Differential diagnosis of monoclonal gammopathy

With a large segment of the adult population now undergoing routine screening tests on a periodic basis, findings such as rouleaux when the complete blood count is performed or an elevated total protein and globulin fraction on serum chemistries often lead to the performance of a serum protein electrophoresis. When a monoclonal gammopathy is confirmed, the clinician is faced with a broad differential diagnosis that includes a variety of distinct malignant plasma cell disorders and lymphoproliferative diseases, as well as the high incidence of MGUS in the otherwise healthy adult population. Other benign causes of secondary monoclonal gammopathy, such as underlying inflammatory or infectious disorders or drug reactions, may add to the diagnostic dilemma in some patients. By following a systematic plan of laboratory evaluation such as that described here, however, and always keeping the patient's clinical status as a primary focus, the clinician should be able to arrive at a diagnosis and formulate a therapeutic plan in most instances. The most common differential diagnosis, that of MGUS versus PCM, still is difficult in some cases, and it is emphasized that careful follow up over time remains the best method at present for differentiating these two conditions. Once the basic laboratory evaluation of monoclonal gammopathy has been completed, further work-up will need to be individualized. In some cases, the preliminary evaluation will reveal a key feature, such as a monoclonal gammopathy that is IgM, which will lead to a rapid diagnosis of WMG and alert the clinician to investigate other nonroutine aspects of the laboratory evaluation, such as a serum viscosity or specific tests of hemostatic function. In other patients, the initial laboratory evaluation of monoclonal gammopathy may lead to other recommendations, such as lymph node biopsy for evaluation of possible lymphoma, or tissue biopsy to confirm the suspicion of amyloidosis. Overall, the evaluation of monoclonal gammopathy remains a challenging one, but one in which the clinician usually is rewarded with a diagnosis that will allow him to make appropriate management plans for his patient.