Tests for Waldenstrom Macroglobulinemia

The CBC measures how many red blood cells, white blood cells, and platelets are in your blood. If lymphoma cells crowd out normal cells in your bone marrow, these blood levels may be low.

In this test, a specialized doctor called a pathologist looks at a small amount of blood under a microscope. This test lets them see the size, shape, and color of your white blood cells, red blood cells, and platelets.

If you have WM, the extra protein in your blood can cause your red blood cells to stick together in stacks, called rouleaux formations. Or, this extra protein can destroy red blood cells, leaving behind parts of red blood cells or damaged red blood cells called schistocytes.

A blood chemistry checks the balance of salts in your blood and the function of your liver and kidneys.

A comprehensive metabolic panel (CMP) is a type of blood chemistry that also measures the total protein in your blood and a specific protein called albumin. Abnormal protein levels may be one of the only signs of WM in some people. This prompts doctors to do more tests to find out about the proteins.

They may also check uric acid and LDH levels, which can be high in many types of blood and immune system cancers.

This test measures the levels of the different antibodies (immunoglobulins) in your blood, such as IgA, IgE, IgG, and IgM, to see if any are abnormally high or low. These proteins normally help your body fight infections.

If your levels are abnormal, for example too much IgM, other tests are needed to find out why.

The abnormal protein made in WM is an IgM antibody. This antibody is monoclonal, meaning that it is many copies of the exact same antibody.

Doctors use several tests to find and identify IgM or other abnormal antibodies.

• Serum protein electrophoresis (SPEP) is a test that measures the total amount of immunoglobulins in your blood and finds any proteins that look the same.
• Another test, such as immunofixation electrophoresis, is then used to figure out what type of abnormal antibody is in the blood (IgM or some other type).

To diagnose WM, a monoclonal IgM antibody must be found in your blood.

This abnormal protein in WM is known by many different names, including monoclonal immunoglobulin M, IgM protein, IgM spike, IgM paraprotein, M protein, and M-spike.

High levels of other types of monoclonal immunoglobulins, like IgA or IgG, are seen in different disorders, such as multiple myeloma and some other lymphomas.

Sometimes, pieces of the IgM protein are removed by the kidneys in urine. These proteins can be detected with a test called urine protein electrophoresis (UPEP).

Viscosity testing measures the thickness of your blood. If the IgM level is too high, your blood will become thick (viscous) and will not flow freely: think about pouring honey compared to pouring water.

This test measures the level of cryoglobulins in your blood. These are proteins that clump together in cold temperatures and can block blood vessels.

Cold agglutinins are antibodies that attack and destroy red blood cells, especially at cold temperatures. These cells can then build up and block blood vessels. A blood test can be used to detect these antibodies.

This test measures another protein made by cancer cells in WM. The protein itself doesn’t cause problems, but it is a useful indicator of prognosis (outlook). High levels of β2M are linked with a worse outlook.

This is the most important type of biopsy for WM. It is needed to confirm the diagnosis.

Having the procedure

The bone marrow aspiration and biopsy are usually done at the same time, either at the doctor’s office or a hospital. The samples are usually taken from your pelvic (hip) bone, although they are sometimes taken from the sternum (breastbone) or other bones.

Before these tests, the skin over the bone is cleaned and numbed by injecting a local anesthetic or applying a numbing cream. In most cases, adults are awake during the procedures.

• Bone marrow aspiration: A thin, hollow needle is inserted into the bone, and a syringe is used to suck out a small amount of liquid bone marrow.
• Bone marrow biopsy: A small piece of bone and marrow is removed by placing a larger needle in the bone.

When the tests are done, pressure is applied to the site to help stop any bleeding. You will have some soreness in the biopsy area when the numbing medicine wears off. Most people can go home right after the procedure.

You can learn more about this procedure in Bone Marrow Biopsy and Aspiration.

Testing to confirm a WM diagnosis

The bone marrow samples are sent to a lab, where they are tested and looked at under a microscope. For a diagnosis of WM, at least 10% of the cells in the bone marrow must be lymphoplasmacytoid lymphoma cells.

Lymph node biopsies can help diagnose some lymphomas, but WM is usually diagnosed with a bone marrow biopsy. You might have a lymph node biopsy if doctors need to find out whether one or more of your lymph nodes are enlarged because of cancer or an infection.

There are a few ways to do a lymph node biopsy:

Core needle biopsy

For a core needle biopsy, a hollow needle is inserted into the node to remove a piece (a core sample). Depending on the location of the lymph node, the doctor might guide the needle by touch or with the help of imaging tests like ultrasound or CT scan.

