{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T12:59:12Z","timestamp":1782219552052,"version":"3.54.5"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:p>Aggressive natural killer cell leukemia (ANKL) is a systemic NK-cell neoplasm, almost always associated with Epstein-Barr virus (EBV). Rare cases of EBV-negative ANKL have been described, and some reports suggested more indolent behavior. We report the clinicopathologic, immunophenotypic, and molecular characteristics of 7 EBV-negative ANKL. All patients were adults, with a median age of 63 years (range 22 to 83 y) and an M:F ratio of 2.5:1. Five patients were White, 1 Black, and 1 Asian. All patients presented acutely, with fever (6\/7), cytopenias (6\/7), and splenomegaly (4\/7). Four patients had lymphadenopathy, 4 had extranodal disease. Bone marrow involvement was present in 5, with hemophagocytosis in 3. Peripheral blood was involved in 5 with the neoplastic cells containing prominent azurophilic granules. By immunohistochemistry and\/or flow cytometry, the tumor cells lacked surface CD3 and were positive for CD56 (7\/7), CD2 (5\/5), CD8 (3\/7), CD30 (4\/5), and granzyme-B (6\/6). They were negative for CD4, CD5, \u03b2F1, TCR\u03b3, LMP1, and EBV-encoded RNA. Polymerase chain reaction for TCRG clonality was polyclonal. Mutational analysis revealed missense mutations in the <jats:italic toggle=\"yes\">STAT3<\/jats:italic> gene in both cases studied. Median survival was 8 weeks from the onset of disease. One patient received allogeneic bone marrow transplant and is alive with no disease (follow-up 15 mo). EBV-negative ANKL exists but is rare. It tends to occur in older patients and is indistinguishable clinically and pathologically from EBV-positive ANKL, with a similar fulminant clinical course. The high prevalence of Asian patients seen with EBV-positive disease seems less evident with EBV-negative cases.<\/jats:p>","DOI":"10.1097\/pas.0000000000000735","type":"journal-article","created":{"date-parts":[[2016,9,15]],"date-time":"2016-09-15T09:11:17Z","timestamp":1473930677000},"page":"67-74","source":"Crossref","is-referenced-by-count":74,"title":["EBV-negative Aggressive NK-cell Leukemia\/Lymphoma"],"prefix":"10.1097","volume":"41","author":[{"given":"Alina","family":"Nicolae","sequence":"first","affiliation":[{"name":"Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik A.","family":"Ganapathi","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trinh Hoc-Tran","family":"Pham","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqiang","family":"Xi","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Torres-Cabala","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Dermatology, UT-MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahid M.","family":"Nanaji","sequence":"additional","affiliation":[{"name":"Department of Veteran Affairs, Maryland Healthcare System, Baltimore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbin D.","family":"Zha","sequence":"additional","affiliation":[{"name":"Kaiser Permanente, Los 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