Fatal Epstein-Barr virus-associated lymphoproliferative disorder in childhood.

Abstract

We report five childhood cases of fatal Epstein-Barr virus-associated lymphoproliferative disorder to determine their immunopathologic and immunogenotypic features. Clinicopathologic features are described, using clinical, histologic, immunophenotypic, and genotypic examinations. Autopsy cases were performed at Nagoya and Tsukuba university hospitals, Japan. Infiltrating lymphocytes, which were positive for the EBV genome by in situ hybridization, were polymorphic and showed polyclonal immunoglobulin staining in all five cases. Two cases, however, showed genetic clonality of EBV termini. In one case, the clonality was observed only in the spleen, and in the other case, clonal rearrangement of the JH gene was also found. The former case showed none of the morphologic features of neoplasia and presented a morphology similar to virus-associated hemophagocytic syndrome. In the latter case, infiltrating lymphoid cells were much less polymorphous, and nodular masses of the lymphoid cells in colon and lung specimens were observed. We suggest that some polyclonal EBV-associated lymphoproliferative disorders develop into polymorphic, but genotypically monoclonal, lymphoproliferative disorders.