question and answer
Investigating monoclonal gammopathies
December 2003
LYNNE DOUGAN, MD, of Powell River, BC, would like to know; "What would you recommend as the most useful and cost-effective way to investigate a monoclonal gammopathy in a 56-year-old clinically well woman?"
The three main monoclonal gammopathies (MG) are of IgA, IgG and IgM (IgD and IgE gammopathies are very rare). Investigating IgA and IgG gammopathies is the same, and is different from that for IgM conditions. MG used to be classified as benign and malignant, but since some of those initially classified as benign develop into a malignant form, the term "monoclonal gammopathy of undetermined significance" has replaced "benign MG." Malignant forms of IgA or IgG MG are multiple myeloma or light chain disease, and malignant forms of IgM MG include Waldenstršm's macroglobulinemia or other lymphoproliferative disorders such as chronic lymphocytic leukemia or lymphoma. Before you decide how far the patient should be investigated, you'll need to know the amount of IgA, IgG and IgM in the serum, the type and the level of monoclonal protein, as well as have a complete blood count, urinalysis, and serum urea, creatinine, protein, albumin and calcium levels. It's unlikely there's a malignant process requiring any therapy if IgA is less than 20 g/L and IgG is below 30 g/L, there's no suppression of normal immunoglobulins and the patient doesn't have anemia or cytopenia, renal impairment, proteinuria or hypercalcemia. Conversely, IgA higher than 20 g/L or IgG above 30 g/L, suppressed normal immunoglobulins or unexplained cytopenias, renal impairment, proteinuria or hypercalcemia call for further investigation, including bone marrow examination and skeletal survey to rule out multiple myeloma. A bone scan shouldn't be ordered, however, as it's not satisfactory for detecting osteolytic lesions of multiple myeloma. At this stage, your best bet is to consult a hematologist or oncologist to complete the investigation and provide advice on managing the case. In cases of IgM MG, if the patient is asymptomatic, IgM is less than 20 g/L and there's no cytopenia, therapy probably isn't required even if the underlying condition is leukemia or lymphoma. Periodic follow-up would be justified. If she has symptoms suggesting lymphoma or hyperviscosity, or cytopenia or IgM above 20 g/L, further investigation is required, so you should refer her to a hematologist or oncologist. MS
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