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 system. The authors report the case of a 24-year-old Vietnamese male who developed a hemophagocytic syndrome associated with Epstein-Barr virus (EBV) and who died following a rapidly progressive course. A proliferation of reactive-appearing lymphoid cells was associated with an extensive proliferation of erythrophagocytic histiocytes. Immunophenotypically, the lymphoid infiltrate consisted of CD56+ natural killer cells, predominantly CD8+ T-cells and rare B-cells (CD20+). Double-label immunohistochemical studies showed CD3+ T-cells and CD56+ natural killer cells to be distinct cell populations. Combined immunohistochemical-in situ hybridization studies localized EBV to CD43+, CD3-, CD68-, lymphoid-appearing cells, indicating the presence of EBV within natural killer cells. Southern hybridization analysis of EBV genomic termini revealed clonal EBV genome. However, there was no detectable immunoglobulin or T-cell receptor gene rearrangements. The findings indicate that this case of hemophagocytic syndrome represents a clonal proliferation of 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 fulminant EBV-associated hemophagocytic syndromes represent clonal natural killer cell proliferations.
Department of Pathology, Stanford University Medical Center, California.
M V
MV
Dolezal
O W
OW
Kamel
M
M
van de Rijn
M L
ML
Cleary
R K
RK
Sibley
R A
RA
Warnke
D000328:Adult; D015139:Blotting, Southern; D005260:Female; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D015616:Histiocytosis, Non-Langerhans-Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization