Diagnosis
Diagnosis of Waldenstrom macroglobulinemia often starts with a physical exam. Your healthcare professional talks with you about your symptoms and checks for swollen lymph nodes and an enlarged liver or spleen. The diagnosis isn't made with a single blood test. Multiple tests and procedures are used to diagnose Waldenstrom macroglobulinemia. These may include blood tests, bone marrow biopsy and aspiration, imaging, and other procedures.
Blood tests
Tests can help make a diagnosis and also estimate risk and outlook. Blood tests can:
- Count the number of cells in a blood sample. A complete blood count can show if there are too few healthy blood cells.
- Detect a protein made by cancer cells. Blood tests can find IgM made by Waldenstrom macroglobulinemia cells. A high IgM level may lead to other tests for Waldenstrom macroglobulinemia. Serum protein electrophoresis can show monoclonal proteins. Immunofixation can confirm that the protein is IgM.
- Show how organs are working. A metabolic panel can show how the kidneys and liver are working.
- Measure how the blood flows. A serum viscosity test measures how easily blood flows through blood vessels. In Waldenstrom macroglobulinemia, higher amounts of IgM proteins can thicken the blood and make it flow more slowly.
- Measure levels of lactate dehydrogenase. Lactate dehydrogenase (LDH) is an enzyme found in cells. LDH levels in the blood are often higher in people with lymphoma.
- Check for viruses. Blood tests may include hepatitis B and hepatitis C testing. Antiviral therapy may be needed before treating Waldenstrom macroglobulinemia.
- Check for MGUS. Monoclonal gammopathy of undetermined significance (MGUS) and Waldenstrom macroglobulinemia can both cause an IgM monoclonal protein, also called an M protein, in the blood. More tests may be needed to tell whether the M protein is from MGUS, Waldenstrom macroglobulinemia or another condition.
Bone marrow biopsy and aspiration
Bone marrow biopsy and aspiration are procedures that involve collecting cells from the bone marrow. The cells are sent for testing. A bone marrow biopsy and aspiration help confirm Waldenstrom macroglobulinemia and rule out other conditions that can produce monoclonal IgM.
- Bone marrow aspiration uses a needle to draw a sample of the fluid.
- Bone marrow biopsy uses a needle to collect a small amount of solid tissue.
The samples most often come from the hip bone. The samples go to a lab where they are tested for cancer cells. If there are cancer cells, more tests can give more information about the cells.
Imaging tests
Imaging tests make pictures of the body. They can show if lymph nodes and the spleen are larger than usual and show if other areas of the body are affected by Waldenstrom macroglobulinemia. Tests may include a CT scan or a positron emission tomography (PET) scan. If Bing-Neel syndrome is suspected, an MRI of the brain and spine may be done.
Lumbar puncture
A lumbar puncture may be done if you have symptoms of Bing-Neel syndrome. A lumbar puncture, also called a spinal tap, collects fluid from around the brain and spinal cord. This fluid is called cerebrospinal fluid. A healthcare professional places a needle between bones in the lower back and removes a small amount of fluid. A lab checks it for cancer cells and signs of other conditions.
Tissue biopsy
If your healthcare professional suspects Bing-Neel syndrome, you may have a biopsy of tissue from the central nervous system. This involves taking a tiny sample of tissue from the brain or spinal cord for testing in a lab.
Testing cells in the lab
Cells collected during testing can help your care team decide if you have Waldenstrom macroglobulinemia. Healthcare professionals in the lab look for:
- Proteins on the surface of the cancer cells. Cancer cells have certain proteins on their surfaces that help identify them. These proteins are known as markers. Common markers in Waldenstrom macroglobulinemia include CD19, CD20 and CD22. Lab tests also can show if the IgM protein is present.
- Changes in cancer cell DNA. DNA gives cells instructions. In Waldenstrom macroglobulinemia, changes often affect the MYD88 and CXCR4 genes. These changes can help cancer cells grow and live too long. The test results may help your healthcare team choose treatment.
These changes can affect how the disease behaves and how well treatment with BTK inhibitors works. Testing for MYD88 and CXCR4 gene changes may help guide treatment with a BTK inhibitor.
