{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T17:20:08Z","timestamp":1762017608228},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,7,4]],"date-time":"2012-07-04T00:00:00Z","timestamp":1341360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Classical Hodgkin lymphoma (<jats:styled-content style=\"fixed-case\">HL<\/jats:styled-content>) exhibits a bi\u2010modal age distribution that suggests an infectious aetiology. However, most cases of nodular sclerosis <jats:styled-content style=\"fixed-case\">HL<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">NSHL<\/jats:styled-content>) are Epstein\u2013Barr virus (<jats:styled-content style=\"fixed-case\">EBV<\/jats:styled-content>) negative (60\u201390%). Previous studies regarding human herpesvirus 6 (<jats:styled-content style=\"fixed-case\">HHV<\/jats:styled-content>\u20106) positivity of <jats:styled-content style=\"fixed-case\">HL<\/jats:styled-content> have led to conflicting results. In order to clarify this situation, we examined <jats:styled-content style=\"fixed-case\">NSHL<\/jats:styled-content> biopsies for the presence and distribution of <jats:styled-content style=\"fixed-case\">HHV<\/jats:styled-content>\u20106 by immunohistochemistry (<jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>), polymerase chain reaction (<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>), and fluorescence <jats:italic>in situ<\/jats:italic> hybridization (<jats:styled-content style=\"fixed-case\">FISH<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> identified <jats:styled-content style=\"fixed-case\">HHV<\/jats:styled-content>\u20106 <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> in 86% of <jats:styled-content style=\"fixed-case\">NSHL<\/jats:styled-content> cases. As <jats:styled-content style=\"fixed-case\">HHV<\/jats:styled-content>\u20106 <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> was also identified in most cases of reactive lymphoid hyperplasia, we sought to localize the virus to specific cells by <jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>, which detected <jats:styled-content style=\"fixed-case\">HHV<\/jats:styled-content>\u20106 in Reed\u2013Sternberg (<jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content>) cells of nearly half (48%) of <jats:styled-content style=\"fixed-case\">NSHL<\/jats:styled-content> cases. Dual <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>30\/<jats:styled-content style=\"fixed-case\">HHV<\/jats:styled-content>\u20106 immunostaining confirmed <jats:styled-content style=\"fixed-case\">HHV<\/jats:styled-content>\u20106 immunoreactivity in <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>30+ <jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content> cells, and <jats:styled-content style=\"fixed-case\">HHV<\/jats:styled-content>\u20106 <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> positivity was confirmed in laser capture microdissection\u2010isolated <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>30+ <jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content> cells. <jats:styled-content style=\"fixed-case\">FISH<\/jats:styled-content> demonstrated multiple copies of <jats:styled-content style=\"fixed-case\">HHV<\/jats:styled-content>\u20106 genome in scattered cells. In contrast, <jats:styled-content style=\"fixed-case\">EBV<\/jats:styled-content>+ <jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content> cells were identified in only 24% of the cases. <jats:styled-content style=\"fixed-case\">HHV<\/jats:styled-content>\u20106+ cases trended toward a younger age than <jats:styled-content style=\"fixed-case\">EBV<\/jats:styled-content>+ cases. These results conclusively demonstrate that <jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content> cells in many cases of <jats:styled-content style=\"fixed-case\">NSHL<\/jats:styled-content> are <jats:styled-content style=\"fixed-case\">HHV<\/jats:styled-content>\u20106 positive, and suggest that <jats:styled-content style=\"fixed-case\">HHV<\/jats:styled-content>\u20106 may play a role in <jats:styled-content style=\"fixed-case\">NSHL<\/jats:styled-content> pathogenesis, particularly in younger patients with <jats:styled-content style=\"fixed-case\">EBV<\/jats:styled-content>\u2010negative disease.<\/jats:p>","DOI":"10.1111\/j.1365-2141.2012.09206.x","type":"journal-article","created":{"date-parts":[[2012,7,4]],"date-time":"2012-07-04T23:34:49Z","timestamp":1341444889000},"page":"635-643","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Human herpesvirus 6 positive Reed\u2013Sternberg cells in nodular sclerosis Hodgkin lymphoma"],"prefix":"10.1111","volume":"158","author":[{"given":"Alexa","family":"Siddon","sequence":"first","affiliation":[{"name":"Department of Pathology Yale University School of Medicine New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larissa","family":"Lozovatsky","sequence":"additional","affiliation":[{"name":"Department of Pathology Yale University School of Medicine New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayman","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Precipio Diagnostics New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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