Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and multiple myeloma

Introduction The plasma cell dyscrasias are a diverse group of disorders characterized by the presence of a monoclonal plasma cell population in the bone marrow. The most common plasma cell disorders include monoclonal gammopathy of undetermined significance (MGUS), solitary plasmacytoma, smoldering myeloma (SMM), multiple myeloma (MM), primary (AL or immunoglobulin light chain) amyloidosis, and Waldenstrom's macroglobulinemia (WM) (Table 10.1). This chapter is focused on the pathogenesis, clinical features, diagnosis, and management of MGUS, SMM, and MM. Laboratory testing for monoclonal proteins Monoclonal immunoglobulins are commonly referred to as monoclonal proteins, M proteins, or paraproteins. The presence of an M protein is indicative of an underlying clonal plasma cell proliferative disorder, although further testing is required to distinguish among the various plasma cell disorders. Serum protein electrophoresis and immunofixation Agarose gel serum protein electrophoresis (SPEP) and serum immunofixation (IF) are the main methods of detection of serum M proteins (Figure 10.1a and b). M proteins appear as localized bands on SPEP. Although presence of a localized band on SPEP is suggestive of M protein, IF is necessary for confirmation as well as to determine the heavy- and light-chain classes of the M protein. In addition, serum IF is more sensitive than SPEP and can detect smaller amounts of M protein, and should therefore be performed whenever MM or a related disorder is suspected. The size of the M protein is measured using the SPEP; small M proteins < 1 g/dL on SPEP and M proteins that are apparent only on serum IF are considered “unmeasurable.”