Multiple Myeloma Diagnosis

Diagnosing multiple myeloma includes blood work, a 24-hour urine collection, a bone marrow biopsy, imaging studies (such as x-rays, MRIs, PET scans), and bone density tests. It sounds like a lot (and it is!) but none are that invasive or painful, with the exception of the bone marrow biopsy, but even that isn’t so bad. Take a deep breath and keep reading. Many of us have been through all of this and you’ll get through it.

Your fight with myeloma is a war. In order to win it, you must know your enemy and know it well. To do that, there are many specific diagnostic tests available for properly and thoroughly diagnosing your type of myeloma.

Do not underestimate the importance of these tests!

They are critical in developing the best treatment plan for you. There are no shortcuts and myeloma is a complicated disease. Just as you would do in fighting a war, you want the best team out there to help you fight.

That means also finding the right doctor. Survival statistics vary dramatically across treatment centers. Yes, it really does matter!

All Myeloma is Not the Same

Did you know that not all myeloma is the same? There are various subtypes of myeloma, some being more aggressive and some being less aggressive. The tests will help to determine your myeloma sub-type and how best to treat it.

An Accurate Multiple Myeloma Diagnosis

The results of any single test are not enough to make a diagnosis of multiple myeloma. Diagnosis is based on a combination of factors, including the patient’s description of symptoms, the doctor’s physical examination, and the results of a variety of tests.

The diagnosis of multiple myeloma requires either:

• A plasma cell tumor (proven by biopsy)
  OR
• At least 10% of the cells in the bone marrow are plasma cells.
  AND one of the following:
• M protein over a certain level in the blood (3g/dL)
  OR
• M protein in the urine over a certain level (1g/dL)
  OR
• Holes in bones due to tumor growth are found in imaging studies.

Smoldering Myeloma

This term used to mean early myeloma that is not causing any symptoms or problems. Those with smoldering myeloma have normal blood counts, normal calcium levels, normal kidney function, and no bone or organ damage.

Laboratory Tests

If symptoms suggest that a person might have multiple myeloma, lab tests on blood and/or urine, x-rays of the bones, and a bone marrow biopsy are usually done.

Blood Counts

The complete blood count (CBC) is a test that measures the levels of red cells, white cells, and platelets in the blood. If myeloma cells occupy too much of the bone marrow, levels of these blood cells will be low and anemia will be common.

Blood tests are necessary to measure white cell and platelet counts, check calcium levels, assess kidney and liver function, and evaluate for anemia.

Quantitative Immunoglobulins (Blood Test)

This test measures the blood levels of the different antibodies (also called immunoglobulins). There are several different types of antibodies in the blood: IgA, IgD, IgE, IgG, and IgM. Each type of antibody fights a different type of infection.

The levels of these immunoglobulins are measured to see if any are abnormally high or low. In multiple myeloma, one type of immunoglobulin has overgrowth that crowds out the other types of immunoglobulins, which is why you may be susceptible to certain kinds of infections, like pneumonia.

You may know that you are IgG Kappa or IgA Lambda, which are identified by the Electrophoresis Tests.

Electrophoresis Tests (Blood and Urine Tests)

The immunoglobulin produced by myeloma cells is abnormal because all paraproteins are monoclonal (identical), which means they are identical clones of a single plasma cell. Also called M-proteins, they crowd out the functional Igs and other components of the immune system, making too much of one type and reducing the ability of your body to create a wide spectrum of immunoglobulins to fight infections.

Serum protein electrophoresis (SPEP) is a test to measure the total amount of immunoglobulin in the blood and find any abnormal immunoglobulin. Then, another test, such as immunofixation or immunoelectrophoresis, is used to determine the exact type of antibody that is abnormal (IgG or some other type).

Finding a monoclonal immunoglobulin in the blood may be the first step in diagnosing multiple myeloma. This abnormal protein is known by several different names, including monoclonal immunoglobulin, M-protein, M-spike, and paraprotein. For a simple explanation of the M-spike, click here: What is a monoclonal protein (m-protein or m-spike) and how is it detected? (HTU Video)

Immunoglobulins are made up of protein chains: 2 long (heavy) chains and 2 shorter (light) chains. Sometimes the kidneys excrete pieces of the M protein into the urine. This urine protein is the part of the immunoglobulin called the light chain.

It is also known as Bence-Jones protein. The tests used for finding a monoclonal immunoglobulin in urine are called urine protein electrophoresis (UPEP) and urine immunofixation.

