Plasmablastic lymphoma, a rare highly aggressive non-Hodgkin's lymphoma subtype, often associated with HIV infection, is a close differential diagnosis of plasmablastic myeloma. The 2 conditions may be morphologically and immunophenotypically identical. However, differentiating between the 2 conditions is critical for adequate patient management. Herein, we describe an unusual case of plasmablastic myeloma with biclonal gammopathy which was initially diagnosed as plasmablastic lymphoma based on lymph node biopsy and immunohistochemistry (IHC) results. The incidental finding of lytic bone lesion on imaging prompted further investigations. The presence of multiple osteolytic lesions, biclonal gammopathy on serum protein electrophoresis and immunofixation, negative Epstein-Barr virus-encoded small RNAs on IHC led to revision of the diagnosis to plasmablastic variant of multiple myeloma. The patient was initially started on bortezomib plus dose-adjusted EPOCH chemotherapy for plasmablastic lymphoma. Subsequently, he was treated with RVD (lenalidomide, bortezomib, dexamethasone) regimen for plasmablastic myeloma and he achieved stringent complete response after 4 cycles.
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