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For further information, see CMDT Part 13-34: Plasma Cell Myeloma

Key Features

Essentials of Diagnosis

  • Bone pain, often in the spine, ribs, or proximal long bones

  • Monoclonal immunoglobulin (ie, paraprotein) in the serum or urine

  • Clonal plasma cells in the bone marrow or in a tissue biopsy, or both

  • Organ damage due to plasma cells (eg, bones, kidneys) or other defined criteria (eg, anemia, hypercalcemia)

General Considerations

  • Myeloma is a malignancy of hematopoietic stem cells terminally differentiated as plasma cells

  • It is characterized by infiltration of bone marrow, bone destruction, and paraprotein elaboration

  • Diagnosis is established when

    • Monoclonal plasma cells (either kappa or lambda light chain restricted) are associated with end organ damage (such as bone disease, anemia, hypercalcemia, or kidney injury) with or without paraprotein elaboration

    • Regardless of end organ damage, criteria for diagnosis include

      • Clonal plasma cells of 60% or more in the bone marrow, or

      • A serum free kappa to lambda ratio of > 100 or < 0.01

  • Plasmacytomas are tumors of malignant plasma cells that may cause spinal cord compression or other soft-tissue problems

  • Light chain components of immunoglobulin often lead to kidney injury

  • Light chain components may be deposited in tissues as amyloid, worsening kidney failure and causing other systemic syndromes (restrictive cardiomyopathy, autonomic and peripheral neuropathy, enlarged tongue, etc)

  • Myeloma patients are especially prone to infections with encapsulated organisms, eg, Streptococcus pneumoniae and Haemophilus influenzae


  • Occurs most commonly in older adults: median age at presentation is 65 years

Clinical Findings

Symptoms and Signs

  • Symptoms of anemia

  • Bone pain and tenderness, most common in back, hips, or ribs or in a pathologic fracture

  • Symptoms of kidney disease

  • Neuropathy or spinal cord compression

  • Soft tissue masses

  • Increased susceptibility to infection

Differential Diagnosis

  • Monoclonal gammopathy of uncertain significance (MGUS)

  • Waldenström macroglobulinemia

  • Primary amyloidosis

  • Chronic lymphocytic leukemia

  • Non-Hodgkin lymphoma (eg, small lymphocyte lymphoma)

  • Cryoglobulinemia


Laboratory Tests

  • Anemia is nearly universal

  • Red blood cell morphology is normal

  • Rouleaux formation is common and may be marked, but absence of rouleaux formation excludes neither plasma cell myeloma nor the presence of a serum paraprotein

  • Elevated erythrocyte sedimentation rate

  • Peripheral blood smear: plasma cells rarely visible (plasma cell leukemia if > 20%)

  • Elevated total protein

  • Hypercalcemia

  • Proteinuria

  • Serum protein electrophoresis (SPEP) usually demonstrates paraprotein, in the majority demonstrable as a monoclonal spike in γ- or β-globulin region

  • Immunofixation electrophoresis (IFE) reveals this to be a monoclonal immunoglobulin; 60% are IgG, 20% IgA, and 15% light chains only

  • Paraprotein may be demonstrated by urine protein electrophoresis (UPEP) or urine IFE even in the absence of demonstrable serum paraprotein

  • The International Staging System for myeloma relies on two ...

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