Detection of Epstein-Barr virus in Hodgkin's disease occurring in an Oriental population.

Like Burkitt's lymphoma, the strength of association of Epstein-Barr virus (EBV) with Hodgkin's disease occurring in different populations and clinical settings is highly variable, being 30% to 50% in Western countries, nearly 100% in Third World countries like Peru and Honduras, and nearly 100% in patients seropositive for human immunodeficiency virus. Data on the Oriental populations are very limited. Therefore, the current study was performed on the Chinese population of Hong Kong, where the incidence of Hodgkin's disease is low and EBV seroconversion occurs early in life. Twenty-three consecutive samples of Hodgkin's disease collected from 18 male and five female patients over a 12-year period were studied. The first age peak occurred in the second decade of life, and the second peak in the seventh decade. Using the sensitive and specific EBV-encoded RNAs (EBERs) in situ localization technique, positive labeling of the Reed-Sternberg cells and their variants was detected in five of five samples (100%) of mixed cellularity, nine of 16 samples (56%) of nodular sclerosing, one of one sample (100%) of lymphocyte depleted, and none of one sample (0%) of nodular lymphocyte predominant Hodgkin's disease. Further analysis of the data by age group yielded the following results: four of five (80%) for age younger than 15 years, three of nine (33%) for age 15 to 49, and eight of nine (89%) for age 50 or higher, confirming the reported strong association of EBV with Hodgkin's disease at the extremes of life. The overall positivity rate was 65%, which was intermediate between that reported in the Western populations and that in the Third World countries. These findings can be explained by the epidemiological pattern of Hodgkin's disease in Hong Kong, in which the first age peak is left-shifted to a younger age compared with that of Western populations (but not as early as that observed in Third World countries), moving the peak toward an age bracket in which Hodgkin's disease shows stronger association with EBV.

Specific association of Epstein-Barr virus with lymphoepithelial carcinoma among tumors and tumorlike lesions of the salivary gland.

The Epstein-Barr virus (EBV)-encoded RNAs in situ localization procedure is a convenient, highly sensitive, and highly specific technique that is applicable to routinely fixed, paraffin-embedded tissue sections; this technique can be used for the study of the association and, hence, the possible causal role of EBV in tumors. This study was performed to elucidate whether EBV plays a role in the pathogenesis of tumors that arise in the salivary glands, since the salivary gland is known to be a reservoir for EBV replication. Cases that were selected included 61 examples of various benign and malignant neoplasms, as well as tumorlike conditions of the major and minor salivary glands. Only the five cases of lymphoepithelial carcinoma (so-called malignant lymphoepithelial lesion) and the single case of metastatic nasopharyngeal undifferentiated carcinoma showed staining with EBV-encoded RNAs, whereas negative findings were found in all of the other cases. In the cases with positive results, all of the neoplastic epithelial cells showed strong nuclear signals, but the lymphoid cells were negative. The consistent association of EBV with lymphoepithelial carcinoma of the salivary gland suggests that the virus probably plays a causal role in this tumor, at least in the Asian population, whereas there is no evidence for a causal role of EBV in other primary tumors of the salivary gland.

Detection of Epstein-Barr viral RNA in malignant lymphomas of the upper aerodigestive tract.

Recent studies have suggested a probable etiologic association between Epstein-Barr virus (EBV) and nasal lymphomas, irrespective of geographic location. This study was performed to investigate the strength of association of EBV with non-Hodgkin's lymphomas of the upper aerodigestive tract, based on a large series of cases that have been thoroughly immunophenotyped on frozen tissues. A sensitive in situ hybridization technique was used to detect EBV encoded RNA (EBER) in paraffin sections. Among 30 cases of nasal/nasopharyngeal T-cell lymphoma, 25 (83.3%) were EBER-positive. In the positive cases, most of the neoplastic cells showed strong nuclear signals. Further analysis of this group of tumors showed that all 21 cases (100%) with a CD56+ CD3-phenotype were EBER positive, whereas four of nine cases (44.4%) with a CD56-negative immunophenotype were positive. Only one of 10 cases (10%) of nasal/nasopharyngeal B-cell lymphoma was EBER positive; the positive case was a diffuse mixed-cell lymphoma and could not be distinguished morphologically from the negative cases. Among the 21 cases of lymphoma of the tonsils and back of the tongue (20 B-lineage and one T-lineage), none was EBER positive. In the normal mucosa of the nose/nasopharynx or tonsil (20 cases studied), only very rare EBER-positive small lymphocytes were found in two cases. The almost exclusive detection of EBER in nasal/nasopharyngeal T-cell neoplasms among the lymphomas of the upper aerodigestive tract suggests that EBV probably plays an etiologic role in the pathogenesis of this group of tumors and is not simply a passenger virus, and neither is this merely a site-dependent phenomenon in view of the weak association with nasal/nasopharyngeal B-cell lymphoma.

In situ localization of Epstein-Barr virus encoded RNA in non-nasal/nasopharyngeal CD56-positive and CD56-negative T-cell lymphomas.

We recently reported a group of non-nasal/nasopharyngeal hematolymphoid malignancies expressing the natural killer cell marker CD56, characterized by frequent extranodal localization, angiocentricity, and aggressive clinical course (HUM PATHOL 23:798-804, 1992). Because we have shown a very strong association of Epstein-Barr virus (EBV) with CD56-positive T-cell lymphomas of the nose nasopharynx, we asked whether a similar association also occurs with the non-nasal CD56-positive T-cell lymphomas. In situ localization of EBV encoded RNA (EBER) was performed on paraffin sections of 15 such cases, including the nine previously reported cases and six new cases (three showing prominent hepatosplenic involvement and three showing involvement of one or more extranodal sites, such as the parotid gland, tonsils, gastrointestinal tract, skeletal muscle, and testis). A case was considered positive when the majority of the tumor cells showed nuclear signal. Ten cases showed EBER positivity, and all but one of them were negative for CD3 and other T-cell markers, except CD2. Only one of four cases showing a CD3-positive phenotype was EBER positive. Of the remaining two CD3-negative EBER-negative cases, one showed a histiocytic phenotype and the other was positive for multiple T-cell markers. Among 15 cases of CD56-negative non-nasal peripheral T-cell lymphoma studied for comparison, six were CD3-negative, among which three showed EBER positivity. All nine CD3-positive cases were EBER negative. Five cases (three CD3 positive and two CD3 negative) showed rare isolated (< 1%) EBER-positive tumor cells. We conclude that among non-nasal T-cell lymphomas, EBV is strongly correlated with CD56 positivity (66.7% v 20%), and the positive cases almost always show an immunophenotype identical to that commonly observed in nasal lymphomas (CD2 positive, CD3 negative, and CD56 positive). Thus, EBV may play an etiologic role in these CD56-positive lymphomas. There is also a correlation between EBER positivity and CD3 negativity, irrespective of the CD56 status. The presence of isolated EBER-positive cells in CD56-negative T-cell lymphomas, occurring at a frequency similar to that reported in the European population, probably represents secondary infection of tumor cells.