{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:18:20Z","timestamp":1790050700704,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T00:00:00Z","timestamp":1557964800000},"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":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Systemic forms of EBV\u2010associated T\u2010cell lymphoproliferative disorders of childhood (S\u2010EBV\u2010T\u2010LPD) comprise three major forms: EBV\u2010positive hemophagocytic lymphohistiocytosis (EBV\u2010HLH), systemic EBV\u2010positive T\u2010cell lymphoma (S\u2010EBV\u2010TCL), and systemic chronic active EBV infection (S\u2010CAEBV). These disorders occur rarely in children in Western countries. Here, we described eight children of such entities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Eight cases (six clinical and two autopsy) with S\u2010EBV\u2010T\u2010LPD of childhood were retrospectively identified from 1990 to 2015. Clinicopathologic parameters including histomorphology, immunophenotype, EBV studies, and T\u2010cell receptor gene rearrangement studies were recorded.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients include five females and three males of Hispanic, Asian, and Caucasian origins with an age range of 14 months to 9 years. Fever, hepatosplenomegaly, cytopenias, abnormal EBV serologies, and very high EBV viral loads were common findings. Histologic findings showed EBV<jats:sup>+<\/jats:sup> T\u2010cell infiltrates with variable degrees of architectural distortion and cytologic atypia ranging from no to mild cytologic atypia to overt lymphoma and tissue hemophagocytosis. All showed aberrant CD4<jats:sup>+<\/jats:sup> or CD8<jats:sup>+<\/jats:sup> T cells with dim to absent CD5, CD7, and CD3, and bright CD2 and CD45 by flow cytometry or loss of CD5 by immunohistochemistry. TCR gene rearrangement studies showed monoclonal rearrangements in all clinical cases (6\/6). Outcomes were poor with treatment consisting of chemotherapy per the HLH\u201094 or HLH\u20102004 protocols with or without bone marrow transplant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this large pediatric clinicopathologic study of S\u2010EBV\u2010T\u2010LPD of childhood in the United States, EBV\u2010HLH, S\u2010EBV\u2010TCL, and S\u2010CAEBV show many overlapping features. Diagnosis is challenging, and overall outcome is poor using current HLH\u2010directed therapies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.27798","type":"journal-article","created":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T05:00:07Z","timestamp":1558069207000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["A clinicopathologic study of the spectrum of systemic forms of EBV\u2010associated T\u2010cell lymphoproliferative disorders of childhood: A single tertiary care pediatric institution experience in North America"],"prefix":"10.1002","volume":"66","author":[{"given":"Amy M.","family":"Coffey","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology Baylor College of Medicine and Texas Children's Hospital  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annisa","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Baylor College of Medicine and Texas Children's Hospital  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea N.","family":"Marcogliese","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Baylor College of Medicine and Texas Children's Hospital  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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