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Multiple Myeloma

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Tests and Staging

The goals of testing for multiple myeloma are to diagnose the condition, determine its severity and spread, monitor its progress, detect complications as they arise, and monitor the effectiveness of treatment. There is no one single test that can diagnose multiple myeloma. Typically, the disease is diagnosed using a combination of a person's signs and symptoms, medical history, physical examination, laboratory tests, and/or imaging tests.

Laboratory tests
Multiple myeloma may first be detected during routine wellness testing, showing up as an abnormal total protein, an elevated calcium, a low white or red blood cell count, and/or moderate to large amounts of protein in the urine. Findings such as these may raise suspicions but are not diagnostic as similar abnormalities may be seen with a variety of other conditions; they indicate the need for further testing.

Tests used as a follow-up to abnormal routine tests and to help diagnose the disease may include one or more of the following:

  • Protein and immunofixation electrophoresis. These tests are used to help diagnose and monitor multiple myeloma. Protein electrophoresis separates the proteins in a blood or urine sample into several groups based on their electrical charge and size. In most people with multiple myeloma, large amounts of an abnormal immunoglobulin protein (M-protein) will show up as a large peak on the electrophoresis graph, also known as an M spike. The amount of normal immunoglobulins in the sample may be visibly decreased as well. Usually, both a blood and a urine sample will be tested during the diagnosis of multiple myeloma because some proteins, such as the Bence Jones proteins (free light chains), may not show up in significant quantities in blood samples, while those with only intact immunoglobulins may not have the abnormal protein in urine. Immunofixation electrophoresis is done to identify the specific type of protein that is being produced by the malignant plasma cells. The amount of protein produced may vary throughout the course of the disease, but the type will remain the same.
  • Bence Jones protein (free light chains) can be detected in the urine of some people with multiple myeloma. The sample tested is usually a 24-hour urine because the total amount of Bence Jones protein in 24 hours is related to the amount of tumor that is present. Either the kappa or lambda light chains (but not both in the same person) may be measured to help diagnose multiple myeloma and monitor the effectiveness of treatment.
  • Serum free light chains (FLC). This test measures the amount of free light chains in the blood. Even in normal circumstances (and for unknown reasons), plasma cells produce an excess of light chains compared to heavy chains, and there is usually a small amount of light chains that do not become incorporated into intact immunoglobulins. These remain as free light chains and are released into the bloodstream. Most people with multiple myeloma produce increased amounts of either kappa or lambda free light chains, which can be measured in blood. Consequently, the ratio of kappa to lambda light chains is abnormal in most people and is a sensitive indicator for this disease. This test is used to monitor progression and/or treatment.
  • Quantitative immunoglobulins. Each of these tests measures amounts of a different type of immunoglobulin. The multiple myeloma protein will be an IgG, IgA or, rarely, an IgD or IgE immunoglobulin. People with a monoclonal IgM immunoglobulin may have a related but different disease (Waldenstrom macroglobulinemia). IgG, IgA, and IgM may be ordered to help diagnose multiple myeloma and to monitor the course of the disease and its effect on the production of normal immunoglobulins. Note that the test does not differentiate abnormal immunoglobulin produced by myeloma cells and the non-tumor immunoglobulin of the same type produced by normal plasma cells.
  • Serum immunoglobulin heavy chain/light chain assays can identify separately the different light chain types of each immunoglobulin class, including IgG-kappa, IgG-lambda, IgA-kappa, IgA-lambda, IgM-kappa, and IgM-lambda. The molecules are then measured in pairs (e.g., IgG-kappa / IgG-lambda) to calculate ratios of involved monoclonal immunoglobulin to background uninvolved immunoglobulin concentrations. The tests can be used to monitor people with multiple myeloma.
  • Bone marrow aspiration and biopsy. 
Multiple myeloma is a disease of the bone marrow. People usually require a bone marrow evaluation to confirm the diagnosis, evaluate how many malignant plasma cells are present in the marrow, and determine to what degree they have affected the production of normal white blood cells, red blood cells, and platelets.

Other laboratory tests
Other tests that may be done as part of an initial diagnostic workup, to monitor the progress of the disease, and to help detect and address complications include:

  • Comprehensive Metabolic Panel (CMP), a group of tests used to evaluate kidney and other organ function, electrolyte status, and to determine calcium, albumin, and total protein levels
  • Complete Blood Count (CBC), counts and evaluates white blood cells, red blood cells, and platelets and determines the extent of anemia (measures hemoglobin)
  • Uric acid levels may be elevated as a complication of multiple myeloma.
  • Beta-2 microglobulin, a protein on the cell surface of myeloma and other cells; increased levels may indicate a poorer prognosis; this test may be used to help stage the disease.
  • Serum viscosity, a measure of how "thick" the fluid portion of the blood is; when levels of the abnormal protein become very high, serum viscosity may increase and cause symptoms.

Non-laboratory tests

  • X-ray, ordered to help diagnose, stage, and monitor; may detect holes in bones, extent of bone damage, and the number and size of tumors in the bones.
  • MRI (Magnetic Resonance Imaging), may be more sensitive than X-ray for evaluating bone destruction.
  • CT (Computed tomography), may be used to evaluate bone tumors.

Staging is an evaluation of how much abnormal immunoglobulin is being produced, how much calcium is in the blood, how extensive and severe the bone damage is, and how anemic the affected person is. Staging helps to determine a person's prognosis and allows the person and their doctor to develop an individualized monitoring and treatment plan.

There are different staging systems available to assess the amount of tumor tissue present (tumor burden) and organ dysfunction. Some test results such as blood levels of beta-2 microglobulin, albumin, creatinine and calcium are especially important in myeloma staging.

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