Introduction Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of diffuse large B-cell lymphoma. Its transformation from multiple myeloma (MM) is an exceptionally rare event, with only nine cases reported in the literature. Differentiating PBL from plasmablastic myeloma (PBM) is a significant diagnostic challenge due to overlapping morphological and immunophenotypic features, yet it is critical for determining the appropriate treatment regimen. Case presentation We report the case of a woman in her 50s with a seven-year history of kappa-restricted MM who presented with a right leg mass. Biopsy confirmed a lambda-restricted plasmacytoma, indicating an extramedullary relapse. Two months after initiating therapy for myeloma relapse, she developed right inguinal lymphadenopathy. A lymph node biopsy revealed lambda-restricted plasmablasts positive for CD138, CD56, C-MYC, and Ki67 (100%), and negative for CD79a and EBER. In the absence of systemic MM-related end-organ damage and the presence of nodal disease, a diagnosis of PBL was favored over PBM. Conclusion The patient was subsequently treated with DA-EPOCH chemotherapy (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), leading to significant regression of disease on interim PET scan. This case represents the 10th reported transformation of MM to PBL and highlights the diagnostic dilemma posed by these entities. It underscores the importance of clinical context, the potential for clonal evolution (evidenced by a light-chain switch), and the efficacy of lymphoma-specific chemotherapy in this setting.
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