Plasmablastic Transformation of CLL/SLL: The Role of Early NGS Diagnosis and Targeted Multimodal Therapy

Abstract

Background: Plasmablastic lymphoma (PBL) is a rare and highly aggressive B-cell neoplasm most often associated with immunodeficiency. Transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) into PBL is exceptionally uncommon, particularly in immunocompetent individuals. This paper describes a rare synchronous SLL-to-PBL transformation and summarizes current knowledge on synchronous and metachronous cases reported in the literature. Methods: A 46-year-old immunocompetent woman presented with generalized lymphadenopathy and lumbar pain. Concurrent biopsies of an axillary lymph node and a retroperitoneal mass were obtained. Diagnostic evaluation included immunohistochemistry, fluorescent in situ hybridization (FISH), PCR-based assessment of IGH, IGK, and IGL loci, and next-generation sequencing (NGS) of IGHV to assess clonal relatedness. The patient was treated with six cycles of Dara-CHOP, followed by autologous stem cell transplantation and maintenance therapy with daratumumab and ibrutinib. Results: The axillary node showed SLL (CD20+, CD5+, CD23+), while the retroperitoneal mass demonstrated classic features of PBL (CD138+, MUM1+, MYC+, Ki-67 ~100%, CD20–). FISH detected MYC rearrangement in the PBL component. PCR and NGS confirmed identical IGHV1-69 rearrangements, establishing clonal relatedness and Richter transformation. Review of published cases shows that both synchronous and metachronous CLL/SLL-to-PBL transformations are exceedingly rare. The patient achieved partial metabolic remission after treatment and remains in sustained metabolic response 24 months after diagnosis. Conclusions: This case highlights a rare example of synchronous CLL/SLL-to-PBL transformation in an immunocompetent patient. Integration of detailed molecular diagnostics enabled early recognition and guided a personalized treatment approach incorporating CD38-targeted therapy and BTK inhibition, resulting in an excellent long-term clinical outcome.

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