1. ¹Laboratory of Pathology, National Cancer Institute, National Institutes of Health; Bethesda, MD, USA
2. ²Department of Pathology, Carolinas Medical Center, Charlotte, NC, USA
3. ³National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

Correspondence: Dr S Pittaluga, Hematopathology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Building 10/ Room 2N202, 10 Center Drive, Bethesda, MD, 20892, USA. E-mail: stefpitt@mail.nih.gov

Received 9 January 2004; Revised 23 April 2004; Accepted 23 April 2004.

Abstract

In contrast to other causes of herpetic lymphadenitis, the histological features associated with human herpesvirus-6 (HHV-6) infection have remained elusive since its discovery in 1986. We describe the histologic and phenotypic changes associated with acute HHV-6 lymphadenitis in two immunocompetent adults who presented with fever, fatigue, generalized lymphadenopathy, and elevated liver enzymes. Serologic tests for human immunodeficiency virus, acute Epstein–Barr virus, and cytomegalovirus infection were negative. Lymph node biopsies were consistent with viral lymphadenitis. Intranuclear and cytoplasmic inclusions were identified in CD4-positive T lymphocytes in expanded paracortical areas. Immunohistochemical staining with monoclonal antibody to the HHV-6 gp60/110 kDa envelope glycoprotein showed that the inclusions were positive for viral antigen. Electron microscopy demonstrated numerous viral particles in the cytoplasm and nucleus, characteristic of Herpesviridae family. Clustering of viral particles was observed, which has previously been reported only in infected tissue culture cells. PCR followed by sequencing of DNA extracted from the lymph nodes identified the virus as HHV-6, type B. This is the first report that documents distinctive histologic features of HHV-6 lymphadenitis and demonstrates that the cells harboring the virus in vivo are CD4-positive T lymphocytes.