Fine needle aspiration (FNA) biopsy

For an FNA biopsy, the doctor uses a very thin, hollow needle attached to a syringe to withdraw (aspirate) a small sample. This is best used for tumors that can be reached easily, such as those just under the skin, although it can also be used for tumors deeper in the body.

Surgical biopsy

In this approach, a node is removed through a cut made in your skin. You may need anesthesia (medicine to put you in a deep sleep). Surgery often lets doctors get larger biopsy samples.

If you have WM, this type of biopsy may be used to check for amyloid.

In this procedure, a thin, hollow needle with a syringe attached is inserted into an area of fat, usually under the skin of your abdomen (belly). A small amount of fat is removed and sent to the lab for special testing.

These tests help doctors figure out the type of lymphoma you have based on certain proteins in or on the cancer cells. This is known as immunophenotyping. It can be done on cells from bone marrow, blood, lymph nodes, and other body fluids.

For both of these tests, samples of cells are treated with antibodies. Antibodies are proteins that stick to other proteins, called antigens, on cancer cells.

• For immunohistochemistry, the cells are examined under a microscope to see if the antibodies are stuck to them (meaning they have these proteins).
• Flow cytometry uses a special machine to look for these proteins.

This testing has become very important in helping doctors determine the exact type of lymphoma, so they can select the best treatment.

For this test, your cells are grown in a lab dish and the chromosomes are looked at under a microscope. These cells are usually from your bone marrow. Doctors look at the number and structure of the chromosomes to find any changes.

In some lymphomas, the cells may have too many chromosomes, too few chromosomes, missing parts of chromosomes (called deletions), or other abnormalities. These changes can help identify the type of lymphoma.

Cytogenetic testing usually takes a few weeks because the cells take time to grow before the chromosomes are ready to be looked at.

FISH is another way to look at chromosomes and genes. It uses special dyes that only attach to specific parts of certain chromosomes.

This test can find:

• Most chromosome changes, such as translocations, that are visible under a microscope in standard cytogenetic tests
• Some changes that are too small to be seen with routine cytogenetic testing

FISH can be used to look for specific changes in chromosomes. It can be used on blood or bone marrow samples. It is very accurate and usually provides results within a couple of days.

This is a very sensitive test that can also find chromosome and gene changes too small to be seen under a microscope, even if there are very few cancer cells in a sample. In WM, testing for MYD88 and CXCR4 gene changes by PCR is recommended.

This test also looks for gene changes in cancer cells that might not be seen on routine cytogenetic tests. NGS can tell us more about the best treatment and prognosis (outlook).

You might get a chest x-ray. This can show enlarged lymph nodes or changes in your lungs, such as pneumonia, which can happen with a weak immune system.

If the test is abnormal, doctors might use a computed tomography (CT) scan to get a more detailed view of your chest.

An ultrasound uses sound waves and their echoes to look inside your body. There is no radiation in an ultrasound test.

Ultrasound can be used to look at lymph nodes near the surface of your skin or to look for enlarged organs inside your abdomen, such as your kidneys, liver, and spleen. It can’t be used to look at organs or lymph nodes in your chest because your ribs block the sound waves.

A CT scan combines many x-ray pictures to make detailed, cross-sectional images of the inside of your body.

Looking for signs of lymphoma

Unlike a regular x-ray, CT scans show the detail in soft tissues, such as internal organs. This can help doctors see if any lymph nodes or organs in your body are enlarged. CT scans are useful when looking for signs of lymphoma in the chest, abdomen, and pelvis.

CT-guided biopsy

CT scans can also be used to guide a biopsy needle into an abnormal lymph node or tumor to get a sample for testing.

For this procedure, you lie on the CT scanning table while the doctor moves a biopsy needle through your skin and toward the area. CT scans are repeated until the needle is in the right place. A biopsy sample is then removed and sent to the lab.

A PET scan can be helpful in spotting small collections of cancer cells.  It uses a radioactive substance (usually a type of sugar called FDG) to mark active cells in your body. Because cancer cells multiply more quickly, they absorb large amounts of sugar and show up on the PET scan.

PET scan can be even more valuable when combined with a CT scan (PET/CT scan).

This test is rarely used in WM, but if your doctor is concerned about your brain or spinal cord, MRI is very useful for looking at these areas. This test doesn’t use radiation. A contrast material called gadolinium may be injected into a vein before the scan to better see details.