by Rosemarie Tremblay-LeMay MD MSc FRCPC and Vathany Kulasingam, PhD, FCACB
October 16, 2025
A plasma cell neoplasm is a group of related diseases that begin when plasma cells, a type of immune cell found in the bone marrow, start growing abnormally.
Normal plasma cells make immunoglobulins (antibodies) that help the body fight infections. In a plasma cell neoplasm, one group of plasma cells grows more than it should and produces large amounts of a single immunoglobulin, called a monoclonal protein or M protein.
Plasma cell neoplasms represent a spectrum of disease ranging from precancerous conditions (such as MGUS and smoldering myeloma) to fully cancerous conditions (such as multiple myeloma, plasmacytoma, or plasma cell leukemia). All of these conditions arise from the same type of abnormal plasma cell but differ in how many abnormal cells are present and whether they are causing organ damage.
What causes a plasma cell neoplasm?
The exact cause of plasma cell neoplasms is not fully understood. Most cases occur by chance and are not inherited. Doctors believe that the disease begins when genetic changes (mutations) occur in a single plasma cell, allowing it to live longer and divide faster than normal.
As these abnormal cells multiply, they fill the bone marrow and release large amounts of monoclonal immunoglobulin into the blood, crowding out normal blood-forming cells.
Factors that may increase the risk include:
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Older age, as the condition is most common in people over 60.
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Male sex, since men are affected slightly more often.
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Chronic immune stimulation from long-term infections or inflammation.
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Exposure to radiation or certain chemicals, which may damage DNA.
What are the symptoms of a plasma cell neoplasm?
Many people have no symptoms in the early stages. As the number of abnormal plasma cells increases, the following symptoms may appear:
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Bone pain or fractures, caused by bone weakening and destruction.
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Fatigue and weakness, due to anemia (low red blood cell count).
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Frequent infections, because the body cannot make enough normal antibodies.
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Kidney problems, as excess immunoglobulin proteins damage the kidneys.
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Nausea, confusion, or constipation, which can occur when calcium levels rise due to bone breakdown.
How is this diagnosis made?
The diagnosis is usually made after a bone marrow biopsy, in which a small sample of bone and marrow is removed for microscopic examination.
Sometimes, the abnormal plasma cells form a tumor outside the bone, called a plasmacytoma. If this occurs, the diagnosis can be made on a biopsy of that mass.
Under the microscope, the pathologist looks for an increased number of plasma cells that are abnormal in shape or size and that produce only one type of light chain (either kappa or lambda).
The percentage of plasma cells in the bone marrow, combined with blood, urine, and imaging results, helps determine the specific type of plasma cell neoplasm.
What additional tests may be performed?
Several laboratory and molecular tests can help confirm the diagnosis and provide information about the behavior of the disease.
Serum and urine protein electrophoresis
This test separates proteins in the blood or urine into visible patterns. A large spike (M spike) indicates a monoclonal immunoglobulin made by abnormal plasma cells.
Immunofixation electrophoresis
This test identifies the exact type of immunoglobulin produced by the abnormal cells, such as IgG kappa or IgA lambda.
Serum free light chain assay
This test measures kappa and lambda light chains in the blood. An imbalance suggests that one clone of plasma cells is producing excessive protein.
Immunohistochemistry
This test uses special stains to show the proteins made by plasma cells in a biopsy. Abnormal plasma cells are typically positive for CD138, MUM1, and CD79a, and may also express CD56, CD117, or Cyclin D1, which are not found in normal plasma cells.
In situ hybridization
This test helps determine whether the plasma cells produce kappa or lambda light chains. Finding only one type confirms that the cells are monoclonal, meaning they all come from the same abnormal clone.
Molecular and genetic testing
Pathologists can use fluorescence in situ hybridization (FISH) and other genetic tests to look for DNA changes that may affect prognosis. Common findings include:
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Translocations involving the IGH gene on chromosome 14.
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Loss of 17p, affecting the TP53 tumor-suppressor gene.
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Gain of 1q or loss of 1p.
These findings help doctors determine how aggressive the disease may be and guide treatment decisions.
What are the types of plasma cell neoplasms?
Monoclonal gammopathy of undetermined significance (MGUS)
MGUS is the earliest and mildest form of plasma cell neoplasm. Fewer than 10% of bone marrow cells are plasma cells, and the level of abnormal protein in the blood is low. There is no organ damage such as bone lesions, anemia, or kidney injury. MGUS is not cancer, but it can slowly progress to myeloma in a small number of people. Patients with MGUS are usually monitored with regular blood tests.
Smoldering plasma cell myeloma
Smoldering myeloma is a more advanced stage than MGUS but still does not cause symptoms or organ damage. The bone marrow contains 10–60% plasma cells, and the blood shows higher levels of abnormal protein. This condition requires close monitoring, as some patients eventually develop multiple myeloma.
Multiple myeloma
Multiple myeloma is the malignant (cancerous) form of plasma cell neoplasm. In this disease, abnormal plasma cells multiply rapidly in the bone marrow or form tumors in other parts of the body. The excess plasma cells and proteins they produce cause organ damage, including bone destruction, anemia, kidney failure, and high calcium levels.
Treatment often includes chemotherapy, targeted therapy, immunotherapy, and sometimes stem cell transplantation.
Plasmacytoma
A plasmacytoma is a localized tumor made up of cancerous plasma cells. When found inside bone, it is called a solitary plasmacytoma of bone. When found outside the bone, it is called an extramedullary plasmacytoma.
Plasmacytomas are true cancers, but they are confined to one location rather than spread throughout the bone marrow like multiple myeloma. They can often be treated successfully with radiation therapy or surgery, but ongoing follow-up is important because some plasmacytomas eventually progress to multiple myeloma.
Plasma cell leukemia
Plasma cell leukemia is a rare and aggressive type of plasma cell neoplasm in which large numbers of abnormal plasma cells circulate in the bloodstream. It may occur on its own (primary) or as a later stage of multiple myeloma (secondary). Because it spreads through the blood, it typically requires more intensive treatment.
Amyloidosis
Amyloidosis occurs when abnormal immunoglobulins produced by plasma cells form amyloid deposits in organs such as the heart, kidneys, or liver. These deposits interfere with organ function and can be identified with a special stain called Congo red, which makes amyloid appear apple-green under polarized light. Amyloidosis can occur on its own or in combination with other plasma cell neoplasms.
What is the prognosis for a plasma cell neoplasm?
The prognosis depends on the type of plasma cell neoplasm, whether organ damage is present, and what genetic changes are found in the tumor cells.
People with MGUS or smoldering myeloma often live many years without symptoms, while those with multiple myeloma or plasmacytoma may need treatment but can achieve long-term control. Newer therapies, including targeted drugs and immunotherapy, have significantly improved survival and quality of life.
Early diagnosis and regular monitoring are key to preventing complications and improving outcomes.
Questions to ask your doctor
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What type of plasma cell neoplasm do I have?
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Is there any organ damage or evidence of spread?
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What type of abnormal protein is being produced?
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Were genetic or molecular tests performed, and what were the results?
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What treatment options are available for my specific condition?
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How often should I have follow-up testing?
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