Epstein-Barr Virus-Associated CD3- Large Granular Lymphocyte Leukemia Presenting With Polycranial Nerve Palsies

A clinical entitity of large granular lymphocyte (LGL) leukemia was established based on the observation of clonality and the demonstration of tissue invasion by LGL of marrow, spleen, and liver.' The clonal expansion of LGL can be divided into two major lineages: CD3+ and CD3(natural killer: NK); however, it is still difficult to prove clonality in CD3NK LGL proliferation because CD3cells do not express the CD3E-cell receptor (TCR) complex or rearrange TCR genes? Usually an immediate diagnosis of CD3NK LGL leukemia has been made by the clinical manifestation such as an extreme increase of CD3LGL in blood and marrow, lymphadenopathy, hepatosplenomegaly, and other invasive symptoms. We present a case with CD3NK LGL proliferation only in cerebrospinal fluid (CSF), which did not have any leukemic features but only polycranial nerve palsies and could not be distinguished from the reactive LGL proliferation until a systemic leukemic progression occurred later. The clonality of LGL from this case was proven finally by analyzing the polymorphic fused termini of Epstein-Barr viral (EBV) g e n ~ m e . ~