Tests to Find Multiple Myeloma

If symptoms suggest that a person might have multiple myeloma, more tests are done.

Lab tests

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 there are too many myeloma cells in the bone marrow, some of these blood cell levels can be low. The most common finding is a low red blood cell count (anemia).

Blood chemistry tests

Levels of blood creatinine, albumin, calcium, and other electrolytes will be checked.

• Creatinine levels show how well your kidneys are working. High levels mean that the kidneys are not functioning well. This is common in people with myeloma.
• Albumin is a protein found in the blood. Low levels can be seen in myeloma.
• Calcium levels may be high in people with advanced myeloma. High calcium levels (hypercalcemia) can cause symptoms of fatigue, weakness, and confusion.

A blood test to measure lactic dehydrogenase (LDH) levels might also be done. It can be a useful indicator of a patient’s prognosis (outlook). High levels mean the disease is more advanced and may have a worse prognosis.

Urine tests

A routine urine sample is typically taken to look 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, so it can measure how much myeloma protein is present. These tests are called urine protein electrophoresis (UPEP) and urine immunofixation. 

Quantitative immunoglobulins

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. 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

The antibody produced by myeloma cells is abnormal because it is monoclonal (all the exact same ). 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, is used to determine the exact type of abnormal antibody (IgG. IgA or some other type). Finding a monoclonal antibody in the blood may be the first step in diagnosing multiple myeloma. This abnormal protein is known by several different names, including monoclonal immunoglobulin, monoclonal protein (M protein), M spike, or paraprotein.

Antibodies are made up of chains of protein : 2 long (heavy) chains and 2 shorter (light) chains. Sometimes pieces of the abnormal myeloma protein are filtered through the kidney into the urine. This urine protein, known as Bence Jones protein, is the part of the antibody called the light chain. 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 blood test can measure the light chain levels in the blood and is done when looking 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 also calculates the light chain ratio which is used to see if there is one type of light chain more than the other. There are 2 kinds of light chains: kappa and lambda. Normally, they are present in equal amounts in the blood, giving a ratio of 1 to 1. If there is more of one type of light chain than the other, the ratio will be different, which can be a sign of myeloma.

Beta-2 microglobulin

This is another protein made by the myeloma cells. Although this protein itself doesn’t cause problems, it can be a useful indicator of a patient’s prognosis (outlook). High levels mean the disease is more advanced and may have a worse prognosis.

Types of Biopsies

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 biopsy and aspiration. It can be done either at the doctor’s office or at the hospital.

In bone marrow aspiration, the back of the pelvic bone is numbed with local anesthetic. Then, 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. For the biopsy, a needle is used to remove a tiny splinter of bone and marrow. Patients may feel some pressure during the biopsy. There is some soreness in the biopsy area when the numbing medicine wears off. Most patients can go home immediately after the procedure.

The bone marrow tissue is examined in the lab 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 (the liquid part of the bone marrow) 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: a part of the biopsy sample is treated with special proteins which cause color changes and help identify myeloma cells.
• Flow cytometry: A sample of bone marrow is treated with special proteins that stick only to certain cells. This can help determine if those cells are abnormal and if they are myeloma cells, lymphoma cells, some other cancer, or a non-cancerous disease.

• Cytogenetics: A test that evaluates 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 (such as translocations and deletions). Finding these changes can sometimes help in to predicting a person’s prognosis (outlook). Cytogenetic testing usually takes about 2 to 3 weeks to get a result.

• Fluorescent in situ hybridization (FISH): It 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 in the lab in standard cytogenetic tests, as well as some changes too small to be seen with usual cytogenetic testing. It’s very accurate and results are often available within a couple of days.

Fine needle aspiration biopsy

Fine needle aspiration (FNA) uses a very thin needle and a syringe to withdraw a small amount of tissue from a tumor or lymph node. The doctor can aim the needle while feeling an enlarged lymph node near the surface of the body. If the abnormal area (tumor) is deep in the body, the needle can be guided while it’s watched on a computed tomography (CT) scan (see discussion of imaging tests later in this section). The main advantage of FNA is that it doesn’t require surgery. The disadvantage is that in some cases the thin needle cannot 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.

If an area looks abnormal on an x-ray, a biopsy may be needed to confirm that it’s a plasmacytoma. Most often, a needle biopsy (fine or core) is used.

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 the 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.

CT scan (Computed tomography scan)

A CT scan uses x-rays taken from different angles, which are combined by a computer to make detailed pictures of the organs. 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) scans

Like CT scans, MRI scans show detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. A contrast material called gadolinium may be injected into a vein before the scan to see details better.

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 the patient 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 patients with multiple myeloma.

Positron emission tomography (PET) scans

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).

When a patient appears to have a solitary plasmacytoma, a PET scan may be used to look for other plasmacytomas. Like MRI scans, PET scans can find plasmacytomas that can’t be seen on regular x-rays, so they are helpful if the patient has pain in a bone but the x-ray result is negative.

Echocardiogram (ECHO)

Amyloidosis often affects the heart, so if your doctor diagnoses or suspects you have this disorder, an echocardiogram (ECHO) may be ordered. This test is basically an ultrasound of the heart. It uses sound waves to look at the heart muscle and how well it’s working. The echocardiogram can see if the heart size is normal and if it is pumping normally. It also is especially 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 tests, the patient’s symptoms and the doctor’s physical exam of the patient. A diagnosis of multiple myeloma requires either:

1. A plasma cell tumor (proven by biopsy) OR at least 10% plasma cells in the bone marrow AND

2. At least one of the following:

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

Smoldering myeloma

This term is used to mean 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 have normal blood counts, normal calcium levels, normal kidney function, no bone or organ damage, and no signs of amyloidosis.

Light chain amyloidosis

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

• Signs and symptoms of amyloidosis
• A biopsy that shows amyloid in any tissue (fat, bone marrow, or organ such as the heart)
• A positive test showing the amyloid protein is a light chain and not a heavy chain
• Abnormal plasma cells in the bone marrow, high levels of M protein in the blood, or high levels of M protein in the urine.  

Amyloid can build up in any tissue, and a biopsy may be able to diagnose this disease. Sometimes it 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). This is after the skin over the biopsy site is numbed with medicine. 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 patient has light chain amyloidosis, but it is sometimes done in someone with amyloid if it isn’t clear that their heart or kidney problems are caused by the amyloid or some other problem.

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