The LMP1 gene isolated from Russian nasopharyngeal carcinoma has no 30-bp deletion.

The Epstein-Barr virus (EBV) is tightly linked to the induction of undifferentiated nasopharyngeal carcinoma (NPC), a tumour endemic in certain areas of southeast Asia. The LMP1 gene encoded by EBV is a classical oncogene due to its ability to transform rodent fibroblasts. LMP1 is absolutely essential for transformation of B cells by the virus and is one of the few EBV genes found to be expressed in NPC. It was originally shown that the LMP1 gene from NPC harbours a deletion of 30 bp in the 3' part of the gene. However, this deletion is also present in the virus spread in healthy people of the areas endemic for NPC and also in other EBV-positive tumours as well as in healthy carriers. We isolated and sequenced the LMP1 gene obtained from tissue of 7 Russian patients with NPC and 1 German patient with an NPC-like tumour of the parotid gland (PG) and compared them with the LMP1 gene isolated from peripheral blood lymphocytes (PBLs) of 6 Russian and 4 German healthy EBV-positive carriers. Neither the Russian NPC cases nor the German NPC-like tumour harboured an LMP1 gene with the 30-bp deletion, while 1 Russian and 2 German carriers contained the LMP1 gene with the 30-bp deletion. In addition, the LMP1 gene isolated from PBLs of the German patient was virtually identical to the gene isolated from the primary tumour. Functional analysis showed no correlation between the presence or absence of the 30-bp deletion and the level of induction of the transcription factors NFkappaB and jun/AP-1 caused by LMP1. These data indicate that the 30-bp deletion is not a factor predisposing for NPC. Comparison of the DNA sequences revealed that the LMP1 genes present in the NPCs most likely represent the "strain" persisting in the general population.

Epidemiology of Warthin's tumour of the parotid gland in an Asian population.

BACKGROUND: Recent studies have documented a number of changing demographic features in the occurrence of Warthin's tumour (adenolymphoma) of the parotid gland. In order to analyse its epidemiology in an Asian population, a retrospective study was performed on all parotid neoplasms (n = 289) operated on between 1988 and 1998. PATIENTS AND METHODS: A total of 209 consecutive patients were selected for study, 136 with pleomorphic adenomas (one bilateral) and 73 with Warthin's tumours (seven bilateral). Patients were analysed with regard to tumour incidence, age, sex and race. Smoking as an aetiological factor in the development of Warthin's tumour was also studied. RESULTS: Warthin's tumour formed 25 per cent of parotid tumours and its ratio to pleomorphic adenomas was 1 : 1.9. Multicentricity was found in 14 patients (19 per cent). The male : female ratio for Warthin's tumours was 4.6 : 1. The proportion of Warthin's tumours did not show any increasing trend relative to pleomorphic adenomas. The racial distribution of Warthin's tumours showed an increased incidence among Chinese and a reduced incidence among Malays and Indians. The adjusted odds ratio for sex and age favouring an association between smoking and Warthin's tumour was 39.5 (95 per cent confidence interval 10.5-149. 0; P < 0.0001). CONCLUSION: The incidence of Warthin's tumour is considerable among Asians although there is still male predominance. There is no rising incidence of Warthin's tumour; the trend parallels the declining smoking rate in the population. The lower incidence among ethnic groups with dark skin seems to suggest concomitant genetic factors other than environmental factors alone in histogenesis. Smokers have a 40-fold greater risk than non-smokers of developing a Warthin's tumour.

Lymphoepithelial carcinoma of salivary glands.

BACKGROUND: Malignant lymphoepithelial lesions (MLEL) or lymphoepithelial carcinoma or undifferentiated carcinoma with lymphoid stroma, is a rare but unique malignancy of the major salivary glands. There is an exceptionally high incidence in Eskimos and native Greenlanders, but it has never been reported in the Arab population. We report the first case from Saudi Arabia in the native Arabs. These are unencapsulated tumors with a strong tendency to metastasize to the regional lymph nodes. METHODS: We reviewed English and Arabic literature and found the total number of reported cases of MLEL to be 103 with predominant involvement of the parotid gland. Parotidectomy followed by neck dissection and radiotherapy was performed, with a survey of the nasopharynx and EB virus titer. RESULTS: The patient underwent radical neck dissection followed by radiation after developing the neck metastasize. Three years to date he remains in remission with no distant or regional metastases. CONCLUSION: Malignant lymphoepithelial lesions of the salivary gland are unencapsulated tumors with poorly differentiated epithelial cells scattered throughout fibrolymphocytic stroma. They have a strong tendency to metastasize to the regional lymph nodes with predominant involvement of the parotid gland. They are commonly associated with Epstein-Barr virus infection. The majority of them are radiosensitive. Combination therapy with surgery and radiation is desirable to control the disease. We recommend complete surgical excision with neck dissection followed by postoperative radiotherapy to the local site as well as to the neck as treatment of choice.

