Lymphoplasmacytic Lymphoma (LPL): Understanding Your Pathology Report

Section Editor: David Li MD
June 24, 2026

Lymphoplasmacytic lymphoma (LPL) is a slow-growing type of blood cancer made up of abnormal immune cells, including lymphocytes and plasma cells. These cells usually build up in the bone marrow and sometimes in the lymph nodes, spleen, or other tissues, reducing the body’s ability to produce healthy blood cells. Most lymphoplasmacytic lymphomas make a type of antibody (immune protein) called IgM. When the disease involves the bone marrow and produces IgM, it is also called Waldenström macroglobulinemia.

This article will help you understand the findings in your pathology report for lymphoplasmacytic lymphoma, what each term means, and why it matters for your care.

What causes lymphoplasmacytic lymphoma?

The exact cause of lymphoplasmacytic lymphoma (LPL) is not known, but several factors are linked to a higher risk:

IgM monoclonal gammopathy of undetermined significance (MGUS) — A condition in which a small amount of IgM protein is present without cancer. It can occasionally progress to lymphoplasmacytic lymphoma over time.
Hepatitis C infection — Long-term infection with the hepatitis C virus has been associated with a higher risk.
Genetic changes — Specific mutations (changes in the DNA), especially in the MYD88 gene and sometimes the CXCR4 gene, are found in the cancer cells. These are acquired during life and are not inherited.

What are the symptoms of lymphoplasmacytic lymphoma?

The symptoms of lymphoplasmacytic lymphoma (LPL) are caused by both the buildup of cancer cells and the IgM protein that the cells release into the blood. Common symptoms include:

Fatigue, weakness, and shortness of breath — Caused by a shortage of red blood cells (anemia).
Fever, night sweats, and unexplained weight loss.
Symptoms of thick blood (hyperviscosity) — When IgM levels are very high, the blood becomes thick, which can cause headaches, blurred vision, dizziness, nosebleeds, and difficulty breathing.
Numbness or tingling — The IgM protein can sometimes affect the nerves, causing a peripheral neuropathy.
Enlarged lymph nodes, spleen, or liver — Less common, but possible.

How is the diagnosis made?

The diagnosis of lymphoplasmacytic lymphoma (LPL) is usually made by examining a sample of the bone marrow, and sometimes a lymph node or other affected tissue, under the microscope. A pathologist looks for the characteristic mixture of small lymphocytes, plasma cells, and intermediate cells (described in the next section).

Specialized tests confirm the diagnosis. Immunohistochemistry and flow cytometry use antibodies to detect proteins on and inside the cells. In lymphoplasmacytic lymphoma, the cells carry B-cell markers such as CD19, CD20, CD22, CD79a, and PAX5, usually show IgM, and are typically negative for CD5, CD10, CD23, and CD103. This pattern helps separate lymphoplasmacytic lymphoma from other slow-growing B-cell cancers such as chronic lymphocytic leukemia. A blood test called serum protein electrophoresis measures the IgM protein and shows it as a sharp peak (an “M-spike”). Testing for the MYD88 mutation, described below, also supports the diagnosis.

What does lymphoplasmacytic lymphoma look like under the microscope?

Under the microscope, lymphoplasmacytic lymphoma (LPL) in the bone marrow consists of an abnormal mixture of small lymphocytes, plasmacytoid lymphocytes (cells that are partway between lymphocytes and plasma cells), and plasma cells. Some additional features are common:

Small bubble-like inclusions inside the nucleus, called Dutcher bodies.
An increased number of mast cells, a type of immune cell that helps regulate inflammation.
Scattered histiocytes, immune cells involved in clean-up, which occasionally store the abnormal protein.

When the disease involves a lymph node or the spleen, a similar mixture of small lymphocytes, plasmacytoid lymphocytes, and plasma cells is seen, sometimes partially replacing the normal tissue architecture.

