Systemic AL amyloidosis associated with Waldenström macroglobulinemia: an unusual presenting complication

A 66-year-old woman developed increasing fatigue over 6 months. Laboratory studies showed anemia (hemoglobin 10.2 g/dL), elevated serum immunoglobulin (Ig)M (1580 mg/dL), and IgM k M-protein. Imaging studies showed an enlarged heart, thickening of the esophagus, and slightly enlarged mediastinal lymph nodes (1.4 cm) without fluorodeoxyglucose-avid skeletal lesions. Serum viscosity was not increased. Bone marrow biopsy showed extensive interstitial and vascular amyloid deposition (panels A-B) associated with a B-cell infiltrate. Congo-red stain showed apple-green birefringence within amyloid deposits (panel C). Aspirate smears showed a mixture of small lymphocytes, lymphoplasmacytoid lymphocytes, and plasma cells. Flow cytometry immunophenotypic studies showed both k monoclonal B cells and k monoclonal plasma cells (panels D and E, respectively). A diagnosis of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (WM) with systemic amyloidosis was made. Mutational studies were negative for MYD88 (L265P) and positive for CXCR4 (G335S). Liquid chromatography tandem mass spectrometry analysis on Congo-red positive microdissected areas in paraffin-embedded tissue confirmed amyloid light-chain (AL) (k)-type. An abdominal fat pad biopsy was also positive for amyloid. The patient was started on rituximab, cyclophosphamide, and dexamethasone therapy.