{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T21:08:29Z","timestamp":1788815309012,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T00:00:00Z","timestamp":1633305600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Human herpesvirus\u20108 (HHV8) is a lymphotropic virus associated with different lymphoproliferative disorders, including primary effusion lymphoma (PEL), multicentric Castleman\u2019s disease (MCD), diffuse large B\u2010cell lymphomas, not otherwise specified, and the rare entity known as germinotropic lymphoproliferative disorder (GLPD). In PELs and GLPD the neoplastic cells also contain Epstein\u2013Barr virus (EBV). In addition, occasional cases with atypical and overlapping features among these entities have been recognised, suggesting that the spectrum of the HHV8\u2010related lesions may not be fully characterised.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>Here, we report two cases of lymphoproliferative disorder associated with HHV8 and EBV that further expand the spectrum of HHV8\/EBV\u2010positive lymphoproliferative disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Case 1 represented HHV8\/EBV\u2010positive extracavitary nodal PEL followed by pleural PEL. The striking characteristic of this case was the almost focal and intrasinusoidal localisation of the neoplastic cells and the association with Castleman\u2019s disease features. In the second case, we found the entire spectrum of HHV8\u2010related disorders, i.e. MCD, GLPD, and PEL, coexisting in the same lymph node, underlining the variability, possible overlap and evolution among these entities. Both cases were well analysed with immunohistochemistry, determination of the EBV latency programme, and molecular analysis for clonality of immnoglobulin genes. In both patients, the disease followed an unexpected indolent course, both being still alive after 8 and 12\u2009months, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings represent further evidence of the overlap among HHV8\/EBV\u2010positive lymphoproliferative disorders, and underline a grey zone that requires further study; they further confirm the experimental evidence that lytic EBV replication influences HHV8\u2010related tumorigenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14551","type":"journal-article","created":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T09:02:12Z","timestamp":1629882132000},"page":"1099-1107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Epstein\u2013Barr virus reactivation influences clonal evolution in human herpesvirus\u20108\u2010related lymphoproliferative disorders"],"prefix":"10.1111","volume":"79","author":[{"given":"Massimo","family":"Granai","sequence":"first","affiliation":[{"name":"Section\u2009of Pathology Department of Medical Biotechnology University of Siena Siena Italy"},{"name":"Institute of Pathology and Neuropathology University Hospital and Comprehensive Cancer Centre T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2605-101X","authenticated-orcid":false,"given":"Mattia","family":"Facchetti","sequence":"additional","affiliation":[{"name":"Section\u2009of Pathology Department of Molecular and Translational Medicine University of Brescia Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4775-3777","authenticated-orcid":false,"given":"Virginia","family":"Mancini","sequence":"additional","affiliation":[{"name":"Section\u2009of Pathology Department of Medical Biotechnology University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Goedhals","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Health Sciences University of the Free State Bloemfontein South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Sherriff","sequence":"additional","affiliation":[{"name":"Department of Oncology Faculty of Health Sciences University of the Free State Bloemfontein South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Mundo","sequence":"additional","affiliation":[{"name":"Health Research Institute University of Limerick Limerick Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"Bellan","sequence":"additional","affiliation":[{"name":"Section\u2009of Pathology Department of Medical Biotechnology University of Siena Siena 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