How is multiple myeloma diagnosed?
Signs and symptoms of multiple myeloma
Although some patients with multiple myeloma have no symptoms at all, the following are the most common symptoms of this disease:
Normally, the 2 major kinds of bone cells work together to keep bones healthy and strong. The cells that lay down new bone are called osteoblasts. The cells that break down old bone are called osteoclasts. Myeloma cells make a substance that tells the osteoclasts to speed up the dissolving of bone. The osteoblasts do not get a signal to put down new bone, so old bone is being broken down without new bone to replace it. This can cause areas of bone weakness that are painful. Any bone can be affected, but pain in the bones in the back, the hips, and skull is particularly common with this disease. Multiple myeloma can also weaken bones all over (osteoporosis). Any of these changes increase the chance that the bones will break (fracture). Sometimes bones break from only a minor stress or injury.
Low blood counts
When myeloma cells replace normal blood-forming marrow cells, shortages of red blood cells, white blood cells, and blood platelets result. A reduced number of red blood cells, a condition called anemia, causes weakness, reduced ability to exercise, shortness of breath, and dizziness. Too few white blood cells (a condition called leukopenia) lowers resistance to infections such as pneumonia. When blood platelet counts are low (a condition called thrombocytopenia), even minor scrapes, cuts, or bruises may cause serious bleeding.
High blood calcium
When the myeloma cells dissolve bone, calcium is released. This can lead to high levels of calcium in the blood (called hypercalcemia). Symptoms include feeling very thirsty, drinking a lot of fluids, and urinating (peeing) a lot. This can cause dehydration and even kidney failure. High calcium can also cause severe constipation, abdominal (belly) pain, and loss of appetite. It can make people feel weak, drowsy, and confused. If the level of calcium gets high enough, it can even cause you to lapse into a coma.
Nervous system symptoms
If myeloma weakens the bones in the spine, they can collapse and press on spinal nerves. This can cause sudden severe back pain, numbness, and/or muscle weakness. This, called spinal cord compression, is a medical emergency and you should contact your doctor right away or go to the emergency room.
Sometimes, the abnormal proteins produced by myeloma cells can be toxic to the nerves. This damage can lead to weakness and numbness.
In some patients, large amounts of myeloma protein can cause the blood to "thicken." This thickening is called hyperviscosity. It can slow blood flow to the brain and cause confusion, dizziness, and stroke-like symptoms. Patients with these symptoms should call their doctor. Removing the protein from the blood using a procedure called plasmapheresis can rapidly reverse this problem (this is not something that can be treated with drugs known as “blood thinners”).
Myeloma protein can damage the kidneys. Early on, this doesn't cause any symptoms, but signs of kidney damage can be seen on a blood test. As the kidneys start to fail, they lose the ability to dispose of excess salt, fluid, and body waste products. This can lead to symptoms like weakness, shortness of breath, itching, and leg swelling.
Myeloma patients are much more likely to get infections. This happens because the body is unable to make the proper antibodies that help fight infection. When someone with myeloma gets an infection, they may be slow to respond to treatment. That person may stay sick for a long time. Pneumonia is a common and serious infection seen in myeloma patients.
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.
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 some of these blood cells will be low. The most common finding is a low red blood cell count (anemia).
This test measures the blood levels of the different antibodies. There are several different types of antibodies in the blood: IgA, IgD, IgE, IgG, and IgM. The levels of these immunoglobulins are measured to see if any are abnormally high or low. In multiple myeloma, the level of one type may be high while the others are low.
The immunoglobulin produced by myeloma cells is abnormal because it is monoclonal (all the exact same antibody). Serum protein electrophoresis (SPEP) is a test that measures the immunoglobulins in the blood and can find a monoclonal immunoglobulin. Then, another test, such as immunofixation or immunoelectrophoresis, is used to determine the exact type of abnormal antibody (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.
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. These are most often done on urine that has been collected over 24 hours.
Free light chains
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.
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 advanced disease and maybe a worse prognosis.
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
People 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.
