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

Demographics

• 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

Diagnosis

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 ...