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Blood tests that accompany some periodic medical examinations include a measurement of plasma proteins, for example albumin. A lab test result of an elevated level of total protein may lead to further blood and marrow tests and to the diagnosis of myeloma.

The diagnosis of myeloma depends on three principal findings:

  • Increased numbers of malignant plasma cells (myeloma cells) are found when a
    bone marrow aspiration and biopsy (usually from the hip bone) are performed.
    Bone marrow containing more than 10 percent plasma cells is suggestive of
  • Intact monoclonal immunoglobulins or immunoglobulin light chains
    (Bence Jones protein) are found in the blood and/or urine.
  • Imaging studies of the bones sometimes identify bone thinning or holes
    or fractures in the bones that characterize myeloma. Magnetic resonance
    imaging (MRI), especially of the spine, can detect bone changes earlier than
    conventional x-ray studies.

Taken together, these findings make it possible for doctors to diagnose myeloma
in patients.

Monoclonal Immunoglobulins (M Protein)

Normal plasma cells produce many types of proteins called immunoglobulins in response to invading viruses, bacteria or other foreign substances (antigens). Different kinds of immunoglobulins protect the body against infection. Normal immunoglobulins are called polyclonal immunoglobulins.

Myeloma cells, on the other hand, don't wait for an invasion of antigens to produce proteins. Instead, they make large amounts of an abnormal protein called monoclonal immunoglobulin, commonly known as M protein (and sometimes called M spike), which doesn't fight infection and has no real use. Most patients with untreated myeloma have high levels of M protein in their blood and urine. Higher levels of M protein mean the disease is more advanced.

Different kinds of myeloma are distinguished by the type of monoclonal immunoglobulin (Ig) (M protein) they produce:

  • Immunoglobulin G (IgG) myeloma: The M protein has all four chains. This is the most common type.
  • Light chain myeloma: The M protein has only light chains.
  • Immunoglobulin A (IgA) myeloma: Two IgG molecules are linked.
  • Immunoglobulin M (IgM) myeloma: Five IgG molecules are linked. This type is rare.
  • Immunoglobulin D (IgD) and immunoglobulin E (IgE) myeloma: Two less common forms in which the myeloma cells produce other kinds of proteins called IgD and IgE.

In a few cases, only low levels of M protein can be detected. This condition is called oligosecretory disease. When no levels can be detected, it's called nonsecretory disease.

Light Chains (Bence Jones Protein)

Normal protein (polyclonal immunoglobulin) in plasma cells is made up of two large pieces (called heavy chains) and two smaller pieces (called light chains). Their size prevents them from leaving the blood and passing through the kidneys.

Not all of myeloma's M proteins have all four chains. Instead, some heavy and light chains may fail to attach to each other. The smaller light chains are called Bence Jones protein, named after the physician who first studied them extensively. The smaller Bence Jones protein can easily slip through the kidneys into the urine where they're excreted quickly. This process can injure the kidneys and cause them to fail.

Blood and Urine Tests

In some cases, myeloma isn't suspected until blood tests for other routine examinations indicate an elevated globulin level. This may lead to more tests, especially if you have no symptoms. If myeloma is suspected as a result, your doctor tests your blood again to help confirm a diagnosis. Your blood is sent to a lab for a complete blood count (CBC), which can reveal whether myeloma cells are affecting normal blood cell development.

Your doctor also checks your blood for:

  • Calcium levels. High levels can mean that calcium has moved out of your bones and into your bloodstream, putting your kidney health at risk.
  • Protein levels. By measuring certain proteins, your doctor can estimate the size and growth rate of myeloma tumors.
  • Urea nitrogen and creatinine levels. These proteins are measured to test your kidney function.

Your doctor tests your urine (urinalysis) for Bence Jones protein, which can indicate the presence of myeloma. Bence Jones protein levels are measured to check kidney function and the extent of the disease.

Understanding blood tests and blood counts
Understanding urine tests

Bone Marrow Tests

Your doctor tests your bone marrow to look for increased numbers of myeloma cells. Bone marrow testing involves two steps usually done at the same time in a doctor's office or a hospital:

  • a bone marrow aspiration to remove a liquid marrow sample
  • a bone marrow biopsy to remove a small amount of bone filled with marrow

Understanding bone marrow tests

Protein Electrophoresis Tests

Serum Protein Electrophoresis (SPEP) and Urine Protein Electrophoresis (UPEP) are tests used to identify the presence of abnormal proteins, to identify the absence of normal proteins, and to determine increases and decreases of different groups of proteins in serum or urine. These tests are typically ordered to detect and identify excessive production of specific proteins (immunoglobulins). All five types of immunoglobulins (IgG, IgA, IgM, IgE, or IgD) are measured by these tests. If present, an excessive production of a monoclonal immunoglobulin may be shown on lab results as a spike on a graph. Most patients with untreated myeloma have a monoclonal immunoglobulin peak in serum, urine, or both.

These tests may be repeated at regular intervals to monitor the course of the patient's myeloma and the effectiveness of treatment.

Imaging Tests

You may need to undergo an X-ray, a computed tomography (CT) scan, a magnetic resonance imaging (MRI) scan or a positron emission tomography (PET) scan. Your doctor looks for any evidence of bone damage, such as thinning, holes or fractures.

Understanding imaging tests

Lab Tests to Confirm a Diagnosis

After your doctor takes samples of your blood and bone marrow, a hematopathologist confirms a diagnosis, identifies the myeloma stage and looks for certain changes in your chromosomes. A hematopathologist is a specialist who studies blood cell diseases by looking at samples of blood and marrow cells and other tissues. The test results determine the direction your treatment will take.

The hematopathologist performs a cytogenetic analysis to identify certain changes in chromosomes and genes. This can involve one or both of the following tests:

  • G-banding karyotyping examines your chromosomes' arrangement, size, shape and number using a special dye called Giemsa to get a better look at the banding patterns of chromosome pairs.
  • Fluorescence in situ hybridization (FISH) is an extra-sensitive test that detects chromosome changes in cells.

Common cytogenetic abnormalities (damage to DNA in chromosomes) that affect myeloma cells include:

  • Deletion of chromosome 13. Deletion of chromosome 13 is associated with myeloma that responds poorly to chemotherapy. Newer drugs, however, are helping to improve response.
  • Translocation of chromosome 14. Chromosome 14 commonly involves translocations between it and chromosomes 4, 11 or 16.
  • An abnormality or loss of chromosome 17p. An important tumor suppressor, a gene called p53, is found in 17p. Damage to 17p can indicate how quickly the disease is progressing.

If you're diagnosed with myeloma, you may need to undergo more tests during or after treatment to see how your myeloma cells are responding to therapy.

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» Myeloma
last updated on Friday, March 16, 2012

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