T-Cell Lymphomas Containing Epstein–Barr Viral DNA in Patients with Chronic Epstein–Barr Virus Infections

Abstract

Fatal T-cell lymphomas developed in three patients with a chronic illness manifested by fever, pneumonia, dysgammaglobulinemia, hematologic abnormalities, and extraordinarily high titers of antibody to the Epstein-Barr virus (EBV) capsid antigen (greater than 10,000) and early antigen (greater than 640) but low titers to the EBV nuclear antigen (less than or equal to 40). To understand the pathogenesis of these tumors better, we determined the immunophenotype of the tumor cells and analyzed tumor-cell DNA for EBV genomes and for lymphoid-cell gene rearrangements. More than 80 percent of the cells in tumors had an activated helper T-cell phenotype (T4, T11, la positive). The EBV genome was found by in situ hybridization in tumor tissue from each patient. Southern blot assay of DNA digests from one patient showed the same pattern as that of the EBV-infected marmoset line, B95-8. DNA digests from two patients showed a monoclonal proliferation of T cells determined on the basis of uniform T-cell-receptor gene rearrangements and a single band for the joined termini of the EBV genome. We conclude that EBV may infect T cells and contribute to lymphomas in selected patients with severe EBV infections.

Epstein-Barr virus–associated lymphoproliferative disorders

“…However, since the EBV association with T-cell proliferation was first described [71], many other T-cell lymphoproliferative entities have been linked to EBV, especially in Asia and Latin America. EBV can infect CD4+ and CD8+ peripheral blood T cells as well as NK cells in a minority of patients with infectious mononucleosis [72].…”

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

“…This disease is characterised by chronic or recurrent infectious mononucleosis-like symptoms, such as fever, hepatosplenomegaly, persistent hepatitis, and extensive lymphadenopathy [2,3]. There is accumulating evidence that the clonal expansion of EBV-infected T or NK cells plays a central role in the pathogenesis of chronic active EBV infection [93][94][95]. We proposed that this disease consists of a T cell-or NK cell-type disease, based on the results of PBMC fractionation and subsequent quantitative PCR [96][97][98].…”

Monitoring of Epstein‐Barr virus load after hematopoietic stem cell transplantation for early intervention in post‐transplant lymphoproliferative disease

“…Tumors classically linked with EBV are the Burkitt´s lymphoma [Burkitt, 1958;Epstein et al, 1964] and the nasopharyngeal carcinoma [zur Hausen et al, 1970]. However, EBV was also found to be involved in the development of other neoplasias, such as B-cell lymphomas in immunocompromised transplant [Hopwood and Crawford, 2000] and AIDS patients [Hamilton-Dutoit et al, 1991;Shibata et al, 1993], certain T-cell lymphomas [Jones et al, 1988;Su et al, 1991;Meijer et al, 1996], Hodgkin´s lymphomas [Staal et al, 1989;Herbst et al, 1990;Niedobitek, 1996] and gastric carcinomas [Leoncini et al, 1993;Fukayama et al, 1994;Osato and Imai, 1996].…”