In this procedure, the back of the pelvic bone is numbed with local anesthetic. Then, to do the bone marrow aspiration, 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. Patients may feel some pressure during the biopsy, but it usually isn’t painful. There is some soreness in the biopsy area when the numbing medicine wears off. Most patients can 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).
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.
Like the immunohistochemistry test, the flow cytometry 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.
This technique lets doctors evaluate the chromosomes (long strands of DNA) in normal bone marrow cells and myeloma cells. Some myeloma cells may have too many chromosomes, too few chromosomes, or other chromosome abnormalities. The cells are looked at under a microscope to see if the chromosomes have any changes, such as translocations (where part of one chromosome has broken off and is now attached to another chromosome) or deletions (where part or all of a chromosome is missing), as can happen in some cases of multiple myeloma. Finding these changes can sometimes help in predicting a person’s prognosis.
Cytogenetic testing usually takes about 2 to 3 weeks because the cells must grow in lab dishes for a couple of weeks before their chromosomes are ready to be seen under the microscope.
Fluorescent in situ hybridization
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 and deletions) 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 as well as bone marrow samples. It is very accurate and because the cells don’t have to grow in a dish first, results are often available within a couple of days.
Other biopsy tests
If an area looks abnormal on an x-ray, a biopsy may be needed to confirm that it is a plasmacytoma. Most often, a needle biopsy is used.
Fine needle aspiration biopsy
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. The doctor can aim the needle while feeling an enlarged node near the surface of the body. If the abnormal area (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 destruction caused by the myeloma cells can be detected with x-rays. Often doctors will do a series of x-rays that includes most of the bones. This is called a bone survey or skeletal survey.
Computed tomography scans
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 your body being studied as it rotates around you. A computer then combines these pictures into an image of a slice of your body. Sometimes, this test can help tell if your bones have been damaged by myeloma.
A CT scanner has been described as a large donut, with a narrow table in the middle opening. You will need to lie still on the table while the scan is being done. CT scans take longer than regular x-rays, and you might feel a bit confined by the ring while the pictures are being taken.
You might be asked to drink 1 to 2 pints of a solution of contrast material before the test. This helps outline the intestine so that it is not mistaken for tumors. You might also receive an intravenous (IV; in the vein) line through which a different contrast dye is injected. This helps better outline structures in your body. The injection can cause a feeling of warmth throughout the body (flushing). Some people are allergic to the IV contrast and get hives. Rarely, more serious reactions like trouble breathing and low blood pressure can occur. Medicine can be given to prevent and treat allergic reactions. Be sure to tell the doctor if you have ever had a reaction to any contrast material used for x-rays. If IV contrast is being used, it is important you tell the radiology people that you have myeloma. Some of these contrast agents can damage the kidneys of people with myeloma.
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 doctors are confident that 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 scans
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. They might be able to find plasmacytomas that cannot be seen on regular x-rays. 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, you have to be placed inside tunnel-like equipment, which is confining and can upset some people. The machine also makes a thumping noise that could be disturbing. Some places provide headphones with music to block this out.
Positron emission tomography scans
In this test, which is also called 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.
Interpreting test results
Results of any single test are not enough to diagnose multiple myeloma. Diagnosis is based on a combination of factors, including the patient's description of symptoms, the doctor's physical examination of the patient, and the results of blood tests and x-rays. The diagnosis of multiple myeloma requires either:
- A plasma cell tumor (proven by biopsy)
- At least 10% of the cells in the bone marrow are plasma cells.
AND one of the following:
- M protein is over a certain level in the blood (3g/dL)
- M protein in the urine is over a certain level (1g/dL)
- Holes in bones due to tumor growth or weak bones (osteoporosis) found on imaging studies.
This term used to mean early myeloma that is not causing any symptoms or problems. People with smoldering myeloma have normal blood counts, normal calcium levels, normal kidney function, and no bone or organ damage. Smoldering myeloma does not need to be treated right away.
Last Medical Review: 01/15/2013
Last Revised: 02/12/2013