Waldenström macroglobulinaemia, often shortened to WM, is a rare type of slow-growing blood cancer, occurring in 4.1 persons per million per year. It belongs to a group of conditions called lymphomas, which affect white blood cells called lymphocytes.
In WM, abnormal lymphoplasmacytic cells build up in the bone marrow and produce too much of a large antibody called IgM. This IgM protein can sometimes cause symptoms by making the blood thicker, affecting nerves, or interfering with normal blood cell production.
Fig 1. Diagram showing abnormal bone marrow cells producing excess IgM protein in Waldenström macroglobulinaemia.
How common is Waldenström macroglobulinaemia?
WM is uncommon. It accounts for about 1% of lymphomas. It is usually diagnosed in older adults, with the median age around the early 70s. Some people are diagnosed after an abnormal blood test, while others present with symptoms such as tiredness, bleeding, nerve symptoms, or infections.
What symptoms can WM cause?
Many people with WM have no symptoms at first. This is sometimes called smouldering WM, and it may only need monitoring.
When symptoms occur, they can be due to either:
- Crowding of the bone marrow by lymphoma cells
- Effects of the IgM protein in the blood
Common problems include:
Fatigue and anaemia
The most common symptom is tiredness due to anaemia, where the body does not have enough healthy red blood cells. This can cause fatigue, shortness of breath, dizziness, or reduced exercise tolerance.
Enlarged lymph nodes, liver, or spleen
Some patients develop swollen lymph nodes, or enlargement of the spleen or liver, although this is not always present.
Thickened blood — hyperviscosity
Because IgM is a large protein, very high levels can make the blood thicker than normal. This is called hyperviscosity syndrome.
Symptoms may include:
- Nosebleeds or gum bleeding
- Blurred vision or visual changes
- Headache, dizziness, or confusion
- Shortness of breath in severe cases
This is an urgent situation and may require a treatment called plasma exchange, which rapidly removes excess IgM from the blood.
Fig 2. Comparison of normal blood flow and thickened blood caused by high IgM levels.
Can WM affect the nerves?
Yes. Some patients develop peripheral neuropathy, usually causing numbness, tingling, imbalance, or difficulty walking. In WM, neuropathy is often related to the IgM protein reacting with nerve components, especially myelin-associated glycoprotein.
This type of neuropathy is usually slow, often painless, and may progress over years. Treatment may help in selected patients, particularly if symptoms are affecting function.
How is WM diagnosed?
The diagnosis usually involves blood tests and a bone marrow biopsy.
Typical tests include:
- Full blood count
- Kidney and liver function tests
- Serum protein electrophoresis
- Immunofixation to identify IgM
- Quantitative immunoglobulins
- Serum free light chains
- Beta-2 microglobulin and LDH
- Bone marrow biopsy
- Genetic testing for mutations such as MYD88 and sometimes CXCR4
- CT or PET/CT imaging in selected cases
A typical diagnosis requires an IgM monoclonal protein in the blood and lymphoplasmacytic lymphoma cells in the bone marrow. The MYD88 mutation is found in more than 90% of patients, but it is not absolutely required for diagnosis.