Coexistence of lymphoplasmacytic lymphoma and multiple myeloma: a case report and review of literature.

Lymphoplasmacytic lymphoma (LPL) and multiple myeloma (MM) are distinct B-cell neoplasms whose synchronous occurrence is extremely rare. We report a case of a 68-year-old man presenting with fatigue and bone pain. Laboratory studies showed hyperglobulinemia (71.1 g/L), severe normocytic anemia (hemoglobin 44 g/L, MCV 79.5 fL), and thrombocytopenia. Serum immunofixation revealed dual IgG-kappa and IgM-kappa monoclonal proteins. Imaging showed diffuse osteolytic lesions in the skull and spine. Bone marrow flow cytometry identified two immunophenotypically distinct populations: CD19+/CD20+/CD5-/CD10- B-cells (34.1%) and CD138+/CD38+/cytoplasmic kappa+ plasma cells (4.5%). Next-generation sequencing on unsorted whole bone marrow detected MYD88 c.779T>C (p.Leu260Pro, canonical L265P) with a variant allele frequency (VAF) of 40.00% and CXCR4 c.1013C>G (p.Ser338*) nonsense mutation with VAF 15.53%, confirming LPL. Although the clonal plasma cell percentage was below the traditional 10% threshold, the presence of unequivocal osteolytic lesions and severe anemia (CRAB criteria) supported a diagnosis of active MM. The patient was treated with zanubrutinib, bortezomib, and dexamethasone, achieving a partial response. This case strongly suggests that LPL and MM can coexist, but definitive proof of biclonality would require sorted-cell molecular studies. We highlight the diagnostic challenges and the importance of integrating clinical, immunophenotypic, and molecular data.