EBV-negative Aggressive NK-cell Leukemia/Lymphoma: Clinical, Pathologic, and Genetic Features.

Nicolae, Alina; Ganapathi, Karthik A; Pham, Trinh Hoc-Tran; Xi, Liqiang; Torres-Cabala, Carlos A; Nanaji, Nahid M; Zha, Hongbin D; Fan, Zhen; Irwin, Sybil; Pittaluga, Stefania; Raffeld, Mark; Jaffe, Elaine S (2017). EBV-negative Aggressive NK-cell Leukemia/Lymphoma: Clinical, Pathologic, and Genetic Features. The American journal of surgical pathology, 41(1), pp. 67-74. Lippincott Williams & Wilkins 10.1097/PAS.0000000000000735

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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, βF1, TCRγ, LMP1, and EBV-encoded RNA. Polymerase chain reaction for TCRG clonality was polyclonal. Mutational analysis revealed missense mutations in the STAT3 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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Nicolae, Alina


500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health




Lippincott Williams & Wilkins




Ekkehard Hewer

Date Deposited:

11 Jul 2017 13:48

Last Modified:

05 Dec 2022 15:03

Publisher DOI:


PubMed ID:






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