PMID- 22757777 OWN - NLM STAT- MEDLINE DCOM- 20121019 LR - 20130606 IS - 1365-2141 (Electronic) IS - 0007-1048 (Linking) VI - 158 IP - 5 DP - 2012 Sep TI - Human herpesvirus 6 positive Reed-Sternberg cells in nodular sclerosis Hodgkin lymphoma. PG - 635-43 LID - 10.1111/j.1365-2141.2012.09206.x [doi] AB - 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. CI - (c) 2012 Blackwell Publishing Ltd. FAU - Siddon, Alexa AU - Siddon A AD - Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA. FAU - Lozovatsky, Larissa AU - Lozovatsky L FAU - Mohamed, Ayman AU - Mohamed A FAU - Hudnall, S David AU - Hudnall SD LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120704 PL - England TA - Br J Haematol JT - British journal of haematology JID - 0372544 RN - 0 (DNA, Viral) SB - IM CIN - Br J Haematol. 2013 May;161(4):594-5. PMID: 23406281 MH - Adolescent MH - Adult MH - Age Factors MH - Aged MH - Blotting, Western MH - Cell Line, Tumor MH - DNA, Viral/isolation & purification MH - Epstein-Barr Virus Infections/virology MH - Female MH - Herpesvirus 4, Human/isolation & purification MH - Herpesvirus 6, Human/*isolation & purification MH - Hodgkin Disease/*virology MH - Humans MH - Immunohistochemistry MH - Lymphoma, Follicular/virology MH - Male MH - Middle Aged MH - Polymerase Chain Reaction MH - Reed-Sternberg Cells/*virology MH - Roseolovirus Infections/*virology MH - Sclerosis MH - Young Adult EDAT- 2012/07/05 06:00 MHDA- 2012/10/20 06:00 CRDT- 2012/07/05 06:00 PHST- 2012/04/10 00:00 [received] PHST- 2012/05/24 00:00 [accepted] PHST- 2012/07/05 06:00 [entrez] PHST- 2012/07/05 06:00 [pubmed] PHST- 2012/10/20 06:00 [medline] AID - 10.1111/j.1365-2141.2012.09206.x [doi] PST - ppublish SO - Br J Haematol. 2012 Sep;158(5):635-43. doi: 10.1111/j.1365-2141.2012.09206.x. Epub 2012 Jul 4.