AGGRESSIVE PERIPHERAL T-CELL LYMPHOMA CONTAINING EPSTEIN-BARR-VIRUS GENOMES

A 42-year-old woman presented in December 1995 with a half-year histor y of asymptomatic erythematous plaques with firm induration on her ext remities (Fig, 1). In the biopsy specimen, they were composed of mediu m-to large-sized pleomorphic lymphoid cells with nuclear atypia and fr equent mitoses, which extensively infiltrated the dermis and subcutis (Pig. 2a). There were also large phagocytic cells filled with nuclear dusts and erythrocytes (Pig. 2b). Immunohistochemical staining perform ed on paraffin-embedded sections using the labeled streptavidine-bioti n-immunoperoxidase technique revealed that the atypical lymphoid cells were positive for CD3, a T-cell marker, but negative for CD20, a B-ce ll marker. Large phagocytic cells were positively stained with PGM1, a macrophage marker. Unfortunately, we could not obtain further informa tion concerning the gene rearrangement or immunostaining of the T-cell receptor because only paraffin-fixed samples were available, A comple te blood cell count revealed mild thrombocytopenia, but it was otherwi se within normal limits. Atypical cells were absent in the peripheral blood and bone marrow, The serum level of lactate dehydrogenase was el evated at 1402 IU/L, Antibodies to human T-lymphotrophic virus (HTLV-1 ) were negative. The titers of antibodies to human Epstein-Barr virus (EBV) were as follows: viral capsid antigen (VCA) IgM type, <10; VCA I gG type, 640; early antigen (EA) IgG, 40; EBV-determined nuclear antig en (EBNA), 40. Under a diagnosis of T-cell lymphoma, we suspected the association of the lymphoma cells with EBV infection from the moderate ly high titers of antibodies to EBV, and performed in situ hybridizati on for EBV-encoded nuclear RNAs (EBER), After hybridization, the detec tion of specifically bound fluorescein (FITC)-conjugated antisense RNA probes (Dako, Kyoto, Japan) was achieved by anti-FITC monoclonal anti body conjugated with alkaline phosphatase. More than 90% of lymphoid c ells exhibited EBER-positive nuclei, and almost all of the infiltratin g cells in the same area expressed CD3 and CD45RO, No signal was obser ved for sense RNA probes, and suitable control specimens from EBV-posi tive and EBV-negative cases were used as controls for EBV detection. T ogether with a rapid exacerbation of the skin tumors, a marked protrus ion of the left eye appeared, behind which computed tomographic (CT) s can demonstrated the presence of a mass. CT scan of the abdomen also r evealed large masses compatible with lymphoma. The patient was treated with cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) . However, the response to this therapeutic regimen was transient with only a brief remission interval, and the patient died of progressive disease 2 months after starting the chemotherapy.