An 82-year-old woman exhibited abdominal lymphadenopathy. Diffuse proliferation of large lymphoid cells with prominent nucleoli in irregular nuclei was observed in a biopsied abdominal lymph node (panel A; 40× objective, hematoxylin and eosin stain). These large cells were positive for CD20, CD10, BCL2 (panel B; 40× objective), BCL6, and multiple myeloma oncogene 1. Epstein-Barr virus (EBV)–encoded small RNA in situ hybridization was also positive (panel C; 40× objective). The t(14;18)(q32;q21) abnormality was identified via karyotyping. EBV infection of lymphoma cells with BCL2 rearrangement is rare, so we performed fluorescence in situ hybridization (FISH) analyses on formalin-fixed, paraffin-embedded specimens using probes for BCL2, immunoglobulin heavy chain (IGH), and EBV (which was made from EBV whole genome). In the assay using EBV (green), 3′IGH (blue), and 5′BCL2 (red) probes (panel D; 40× objective), BCL2::IGH translocation (arrowhead) was observed in the cells both with (panel E; 60× objective) (≈90%) and without (≈10%) EBV infection. Using EBV (blue), 5′BCL2 (red), and 3′BCL2 (green) probes, this result was confirmed, and EBV-negative cells with BCL2 rearrangement were clearly shown (panel F; 60× objective).
BCL2::IGH translocation is acquired in pro-B cells as a result of a mistake of IGH recombination during early B-cell development. In the present case, FISH for EBV genome, IGH, and BCL2 showed that EBV infection occurred in the course of lymphomagenesis probably after the BCL2 rearrangement.
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