Tests for Multiple Myeloma

If signs, symptoms, or the results of certain lab tests suggest a person might have multiple myeloma, other tests will be done to find out for sure.

If multiple myeloma is found, further tests might also be done to learn more about it and help decide the best treatments.

Lab tests

Different types of lab tests can be helpful in finding multiple myeloma, learning more about it, and seeing how well treatment is working.

Blood cell counts

The complete blood count (CBC) is a test that measures the levels of red blood cells, white blood cells, and platelets in the blood. If too many myeloma cells are in the bone marrow (where new blood cells are made), some of these blood cell levels can be low. The most common finding is a low red blood cell count (anemia).

Blood chemistry and protein tests

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

• BUN and creatinine levels show how well your kidneys are working. The kidneys are often affected in people with myeloma.
• Albumin is a protein found in the blood. Low levels can sometimes be seen in people with myeloma.
• Calcium levels may be high in people with advanced myeloma. High calcium levels (hypercalcemia) can cause symptoms such as fatigue, weakness, and confusion.

Blood tests measuring levels of lactic dehydrogenase (LDH) and beta-2 microglobulin (B2M) are also often done. levels of these substances are used to help determine the stage of the myeloma. High levels of either of these substances often means the disease is more advanced.

Urine tests

A routine urine sample is checked for myeloma protein that has filtered through the kidney.

You most likely also will be asked to give a sample of urine that has been collected over a 24-hour period, to measure how much myeloma protein is present (see Electrophoresis, below). You will be given instructions on how to do this.

Quantitative immunoglobulins

This test measures the blood levels of the different antibodies (immunoglobulins), including 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.

Electrophoresis

Finding a monoclonal antibody in the blood is often a first step in diagnosing multiple myeloma. A test known as electrophoresis can be done on blood or urine samples to find these antibodies. The antibodies made by myeloma cells are abnormal because they are all the same (monoclonal). This abnormal protein is known by several different names, including monoclonal immunoglobulin, monoclonal protein (M protein), M spike, or paraprotein.

Serum protein electrophoresis (SPEP) is a test that measures the antibodies in the blood and can find a monoclonal antibody.

Another test, called immunofixation or immunoelectrophoresis, can be used to determine the exact type of abnormal antibody (IgG, IgA, or some other type).

Antibodies are made up of chains of proteins, including 2 long (heavy) chains and 2 shorter (light) chains. Sometimes pieces of the abnormal myeloma protein are filtered through the kidney and into the urine. This urine protein, known as Bence Jones protein, is the part of the light chain of the antibody. The tests used for finding a monoclonal antibody in urine are called urine protein electrophoresis (UPEP) and urine immunofixation. These are done most often on urine that has been collected over a 24-hour period, not just on a routine urine sample.

Serum free light chains

This test can measure the light chain levels in the blood. It is done to look for myeloma or light chain amyloidosis.

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) antibodies, it cannot measure the amount of light chains only.

This test can also be used to calculate the serum free light chain ratio, which can show if there is more of one type of light chain than the other. There are 2 kinds of light chains: kappa and lambda. Normally, there are equal amounts of them in the blood, giving a ratio of 1 to 1. Having more of one type of light chain than the other can be a sign of myeloma.

Biopsies

For a biopsy, pieces (samples) of body tissue are removed for testing in a lab. Different types of biopsies might be used in people known or suspected to have multiple myeloma. Doctors choose which one to use based on each person’s situation.

Bone marrow biopsy

People with multiple myeloma have too many plasma cells in their bone marrow. The procedure used to check the bone marrow is called a bone marrow aspiration and biopsy. It can be done either at the doctor’s office or at the hospital. The bone marrow samples are usually taken from the back of the pelvic (hip) bone, although sometimes they may be taken from other bones.

For a bone marrow aspiration, you lie on a table (either on your side or on your belly). After cleaning the skin over the hip, the doctor numbs the area and the surface of the bone with local anesthetic, which can cause a brief stinging or burning sensation. A thin, hollow needle is then inserted into the bone and a syringe is used to suck out a small amount of liquid bone marrow. Even with the anesthetic, most people still have some brief pain when the marrow is removed.

A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow is removed with a slightly larger needle that is pushed into the bone. The biopsy can also cause some brief pain.

The bone marrow tissue is sent to a lab, where it is examined ito check the appearance, size, and shape of the cells, and how the cells are arranged. This test can determine if there are myeloma cells in the bone marrow and, if so, how many. The aspirate (the liquid part of the bone marrow) may also be sent for other tests:

• Immunohistochemistry: For this test, a part of the biopsy sample is treated with special lab-made antibodies (immune proteins) that cause color changes on the cells if they contain certain proteins. This can be used to help identify myeloma cells.
• Flow cytometry: This test also uses antibodies, but it uses a special machine to see if the antibodies attached to the cells.
• Cytogenetics (karyotyping): This test looks at the chromosomes (long strands of DNA) in the cells. Sometimes myeloma cells have too many chromosomes, too few chromosomes, or other chromosome abnormalities, such as translocations (the swapping of DNA between chromosomes) or deletions (loss of part of a chromosome). Finding these changes can sometimes help predict a person’s prognosis (outlook). Cytogenetic testing usually takes about 2 to 3 weeks to get a result.
• Fluorescent in situ hybridization (FISH): This test uses special fluorescent dyes that only attach to specific parts of chromosomes. It can find most chromosome changes (such as translocations and deletions) that can be seen with standard cytogenetic tests, as well as some changes too small to be seen with cytogenetic testing. It’s very accurate, and the results are often available within a couple of days.

