{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T22:35:38Z","timestamp":1781822138153,"version":"3.54.5"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"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":["Histopathology"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>It is unknown whether Epstein\u2013Barr virus (EBV) infection can occur in high\u2010grade B cell lymphoma with <jats:italic>MYC<\/jats:italic> and <jats:italic>BCL2<\/jats:italic> and\/or <jats:italic>BCL6<\/jats:italic> rearrangements, also known as double\u2010 or triple\u2010hit lymphoma (DHL\/THL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Here we report 16 cases of EBV<jats:sup>+<\/jats:sup> DHL\/THL from screening 846 cases of DHL\/THL and obtaining additional EBV<jats:sup>+<\/jats:sup> cases through multi\u2010institutional collaboration: eight <jats:italic>MYC<\/jats:italic> and <jats:italic>BCL2<\/jats:italic> DHL, six <jats:italic>MYC<\/jats:italic> and <jats:italic>BCL6<\/jats:italic> DHL and two THL. There were eight men and eight women, with a median age of 65\u2009years (range\u2009=\u200932\u201386). Two patients had a history of follicular lymphoma and one had AIDS. Nine of 14 patients had an International Prognostic Index of \u22653. Half of the cases showed high\u2010grade\/Burkitt\u2010like morphology and the other half diffuse large B cell lymphoma morphology. Using immunohistochemistry, the lymphoma cells were positive for MYC (<jats:italic>n<\/jats:italic>\u2009=\u200914 of 16), BCL2 (<jats:italic>n<\/jats:italic>\u2009=\u200912 of 16), BCL6 (<jats:italic>n<\/jats:italic>\u2009=\u200914 of 16), CD10 (<jats:italic>n<\/jats:italic>\u2009=\u200913 of 16) and MUM1 (<jats:italic>n<\/jats:italic>\u2009=\u2009six of 14). Using Hans\u2019 algorithm, 13 cases were classified as germinal centre B cell (GCB) and three as non\u2010GCB. The lymphomas frequently showed an EBV latency Type I with a median EBV\u2010encoded small RNAs of 80% positive cells (range\u2009=\u200920\u2013100%). After a median follow\u2010up of 36.3\u2009months (range\u2009=\u20092.0\u201341.6), seven patients died, with a median survival of 15.4\u2009months (range\u2009=\u20093.4\u201347.3) after diagnosis of EBV<jats:sup>+<\/jats:sup> DHL\/THL. Five of six patients with <jats:italic>MYC<\/jats:italic> and <jats:italic>BCL6<\/jats:italic> DHL were alive, including four in complete remission. In contrast, only four of 10 patients with <jats:italic>MYC<\/jats:italic> and <jats:italic>BCL2<\/jats:italic> DHL or THL were alive, including two in complete remission. The median survival in patients with <jats:italic>MYC<\/jats:italic> and <jats:italic>BCL6<\/jats:italic> DHL was unreached and was 21.6\u2009months in patients with <jats:italic>MYC<\/jats:italic> and <jats:italic>BCL2<\/jats:italic> DHL or THL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>EBV infection in DHL\/THL is rare (~1.5%). Cases of EBV<jats:sup>+<\/jats:sup> DHL\/THL are largely similar to their EBV<jats:sup>\u2013<\/jats:sup> counterparts clinicopathologically. Our findings expand the spectrum of EBV<jats:sup>+<\/jats:sup> B cell lymphomas currently recognised in the World Health Organisation classification and suggest differences between EBV<jats:sup>+<\/jats:sup> <jats:italic>MYC<\/jats:italic> and <jats:italic>BCL2<\/jats:italic> DHL versus EBV+<jats:italic>MYC<\/jats:italic> and <jats:italic>BCL6<\/jats:italic> DHL that may have therapeutic implications.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14585","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:06:46Z","timestamp":1634083606000},"page":"575-588","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["EBV<sup>+<\/sup> high\u2010grade B cell lymphoma with <i>MYC<\/i> and <i>BCL2<\/i> and\/or <i>BCL6<\/i> rearrangements: a multi\u2010institutional study"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7669-9386","authenticated-orcid":false,"given":"Hui","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Hematopathology The University of Texas MD Anderson Cancer Center Houston TX USA"},{"name":"Department of Pathology Xuzhou Medical University Affiliated Hospital Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijun Y","family":"Xu\u2010Monette","sequence":"additional","affiliation":[{"name":"Department of Pathology Duke University Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilin","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Hematopathology The University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematopathology The University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology City of Hope National Medical Center Duarte CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Nebraska Medical Center Omaha NE USA"},{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology Chongqing University Cancer Hospital Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weina","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology The University of Texas Southwestern Medical Center Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Pittsburgh Medical Center Pinnacle Harrisburg PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George Y","family":"Fedoriw","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of North Carolina Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology Xuzhou Medical University Affiliated Hospital Xuzhou China"},{"name":"Department of Pathology Duke University Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosheng","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Pathology Duke University Medical Center Durham NC 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