Waldenstrom’s macroglobulinemia (WM) is a lymphoma, or cancer of the lymphatic system. It is sometimes referred to as a lymphoplasmacytic lymphoma (LPL) with an associated monoclonal IgM paraprotein. The disease occurs in a type of white blood cell called a B-lymphocyte or B-cell, which normally matures into a plasma cell whose job is to manufacture immunoglobulins (antibodies) to help the body fight infection. In WM, there is a malignant change to the B-cell in the late stages of maturing, and it continues to proliferate into a clone of identical cells, primarily in the bone marrow but also in the lymph nodes and other tissues and organs of the lymphatic system. These clonal cells over-produce an antibody of a specific class called IgM.
Under the microscope, WM cells have characteristics of both B-lymphocytes and plasma cells, and they are called lymphoplasmacytic cells. For that reason, WM is classified as a type of non-Hodgkin’s lymphoma called lymphoplasmacytic lymphoma (LPL). About 95% of LPL cases are WM; the remaining 5% do not secrete IgM and consequently are not classified as WM. WM is a very rare disease – only about 1,500 patients are diagnosed with it each year in the US. WM is usually indolent (slow growing) and can be managed as a chronic disease for a number of years. However, it is not yet curable.
As a result of proliferation in the bone marrow and other sites, the lymphoplasmacytic cells of WM may interfere with normal functioning. In the bone marrow where blood cells are produced, the WM cells “crowd out” the normal blood cells and may lead to a reduction in normal blood counts; in the lymph nodes and other organs, the WM cells may lead to enlargement of these structures and other complications.
The over-production of IgM may also cause many of the symptoms associated with the disease. IgM is a large antibody and tends to make the blood thicker than normal, a condition called hyperviscosity. Unlike normal antibodies that fight infection, the IgM produced by WM cells has no useful function. Sometimes the IgM may incorrectly recognize the body’s tissues as “foreign” and attach to them, causing inflammation and injury.
Waldenstrom’s macroglobulinemia is named for the Swedish physician Jan Gosta Waldenström (1906-1996), who in 1944 identified a rare condition in which two patients experienced a thickening of their blood serum, bleeding of the mouth, nose, and blood vessels of the retina, low red blood cell and platelet counts, high erythrocyte sedimentation rates, and lymph node involvement. Bone marrow biopsies showed an excess of lymphoid cells and bone X-rays were normal, excluding a diagnosis of multiple myeloma. Both patients also had a large amount of a single unknown blood protein with an extremely high molecular weight, a “macro” globulin. We now know this globulin as IgM.