The terms “plasma cell disorders” or “plasma cell dyscrasias” are used interchangeably for a group of diseases characterized by transformation and monoclonal expansion of plasma cells, that, in the majority of cases, secrete a product called the M-protein or paraprotein.

Unexplained bone pain, spontaneous fractures, elevated serum total protein, renal insufficiency, proteinuria, neuropathy, recurrent infections, and anemia should prompt investigation for plasma cell dyscrasia.

Baseline assessment of any plasma cell disorder includes quantification of the clonal protein by serum protein electrophoresis, serum-free light chain assay, and since urine protein excretion varies during the day, 24-hour urine collection for urine protein electrophoresis.

The combination of serum immunofixation, urine immunofixation, and serum-free light chain assay will reliably rule out secretory plasma cell disorders if negative (no monoclonal band on immunofixation and normal serum-free kappa/lambda ratio) but, if multiple myeloma is strongly suspected, a bone marrow examination is indicated to rule out nonsecretory myeloma.

Skeletal survey (plain X-rays from skull to ankles) remains a standard test to evaluate for lytic bone disease in all plasma cell disorders but patients with otherwise asymptomatic myeloma should undergo additional imaging (PET/CT or whole-body MRI) to rule out early myeloma-related bone disease.

Multiple myeloma (MM) is the second most frequent hematologic malignancy with an incidence of 6 to 7 cases per 100,000 per year.

Both monoclonal gammopathy of undetermined significance (MGUS) and MM affect African Americans more frequently than Caucasians, and in all races are more common in men.

Symptomatic multiple myeloma (sMM) differs from asymptomatic multiple myeloma (aMM) and MGUS by the presence of significant organ dysfunction, now called myeloma-defining events (MDEs).

Myeloma-defining events include plasma cell disorder-related hyperCalcemia, Renal insufficiency, Anemia, Bone lesions (CRAB symptoms), and hyperviscosity.

The quantity of monoclonal protein and/or bone marrow plasma cells differentiates MGUS from aMM. Both conditions require the absence of significant clonal plasma cellrelated organ dysfunction.