Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of B-cell lymphoma associated with immunodeficiency and Epstein–Barr virus (EBV) infection. Although PBL can develop from indolent lymphomas, its occurrence long after diffuse large B-cell lymphoma (DLBCL) is rare. A 67-year-old man was diagnosed with EBV-positive DLBCL 17 years ago and achieved a sustained remission following six cycles of R-CHOP therapy. Seventeen years after the initial DLBCL diagnosis, the patient developed PBL with EBV-positive tumor cells. After three cycles of EPOCH therapy, the patient achieved a partial response and underwent upfront autologous stem cell transplantation, resulting in complete remission. To investigate the clonal relationship between DLBCL and PBL, immunoglobulin gene repertoire analysis using next-generation sequencing was performed on both specimens. In the PBL specimen, immunoglobulin heavy chain rearrangement revealed a dominant clone with a complementarity-determining region 3 (CDR3) length of 38 amino acids. Although the DLBCL specimen lacked a dominant clone meeting the clonality criteria, a minor clone with a CDR3 sequence similar to that of the PBL dominant clone was detected. This clone exhibited an unusually long CDR3 sequence (37 amino acids), likely contained stop codons, and was considered a nonfunctional clone. These findings suggest that PBL originated through expansion of a pre-existing minor subclone that persisted since the initial DLBCL diagnosis, driven by long-term clonal dynamics. Our case highlights the potential utility of immunoglobulin repertoire analysis in identifying clonal relationships among lymphomas, supporting treatment decisions, and understanding the pathogenesis of secondary lymphomas.
Ishii et al. (Thu,) studied this question.