Infrequent Association of Epstein-Barr Virus with CD30-Positive Anaplastic Large Cell Lymphomas from American and Asian Patients
CD30 (Ki-1)-positive anaplastic large cell lymphoma (CD30+ ALCL) is a morphologically and immunophenotypically distinct subset of non-Hodgkin's lymphoma. Although the presence of Epstein-Barr virus (EBV) has been well documented in a significant proportion of cases of Hodgkin's disease, another CD30+ malignancy, few studies have examined the association of EBV with CD30+ ALCL. These latter studies have produced conflicting findings. To further investigate the existence of a putative association of EBV with CD30+ ALCL, and whether this association, if present, shows geographic variation, we examined 34 formalin-fixed, paraffin-embedded specimens from cases of CD30+ ALCL from the United States and Hong Kong. Immunophenotypically, 15 cases were of B lineage, 15 cases were of T lineage, one case expressed both B- and T-cell markers, and three were of null lineage. A highly sensitive in situ hybridization method was performed with use of an antisense oligonucleotide probe to the EBV-encoded RNA (EBER-1). EBV-RNA was identified in 3 of 14 CD30+ ALCL specimens from Hong Kong patients and in 1 of 20 from the American patients. The EBER-1 signal was present in all or virtually all of the tumor cell nuclei in the three EBV-RNA-positive CD30+ ALCL Hong Kong cases, but was only focally present in the single EBV-positive American case. The latent membrane protein-1 (LMP1) of EBV was identified in only one of the four positive cases, a Hong Kong case. Our results suggest that in contrast to Hodgkin's disease, EBV has no significant association with CD30+ ALCL.
- [Show abstract] [Hide abstract] ABSTRACT: Although cytogenetic data suggest that the t(2;5)-(p23;q35) translocation occurs in many cases of CD30+ lymphomas, the exact frequency of this event is still unknown. To clarify this issue and its epidemiological characteristics, we examined 37 formalin-fixed, paraffin-embedded specimens of CD30+ lymphomas from the United States and Hong Kong by reverse transcriptase-polymerase chain reaction (RT-PCR) for the status of the NPM and ALK genes, which are typically juxtaposed by the t(2;5) translocation. Thirty-four cases were classified as anaplastic large cell lymphomas (ALCL), 2 cases as non-anaplastic large cell lymphomas (LCL), and 1 case as the small cell variant of CD30+ lymphoma. The t(2;5) translocation was detected in 6 cases (16%), including 3 of 18 American patients and 3 of 19 cases from Hong Kong. All cases had a 185-bp NPM RT-PCR product as detected by Southern blot analysis, indicating adequate preservation of mRNA. The 6 positive cases were among 4 of 34 adult lymphomas, as compared with 2 of 3 childhood cases. Five of 17 T-lineage cases were t(2;5)-positive, compared with 1 of 15 B-lineage cases and none of the 5 null-cell or mixed lineage cases. Our results therefore show that t(2;5) occurs at a low frequency among CD30+ lymphomas, at least in our adult-dominated series.0Comments 45Citations
- [Show abstract] [Hide abstract] ABSTRACT: There is a strong association (approximately 95%) of endemic Burkitt's lymphoma with Epstein-Barr virus (EBV), whereas the association is weak for the sporadic form occurring in Western countries (approximately 15%). In the Middle East, North Africa and South America, 60-80% of Burkitt's lymphomas harbour EBV. These epidemiological differences suggest that either the endemicity of EBV or socio-economic conditions, or both, may influence the pathogenetic role of EBV in Burkitt's lymphoma. Since only meagre data are available on Asians, this study was performed to address this issue by studying cases from Hong Kong, where EBV seroconversion occurs in the first few years of life but the socio-economic conditions approach those of Western countries. In situ hybridization for EBV encoded RNAs (EBERs) was performed on paraffin sections of 18 cases of Burkitt's lymphoma. Labelling of the neoplastic cells was detected in five cases (27.7%). In contrast, among 54 cases of B-cell lymphomas of various subtypes studied for comparison, signals for EBER were detected in only one case each of T-cell-rich large B-cell lymphoma, anaplastic large cell lymphoma and Reed-Sternberg-like cells occurring in B-cell chronic lymphocytic leukaemia/small lymphocytic lymphoma. The strong labelling with oligo-dT probe (which hybridized with the polyadenylated ends of mRNA) in all cases suggested that the negative results were genuine and not due to poor preservation of RNA in the tissues. Thus, among B-cell neoplasms occurring in Chinese, Burkitt's lymphoma shows a statistically stronger association (P < 0.01) with EBV than with other types of B-cell lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)0Comments 24Citations
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- [Show abstract] [Hide abstract] ABSTRACT: The Epstein-Barr virus, a human herpesvirus, has been found in the neoplastic cells of numerous lymphoid malignancies, including Burkitt's lymphoma, immunodeficiency-associated lymphoproliferative disorders, nasal T/NK lymphoma, and Hodgkin's disease. The available data suggest that Epstein-Barr virus contributes to the pathogenesis of many of these neoplasms but is not directly linked to the etiology of any of these lymphomas.0Comments 16Citations
- [Show abstract] [Hide abstract] ABSTRACT: Hodgkin's disease rarely involves the skin and when it does is an indication of advanced stage disease. Primary cutaneous Hodgkin's disease is exceedingly rare, and only a few cases are reported. We describe a patient who developed multiple cutaneous lesions of Hodgkin's disease 2 years before manifesting nodal disease of mixed cellularity subtype. Reed-Sternberg cells in the skin as well as lymph nodes and bone marrow were positive for Epstein-Barr viral transcripts and expressed viral latent membrane protein. Epstein-Barr virus has not previously been demonstrated in primary cutaneous Hodgkin's disease, and its presence in lesions in all sites in this case supports a diagnosis of primary cutaneous disease with subsequent evolution into systemic disease.0Comments 12Citations
- [Show abstract] [Hide abstract] ABSTRACT: The clinicopathological features, the immunophenotype, and the presence of Epstein-Barr virus (EBV)-associated genomes and gene products were examined in 17 cases of CD30+ anaplastic large cell lymphoma (ALCL) of B-cell type. Microscopically, the 17 cases were divided into ten cases of the monomorphic type and seven cases of the pleomorphic type. EBV was detected in 6 of 17 cases (38 per cent) by RNA in situ hybridization (ISH) with EBV-encoded RNA (EBER1). EBER1+ cases consisted of two cases (20 per cent) of the monomorphic type and four cases (57 per cent) of the pleomorphic type. The five EBER1+ cases showed clonality of the EBV genome by Southern blotting, consistent with the presence of EBV in a monoclonal proliferation. The EBV-encoded latent membrane protein 1 (LMP1) was found in all six EBER1+ cases and EBV-encoded nuclear antigen 2 (EBNA2) was present in two cases by immunohistochemistry. No expression of LMP1 or EBNA2 was observed in the EBER1-cases. The EBER1+ cases had a tendency for a more favourable prognosis than the EBER1-cases. It is concluded that EBV has an association with CD30+ ALCL of B-cell type in the Japanese population studied, and especially with the large pleomorphic type. EBV infection may play a pathoaetiological role and may influence clinical behaviour.0Comments 26Citations