{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:47:41Z","timestamp":1791920861123,"version":"4.3.4"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T00:00:00Z","timestamp":1626480000000},"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":[[2021,9]]},"abstract":"Summary<\/jats:title>\n \n Even in the era of highly active combination antiretroviral therapy (cART), patients with HIV have a disproportionate risk of developing aggressive lymphomas that are frequently Epstein\u2010Barr virus (EBV)\u2010related. Here, we investigate HIV\u2010associated diffuse large B\u2010cell lymphoma (HIV\u2010DLBCL) and compare EBV\u2010positive and EBV\u2010negative cases. HIV\u2010DLBCL were identified from two academic medical centres and characterised by immunohistochemistry, EBV status, fluorescence\n in\u00a0situ<\/jats:italic>\n hybridisation, cell of origin determination by gene expression profiling, and targeted deep sequencing using a custom mutation panel of 334 genes. We also applied the Lymphgen tool to determine the genetic subtype of each case. Thirty HIV\u2010DLBCL were identified, with a median patient age of 46\u00a0years and male predominance (5:1). Thirteen cases (48%) were EBV\u2010positive and 14 (52%) EBV\u2010negative. Nine of the 16 tested cases (56%) had\n MYC<\/jats:italic>\n rearrangement, three (19%) had\n BCL6<\/jats:italic>\n (two of which were double hit\n MYC<\/jats:italic>\n \/\n BCL6<\/jats:italic>\n ) and none had\n BCL2<\/jats:italic>\n rearrangements. Using the Lymphgen tool, half of the cases (15) were classified as other. All HIV\u2010DLBCL showed mutational abnormalities, the most frequent being\n TP53<\/jats:italic>\n (37%),\n MYC<\/jats:italic>\n (30%),\n STAT3<\/jats:italic>\n (27%),\n HIST1H1E<\/jats:italic>\n (23%),\n EP300<\/jats:italic>\n (20%),\n TET2<\/jats:italic>\n (20%),\n SOCS1<\/jats:italic>\n (17%) and\n SGK1<\/jats:italic>\n (17%). EBV\u2010negative cases were mostly of germinal centre B\u2010cell (GCB) origin (62%), showed more frequent mutations per case (a median of 13\u00b75\/case) and significant enrichment of\n TP53<\/jats:italic>\n (57% vs. 15%;\n P<\/jats:italic>\n \u00a0=\u00a00\u00b7046),\n SGK1<\/jats:italic>\n (36% vs. 0%;\n P<\/jats:italic>\n \u00a0=\u00a00\u00b704),\n EP300<\/jats:italic>\n (43% vs. 0%;\n P<\/jats:italic>\n \u00a0=\u00a00\u00b702) and histone\u2010modifying gene (e.g.\n HIST1H1E<\/jats:italic>\n ,\n HIST1H1D<\/jats:italic>\n , 79% vs. 31%;\n P<\/jats:italic>\n \u00a0=\u00a00\u00b702) mutations. EBV\u2010positive cases were mostly of non\u2010GCB origin (70%), with fewer mutations per case (median 8\/case;\n P<\/jats:italic>\n \u00a0=\u00a00\u00b7007), and these tumours were enriched for\n STAT3<\/jats:italic>\n mutations (\n P<\/jats:italic>\n \u00a0=\u00a00\u00b710). EBV\u2010positive cases had a higher frequency of\n MYC<\/jats:italic>\n mutations but the difference was not significant (36% vs. 15%;\n P<\/jats:italic>\n \u00a0=\u00a00\u00b738). EBV\u2010association was more frequent in HIV\u2010DLBCLs, arising in patients with lower CD4 counts at diagnosis (median 46\u00b75 vs. 101,\n P<\/jats:italic>\n \u00a0=\u00a00\u00b7018). In the era of cART, approximately half of HIV\u2010DLBCL are EBV\u2010related. HIV\u2010DLBCL are enriched for\n MYC<\/jats:italic>\n rearrangements,\n MYC<\/jats:italic>\n mutations and generally lack\n BCL2<\/jats:italic>\n rearrangements, regardless of EBV status. Among HIV\u2010DLBCL, tumours that are EBV\u2010negative and EBV\u2010positive appear to have important differences, the latter arising in context of lower CD4 count, showing frequent non\u2010GCB origin, lower mutation burden and recurrent\n STAT3<\/jats:italic>\n mutations.\n <\/jats:p>","DOI":"10.1111\/bjh.17708","type":"journal-article","created":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T03:21:50Z","timestamp":1626492110000},"page":"870-878","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["EBV\u2010positive HIV\u2010associated diffuse large B cell lymphomas are characterized by JAK\/STAT (STAT3) pathway mutations and unique clinicopathologic features"],"prefix":"10.1111","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6214-4152","authenticated-orcid":false,"given":"Jennifer R.","family":"Chapman","sequence":"first","affiliation":[{"name":"Division of Hematopathology Department of Pathology University of Miami and Sylvester Comprehensive Cancer Center Miami FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa C.","family":"Bouska","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology University of Nebraska Medical Center Omaha NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology University of Nebraska Medical Center Omaha NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2690-3377","authenticated-orcid":false,"given":"Juan Pablo","family":"Alderuccio","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine University of Miami and Sylvester Comprehensive Cancer Center Miami FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izidore S.","family":"Lossos","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine University of Miami and Sylvester Comprehensive Cancer Center Miami FL USA"},{"name":"Department of Molecular and Cellular Pharmacology University of Miami Miami FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1268-2750","authenticated-orcid":false,"given":"Lisa M.","family":"Rimsza","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Scottsdale AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alanna","family":"Maguire","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Scottsdale AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhua","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Pathology City of Hope National Medical Center Duarte CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing C.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pathology City of Hope National Medical Center Duarte CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Vega","sequence":"additional","affiliation":[{"name":"Department of Hematopathology MD Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Y.","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pathology City of Hope National Medical Center Duarte CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,17]]},"reference":[{"key":"e_1_2_5_2_1","volume-title":"WHO classification of tumours of haematopoietic and lymphoid tissues","author":"Swerdlow 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