title: Epstein-Barr virus-associated natural killer-large granular lymphocyte leukemia.
abstract: We describe the first case of an Epstein-Barr virus (EBV)-associated natural killer-large granular lymphocyte (NK-LGL) leukemia in the United States to the best of our knowledge. A 29-year-old woman of Japanese descent developed EBV infection after a blood transfusion as indicated by a rise in serum antibody titers. Peripheral blood and bone marrow aspirate smears demonstrated increased LGLs. Flow cytometry showed that these cells expressed NK-associated surface antigens. Cytogenetic analysis of the bone marrow aspirate showed two distinct but related clones with multiple copies of a modified 7 marker chromosome. Death followed colonic perforation. Findings at necropsy included bone marrow lymphocytosis and erythrophagocytosis, a mononucleosis-like lymphadenitis, atypical hepatitis with a mixed, predominantly T-cell infiltrate, interstitial pneumonitis, and multiorgan system vasculitis with perforation of the transverse colon. Epstein-Barr virus transcripts were identified in lymphocytes infiltrating liver and peripheral nerve by in situ hybridization. In addition, Southern blot analyses showed monoclonal bands superimposed on oligoclonal ladders of EBV termini in liver and lymph node. The identical episomal form of EBV was found in the bone marrow, lymph node, and liver. No immunoglobulin (Ig), T-cell receptor beta, or T-cell receptor gamma chain gene rearrangements were identified. These studies support the hypothesis that the LGL population was a neoplastic EBV-related clonal proliferation of NK cells.
authors.affiliation: Department of Pathology, Stanford University, CA.
authors.forename: A B
authors.initials: AB
authors.lastname: Gelb
authors.forename: M
authors.initials: M
authors.lastname: van de Rijn
authors.forename: D P
authors.initials: DP
authors.lastname: Regula
authors.forename: J P
authors.initials: JP
authors.lastname: Cornbleet
authors.forename: O W
authors.initials: OW
authors.lastname: Kamel
authors.forename: D S
authors.initials: DS
authors.lastname: Horoupian
authors.forename: M L
authors.initials: ML
authors.lastname: Cleary
authors.forename: R A
authors.initials: RA
authors.lastname: Warnke
mesh_terms: D000328:Adult; D015139:Blotting, Southern; D005260:Female; D005434:Flow Cytometry; D006566:Herpesviridae Infections / Q000473:pathology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D007621:Karyotyping; D007694:Killer Cells, Natural / Q000473:pathology*; D007945:Leukemia, Lymphoid / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D014412:Tumor Virus Infections / Q000473:pathology*