Rare Concomitance of Primary Systemic Amyloidosis with Immunoglobulin M Monoclonal Gammopathy or Waldenstrom Macroglobulinemia.

Introduction: Primary systemic amyloidosis occurs when a clonal plasma cell population secretes light chains (or light chain fragments) that deposit in tissues as amyloid and cause organ failure and ultimately patient death. Primary systemic amyloidosis generally results from non-proliferative small populations of plasma cells. While it is known that IgG, IgA and light chain producing plasma cells can secrete amyloid in association with myeloma, fewer medical professionals recognize that IgM-secreting lymphoplasmacytic cells can produce amyloid proteins. When monoclonal IgM secreting marrow lymphocytes are present, amyloidosis can result with or without overt Waldenstrom Macroglobulinemia. Patients and Methods: All patients seen at the Mayo Clinic between January 1968 and August 2000 with both a serum IgM monoclonal protein and biopsy-proven amyloidosis were analyzed. The Mayo Clinic Dysproteinemia Database recognized 128 patients (42 female, 86 male) with a median age of 65 years. Results: Seventy-two percent (n=92) of the patients have died with a median survival of 1.72 years following biopsy proven amyloidosis (figure 1). Median serum IgM monoclonal spike was 1.38 g/dL. In addition, serum IgM kappa to lambda light chain ratios (1:3) were found to be reversed in patients with IgM gammopathy when amyloid was present (compared to the reverse ratio (3:1) in patients with Waldenstrom macroglobulinemia in the absence of amyloidosis). Subcutaneous fat, rectum and bone marrow revealed amyloid in 72%, 69% and 70%, respectively, providing non-invasive techniques for amyloidosis diagnosis without the risks of bleeding associated with renal or hepatic percutaneous biopsy. Variables not shown to affect survival included the following: age, gender, serum M spike, urine protein, alkaline phosphatase, creatinine, light chain isotype, ejection fraction, and percent marrow plasma cells. The presence of amyloid cardiomyopathy (defined as a cardiac interventricular septal thickness greater than 12 mm.) was the only variable to adversely affect survival. Of the patients with echocardiographic evidence of cardiomyopathy, the median survival was 10.8 months. In contrast, the patients without echocardiographic evidence of cardiomyopathy at diagnosis had a median survival of 39 months (figure 2). Conclusion: Amyloidosis is underappreciated and should be considered in the differential diagnosis of all patients presenting with IgM gammopathy. Patients found to have amyloidosis in this setting should be tested for amyloid cardiomyopathy, as its presence predicts poor outcome. Lambda light chain in serum IgM samples should increase the index of suspicion for the presence of amyloid since IgM lambda is present in only 25% of IgM MGUS or Macroglobulinemia patients but is seen in 75% of IgM amyloidosis patients. Figure Figure