Free Light Chains (Blood Test)

This test measures the amount of light chains in the blood. This is most helpful in the rare cases of myeloma in which no M protein is found by SPEP. Since the SPEP measures the levels of intact (whole) immunoglobulins, it cannot measure the amount of light chains.

Beta-2 Microglobulin (Blood Test)

This is another protein produced by the malignant cells. Although this protein itself doesn’t cause problems, it can be a useful indicator of a patient’s prognosis (outlook). High levels indicate more aggressive disease.

Blood Chemistry Tests

Levels of blood urea nitrogen (BUN) and creatinine, albumin, calcium, and other electrolytes will be checked:

• BUN and creatinine (Cr) levels show how well your kidneys are working. Higher levels mean that kidney function is impaired. This is common in people with myeloma.
• Albumin is a protein found in the blood. Low levels can be a sign of more advanced myeloma.
• Calcium levels may be higher in people with advanced myeloma. High calcium levels can cause severe symptoms of fatigue, weakness, and confusion.
• Levels of electrolytes such as sodium and potassium may be affected as well.

Bone Marrow Biopsy

Those with multiple myeloma have too many plasma cells in their bone marrow. The procedure to check the bone marrow is called a bone marrow biopsy and aspiration. It can be either done at the doctor’s office or at the hospital.

This is the most invasive of the most diagnostic tests but the discomfort is literally just a few seconds. If you prefer, the procedure can be done under light anesthesia called conscious sedation. It makes you tired for an hour or two but doesn’t knock you out. Many patients prefer to go without any pain medication. There is no “wrong” decision.

In this procedure, the back of the pelvic bone is numbed with local anesthetic. A needle is inserted into the bone and a syringe is used to remove a small amount of liquid bone marrow.

This causes a brief, sharp pain. Then for the biopsy, a needle is used to remove a tiny sliver of bone and marrow, about 1/16-inch across and 1-inch long. There is some soreness in the biopsy area when the numbing medicine wears off. Most patients go home immediately after the procedure.

A doctor will use a microscope to look at the bone marrow tissue to see the appearance, size, and shape of the cells, how the cells are arranged and to determine if there are myeloma cells in the bone marrow and, if so, how many.

The aspirate may also be sent for other tests, including immunohistochemistry and flow cytometry, and chromosome analyses, including karyotype and fluorescent in situ hybridization (also known as FISH).

Immunohistochemistry

In this test, a part of the biopsy sample is treated with special antibodies (man-made versions of immune system proteins) that attach only to specific molecules on the cell surface. These antibodies cause color changes, which can be seen under a microscope. This test may be helpful in telling different types of cells apart and in finding myeloma cells.

Flow Cytometry

Like immunohistochemistry, this test looks for certain substances on the outside surface of cells that help identify what types of cells they are. But this test can look at many more cells than immunohistochemistry.

For this test, a sample of cells is treated with special antibodies that stick to the cells only if certain substances are present on their surfaces. The cells are then passed in front of a laser beam. If the cells now have antibodies attached to them, the laser will cause them to give off light, which can be measured and analyzed by a computer. Groups of cells can be separated and counted by these methods.

This is the most commonly used test for immunophenotyping — classifying cells according to the substances (antigens) on their surfaces. Different cells and cell types have different antigens on their surface. These antigens may also change as each cell matures.

Flow cytometry can help determine if there are abnormal cells in the bone marrow and if they are myeloma cells, lymphoma cells, some other cancer, or a non-cancerous disease.

Cytogenetics

This technique allows doctors to evaluate the chromosomes (long strands of DNA) in normal bone marrow cells and myeloma cells. The cells are looked at under a microscope to see if the chromosomes have any translocations (where part of one chromosome has broken off and is now attached to another chromosome), as can happen in some cases of multiple myeloma. Some myeloma cells may have too many chromosomes, too few chromosomes, or other chromosome abnormalities. Finding these changes can sometimes help in predicting prognosis.

Cytogenetic testing usually takes about 2 to 3 weeks because the lymphoma cells must grow in lab dishes for a couple of weeks before their chromosomes are ready to be viewed under the microscope.

Fluorescent in situ hybridization (FISH analysis)

Fluorescent in situ hybridization (FISH) is similar to cytogenetic testing. It uses special fluorescent dyes that only attach to specific parts of chromosomes. FISH can find most chromosome changes (such as translocations) that can be seen under a microscope in standard cytogenetic tests, as well as some changes too small to be seen with usual cytogenetic testing.