Needle biopsies

If an area looks abnormal on an x-ray and a plasmacytoma is suspected, a biopsy may be needed to confirm this. Most often, some type of needle biopsy is used. If a tumor is near the surface of the body, the doctor can aim the needle while feeling the tumor. If the abnormal area is deep in the body, the needle can be guided while using an imaging test such as a CT or MRI scan (see below).

Fine needle aspiration (FNA) biopsy

For an FNA, the doctor uses a very thin needle and a syringe to withdraw a small amount of tissue from a tumor. The main advantage of FNA is that it uses a thin needle and doesn’t require surgery. The downside is that sometimes the needle is too small to remove enough tissue for a definite diagnosis.

Core needle biopsy

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

Imaging tests

Imaging tests use sound waves, x-rays, magnetic fields, or radioactive substances to create pictures of the inside of your body. Imaging tests may be done for a number of reasons, such as:

• To look at suspicious areas that might be cancer
• To learn how far cancer has spread
• To help determine if treatment is working

Bone x-rays

X-rays can detect bone destruction caused by myeloma cells. 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 (CT) scan

A CT scan uses x-rays taken from different angles, which are combined by a computer to make detailed pictures of the inside of your body. Sometimes, this test can help tell if your bones have been damaged by myeloma. It can also be used to guide a biopsy needle into an area of concern.

Magnetic resonance imaging (MRI) scan

Like CT scans, MRIs show detailed images of soft tissues in the body. But MRIs use radio waves and strong magnets instead of x-rays.

MRI scans are very helpful in looking at bones, the brain, and the spinal cord. Because MRI can find plasmacytomas that can’t be seen on regular x-rays, they can be helpful if a person has pain in a bone but nothing abnormal is seen on the x-ray. MRI can also be used to look at the bone marrow in people with multiple myeloma.

Positron emission tomography (PET) scan

For this test, a form of radioactive sugar is put into a vein and travels throughout the body. Cancer cells absorb high amounts of this sugar. A special camera then takes pictures that show the areas where the sugar collected throughout the body. A PET scan is often combined with a CT scan (known as a PET/CT scan).

Like MRI scans, PET scans can find plasmacytomas (tumors) that can’t be seen on regular x-rays, so they are helpful if a person has pain in a bone but the x-ray doesn't show anything.

Echocardiogram (ECHO)

Amyloidosis often affects the heart, so if your doctor suspects you have this disorder, an echocardiogram (ECHO) may be done.

This test is an ultrasound of the heart. It uses sound waves to look at the heart muscle and see how well it’s working. The echocardiogram can see if the heart size is normal and if it is pumping normally. It also is helpful if amyloid is suspected because amyloid in the heart muscle looks different from normal heart muscle.

Diagnosing multiple myeloma

Multiple myeloma is often diagnosed based on test results, a person's symptoms, and the results of the physical exam. A diagnosis of multiple myeloma requires:

Either a plasma cell tumor (proven by biopsy) OR at least 10% plasma cells in the bone marrow, AND

At least one of the following:

• High blood calcium level
• Poor kidney function
• Low red blood cell count (anemia)
• Holes in the bones from tumor(s) found on imaging tests (CT, MRI, PET scan)
• Increase in one type of light chain in the blood so that one type is at least 100 times more common than the other
• 60% or more plasma cells in the bone marrow

Diagnosing smoldering myeloma

This term is used to describe early myeloma that is not causing any symptoms. People with smoldering myeloma have some signs of multiple myeloma, such as any of the following:

• Plasma cells in the bone marrow between 10% and 60%
• High level of monoclonal immunoglobulin (M protein) in the blood
• High level of light chains in the urine (also called Bence Jones protein)

But they do not meet the requirements for multiple myeloma, as defined above. That is, they have normal blood counts, normal calcium levels, normal kidney function, and no bone or organ damage. They also have no signs of amyloidosis.

Diagnosing monoclonal gammopathy of undetermined significance (MGUS)

To be diagnosed with MGUS, a person must have ALL of these:

• Higher than normal level of monoclonal immunoglobulin (M protein) in the blood, but less than that for smoldering myeloma
• Less than 10% plasma cells in the bone marrow
• None of the requirements for multiple myeloma, as defined above. That is, they have normal blood counts, normal calcium levels, normal kidney function, and no bone or organ damage. They also have no signs of amyloidosis.

Diagnosing light chain amyloidosis

A diagnosis of light chain amyloidosis is made when a person has ALL of the following:

• Evidence of amyloid-related damage to an organ or system (such as the kidneys, heart, liver, digestive tract, or nerves)
• A biopsy that shows amyloid in any tissue (fat, bone marrow, or an organ such as the heart)
• A positive test showing the amyloid is a light chain protein
• Abnormal plasma cells in the bone marrow, an abnormal serum free light chain ratio (discussed above), or high levels of M protein in the blood or urine  

A biopsy of any body tissue can help diagnose this disease. Sometimes amyloid can be seen on a bone marrow biopsy. The biopsy done most often to look for amyloid uses a needle to remove some fat from the wall of the abdomen (belly). A doctor uses a special stain on the removed fat to look for amyloid.

Because amyloid often affects the heart and kidneys, they may also be biopsied to look for amyloid. This is rarely needed to find out if a person has light chain amyloidosis, but it is sometimes done in someone with amyloidosis if it isn’t clear what is causing their heart or kidney problems.

Other tests are often done as well to help confirm that a person has light chain amyloidosis and not some other type of amyloidosis. These include a bone marrow biopsy, serum free light chains, and electrophoresis of the urine (discussed earlier in this section).