Clonal karyotype abnormalities in EBV-associated hemophagocytic syndrome

Abstract

Background and objective: An EBV-associated hemophagocytic syndrome (HS) in previously healthy children or young adults has been documented in Taiwan. The exact nature of this syndrome, i.e., either an infectious process or a neoplastic disease, remains to be clarified.

Methods: Three patients diagnosed as having HS were studied retrospectively. Chromosomes from bone marrow were examined by a conventional trypsin-Giemsa banding technique and karyotyped at the beginning of diagnosis or during treatment. In situ hybridization studies for EBV using EBER1 were performed.

Results: All three patients presented the classic manifestations of HS including fever, splenomegaly, jaundice, pancytopenia and coagulopathy. Bone marrow aspiration revealed atypical lymphocyte and histiocyte infiltration with hemophagocytosis. EBV genomes were found in bone marrow in all patients. In addition to normal mitotic cells, clonally karyotypically abnormal cells were demonstrated in all three patients whose diseases were rapidly progressive and eventually refractory to etoposide-based therapy. The consistent karyotypical abnormality of add(9)(p24) was noted in two of them.

Interpretation and conclusions: Although HS is usually considered a reactive process, the emergence of clonal cytogenetic abnormalities should be considered a malignant entity and treated with more intensive chemotherapy. A large series of cytogenetic and molecular studies is needed to clarify the exact nature of this fatal disease.