The relationship of Epstein-Barr virus to infection-related (sporadic) and familial hemophagocytic syndrome and secondary (lymphoma-related) hemophagocytosis: an in situ hybridization study

Abstract

Many cases of hemophagocytic syndrome have been associated with viral infections, particularly Epstein-Barr virus (EBV), but the pathogenesis of the syndrome remains unclear. We have examined lymph node, spleen, liver, and bone marrow sections from 12 cases, including four cases of proven or probable infection-related hemophagocytic syndrome (IHPS), three cases of familial hemophagocytic syndrome (FHPS), and five cases of secondary hemophagocytosis associated with T-cell malignant lymphoma (SHPC), for EBV RNA using a sensitive and specific in situ hybridization technique. Epstein-Barr virus RNA was detected in seven of 12 cases (58%), including three cases of IHPS, one case of FHPS, and three cases of SHPC. Numerous EBV-positive cells were detected in two cases of IHPS (in multiple anatomic sites) and in one case of FHPS (in the spleen). Diffuse EBV positivity also was noted within the neoplastic cells of one case of SHPC. Rare to occasional EBV-positive cells were found in multiple sites in another case of IHPS and within admixed, reactive lymphoid cells in two cases of SHPC. The results indicate that numerous EBV-positive cells can be identified in some cases of IHPS, FHPS, and SHPC, suggesting a pathogenetic role for the virus. However, the absence of EBV from a proportion of cases of IHPS and FHPS in this study suggests that other infectious agents also play a role in the pathogenesis of this syndrome.