Genetic changes and molecular testing in lymphoplasmacytic lymphoma

Molecular tests look for specific genetic changes inside the cancer cells of lymphoplasmacytic lymphoma (LPL). Two are especially important because they help confirm the diagnosis and guide treatment:

MYD88 (especially MYD88 L265P) — Found in more than 90% of cases. It strongly supports the diagnosis, and its presence predicts that a class of drugs called BTK inhibitors is more likely to work.
CXCR4 — Found in a smaller number of cases. It is associated with higher IgM levels and a greater tendency toward thick blood (hyperviscosity), and it can make the disease respond more slowly to some BTK inhibitors.

Your report will state whether these mutations were found.

What is the difference between lymphoplasmacytic lymphoma and Waldenström macroglobulinemia?

Waldenström macroglobulinemia is a type of lymphoplasmacytic lymphoma (LPL) characterized by the buildup of cancer cells in the bone marrow and elevated levels of IgM in the blood. Because most lymphoplasmacytic lymphomas make IgM and involve the bone marrow, the two terms are often used to describe the same disease. A small number of lymphoplasmacytic lymphomas make a different protein (such as IgG or IgA) or make no protein at all, and these are not called Waldenström macroglobulinemia.

What is the difference between lymphoplasmacytic lymphoma and multiple myeloma?

Both lymphoplasmacytic lymphoma (LPL) and multiple myeloma involve abnormal plasma cells, but they behave differently. Multiple myeloma usually causes bone damage, high calcium levels, and kidney injury, and it most often makes IgG or IgA protein. Lymphoplasmacytic lymphoma usually does not cause these problems; it more often produces IgM and is composed of a mixture of lymphocytes and plasma cells rather than plasma cells alone.

What is the prognosis for lymphoplasmacytic lymphoma?

Lymphoplasmacytic lymphoma (LPL) is a slow-growing cancer, and many patients live for many years after diagnosis, often more than a decade. The prognosis depends on a combination of factors rather than any single result:

Age and overall health.
Blood counts — Lower red blood cell and platelet counts are linked with a less favorable outlook.
Blood test results — A higher level of a protein called beta-2-microglobulin and a very high IgM level are associated with higher-risk disease.
Genetic changes — Cases without the MYD88 mutation tend to respond less well to BTK inhibitors and may have a less favorable outlook, while CXCR4 mutations can affect treatment response.

Your prognosis depends on your own combination of these factors, which your care team can explain in the context of your specific report.

What happens after a diagnosis of lymphoplasmacytic lymphoma?

Once lymphoplasmacytic lymphoma (LPL) is confirmed, treatment is based on whether the disease is causing symptoms, the IgM level, and the genetic findings. The pathology findings help guide several decisions:

Observation — Many patients have no symptoms at the time of diagnosis and do not need immediate treatment. Instead, the disease is watched closely and treatment begins only when symptoms develop.
BTK inhibitors — When treatment is needed, oral drugs such as zanubrutinib or ibrutinib block a signal the cancer cells depend on. They work especially well when the MYD88 mutation is present.
Chemoimmunotherapy — A combination such as bendamustine plus the antibody drug rituximab is another standard option, sometimes preferred for a time-limited course of treatment.
Plasma exchange (plasmapheresis) — When very high IgM makes the blood dangerously thick, this procedure removes the excess protein quickly while other treatment takes effect.

Care is usually provided by a hematologist or oncologist, along with other specialists, and the MYD88 and CXCR4 results help the team decide which treatment is most likely to be effective. Decisions about whether and when to treat are made by the care team together with the patient, based on the specific findings in the report. Clinical trials may also be an option to discuss.

Questions to ask your doctor

Is my diagnosis lymphoplasmacytic lymphoma, Waldenström macroglobulinemia, or both?
What is my IgM level, and is it high enough to cause symptoms?
Do I have any signs of thick blood (hyperviscosity) that need urgent treatment?
Were the MYD88 and CXCR4 mutations tested, and what were the results?
What did the flow cytometry and immunohistochemistry show about the cells?
Do I need treatment now, or is close monitoring reasonable for me?
If I need treatment, would a BTK inhibitor or chemoimmunotherapy be better for my situation?
Could I need plasma exchange to lower my IgM quickly?
Do I have any nerve symptoms that could be related to IgM?
What is my prognosis based on my specific results?
Are there clinical trials that I should consider?