More Information
Treatment
Waldenstrom macroglobulinemia is not curable with current treatments. Treatment is based mainly on symptoms and complications. The goals of treatment are to ease symptoms, prevent or limit organ damage, and control the condition.
Even though the condition is not curable, many people live with it for years. Some people do not need treatment right away. When treatment is needed, it can control symptoms and complications.
Waldenstrom macroglobulinemia treatment may include watchful waiting, plasma exchange, immunotherapy, targeted therapy and chemotherapy. A bone marrow transplant, also called a stem cell transplant, may be right for some people. Your plan depends on your symptoms, test results and how fast the condition is changing. Your healthcare professional also considers your overall health and your choices.
Watch and wait
If you have smoldering Waldenstrom macroglobulinemia without symptoms or organ damage that calls for treatment, you may not need treatment right away. Instead, you might have regular blood tests to monitor your condition. Healthcare professionals sometimes call this watchful waiting. Treatment may not be needed for years. Some people with smoldering Waldenstrom macroglobulinemia never need treatment.
Watchful waiting also is called active surveillance. Follow-up often includes a review of symptoms, blood counts and IgM levels. How often you're checked depends on your risk and how quickly the condition is changing.
When treatment begins
Treatment usually starts when Waldenstrom macroglobulinemia causes symptoms or health issues. The IgM level alone usually is not a reason to start treatment. Your healthcare team looks at your symptoms and test results to decide when and what treatment is right for you.
Treatment may begin for symptoms or health issues such as:
- Anemia or other low blood counts that cause symptoms.
- Hyperviscosity syndrome.
- Enlarged lymph nodes, liver or spleen that cause symptoms.
- Moderate to severe nerve problems.
- Amyloidosis.
- Symptoms such as fever, night sweats, weight loss or severe tiredness.
- A switch to a more aggressive lymphoma.
Plasma exchange
Plasma exchange, also called plasmapheresis, removes IgM from the blood and replaces plasma with healthy plasma. It may be used if you have hyperviscosity syndrome.
Plasma exchange can lower IgM quickly and ease symptoms from thick blood. But the effect does not last. Other treatments are then used to control the cells that make IgM.
Possible side effects from plasma exchange include discomfort from IV lines and a drop in calcium that can cause tingling or muscle spasms.
Immunotherapy
Immunotherapy uses medicine to help the immune system attack cancer cells. The immune system typically finds and attacks germs and changed cells. Cancer cells can hide from the immune cells. Immunotherapy can help immune cells find and kill cancer cells.
Rituximab (Rituxan) is an immunotherapy used often for Waldenstrom macroglobulinemia. It may be combined with chemotherapy or targeted therapy. It also may be used if Waldenstrom macroglobulinemia comes back or earlier treatment does not work.
Rituximab can cause reactions during an infusion, such as chills, fever, nausea, rash, fatigue or headache.
Targeted therapy
Targeted therapy uses medicines that attack specific parts of cancer cells. Blocking these targets can cause cancer cells to die. It may be combined with immunotherapy. It also may be used if Waldenstrom macroglobulinemia doesn't respond to treatment or comes back after treatment.
Bruton tyrosine kinase (BTK) inhibitors are targeted medicines used for Waldenstrom macroglobulinemia. BTK inhibitors include ibrutinib (Imbruvica) and zanubrutinib (Brukinsa).
Pirtobrutinib (Jaypirca) is another BTK inhibitor that has shown promise in treating Waldenstrom macroglobulinemia that has come back, including after some prior BTK inhibitor treatments.
Ibrutinib can cross the blood-brain barrier, a protective layer around the brain and spinal cord, and is used to treat Bing-Neel syndrome. Zanubrutinib also is an effective treatment for Bing-Neel syndrome.
BTK inhibitors can cause diarrhea, bruising, low blood counts, bleeding, infections and heart rhythm issues. Your healthcare team can tell you whether targeted therapy is an option for you.
Chemotherapy
Chemotherapy treats cancer with strong medicines. There are many chemotherapy medicines. Most chemotherapy medicines are given through a vein. Some are taken by mouth.
Chemotherapy may be used for Waldenstrom macroglobulinemia. It often is combined with immunotherapy. It also may be used if Waldenstrom macroglobulinemia comes back or treatment doesn't work.
