Abstract
A 22-year-old male was admitted for a sustained fever of 2 months, lymphadenopathy, and liver dysfunction. Anti-VCA-IgM antibody was positive, with elevated Epstein–Barr virus (EBV)-DNA load in the peripheral blood. Liver biopsy revealed infiltration of CD8-positive and EBV-positive cells. Most peripheral blood mononuclear cells (PBMCs) were also positive for CD8, and showed detectable levels of EBV-DNA. Monoclonal proliferation of EBV-infected cells was detected in the PBMCs by Southern blotting for EBV-terminal repeat (EBV-TR). Although EBV-positive T-cell lymphoproliferative disease (EBV-T-LPD) was suspected, the symptoms spontaneously resolved within 12 months. Anti-VCA-IgM antibody and the clonal band of EBV-TR were negative 1 year after the onset, while anti-EBNA antibody was positive. The final diagnosis was thus confirmed as infectious mononucleosis (IM). Our results indicate that EBV-infected CD8-positive cells and clonal proliferation of EBV-infected cells may be temporally detected in IM. EBV-T-LPDs should be carefully excluded in such cases.
References
Young KH, Zhang D, Malik JT, et al. Fulminant EBV-driven CD8 T-cell lymphoproliferative disorder following primary acute EBV infection: a unique spectrum of T-cell malignancy. Int J Clin Exp Pathol. 2008;1:185–97.
Leight ER, Sugden B. EBNA-1: a protein pivotal to latent infection by Epstein–Barr virus. Rev Med Virol. 2000;10:83–100.
Heslop HE. Biology and treatment of Epstein–Barr virus-associated non-Hodgkin lymphomas. Hematol Am Soc Hematol Educ Progr 2005:260–266.
Quintanilla-Martinez L, Kimura H, Jaffe ES. EBV-positive T-cell lymphoproliferative disorders of childhood. World Health Organization Classification of Tumors Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2008. p. 278–80.
Raab-Traub N, Flynn K. The structure of the termini of the Epstein–Barr virus as a marker of clonal cellular proliferation. Cell. 1986;47:883–9.
Sandberg Y, van Gastel-Mol EJ, Verhaaf B, et al. BIOMED-2 multiplex immunoglobulin/T-cell receptor polymerase chain reaction protocols can reliably replace Southern blot analysis in routine clonality diagnostics. J Mol Diagn. 2005;7:495–503.
Tokunaga M, Uemura Y, Tokudome T, et al. Epstein–Barr virus-infected T cells in infectious mononucleosis. Acta Pathol Jpn. 1993;43:146–7.
Anagnostopoulos I, Hummel M, Kreschel C, et al. Morphology, immunophenotype, and distribution of latently and/or productively Epstein–Barr virus-infected cells in acute infectious mononucleosis: implications for the interindividual infection route of Epstein–Barr virus. Blood. 1995;85:744–50.
He HL, Wang MC, Huang WT. Infectious mononucleosis mimicking malignant T-cell lymphoma in the nasopharynx: a case report and review of the literature. Int J Clin Exp Pathol. 2013;6:105–9.
Fischer E, Delibrias C, Kazatchkine MD. Expression of CR2 (the C3dg/EBV receptor, CD21) on normal human peripheral blood T lymphocytes. J Immunol. 1991;146:865–9.
Tabiasco J, Vercellone A, Meggetto F, et al. Acquisition of viral receptor by NK cells through immunological synapse. J Immunol. 2003;170:5993–8.
Stinchcombe JC, Bossi G, Booth S, et al. The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity. 2001;15:751–61.
Hodges E, Krishna MT, Pickard C, et al. Diagnostic role of tests for T cell receptor (TCR) genes. J Clin Pathol. 2003;56:1–11.
Plumbley JA, Fan H, Eagan PA, et al. Lymphoid tissues from patients with infectious mononucleosis lack monoclonal B and T cells. J Mol Diagn. 2002;4:37–43.
Virelizier JL, Lenoir G, Griscelli C. Persistent Epstein–Barr virus infection in a child with hypergammaglobulinaemia and immunoblastic proliferation associated with a selective defect in immune interferon secretion. Lancet. 1978;2:231–4.
Jones JF, Shurin S, Abramowsky C, et al. T-cell lymphomas containing Epstein–Barr viral DNA in patients with chronic Epstein–Barr virus infections. N Engl J Med. 1988;318:733–41.
Arai A, Imadome K, Watanabe Y, et al. Clinical features of adult-onset chronic active Epstein–Barr virus infection: a retrospective analysis. Int J Hematol. 2011;93:602–9.
Kimura H, Ito Y, Kawabe S, et al. EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases. Blood. 2012;119:673–86.
Arai A, Nogami A, Imadome KI, et al. Sequential monitoring of serum IL-6, TNF-α, and IFN-γ levels in a CAEBV patient treated by plasma exchange and immunochemotherapy. Int J Hematol. 2012;96:669–73.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Arai, A., Yamaguchi, T., Komatsu, H. et al. Infectious mononucleosis accompanied by clonal proliferation of EBV-infected cells and infection of CD8-positive cells. Int J Hematol 99, 671–675 (2014). https://doi.org/10.1007/s12185-014-1548-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12185-014-1548-4