Snapshot A 72-year-old man presents to his primary care physician with fatigue. His symptoms are associated with fevers, chills, and nightsweats. He lost 25 pounds over the course of 3 months unintentionally. Laboratory studies are remarkable for an anemia. Other serum studies demonstrates a monoclonal IgM gammopathy. Bone marrow biopsy demonstrates 12% bone marrow infiltration of small lymphocytes with plasma cell differentiation. Introduction Overview B-cell lymphoproliferative neoplasm leading to excess production of monoclonal immunoglobulin (IgM) protein secondary to lymphoplasmacytic cell infiltration in the bone marrow ETIOLOGY Pathophysiology excessive proliferation of IgM-producing plasmacytoid lymphocytes, leading to the overproduction of abnormal IgM antibodies autoantibody attack against myelin-associated glycoprotein login to view 1 more bullet IgM against the patient's red blood cells login to view 1 more bullet IgM deposition in the kidneys, gastrointesttinal tract, or skin leads to serum hyperviscosity login to view 1 more bullet precipitates in serum in cold temperatures login to view 1 more bullet malignant B cells may infiltrate hematopoietic tissues leading to cytopenias lymphadenopathy hepatomegaly splenomegaly Genetics inheritance pattern somatic mutation mutations MDY88 gene Associated conditions anemia Epidemiology Demographics elderly patients Caucasian males Presentation Symptoms fatigue hyperviscosity syndrome headache vision impairment epistaxis leg cramps Studies Serum labs IgM monoclonal gammopathy any concentration Invastive studies bone marrow biopsy indication login to view 1 more bullet Histology ≥ 10% infiltration by small lymphocytes with plasmacytoid or plasma cell differentiation Differential Multiple myeloma differentiating factors CRAB findings login to view 4 more bullets ≥ 10% clonal plasma cells Monoclonal gammopathy of undetermined significance (MGUS) differentiating factors < 10% clonal plasma cells absence of lytic lesions serum M-protein is low Treatment There is no standard therapy Medical rituximab with chemotherapy indication login to view 1 more bullet Complications Hyperviscosity Peripheral neurology Cryoglobulinemia Amyloid amyloidosis Prognosis Median survival is ~10 years from time of diagnosis