Human herpesvirus 6 positive Reed-Sternberg cells in nodular sclerosis Hodgkin lymphoma

Br J Haematol. 2012 Sep;158(5):635-43. doi: 10.1111/j.1365-2141.2012.09206.x. Epub 2012 Jul 4.

Abstract

Classical Hodgkin lymphoma (HL) exhibits a bi-modal age distribution that suggests an infectious aetiology. However, most cases of nodular sclerosis HL (NSHL) are Epstein-Barr virus (EBV) negative (60-90%). Previous studies regarding human herpesvirus 6 (HHV-6) positivity of HL have led to conflicting results. In order to clarify this situation, we examined NSHL biopsies for the presence and distribution of HHV-6 by immunohistochemistry (IHC), polymerase chain reaction (PCR), and fluorescence in situ hybridization (FISH). PCR identified HHV-6 DNA in 86% of NSHL cases. As HHV-6 DNA was also identified in most cases of reactive lymphoid hyperplasia, we sought to localize the virus to specific cells by IHC, which detected HHV-6 in Reed-Sternberg (RS) cells of nearly half (48%) of NSHL cases. Dual CD30/HHV-6 immunostaining confirmed HHV-6 immunoreactivity in CD30+ RS cells, and HHV-6 PCR positivity was confirmed in laser capture microdissection-isolated CD30+ RS cells. FISH demonstrated multiple copies of HHV-6 genome in scattered cells. In contrast, EBV+ RS cells were identified in only 24% of the cases. HHV-6+ cases trended toward a younger age than EBV+ cases. These results conclusively demonstrate that RS cells in many cases of NSHL are HHV-6 positive, and suggest that HHV-6 may play a role in NSHL pathogenesis, particularly in younger patients with EBV-negative disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Blotting, Western
  • Cell Line, Tumor
  • DNA, Viral / isolation & purification
  • Epstein-Barr Virus Infections / virology
  • Female
  • Herpesvirus 4, Human / isolation & purification
  • Herpesvirus 6, Human / isolation & purification*
  • Hodgkin Disease / virology*
  • Humans
  • Immunohistochemistry
  • Lymphoma, Follicular / virology
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Reed-Sternberg Cells / virology*
  • Roseolovirus Infections / virology*
  • Sclerosis
  • Young Adult

Substances

  • DNA, Viral