Lymphoplasmacytic lymphoma—also called Waldenstrom macroglobulinemia (WM)—is a relatively rare and slow-growing type of blood cancer. It is classified as a non-Hodgkin lymphoma and affects only about 5 people per 1 million in the United States, with approximately 1,000 to 1,500 new cases diagnosed each year.

Lymphoplasmacytic lymphoma originates in the bone marrow where white blood cells called B-cells are formed. In Waldenstrom macroglobulinemia, genetic mutations in the B-cells cause them to develop abnormally into lymphoplasmacytoid cells. These cells generate an overabundance of immunoglobulin M, or M protein, which thickens the blood to a consistency similar to syrup and makes it more difficult for blood to flow through small blood vessels.

Meanwhile, the abnormal B-cells build up within the bone marrow, which prevents healthy blood cells from developing. This can lead to a variety of conditions that affect the entire body and can be serious if left untreated.

Older male patient with Lymphoplasmacytic lymphoma and nurse

Causes of and risk factors for lymphoplasmacytic lymphoma

Waldenstrom macroglobulinemia is triggered by genetic mutations, but the cause of those mutations is unknown. However, researchers have identified certain risk factors that can increase the likelihood of developing the disease. These risk factors include:

Being older than 65
Being white
Being male or assigned male at birth
Having hepatitis C, acquired immunodeficiency syndrome (AIDS), Sjögren’s syndrome or monoclonal gammopathy of undetermined significance (MGUS)
Having biological family members who have Waldenstrom macroglobulinemia or other types of lymphoma
Exposure to certain types of pesticides, solvents or dyes

Signs and symptoms of lymphoplasmacytic lymphoma

Since Waldenstrom macroglobulinemia is a slow-growing type of lymphoma, the onset of symptoms is typically very gradual. Some asymptomatic patients learn of their diagnosis when visiting a healthcare provider for a routine checkup or for another unrelated reason.

The most common Waldenstrom macroglobulinemia symptoms include:

Anemia – If the bone marrow cannot produce enough red blood cells, fatigue, shortness of breath and dizziness may occur.
Neutropenia – WM can cause a shortage of infection-fighting white blood cells, or neutrophils, which can lead to frequent infections.
Thrombocytopenia – Excessive bleeding and easy bruising can occur due to a lack of platelets to help the blood clot.
Cryoglobulinemia – Proteins that are reactive to cold can build up in the hands and feet, causing them to turn to blue or white and be painful.
Peripheral neuropathy – WM can cause neurological symptoms such as weakness, numbness, tingling and pain in the hands and feet.
Hyperviscosity – As the blood thickens to a syrup-like consistency, various symptoms can occur, such as bleeding gums, nosebleeds, blood in the retinas (which can cause vision loss or double vision), dizziness, confusion, loss of coordination and headaches.

Other signs and symptoms may include:

Fever
Loss of appetite
Weakness
Unexplained weight loss
Night sweats
Enlarged spleen or liver
Swollen lymph nodes
Itchy skin
Raised lesions on the skin
Diarrhea and swelling of the stomach region

Diagnosing lymphoplasmacytic lymphoma

A physician will generally start with a physical examination and, if lymphoplasmacytic lymphoma is suspected, may use several tests to confirm the diagnosis. Testing methods include:

Blood tests – A physician may order a complete blood count (CBC) to determine the amount and type of cells present in the blood. M protein levels may be checked with electrophoresis, which uses an electric field to isolate proteins in the blood.
Urine tests – Abnormal protein levels in the urine can be identified with a urine test.
Bone marrow biopsy – A sample of bone marrow is collected and examined under a microscope to check for lymphoma cells.
Tissue biopsy – A tissue sample from a lymph node or another area of the body may be examined to determine if lymphoma cells are present and to find out whether the cancer has spread.
Imaging tests – Imaging tests such as X-rays, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans and positron emission tomography (PET) scans can reveal enlarged lymph nodes and other signs of lymphoplasmacytic lymphoma.
Funduscopic testing – An ophthalmologist (eye specialist) may examine the blood vessels within the eye to look for signs of hyperviscosity and high M protein levels.

Lymphoplasmacytic lymphoma treatment

For asymptomatic lymphoplasmacytic lymphoma, physicians may recommend watchful waiting. Due to the slow-growing nature of Waldenstrom macroglobulinemia, the waiting period before beginning treatment may last for months or years. If treatment becomes necessary, there are several options available, including:

Plasmapheresis (plasma exchange) – A machine filters out the high concentration of M proteins from the liquid component of blood (plasma), then returns the plasma to the bloodstream. Plasma exchange can help ease the symptoms of hyperviscosity.
Chemotherapy – Oral or intravenous (IV) chemotherapy medication may be given to destroy widespread cancerous cells.
Radiation therapy – High-energy beams are strategically aimed at the body to destroy lymphoma cells.
Immunotherapy – These treatments help the body’s own immune system slow the growth of WM cells or destroy them altogether.
Targeted therapy – Medications specifically target cancer cells without damaging healthy cells.

The Moffitt Cancer Center difference for lymphoplasmacytic lymphoma

At Moffitt, our multispecialty team within the Malignant Hematology Program works together to create an individualized treatment plan for each patient with Waldenstrom macroglobulinemia. Our patients can access cutting-edge treatment and emerging therapies through our clinical trials program. Moffitt Cancer Center is the only National Cancer Institute (NCI) Designated Comprehensive Cancer Center based in Florida.

If you are concerned that you may have lymphoplasmacytic lymphoma or if you’ve already received a diagnosis and want to explore your treatment options, call Moffitt Cancer Center at 1-888-663-3488 or complete our patient registration form online to request an appointment with a cancer specialist. No referral is required to schedule your appointment.