MGUS and Its Clinical Variants

Monoclonal gammopathy of undetermined significance (MGUS) represents a premalignant plasma cell disorder characterized by the presence of a small clone of plasma cells producing monoclonal immunoglobulin in the absence of overt organ damage. Most individuals with MGUS remain asymptomatic and never develop clinically significant disease. Nevertheless, a subset of patients may progress to multiple myeloma or related lymphoproliferative disorders over time. In recent years, it has become evident that monoclonal proteins may themselves cause tissue injury even when diagnostic criteria for hematologic malignancy are not fulfilled. These disorders are collectively described as monoclonal gammopathies of clinical significance (MGCS). Renal involvement is the most frequently recognized manifestation and is termed monoclonal gammopathy of renal significance (MGRS). Other organs that may be affected include the peripheral nervous system, skin, eyes, and components of the hemostatic system. This chapter provides an overview of MGUS and reviews the spectrum of organ-specific disorders associated with pathogenic monoclonal proteins.