In 1944 the Swedish physician Jan Gosta Waldenström (1906 - 1996) identified a rare condition in which patients experienced a thickening of the serum (the liquid portion) of the blood. He described two patients who had bleeding in the area of the mouth and nose as well as in the retina of the eye, low red cell and platelet counts, high sedimentation rate, and lymph node involvement. Bone marrow biopsy showed excess lymphoid cells, yet there was no bone pain, excluding a diagnosis of multiple myeloma. Both patients had a large amount of a single unknown globulin with an extremely high molecular weight. We now know this globulin as IgM. His patients, as Dr. Waldenström himself described in 1961, had a “monoclonal gammopathy.”
Waldenstrom’s macroglobulinemia (WM) is a malignant monoclonal gammopathy. It is considered to be lymphoplasmacytic lymphoma as defined by the Revised European American Lymphoma Classification (REAL) and the World Health Organization (WHO). The clinical features of this rare and indolent disease result from the presence of IgM paraprotein and infiltration of the bone marrow with lymphoplasmacytic cells. The clinical features are similar to those of multiple myeloma (MM) except that an enlarged spleen or liver is common in WM and uncommon in MM, while bone lesions and renal disease are common in MM and uncommon in WM.
The disease begins with a malignant change to the B-cell during its maturation so that it continues to reproduce more malignant B-cells. The result is an overproduction by the malignant B-cells of a protein called monoclonal immunoglobulin M antibody (IgM). WM is also characterized by a highly variable degree of bone marrow involvement. As a result of the cell changes and marrow involvement, normal functions of blood and lymph tissue are suppressed. WM is usually an indolent and chronic disease that is treatable. It is not yet curable.
The diagnosis of Waldenstrom’s macroglobulinemia generally depends on the results of blood and urine tests and a bone marrow biopsy. During this biopsy a needle is inserted into a bone and a small amount of bone marrow is withdrawn and examined under a microscope. More details of the diagnostic tests are available on the Prognosis page.
The causes of WM are as yet unknown. There are studies showing a degree of familial clustering of WM or a related disease in about 20% of the cases examined. Familial clusters of WM patients are now the basis for genetic investigations. Hepatitis C, hepatitis G, and herpes virus 8 have been implicated as causes of WM, but there are no strong data to support these links at this time.
Approximately 1,500 new cases of WM are diagnosed each year in the United States. The median age at diagnosis is 63 years; however, with better diagnostic tests and earlier diagnosis, the median age may change in the future.
After learning that you have a blood cancer, an incurable disease, the next question that comes to mind is “How long will I live?” There are older studies that suggest a median of 6.5 years beyond diagnosis, and more recent studies reporting average expectancy of 11.5 yeas. However, a median range of 6.5 or even 11.5 years is just a statistic. It is important to remember that we all have vastly different experiences with WM, with many living 3 to 4 times longer than the statistics might indicate. New studies are necessary in order to evaluate this statistic which is so important to patients and their families. You will, however, be interested in the recent development of an International Prognostic Scoring System for Waldenstrom’s macroglobulinemia (IPSSWM) that has been accepted globally. You will find it explained on the Prognosis page.