Review Question - QID 104646

The clinical presentation is consistent with Waldenstrom’s macroglobulinemia, which is associated with hyperviscosity syndrome (e.g. blurring or loss of vision, headache, ataxia, dementia, stroke, or coma) and a monoclonal IgM spike on serum protein electrophoresis.

Waldenstrom’s macroglobulinemia is a rare clinicopathological entity defined by 10 percent or more infiltration of bone marrow by clonal lymphoplasmacytic cells and a monoclonal IgM gammopathy. Symptoms range from non-specific (pallor, fatigue, weight loss) to organomegaly (lymphadenopathy, hepatosplenomegaly) to central nervous system signs and symptoms constituting hyperviscosity syndrome. IgM forms pentamers and the high levels of IgM antibodies in patients with Waldenstrom’s macroglobulinemia increases serum viscosity and can slow the passage of blood through capillaries, causing important neurologic manifestations and retinal vein engorgement. The diagnosis of Waldenstrom’s macroglobulinemia is based on bone marrow evaluation, in which at least 10% of the bone marrow is infiltrated by small lymphocytes.

O’Connell et al. present an approach to interpreting the serum protein electrophoresis laboratory test. A homogeneous spike in a focal region of the gamma-globulin zone indicates a monoclonal gammopathy; potential causes include multiple myeloma, Waldenstrom’s macroglobulinemia, plasmacytoma, monoclonal gammopathy of undetermined significance, and amyloidosis. Polyclonal gammopathies are more often associated with reactive or inflammatory processes.

Ghobrial et al. present results from a phase II trial of an oral mTOR inhibitor, everolimus, in the treatment of relapsed or refractory Waldenstrom’s macroglobulinemia, finding that the median progression-free survival was 21 months and the overall response rate was 50%. Setting the ground for further rigorous trials, this study provides support for the notion that everolimus is an active agent in relapsed or refractory Waldenstrom’s macroglobulinemia.

Illustration A depicts the fundoscopic exam of a patient with Waldenstrom’s macroglobulinemia exhibiting hyperviscosity-related changes including dilated retinal vessels, peripheral hemorrhages, and “venous sausaging.” Illustration B depicts a normal serum protein electrophoresis with the characteristic spikes for proteins such as albumin and antibodies (the gamma region on the right side). Illustration C depicts a serum protein electrophoresis with a monoclonal gammopathy, indicated by the unusually sharp band in the gamma region (the final red spike on the right side). In Waldenstrom’s macroglobulinemia, this sharp gamma band is related to IgM.

Incorrect Answers:
Answer 1: IgM monoclonal gammopathy of undetermined significance (MGUS) is defined by serum IgM concentration < 3.0 g/dL and the absence of anemia or other systemic symptoms. This can be a precursor state to multiple myeloma or Waldenstrom’s macroglobulinemia.
Answer 2: Multiple myeloma is a malignancy involving plasmacytes in the bone marrow, characterized by lytic bone lesions, formation of immunoglobulins (usually IgG and IgA), and renal failure.
Answer 4: Non-Hodgkin’s lymphoma defines a large group of malignancies involving lymphocytes, but would not be associated with a monoclonal IgM spike on SPEP.
Answer 5: Chronic lymphocytic leukemia is the most common type of leukemia in adults, affecting B cell lymphocytes, but would not be associated with a monoclonal IgM spike on SPEP.