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