Langerhans cell histiocytosis: a primary viral infection of bone? Human herpes virus 6 latent protein detected in lymphocytes from tissue of children.

To better understand the etiology of Langerhans cell histiocytosis (LCH), the authors analyzed tissue from 35 children diagnosed with LCH for the presence of viral proteins and DNA by immunohistochemistry (IHC) and in situ hybridization (ISH). Eighteen control biopsies were obtained from patients without LCH. Confirmatory ISH was randomly performed on four positive and two negative cases determined by IHC. Twenty-five (71.4%) tissue samples with LCH involvement stained by IHC with the 101-kDa antibody against human herpesvirus-6 (HHV-6). None were positive with antibodies against the p41/38 or gp110 viral proteins. Five (27.7%) positive control tissues demonstrated presence of the 101-kDa viral protein in a similar fashion. The difference in the prevalence of HHV-6 in LCH-positive tissues (25/35) when compared with control tissues from patients without LCH involvement (5/18) was statistically significant. ISH confirmed the IHC in all six tissues tested. These findings demonstrate an association between HHV-6 and LCH, suggesting a role for the HHV-6B in the etiology of this disease.