Telling the difference between Waldenström’s macroglobulinemia (WM) and multiple myeloma is a little like differentiating between jam and jelly. They may seem a lot alike at first glance, but a closer look reveals their differences. That may not matter much in terms of what you spread on your bread, but telling WM from multiple myeloma has high stakes — properly managing each condition depends on a correct diagnosis.

Read on to learn more about the similarities between WM and multiple myeloma, along with four key differences that can help you and your hematologist (blood doctor) tell these conditions apart.

Two Blood Cancers With Key Differences

Both Waldenström’s macroglobulinemia and multiple myeloma are blood cancers that can develop from monoclonal gammopathy of undetermined significance (MGUS). As the name suggests, researchers don’t know what causes MGUS. However, the buildup of an abnormal protein in the blood, called monoclonal protein, characterizes MGUS.

Both multiple myeloma and WM can also cause immunoglobulin M (IgM) monoclonal gammopathy (high levels of the IgM antibody). Antibodies are proteins released by plasma cells in response to infection. Plasma cells are mature B lymphocytes, a type of white blood cell. Although the presence of IgM monoclonal antibodies defines WM, IgM multiple myeloma is rare and accounts for less than 0.5 percent of all myeloma cases. Still, this form of multiple myeloma must be considered when someone has high blood levels of IgM.

Symptoms and Treatment

Because they’re both blood cancers, Waldenström’s macroglobulinemia and multiple myeloma can have similar symptoms, including:

• Extreme tiredness
• Weight loss
• Confusion
• Anemia (low red blood cell count)
• Lymphadenopathy (enlarged lymph nodes)

Both conditions also lead to life-threatening hyperviscosity — thick blood caused by high IgM levels. Symptoms include:

• Severe headaches
• Dizziness
• Visual disturbances
• Discolored skin
• Bleeding problems

Importantly, hyperviscosity syndrome and lymphadenopathy are more common in WM.

With both conditions, people who have no symptoms usually aren’t treated. Researchers and doctors base this recommendation on the fact that people with asymptomatic WM or smoldering multiple myeloma (the name given when the condition isn’t causing symptoms) don’t seem to benefit from early treatment.

With these similarities in mind, read on to discover four key ways that experts tell Waldenström’s macroglobulinemia and multiple myeloma apart.

1. Bone Marrow Involvement and Cell Types

A primary difference between Waldenström’s macroglobulinemia and multiple myeloma is their respective effects on bone marrow, the spongy material found inside bones where blood cells are created. Multiple myeloma commonly causes lytic bone lesions — soft areas caused by cancer cells growing in the bone — and bone pain. WM rarely causes these bone marrow changes, so bone pain is less common.

WM and multiple myeloma are also distinguishable by the type of cells they make. WM, a type of lymphoplasmacytic lymphoma, is diagnosed when a bone marrow biopsy (removing a tissue sample to be examined under a microscope) shows at least 10 percent lymphoplasmacytic cells. These cancer cells have characteristics of both lymphocytes and plasma cells because they haven’t properly matured.

A multiple myeloma diagnosis, on the other hand, requires at least 10 percent mature, clonal (identical) plasma cells on a bone marrow biopsy. Unlike WM cells, multiple myeloma plasma cells have only plasma cell characteristics.

Importantly, multiple myeloma cells usually make immunoglobulins other than IgM. If someone’s blood contains higher-than-normal levels of IgG, IgA, or IgD, it’s often easier to distinguish their condition from WM.

Because of the differences in these blood cancers’ cell types and their effects on bone marrow, bone marrow biopsies are important for diagnosing them.

2. Genetic Changes

Doctors can also perform genetic testing to tell Waldenström’s macroglobulinemia and multiple myeloma apart. Genetic differences are especially important when trying to distinguish IgM multiple myeloma from WM because both cause IgM monoclonal gammopathy. For example, the MYD88 mutation (change) is characteristic of Waldenström’s macroglobulinemia but rarely present in IgM multiple myeloma.

“MYD88” stands for ”myeloid differentiation primary response 88 gene.” This gene encodes a protein that immune cells require to mature. Importantly, the MYD88 mutation alone doesn’t indicate WM because this genetic variation is also present in other lymphomas.

IgM multiple myeloma also has characteristic mutations. The most common mutation is known as gene translocation t(11;14) — this occurs when chromosomes 11 and 14 exchange genetic information, which changes the proteins they encode. This specific mutation is common among all types of multiple myeloma but isn’t seen in WM.

3. Disease Progression and Outlook

Because of their unique effects on the body, doctors can distinguish Waldenström’s macroglobulinemia and multiple myeloma based on how they progress. For example, the most common symptom of multiple myeloma is bone pain, while WM usually causes anemia, fatigue, weakness, and peripheral neuropathy (numbness and tingling in the legs caused by nerve damage).

People with advanced multiple myeloma are also more likely than people with WM to experience kidney failure and hypercalcemia (elevated calcium levels). However, organomegaly (organ enlargement) is more common in Waldenström’s macroglobulinemia. In WM and other lymphomas, the liver and spleen may get bigger.

Based on the National Cancer Institute Surveillance, Epidemiology, and End Results database, the prognosis (outlook) also differs between these conditions. The average five-year relative survival rates are 78 percent for WM and 58 percent for multiple myeloma.

The relative survival rate, which compares people with cancer to those who don’t have that cancer type, provides a way to estimate cancer survival. A five-year relative survival rate of 78 percent means that people with WM are about 78 percent as likely as people who don’t have this disease to live at least five years after diagnosis.

4. Choice of Treatment

Distinguishing between Waldenström’s macroglobulinemia and multiple myeloma is essential because they require different treatment strategies once symptoms occur.

There are several preferred drug therapies for Waldenström’s macroglobulinemia. The most commonly used drug to treat WM is rituximab (Rituxan), a monoclonal antibody that helps kill lymphoma cells. Rituximab is usually combined with other drugs.

Multiple myeloma, on the other hand, has two preferred three-drug regimens. These are:

• Bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone
• Carfilzomib (Kyprolis), lenalidomide, and dexamethasone

Bortezomib and carfilzomib are targeted drugs that affect specific substances to treat cancer. Dexamethasone is a steroid, and lenalidomide affects the immune system. Scientists aren’t exactly sure how lenalidomide works, but researchers have found it to be effective in helping people with multiple myeloma.

Along with these drug therapy differences, the use of other treatment strategies also distinguishes WM and multiple myeloma. For example, stem cell transplant is a common option for multiple myeloma but rarely used to treat WM.

Plasmapheresis is the treatment of choice for people with WM who develop hyperviscosity syndrome, which increases the risk of stroke and heart disease. During this procedure, the blood’s plasma (liquid) with the abnormal IgM is separated from the blood cells and replaced with fluids and plasma from a healthy blood donor.

Consult Your Doctor

If you or a loved one is diagnosed with multiple myeloma or WM and you’re concerned about misdiagnosis, it’s essential to discuss this issue with a hematology/oncology doctor. They’ll review your symptoms and previous therapies to ensure that the proper evaluation is completed and the best treatment plan is being followed.

Talk With Others Who Understand

MyMyelomaTeam is the social network for people with multiple myeloma and their loved ones. On MyMyelomaTeam, more than 15,000 members come together to ask questions, give advice, and share their stories with others who understand life with multiple myeloma.

Have you been diagnosed with multiple myeloma? Are you concerned that you may actually have Waldenström’s macroglobulinemia? Share your experiences in the comments below, or start a conversation by posting on your Activities page.