Undifferentiated carcinoma of the parotid gland in a white patient: detection of Epstein-Barr virus by in situ hybridization.

Paraffin sections of an undifferentiated salivary gland carcinoma of lymphoepithelioma type, arising in a white (Greek) patient and confirmed by immunohistochemistry, were examined for the presence of Epstein-Barr virus (EBV), using in situ hybridization to detect EBV-specific EBER1 message. Epstein-Barr virus was detected in malignant epithelial cells, but was not found in lymphoid stroma or in residual benign salivary epithelium. These results confirm the existence of an association between EBV and tumor cells of undifferentiated carcinoma of parotid gland. This is the first demonstration of EBV in a salivary gland lymphoepithelioma arising in a non-Eskimo, white patient. This finding suggests that the association of EBV with undifferentiated salivary gland carcinoma may exist in geographic regions remote from Greenland.

Lymphoepithelial carcinoma of the parotid gland.

BACKGROUND: Primary lymphoepithelial carcinoma of the parotid gland is a rare tumor with an increased incidence among Eskimos and Orientals. We reviewed our experience with parotid lymphoepithelial carcinoma and investigated its pathophysiology and possible association with Epstein-Barr virus. METHODS: We performed a retrospective review of records of patients diagnosed with lymphoepithelial carcinoma of the parotid gland. RESULTS: We identified two women of Hispanic origin diagnosed with primary lymphoepithelial carcinoma of the parotid gland. In one of the cases, the carcinoma was intimately associated with a benign lymphoepithelial lesion. In both cases, there was no demonstration of Epstein-Barr virus. CONCLUSION: Primary lymphoepithelial carcinoma of the parotid gland may arise from malignant transformation of a benign lymphoepithelial lesion.

Epstein-Barr virus (EBV) infection and undifferentiated carcinoma of the parotid gland in Caucasian patients.

The Epstein-Barr virus (EBV) has been detected in certain types of lymphoma and some epithelial neoplasms such as nasopharyngeal lymphoepithelioma and occasional undifferentiated carcinomas in several organs including the salivary glands. However, clonal EBV genomes have been detected in undifferentiated carcinomas of the parotid gland exclusively in Alaskan natives and Eskimos, both groups being at the highest risk for nasopharyngeal carcinoma. The authors investigated the possibility that EBV may be present in undifferentiated parotid carcinomas in Caucasian subjects. To test this hypothesis, in situ hybridization (ISH) technique with biotinylated EBV-DNA probes was utilized on routinely processed, paraffin-embedded tissues from 7 cases of undifferentiated carcinomas of the parotid gland. EBV genomes were demonstrated in the cytoplasm of tumor cells from 3 out of 7 specimens tested. Surprisingly, EBV genomes were found in 3 out of 5 (60%) undifferentiated carcinomas that had developed in patients with a history of a long-persisting asymptomatic parotid mass, which had suddenly increased in size. Conversely, none of the undifferentiated carcinomas with continuous and rapid growth studied was found to be positive for EBV-DNA by ISH technique. Taken together, these data might suggest a possible role of EBV in the transformation of benign parotid gland lesions into malignant and aggressive undifferentiated carcinoma of the parotid gland, the so-called carcinoma expleomorphic adenoma.

Warthin's tumor: a 40-year experience at The Johns Hopkins Hospital.

Warthin's tumor previously has been thought to occur much more commonly in men than in women and rarely in African Americans. One hundred thirty-two cases of Warthin's tumor treated at The Johns Hopkins Hospital from 1952 to 1992 were retrospectively reviewed. There were 90 (68%) men and 42 (32%) women, with an overall man-to-woman ratio of 2.2:1. The number and percentage of women with Warthin's tumor increased over each consecutive decade: 1952 to 1962, 5 (21%); 1963 to 1972, 6 (29%); 1973 to 1982, 11 (31%); and 1983 to 1992, 20 (39%). A positive smoking history was found in 88% of the men and in 89% of the women with a Warthin's tumor. Eleven (8%) African Americans and 1 (0.75%) Asian American were diagnosed to have a Warthin's tumor. Also, the incidence of African Americans with a Warthin's tumor increased over each decade: 0 (0%), 1 (4.8%), 2 (5.5%), and 8 (16%). This study's results indicate a progressive increase in the occurrence of this tumor in women and in African Americans and a higher overall incidence in African Americans than previously reported.