Multiple Myeloma: Understanding Your Pathology Report

Section Editor: David Li MD
June 28, 2026

Multiple myeloma (also called plasma cell myeloma) is a type of blood cancer that starts from plasma cells, a kind of white blood cell that lives in the bone marrow and makes antibodies (immunoglobulins) to help fight infection. In multiple myeloma, a group of abnormal plasma cells grows out of control inside the bone marrow. Sometimes these cells also grow outside the marrow and form masses, or they can weaken and break the bone. The abnormal cells often produce large amounts of one specific antibody, called a monoclonal protein (M-protein). Normally the body makes a wide variety of antibodies, but in multiple myeloma one type takes over. The buildup of abnormal cells and excess protein can damage the bones, kidneys, and other organs.

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

What are the symptoms of multiple myeloma?

Many people with multiple myeloma have no symptoms early in the disease. When symptoms appear, they may include:

Bone problems — Bone pain (especially in the back or ribs), fractures, or “holes” in the bone called lytic lesions.
Fatigue and weakness — From anemia (a low red blood cell count).
Kidney problems — Caused by abnormal proteins blocking the filtering units of the kidneys.
Frequent or severe infections — Because the body cannot make enough normal antibodies.
High calcium symptoms — Nausea, confusion, or constipation caused by high calcium levels from bone breakdown.
Nerve symptoms — Numbness or weakness if bones in the spine collapse and press on nerves.

What causes multiple myeloma?

The exact cause of multiple myeloma is not known. Most cases happen by chance, although several factors can increase the risk:

Age — Most people diagnosed are over 60.
Family history — Having a close relative with myeloma or MGUS increases the risk.
Genetic changes — Changes in the DNA of plasma cells help the cells grow and survive longer than normal.
Ancestry — Myeloma is more common in people of African ancestry.
Previous plasma cell conditions — Almost all cases develop from earlier conditions called MGUS (monoclonal gammopathy of undetermined significance) or smoldering myeloma.

How is the diagnosis made?

The diagnosis of multiple myeloma is made by a pathologist after examining a bone marrow sample and reviewing blood, urine, and imaging results. Two requirements must be met: at least 10% abnormal plasma cells in the bone marrow (or a biopsy-proven plasmacytoma), together with one or more SLiM-CRAB features. The CRAB features show that organ damage has already occurred, while the SLiM features predict a high chance of damage developing soon:

C (calcium) — High calcium level in the blood.
R (renal) — Kidney impairment.
A (anemia) — Low red blood cell count.
B (bone) — Bone lesions or bone destruction.
S — Sixty percent or more plasma cells in the bone marrow.
Li — A very abnormal ratio of free light chains in the blood (100 or higher).
M — More than one focal lesion at least 5 mm in size on MRI.

Several tests work together to confirm the diagnosis. A bone marrow biopsy and aspirate are essential; the pathologist looks for abnormal plasma cells, which may be larger than normal, have irregular nuclei, and grow in sheets or clusters. Blood and urine protein electrophoresis separate proteins into distinct patterns; in myeloma, the single abnormal antibody produces a sharp, tall peak called an M-spike. A related test called immunofixation identifies the exact type of antibody (for example, IgG kappa or IgA lambda), and a serum free light chain assay measures the kappa and lambda light chains and detects an abnormal imbalance, which is especially useful when the myeloma produces only light chains.

Flow cytometry and immunohistochemistry use antibodies to detect proteins on and inside the cells. Myeloma cells typically express CD138 and CD38, and showing that all cells produce the same single light chain (either kappa or lambda, a finding called light chain restriction) confirms that they come from a single abnormal clone. Flow cytometry is also used to detect tiny amounts of remaining disease (minimal residual disease) after treatment. Finally, imaging tests, including low-dose whole-body CT, MRI, and PET-CT, show bone damage and reveal disease outside the bone marrow; they are essential for assessing the extent of disease and monitoring the response to treatment.

What does multiple myeloma look like under the microscope?

Under the microscope, multiple myeloma shows an increased number of plasma cells, which may appear mature or abnormal. The cells are often larger than normal and may have irregular nuclei or prominent nucleoli. They can grow in clusters or sheets, replacing normal bone marrow cells. Special stains confirm that the plasma cells all produce the same light chain (kappa or lambda), indicating they arise from a single clone.

