Lymphoplasmacytic lymphoma

by Jason Wasserman MD PhD FRCPC and David Li MD
March 8, 2025

Lymphoplasmacytic lymphoma is a type of blood cancer involving abnormal immune cells called lymphocytes and plasma cells. These cells typically build up in the bone marrow, and occasionally in lymph nodes, the spleen, or other body parts. This abnormal buildup interferes with the body’s ability to produce healthy blood cells. When lymphoplasmacytic lymphoma is found in the bone marrow along with a special type of protein called IgM, it is called Waldenström macroglobulinaemia.

What are the symptoms of lymphoplasmacytic lymphoma?

Common symptoms include tiredness, weakness, and symptoms caused by anemia (low red blood cell counts), such as fatigue and shortness of breath. Some people also experience general symptoms such as weight loss, fever, and night sweats. If the IgM protein levels become very high, you may experience symptoms like headaches, blurred vision, dizziness, nosebleeds, and difficulty breathing. Less common symptoms include enlarged lymph nodes or an enlarged spleen.

What causes lymphoplasmacytic lymphoma?

The exact cause of lymphoplasmacytic lymphoma isn’t known, but certain risk factors increase the likelihood of developing this condition. These include previous infection with hepatitis C virus, a prior condition called IgM monoclonal gammopathy of undetermined significance (MGUS), and certain genetic mutations (changes) such as those found in the MYD88 or CXCR4 genes.

How is this diagnosis made?

A diagnosis is typically made after a pathologist examines a sample of your bone marrow, lymph node, or another affected tissue under a microscope. Additional laboratory tests, including immunohistochemistry and molecular tests, help confirm the diagnosis by identifying specific types of cells and genetic changes.

Microscopic features of lymphoplasmacytic lymphoma

• Bone marrow: The bone marrow usually contains an abnormal mixture of small lymphocytes (small white blood cells involved in the immune response), plasmacytoid lymphocytes (cells intermediate between lymphocytes and plasma cells), and plasma cells (cells that produce antibodies). Special microscopic features often seen include Dutcher bodies (small inclusions inside cells), an increased number of mast cells (cells that help regulate inflammation), and histiocytes (cells involved in immune response and clean-up).
• Lymph node: Typically, lymph nodes show small lymphocytes mixed with plasmacytoid lymphocytes and plasma cells. These cells may appear clustered or scattered and sometimes show unique patterns such as follicular colonization, where abnormal cells fill or replace normal lymph node structures. Rarely, histiocytes may store abnormal immunoglobulin (crystal-storing histiocytosis).
• Spleen: In the spleen, abnormal cells usually involve both the white and red pulp areas, particularly in the mantle and marginal zones. Microscopic features can range from predominantly plasmacytic (mostly plasma cells) to lymphoplasmacytoid (a combination of lymphocytes and plasma cells).
• Other body sites: Occasionally, abnormal cells may appear in other body tissues such as the skin, central nervous system (brain), or other organs. These sites often require additional specialized testing for accurate diagnosis.

Immunohistochemistry

Immunohistochemistry is a laboratory technique that pathologists use to identify specific proteins on cells. This helps confirm the diagnosis. For lymphoplasmacytic lymphoma, the cells typically express proteins like CD20, CD19, CD22, CD79a, and PAX5. They usually show the presence of IgM protein. The cells are typically negative for CD10, CD23, and CD103, although variations exist.

Molecular tests

Molecular tests look for specific genetic mutations within cancer cells. In lymphoplasmacytic lymphoma, pathologists often test for mutations in a gene called MYD88 (especially MYD88 L265P) and occasionally CXCR4. These mutations help confirm the diagnosis and guide treatment decisions.

What is the prognosis for a person diagnosed with lymphoplasmacytic lymphoma?

Prognosis depends on various factors such as age, severity of symptoms, blood test results, and genetic mutations. Many patients live for years after their diagnosis. The presence or absence of specific genetic changes, such as the MYD88 mutation, can affect prognosis, with some mutations associated with a more aggressive disease.

What is the difference between lymphoplasmacytic lymphoma and Waldenström macroglobulinaemia?

Waldenström macroglobulinaemia is a type of lymphoplasmacytic lymphoma characterized by an excess of the IgM protein in the blood. Lymphoplasmacytic lymphoma without this protein excess is simply known as lymphoplasmacytic lymphoma.

What is the difference between lymphoplasmacytic lymphoma and multiple myeloma?

Both conditions involve abnormal plasma cells, but multiple myeloma usually causes bone lesions, high calcium levels, kidney damage, and often affects different areas of the body. Lymphoplasmacytic lymphoma typically does not involve these symptoms and often features IgM protein, whereas multiple myeloma usually involves different proteins like IgG or IgA.