditionallywith Doppler spectral analysis, vascular pattern and vascular density assessedwith power Doppler sonogra phy can better differentiate the nature of lymphadenopathies. Our study investigatedthe usefulnessof color Doppler spectral analysis and power Doppler sonography for differentiation of vim ous cervical lymphadenopathies (metastasis, lymphoma, tuberculosis, and other benign lymphadenopathies)in terms of vascularresis tance, vascular pattern, and vascular density.The clinical and biologic implications of these vascularparameterswere also investigated.

Vascular leiomyoma usually presents as a small, painless mass. Auricle, nose, lip, and neck are the most common sites of occurrence. Unusually large vascular leiomyomas are developed in the deep space of the neck. Imaging study or cytological examination is not helpful for diagnosis. Histological classification is not necessary. Simple excision yields excellent results.

The BARF1 gene is located in the BamHI-A fragment of the Epstein-Barr virus (EBV) genome, encodes 221 amino acids, and has activity as an oncogene. Several reports have demonstrated that BARF1 is expressed in the tissues of various EBV-associated epithelioid malignancies. However,BARF1 is thought to be a lytic gene, since its expression is induced upon induction of the lytic cycle in Burkitt's lymphoma cell lines. Therefore, the possibility cannot be excluded that BARF1 expression in EBV-associated epithelioid malignancies reflects spontaneous induction of the lytic cycle in carcinoma cells. The present study aimed to clarify whether BARF1 was expressed as a latent gene or a lytic gene in epithelioid malignancies. Quantitative real-time RT-PCR assay revealed that BARF1 was highly expressed in nasopharyngeal carcinoma (NPC) and EBV-positive gastric carcinoma tissues in the absence of expression of lytic genes. On the other hand, BARF1 protein was detectable only in two of seven NPC tissue samples by immunoblot analysis. Analysis of BARF1-transfected CNE1 cells revealed that BARF1 was quickly secreted into culture medium and was hardly detectable in the cell lysate, which would account for why some NPC tissues were negative for BARF1 protein expression even though they were strongly positive forBARF1 expression at the transcriptional level. The present findings indicate that BARF1 is expressed in NPC and EBV-positive gastric carcinoma tissues as a latent gene and suggest that BARF1 plays a role in the pathogenesis of these malignancies.

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.

Nasopharyngeal carcinoma (NPC) is distinctive in head and neck carcinomas for its close association with Epstein-Barr virus and its highly metastatic nature. Up-regulation of cell motility is essential for enhancement of metastatic potential. The expression of c-Met proto-oncogene, a high-affinity receptor for hepatocyte growth factor/scatter factor, has been reported to correlate with metastatic ability of the tumor cell. We observed close association of c-Met expression with cervical lymph node metastasis (P = 0.0272) in 39 NPC specimens studied immunohistochemically. Epstein-Barr virus-encoding latent membrane protein-1 (LMP-1) is a primary oncogene and is suggested to enhance the metastatic property of NPC. Previously, we reported that LMP-1 enhanced the motility of Madin-Darby canine kidney (MDCK) epithelial cells that was mediated by activation of Ets-1 transcription factor. Therefore, we examined the interrelationships of LMP-1, Ets-1, and c-Met. In immunohistochemical studies, the expression of LMP-1, Ets-1, and c-Met correlated significantly with each other in NPC (LMP-1 versus Ets-1, P < 0.0001; Ets-1 versus c-Met, P = 0.0012; LMP-1 versus Met, P = 0.0005). Transfection of LMP-1-expressing plasmid in MDCK cells induced c-Met protein expression. The c-Met protein was also induced by Ets-1 expression, and induction of c-Met by LMP-1 was suppressed by introducing a dominant-negative form of Ets-1 in LMP-1-expressing MDCK cells. These results suggest that LMP-1 induces c-Met through the activation of Ets-1, which may contribute in part to the highly metastatic potential of NPC.

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.

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The good 5-year survival of N3 disease supports the effectiveness of induction MEPFL in the primary treatment of advanced NPC. Further investigation to incorporate concurrent chemoradiotherapy is warranted.