Genetic changes and molecular testing in multiple myeloma

Genetic testing examines the chromosomes inside the myeloma plasma cells for changes that affect how the disease behaves and responds to treatment. Cytogenetic testing examines whole chromosomes for large gains or losses, while fluorescence in situ hybridization (FISH) uses fluorescent probes to detect specific changes that are too small to see by routine methods. Common findings include:

Loss of chromosome 17p (involving the TP53 gene) — Associated with higher-risk, faster-growing disease.
Gain of chromosome 1q — Linked with resistance to treatment.
Translocations involving chromosome 14 — Such as t(4;14) or t(14;16).

These results help doctors classify myeloma as standard-risk or high-risk, which guides treatment and helps estimate the outlook. Your report will list any chromosome changes that were found.

Subtypes of multiple myeloma

Smoldering (asymptomatic) myeloma — An early, slower-growing form. There are more plasma cells and higher M-protein levels than in MGUS, but no CRAB or SLiM features. Treatment is usually not required, but regular monitoring is important because some patients progress to active myeloma.
Non-secretory myeloma — A rare form in which the myeloma cells do not release detectable M-protein into the blood or urine, so the diagnosis depends on bone marrow findings and imaging. Sensitive tests can sometimes still detect light chains.
Plasma cell leukemia — A rare, fast-growing form in which large numbers of plasma cells are found in the bloodstream. It may occur on its own or as a late stage of myeloma, and treatment begins promptly after diagnosis.

How do doctors stage and assess risk?

Unlike most solid tumors, multiple myeloma is not staged by size or spread. Instead, doctors use the Revised International Staging System (R-ISS), and its newest update the R2-ISS, to estimate the outlook and guide treatment. These systems combine blood levels of beta-2 microglobulin, albumin, and LDH with the presence of certain high-risk chromosome changes found by FISH. Patients are grouped into stages that help predict outcomes and inform treatment decisions.

What is the prognosis for multiple myeloma?

The outlook for multiple myeloma varies greatly from person to person and depends on the stage, the genetic changes in the cancer cells, kidney function, and how well the disease responds to treatment. Multiple myeloma is usually not curable, but modern treatments have greatly improved survival and quality of life, and many people live well for many years with ongoing treatment and monitoring. 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 multiple myeloma?

After multiple myeloma is confirmed, treatment depends on whether the disease is active or smoldering, the risk category, and the patient’s overall health. The pathology and laboratory findings help guide several decisions:

Monitoring — Smoldering myeloma, which has no organ damage, is often watched closely without treatment until signs of progression appear.
Combination therapy — Active myeloma is usually treated with a combination of drugs, often four together: a proteasome inhibitor (such as bortezomib), an immunomodulatory drug (such as lenalidomide), an antibody that targets the protein CD38 (such as daratumumab), and a steroid.
Stem cell transplant — An autologous stem cell transplant, which uses the patient’s own blood-forming cells, may follow the initial treatment in patients who are well enough, and is usually followed by ongoing maintenance therapy.
Treatment for relapse — If the myeloma returns, newer immunotherapies, including CAR T-cell therapy and bispecific antibodies, can be very effective.
Supportive care — Medicines that strengthen the bones, along with care to protect the kidneys and manage calcium levels and infections, are an important part of treatment.

Care is provided by a team that usually includes a hematologist or oncologist and other specialists, and the response to treatment is followed with blood tests, imaging, and sometimes repeat bone marrow testing. Clinical trials of newer therapies may also be an option to discuss. Decisions about treatment are made by the care team together with the patient, based on the specific findings in the report.

Questions to ask your doctor

Do I have active myeloma or smoldering myeloma?
Which SLiM or CRAB features are present in my case?
What type of M-protein or light chain is my myeloma producing?
What did my bone marrow biopsy and genetic tests show?
Do I have any high-risk chromosome changes, such as a 17p deletion or a 1q gain?
What is my R-ISS stage and overall risk category?
What treatment combination is recommended for me?
Am I a candidate for a stem cell transplant?
What can be done to protect my bones and kidneys?
How will my response to treatment be measured and monitored?
Are there clinical trials or newer therapies that might benefit me?