Diagnosis

The detection of a paraprotein in the serum is often an incidental finding in a healthy individual undergoing routine testing, or in someone undergoing evaluation for an unrelated disorder. An agarose gel electrophore-sis is the preferred method for evaluation of M protein in the serum, and is more sensitive than cellulose acetate. The monoclonal protein appears as a localized band on the agarose gel electrophoresis, and when converted to a densitometric tracing appears as a tall spike or peak (Figure 89.1). The M spike is usually seen in the P or y region of the densitometer tracing, though occa sionally it can occupy the a2-globulin region. In contrast, a polyclonal increase in the gamma globulin is manifested as a broad peak in the y region. Once an electrophoretic abnormality suggestive of M protein is seen on the electrophoresis, immunofixation should be performed to confirm the presence of the monoclonal protein as well as to characterize the heavy-chain class (G, A, M, E, or D) and the type of light chain (k or X). In addition to identifying the presence of the monoclonal protein, the protein can be quantitated by rate neph-elometry, which is important for the follow-up of these patients. Nephelometry results may be higher than those expected on the basis of the densitometry tracing from serum protein electrophoresis, especially in the case of IgM.

An M protein may also be present in the urine, which should be examined in patients with monoclonal gammopathies. Similar techniques are used for urine protein electrophoresis, and should be performed on 24-h collections. The percentage of M protein on the densitometer tracing, and the total protein excretion over a 24-hour period, will allow calculation of the M protein excreted during this time period.

Once an M protein is identified, the next step is to rule out the presence of another plasma cell disorder, such as MM, amyloidosis, or macroglobulinemia (see differential diagnosis, below). A compete blood count

Figure 89.1 Serum protein electrophoresis and immunofixation. The left side panels show the protein electrophoresis and immunofixation pattern from a normal serum sample. On the right is a patient with myeloma and IgG kappa monoclonal protein. The monoclonal protein appears as an abnormal band on the agarose gel elec-trophoresis that is converted to an M-spike in the gamma region on the densitometric tracing. The immunofixation demonstrates the type pf M-protein as an IgG kappa

Figure 89.1 Serum protein electrophoresis and immunofixation. The left side panels show the protein electrophoresis and immunofixation pattern from a normal serum sample. On the right is a patient with myeloma and IgG kappa monoclonal protein. The monoclonal protein appears as an abnormal band on the agarose gel elec-trophoresis that is converted to an M-spike in the gamma region on the densitometric tracing. The immunofixation demonstrates the type pf M-protein as an IgG kappa and chemistry panel, including calcium and creatinine, should be obtained in all individuals. C-reactive protein and ^-microglobulin levels should be obtained as well. The presence of anemia or renal insufficiency points toward a more advanced plasma cell proliferative disorder, unless another explanation is found. A bone marrow biopsy to estimate the plasma cell percentage is not necessary for the diagnosis of MGUS, and should be reserved for those with higher amounts of M protein (>1.5 gm/dL) or if there is a strong clinical suspicion for another plasma cell disorder. A skeletal survey that includes films of the long bones and skull should be obtained, especially in those with larger M-protein levels and in those whom clinical suspicion for MM is high.

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