EPSTEIN-BARR VIRUS-ASSOCIATED NATURAL-KILLER LARGE GRANULAR LYMPHOCYTE LEUKEMIA

We describe the first case of an Epstein-Barr virus (EBV)-associated n atural killer-large granular lymphocyte (NK-LGL) leukemia in the Unite d States to the best of our knowledge. A 29-year-old woman of Japanese descent developed EB V infection after a blood transfusion as indicat ed by a rise in serum antibody titers. Peripheral blood and bone marro w aspirate smears demonstrated increased LGLs. Flow cytometry showed t hat these cells expressed NK-associated surface antigens. Cytogenetic analysis of the bone marrow aspirate showed two distinct but related c lones with multiple copies of a modified 7 marker chromosome. Death fo llowed colonic perforation. Findings at necropsy included bone marrow lymphocytosis and erythrophagocytosis, a mononucleosis-like lymphadeni tis, atypical hepatitis with a mixed, predominantly T-cell infiltrate, interstitial pneumonitis, and multiorgan system. vasculitis with perf oration of the transverse colon. Epstein-Barr virus transcripts were i dentified in lymphocytes infiltrating liver and peripheral nerve by in situ hybridization. In addition, Southern blot analyses showed monocl onal bands superimposed on oligoclonal ladders of EBV termini in liver and lymph node. The identical episomal form of EBV was found in the D one marrow lymph node, and liver. No immunoglobulin (Ig), T-cell recep tor beta, or T-cell receptor gamma chain gene rearrangements were iden tified. These studies support the hypothesis that the LGL population w as a neoplastic EBV-related clonal proliferation of NK cells. HUM PATH OL 25:953-960. Copyright (C) 1994 by W.B. Saunders Company