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Learning Objectives

  • Differentiate the plasma cell disorders (PCDs)—monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, multiple myeloma (MM), solitary plasmacytoma, and primary amyloidosis.

  • Identify the common clinical clues that should trigger concern for the PCDs.

  • Apply preventive measures to reduce the risk of fractures and infection in those being treated for PCDs.

Key Clinical Points

  1. PCDs are among the few neoplasms where routine laboratory testing other than by tissue biopsy can detect a clonal population by detection of monoclonal protein in the serum or urine.

  2. Male gender and African-American race are risk factors for all PCDs.

  3. All patients with PCDs require evaluation for associated abnormalities, that is, “CRAB” criteria: hypercalcemia, renal insufficiency, anemia, or bone lesions.

  4. Prevention of complications in those with MM includes intravenous bisphosphonates to reduce the risk of pathologic fractures or painful lytic lesions requiring radiation and infection prophylaxis with pneumococcal vaccine, annual influenza vaccine, and, for patients receiving proteasome inhibitors (bortezomib and carfilzomib), herpes zoster prophylaxis with acyclovir or valacyclovir.


Plasma cell disorders (PCDs) encompass a range of clonal conditions, ranging from monoclonal gammopathy of undetermined significance (MGUS), which is by definition asymptomatic and requires no treatment, through multiple myeloma, wherein the clonal plasma cells cause end-organ damage, require therapy, and will ultimately cause the patient’s death if left untreated. The incidence of PCDs increases with age, and the presence of multimorbidity may make it a challenge to distinguish between end-organ damage (ie, anemia, renal insufficiency, or vertebral compression fractures) related to a plasma cell disorder versus another underlying comorbid condition.

Laboratory Evaluation

Plasma cell disorders are among the few neoplasms where routine laboratory testing other than tissue biopsy can detect the “fingerprint” of a clonal population, in this case detection of a monoclonal protein in the serum or urine. This protein may be referred to as a paraprotein, M-component/M-spike or restricted peak. The monoclonal protein may be an intact immunoglobulin (comprised of both heavy and light chains), light chain only or, rarely, heavy chain only. Advances in laboratory technology have allowed more sensitive and specific detection and identification of a paraprotein and have improved our ability to monitor response to treatment in those PCDs that require treatment.

Serum protein electrophoresis

In serum protein electrophoresis (SPEP), the serum proteins are separated by an electric field on an agarose gel and stained with Amido black, and quantitated by densitometer tracing of the gel. An alternate, more sensitive SPEP method, involves separation of serum proteins in a capillary tube in a liquid phase buffer by a high-voltage current and quantitation by light absorbance. The latter mechanism is more accurate as it does not rely on uptake of dye. Monoclonal proteins are named for the protein region in which they migrated, such as α1, α2, β, or ...

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