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

<b>Background and Clinical Significance:</b> 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. <b>Case Presentation</b> A midle-aged immunocompetent patent 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. 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. A 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. <b>Conclusions</b>: 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.