title: Human herpesvirus 6 positive Reed-Sternberg cells in nodular sclerosis Hodgkin lymphoma.
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.
authors: Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Alexa
authors: A
authors: Siddon
authors: Larissa
authors: L
authors: Lozovatsky
authors: Ayman
authors: A
authors: Mohamed
authors: S David
authors: SD
authors: Hudnall
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000302:isolation & purification; D020031:Epstein-Barr Virus Infections / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D015654:Herpesvirus 6, Human / Q000302:isolation & purification*; D006689:Hodgkin Disease / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D008224:Lymphoma, Follicular / Q000821:virology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016539:Reed-Sternberg Cells / Q000821:virology*; D019349:Roseolovirus Infections / Q000821:virology*; D012598:Sclerosis; D055815:Young Adult
chemical_list: D004279:DNA, Viral