FISH can be used to look for specific changes in chromosomes. It can be used on regular blood or bone marrow samples. It is very accurate and can usually provide results within a couple of days, which is why this test is now used in many medical centers.

Gene Array Analysis/Gene Expression Profile

Using a bone marrow biopsy sample, the leukemia cells are purified and the genetic material is extracted. This test provides everything that the FISH test provides in terms of translocations, but also identifies gene “signatures” or genes that are turned on or off, or are over or under-expressed. This provides redundant information from the FISH but looks at the myeloma at a molecular level and can test for 35,000 genes in a single test. Several facilities rely heavily on this test including UAMS and the University of Iowa. Not every doctor performs this test but it can provide valuable genetic information about the sub-type of myeloma, getting patients closer to personalized treatments.

Fine Needle Aspiration Biopsy

If an imaging study shows a potential tumor or other abnormality, an additional aspiration during the bone marrow biopsy can be performed. A fine needle aspiration (FNA) uses a very thin needle and an ordinary syringe to withdraw a small amount of tissue from a tumor or lymph node. If the tumor is deep inside the body, the needle can be guided while it is viewed on a computed tomography (CT) scan (see discussion of imaging tests later in this section). The main advantage of FNA is that it does not require surgery. The disadvantage is that in some cases the thin needle cannot remove enough tissue for a definite diagnosis. FNA can be useful in diagnosing cancers that have spread to nodes from other organs.

Core Needle Biopsy

This test is similar to FNA but a larger needle is used and a larger tissue sample is removed.

Bone X-rays

Bone destruction caused by myeloma cells can be detected with x-rays. This is called a bone survey or skeletal survey.

Computed Tomography (CAT Scan)

The computed tomography (CT) scan (also known as a CAT scan) is an x-ray procedure that produces detailed cross-sectional images of your body. Instead of taking one picture, like a conventional x-ray, a CT scanner takes many pictures of the part of the body being studied as it rotates. Sometimes, this test can determine if bones have been damaged by myeloma.

Oftentimes, a patient will drink 1 to 2 pints of a solution of contrast material before the scan. This helps outline the intestine so that it is not mistaken for tumors. A patient may also receive an intravenous (IV; in the vein) line through which a different contrast dye is injected.

This helps better outline body structures. The injection can cause a feeling of warmth throughout the body (flushing). Some people are allergic to the IV contrast and should tell their doctor if they have ever had a reaction to any contrast material used for x-rays.

CT scans take longer than regular x-rays and requires lying motionless on a table while images are taken. Some patients might feel a bit confined during the scan, but the tests are over relatively quickly.

CT scans can also be used to guide a biopsy needle precisely into a suspected tumor. For this procedure, called a CT-guided needle biopsy, the patient remains on the CT scanning table while a radiologist advances a biopsy needle toward the location of the tumor.

CT scans are repeated until the needle is within the mass. A fine needle biopsy sample (tiny fragment of tissue) or a core needle biopsy sample (a thin cylinder of tissue about ½-inch long and less than 1/8 inch in diameter) is removed and examined under a microscope.

Magnetic Resonance Imaging (MRI)

MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of tissue and by certain diseases. A computer translates the pattern of radio waves given off by the tissues into a very detailed image of parts of the body. Not only does this produce cross-sectional slices of the body like a CT scanner, it can also produce slices that are parallel with the length of your body. A dye (contrast material) might be injected just as with CT scans but is used less often.

MRI scans are very helpful in looking at bones, the brain, and the spinal cord. Plasmacytomas that cannot be seen on regular x-rays can be located. MRI can also be used to look at the bone marrow in patients with multiple myeloma.

MRI scans are a little more uncomfortable than CT scans. First, they can take an hour or longer. Also, the patient is placed inside tunnel-like equipment, which is confining. The machine makes a thumping noise but the facility can provide headphones with music to block it out.

Positron Emission Tomography (PET Scan)

With a PET scan, radioactive glucose (sugar) is injected into the patient’s vein to look for cancer cells. Because cancers use glucose (sugar) at a higher rate than normal tissues, the radioactivity will tend to concentrate in the cancer. A scanner is used to spot radioactive deposits. When a patient appears to have a solitary plasmacytoma, a PET scan may be used to look for other plasmacytomas.

Source: American Cancer Society