EBV infection induced transformation of benign T lymphoproliferative state in patient with chronic active EBV infection into malignant lymphoma: implication of EBV infection as additive oncogenic factor in tumorigenesis

An 11-year-old girl with chronic EBV (Epstein-Barr virus) infection, who later developed malignant lymphoma in the lung, is reported. She had an increased number of V alpha2, V beta8, CD3, CD4, and HLADR positive activated lymphocytes (20-30% of total lymphocytes) in peripheral blood. One year later, she developed lymphoma in the lung, which was V alpha2, V beta8, CD3, CD4, HLADR and IL2Rbeta positive. At that time, the population in the peripheral blood increased up to 40%, but there was no evidence of lymphoma in the bone marrow. In situ hybridization revealed lymphoma cells were EBER-1 positive but gp350/220 and LMP mRNA negative. The EBV genome was detected in the tumor, but not in the peripheral T cells. Clonal analysis of the lymphoma cells revealed monoclonal rearrangement of the TcRbeta and gamma gene, however, investigation of the terminal repeat of EBV gene did not show the monoclonal pattern. These results indicate that infection of EBV into clonally activated T cells was related with transformation from benign lymphoproliferative disease to malignant lymphoma in this patient.