Plasmablastic lymphoma through clonal expansion 17 years after EBV-positive DLBCL: case report and review.

Abstract

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.