VIRUS-ASSOCIATED HEMOPHAGOCYTIC SYNDROME CHARACTERIZED BY CLONAL EPSTEIN-BARR-VIRUS GENOME

Virus-associated hemophagocytic syndromes are a heterogeneous group of disorders in which viral infection is associated with a proliferation of hemophagocytic histiocytes throughout the reticuloendothelial syst em. The authors report the case of a 24-year-old Vietnamese male who d eveloped a hemophagocytic syndrome associated with Epstein-Barr virus (EBV) and who died following a rapidly progressive course. A prolifera tion of reactive-appearing lymphoid cells was associated with an exten sive proliferation of erythrophagocytic histiocytes. Immunophenotypica lly, the lymphoid infiltrate consisted of CD56+ natural killer cells, predominantly CD8+ T-cells and rare B-cells (CD20+). Double-label immu nohistochemical studies showed CD3+ T-cells and CD56+ natural killer c ells to be distinct cell populations. Combined immunohistochemical-in situ hybridization studies localized EBV to CD43+, CD3-, CD68-, lympho id-appearing cells, indicating the presence of EBV within natural kill er cells. Southern hybridization analysis of EBV genomic termini revea led clonal EBV genome. However, there was no detectable immunoglobulin or T-cell receptor gene rearrangements. The findings indicate that th is case of hemophagocytic syndrome represents a clonal proliferation o f natural killer cells containing EBV and highlights the importance of the analysis of EBV genomic termini for determination of clonality in EBV-associated proliferations. It is possible that other cases of ful minant EBV-associated hemophagocytic syndromes represent clonal natura l killer cell proliferations.