Waldenstrom Macroglobulinemia, A Rare and Complicated Disease

WM is a rare disorder with an incidence of approximately three per million people per year with 1400 new cases diagnosed in the United States each year . The median age at diagnosis is 64 years; less than 1 percent of patients are under 40 years of age, and approximately 60 percent are males. WM is much more common in Caucasians than in other ethnic groups . Specifically, it is uncommon in Blacks and those of Mexican descent who make up approximately 5 percent of cases.
The majority of patients with the histopathologic finding of lymphoplasmacytic lymphoma (LPL) have a circulating monoclonal IgM consistent with the diagnosis of WM. In the past, LPL and WM have been arbitrarily differentiated from each other based on the level of the monoclonal IgM protein. Currently, the preferred terminology in cases of LPL with circulating monoclonal IgM is WM, rather than lymphoplasmacytic lymphoma, regardless of the size of the monoclonal IgM protein.

Waldenström macroglobulinemia, one of the malignant monoclonal gammopathies, is a chronic, indolent, lymphoproliferative disorder.It is characterized by the presence of a high level of a macroglobulin (immunoglobulin M [IgM]), elevated serum viscosity, and the presence of a lymphoplasmacytic infiltrate in the bone marrow. (See Pathophysiology, Etiology, and Workup.)
A clonal disease of B lymphocytes, Waldenström macroglobulinemia is considered to be a lymphoplasmacytic lymphoma, as defined by the Revised European American Lymphoma Classification (REAL) and World Health Organization (WHO) classification.
The clinical manifestations of Waldenström macroglobulinemia result from the presence of the IgM paraprotein and malignant lymphoplasmacytic cell infiltration of the bone marrow and other tissue sites. The clinical presentation is similar to that of multiple myeloma except that organomegaly is common in Waldenström macroglobulinemia and is uncommon in multiple myeloma and  lytic bony disease and renal disease are uncommon in Waldenström macroglobulinemia but are common in multiple myeloma. (See Pathophysiology, Presentation, and Workup.)

Complications

Complications of Waldenström macroglobulinemia include the following:

• Hyperviscosity syndrome
• Visual disturbances secondary to hyperviscosity syndrome
• Diarrhea and malabsorption secondary to gastrointestinal (GI) involvement
• Renal disease (less common)
• Amyloidosis of the heart, kidney, liver, lungs, and joints
• Bleeding manifestations secondary to platelet dysfunction and coagulation factor and fibrinogen abnormalities due to interaction with  plasma IgM
• Raynaud phenomenon secondary to cryoglobulinemia
• Increased predisposition to infection due to B-cell dysfunction (disease related) or T-cell dysfunction (therapy related, particularly after nucleoside analogues)
• Cardiac failure
• Increased incidence of lymphomas, myelodysplasia, and leukemias
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  Initially this disease may look like Multiple Myeloma, but one can see that extensive testing is required for diagnosis. Of course, a bone marrow biopsy is important so the pathologist can look for abnormalities in the bone marrow tissue.
   

  Blood counts

  The complete blood count (CBC) is a test that measures the levels of red cells, white cells, and platelets in the blood. If the lymphoma cells occupy too much of the bone marrow, these levels will be low.
  

  Quantitative immunoglobulins

  This test measures the blood levels of the different antibodies. There are several different types of antibodies in the blood: IgA, IgE, IgG, and IgM. The levels of these immunoglobulins are measured to see if any are abnormally high or low. In WM the level of IgM is high but the IgG level is often low.
  

  Electrophoresis

  The immunoglobulin produced in WM (IgM) is abnormal because it is monoclonal -- meaning that it is just many copies of the exact same antibody. Serum protein electrophoresis (SPEP) is a test that measures the total amount of immunoglobulins in the blood and finds any abnormal (monoclonal) immunoglobulin. Then, another test, such as immunofixation or immunoelectrophoresis, is used to determine the type of antibody that is abnormal (IgM or some other type). Finding a monoclonal IgM immunoglobulin in the blood is necessary to make a diagnosis of WM. The abnormal protein in WM is known by several different names, including monoclonal immunoglobulin M, IgM protein, IgM spike, IgM paraprotein, and M-spike. Other types of monoclonal immunoglobulins, like IgA or IgG, are seen in different disorders (like multiple myeloma and some lymphomas).
  Sometimes pieces of the IgM protein are excreted by the kidneys into the urine. The procedure used for finding a monoclonal immunoglobulin in the urine is called urine protein electrophoresis (UPEP).
  

  Viscosity

  Viscosity measures how thick the blood is. If the IgM level is too high, it will cause the blood to become thick (viscous) so that it can't flow freely. Think about pouring honey compared to pouring water. If the blood becomes too thick, the brain doesn't get enough blood and oxygen. This can be treated with plasmapheresis (see below).
  

  Cryocrit

  This tests the blood for a cryoglobulin (a protein that causes the blood to clump together in cool temperatures).
  

  Beta-2-microglobulin

  This is another protein produced by the malignant lymphoplasmacytoid cells. This protein itself doesn't cause any problems, but it is a useful indicator of a patient’s prognosis (outlook). High levels mean a poor outlook.
  
  WM is a rare disorder with an incidence of approximately three per million people per year with 1400 new cases diagnosed in the United States each year. The median age at diagnosis is 64 years; less than 1 percent of patients are under 40 years of age, and approximately 60 percent are males . WM is much more common in Caucasians than in other ethnic groups . Specifically, it is uncommon in Blacks and those of Mexican descent who make up approximately 5 percent of cases .
  The majority of patients with the histopathologic finding of lymphoplasmacytic lymphoma (LPL) have a circulating monoclonal IgM consistent with the diagnosis of WM. In the past, LPL and WM have been arbitrarily differentiated from each other based on the level of the monoclonal IgM protein. Currently, the preferred terminology in cases of LPL with circulating monoclonal IgM is WM, rather than lymphoplasmacytic lymphoma, regardless of the size of the monoclonal IgM protein.
  
  
  
• For more information:  www.medscape.com, www.uptodate.com, www.cancer.org