Differential diagnosis of multiple myeloma

Distinguishing multiple myeloma from B-cell lymphomas can be a diagnostic challenge. There can be significant morphologic, immunophenotypic and clinical overlap that may require additional molecular genetic ancillary studies and careful clinical review to render an accurate diagnosis. The focus of this review will be on the differential diagnosis of multiple myeloma with an emphasis on low-grade B-cell lymphomas with plasmacytic differentiation and aggressive B-cell lymphomas with plasmablastic morphology that can mimic true plasma cell neoplasms. Diagnostic approaches to plasmablastic neoplasms, including extramedullary plasmablastic plasmacytoma and distinguishing features of B-cell lymphomas with plasmablastic morphology are discussed. Low-grade B-cell lymphomas with plasmacytic differentiation, including lymphoplasmacytic lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and other low-grade B-cell lymphomas that less frequently exhibit plasmacytic differentiation such as follicular lymphoma and mantle cell lymphoma are also included. Multiple myeloma with CCND1:IGH, which can mimic low-grade B-cell lymphomas and post-treatment plasmacytic proliferations following treatment for B-cell lymphomas with plasmacytic differentiation are also discussed.