Chemotherapy side effects can include nausea, hair loss, mouth sores, diarrhea or constipation, and low blood counts. Some chemotherapy medicines also can damage nerves or the heart.
Bone marrow transplant
A bone marrow transplant, also called a stem cell transplant, may be an option for some people if treatment doesn't work or Waldenstrom macroglobulinemia comes back.
A bone marrow transplant puts healthy blood-forming stem cells into the body after treatment. The cells can come from your own body. This is called an autologous stem cell transplant. They also can come from a donor. This is called an allogeneic stem cell transplant.
Chemotherapy usually is given before the transplant. The high-dose treatment used with a stem cell transplant can cause serious, sometimes life-threatening side effects.
Monitoring after treatment
After treatment, you'll likely have regular follow-up visits to check for signs that Waldenstrom macroglobulinemia has come back. This is called a relapse. Blood tests can help check for relapse.
Follow-up may include a complete blood count, an IgM test and serum protein electrophoresis. You may have kidney and liver tests. Your healthcare team also checks for new or returning symptoms. The schedule depends on your condition and the treatment you had.
More Information
Coping and support
With time, you'll likely find what helps you cope with the uncertainty and worry of a cancer diagnosis. Until then, these ideas may help you decide what to do next.
- Learn about Waldenstrom macroglobulinemia so that you can make decisions about your care. Ask your healthcare team about your test results, treatment choices and, if you want, your outlook. Learning about Waldenstrom macroglobulinemia can help you feel more prepared to make treatment decisions.
- Stay connected with people you care about. Strong relationships can help you cope with Waldenstrom macroglobulinemia. People you trust may be able to help with daily tasks, such as caring for your home if you're in the hospital. They also can support you when you feel worried or overwhelmed.
- Find someone to talk with. Find someone who will listen to your hopes and worries. This may be a friend or family member. A counselor, social worker, clergy member or cancer support group also may help. Ask your healthcare team about support groups.
Other sources of help include the International Waldenstrom's Macroglobulinemia Foundation, the National Cancer Institute, the American Cancer Society, Blood Cancer United and the Lymphoma Research Foundation. Mayo Clinic Connect also lets you talk with others for support and practical tips.
Preparing for your appointment
Make an appointment with a healthcare professional if you have any symptoms that worry you. If your healthcare team thinks that you may have Waldenstrom macroglobulinemia, you'll likely see a doctor who treats blood and bone marrow conditions, called a hematologist.
Here's some information to help you get ready for your appointment.
What you can do
Ask if you need to do anything before the appointment. For example, you may need to change what you eat or drink before a test.
Bring a person you trust, such as a family member or friend, if you can. It can be hard to remember everything you hear during an appointment. Another person may help you remember key details.
Before your appointment, make a list of:
- Symptoms you're having, even if some don't seem related to the reason for your visit.
- Major stresses, recent life changes and other important personal information.
- All medicines, vitamins, herbs and other supplements you're taking, and the doses.
- Questions to ask your healthcare professional.
Basic questions may include:
- Do I have Waldenstrom macroglobulinemia?
- What is my risk group?
- Will I need more tests?
- What are the treatment options?
- How does each treatment affect my survival?
- What are the potential side effects of each treatment?
- How will each treatment affect my daily life?
- Which treatment option is the right choice for me, and why?
- Should I see a specialist?
- Are there any brochures or other printed material that I can take? What websites do you suggest?
- What will decide whether I should plan for a follow-up visit?
Feel free to ask other questions during your appointment.
What to expect from your doctor
Your healthcare professional may ask you questions, such as:
- When did your symptoms begin?
- Do your symptoms happen all the time or do they come and go?
- How do your symptoms affect your daily life?
- What, if anything, seems to make symptoms better?
- What, if anything, seems to make symptoms worse?
- Have you had fevers, night sweats or weight loss?
- Have you noticed any lumps, swelling or pain anywhere in your body?
- Do you have other medical conditions?
- Has anyone in your family had lymphoma?
- What are your biggest worries about your diagnosis or treatment?
Be ready to answer questions so that you have time to talk about what's most important to you.
Clinical trials
Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this condition.
Oct. 17, 2026