Your pathology report for multiple myeloma (plasma cell myeloma)

by Jason Wasserman MD PhD FRCPC and Kamran M. Mirza MBBS PhD
October 19, 2025

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 infections.

In multiple myeloma, a group of abnormal plasma cells grows uncontrollably inside the bone marrow. Sometimes these cells can also grow outside the marrow as present as masses or cause fractures in bone. These cells often produce large amounts of one specific antibody, called a monoclonal protein (M-protein). Normally, our bodies use a variety of antibodies to help support the immune system but in multiple myeloma one type of antibody takes over. The buildup of abnormal cells and excess protein can damage the bones, kidneys, and other organs.

Doctors diagnose multiple myeloma when abnormal plasma cells are found in the bone marrow along with either:

  • Organ damage caused by the disease (such as bone destruction, kidney injury, or anemia).

  • High-risk laboratory findings showing a strong chance of organ damage developing soon (known as the SLiM criteria).

What are the symptoms?

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

  • Bone pain (especially in the back or ribs), bone fractures, or “holes” in the bone (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 normal antibodies.

  • Nausea, confusion, or constipation caused by high calcium levels from bone breakdown.

  • 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 risk:

  • Age: Most people diagnosed are over 60.

  • Family history: Having a close relative with myeloma or MGUS increases risk.

  • Genetic changes: Abnormalities in plasma cell DNA help the cells grow and survive longer than normal.

  • Race: Myeloma is more common in people of African ancestry.

  • Previous plasma cell conditions: Almost all cases of myeloma develop from precancerous conditions called MGUS (monoclonal gammopathy of undetermined significance) or smoldering myeloma.

How is the diagnosis made?

A pathologist makes the diagnosis after examining a bone marrow biopsy and reviewing blood, urine, and imaging test results.

In order to make the diagnosis of multiple myeloma, the following two criteria must be met:

SLiM criteria predict a high likelihood of organ damage:

  • S: Sixty percent or more plasma cells in the bone marrow.

  • Li: Very abnormal ratio of free light chains in the blood (≥100).

  • M: More than one focal lesion ≥5 mm on MRI imaging.

CRAB features represent actual organ damage, such as high calcium, kidney injury, anemia, or bone destruction.

  • C – Calcium (high levels in the blood).

  • R – Renal (kidney) impairment.

  • A – Anemia.

  • B – Bone lesions or bone pain.

What additional tests may be performed?

Doctors perform several laboratory and imaging tests to confirm multiple myeloma, determine its extent, and guide treatment. These tests detect the abnormal antibody (M-protein), measure disease activity, and assess organ function.

Serum and urine protein electrophoresis

Protein electrophoresis separates the proteins in blood or urine into patterns that appear as peaks or bands. Normally, the peaks are small and spread out. In multiple myeloma, the abnormal plasma cells produce a single type of antibody, creating a sharp, tall peak called an M-spike.
This test confirms that a monoclonal protein is present and measures how much of it the body is producing. Repeating the test after treatment helps monitor response.

Immunofixation electrophoresis

Immunofixation identifies the specific type of antibody produced by the myeloma cells. Each antibody has a heavy chain (IgG, IgA, IgM, IgD, or IgE) and a light chain (kappa or lambda). This test determines which combination is being made—for example, IgG kappa or IgA lambda. Knowing the type helps track the same abnormal protein over time.

Serum free light chain assay

This test measures the amount of free light chains—kappa and lambda—in the blood. Normally, these are made in small amounts and remain balanced. In myeloma, one type is produced in excess, creating a large imbalance.

An abnormal ratio (≥100) between the two types is part of the SLiM criteria and indicates a high risk of developing symptoms. The test also helps detect and monitor patients whose myeloma produces only light chains rather than whole antibodies.

Bone marrow examination

A bone marrow biopsy and aspirate are essential for confirming multiple myeloma. The pathologist examines the sample under the microscope to look for abnormal plasma cells, which may appear larger, have irregular nuclei, or be arranged in sheets or clusters.

The percentage of plasma cells in the marrow helps determine the severity of the disease. In active myeloma, at least 10% of the marrow is composed of abnormal plasma cells, and in advanced cases, the number may be much higher.

Flow cytometry

Flow cytometry is a test that identifies and counts specific types of cells based on proteins found on their surface. In this test, fluorescent dyes attach to antibodies that recognize certain plasma cell proteins.

Normal plasma cells and myeloma cells have distinct patterns. Myeloma cells typically express CD138 and CD38 but often lack CD19 or CD45. Detecting a population of identical plasma cells with the same light chain (either kappa or lambda) confirms the presence of a clonal (neoplastic) plasma cell population. Flow cytometry also helps detect minimal residual disease (MRD) after treatment.

Immunohistochemistry

Immunohistochemistry (IHC) uses special antibodies that attach to specific proteins within cells, allowing the pathologist to visualize them under the microscope.

Plasma cells are identified using markers such as CD138, MUM1, and CD79a. To confirm that the plasma cells are abnormal, the pathologist checks for light chain restriction—meaning all the cells produce either kappa or lambda light chains, but not both. This pattern indicates that the cells all come from one abnormal clone. IHC can also detect other markers, such as Cyclin D1 or CD56, which can provide additional information about tumor behavior.

Genetic testing

Genetic (cytogenetic and FISH) testing examines the chromosomes inside plasma cells for changes that can affect how the disease behaves or responds to treatment.

  • Cytogenetics studies whole chromosomes to look for large changes, such as gains or losses.

  • Fluorescence in situ hybridization (FISH) uses fluorescent probes to identify specific genetic alterations too small to see by routine methods.

Common findings include:

  • Loss of chromosome 17p (TP53 gene) – associated with more aggressive disease.

  • Gain of chromosome 1q – linked to treatment resistance.

  • 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, guiding treatment and prognosis.

Imaging studies

Imaging shows how the disease affects the bones and whether it has spread outside the bone marrow.

  • Low-dose whole-body CT identifies areas of bone loss (lytic lesions) and fractures.

  • Whole-body MRI detects early marrow involvement and focal lesions larger than 5 mm, which meet the SLiM criteria.

  • PET-CT (positron emission tomography) highlights areas of active disease and may reveal tumors outside the bones (extramedullary disease).

These imaging tests are essential for staging, treatment planning, and monitoring response.

What does multiple myeloma look like under the microscope?

Under the microscope, myeloma shows an increased number of plasma cells that may look 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), showing that they come from a single clone.

Subtypes of multiple myeloma

Smoldering (asymptomatic) myeloma

Smoldering myeloma is an early, slower-growing form of the disease. Patients have more plasma cells in the bone marrow and higher M-protein levels than in MGUS, but no CRAB or SLiM features. No treatment is required, but regular monitoring is essential because some patients will progress to active myeloma.

Non-secretory myeloma

In this rare subtype, the myeloma cells do not release detectable M-protein into the blood or urine. Diagnosis depends on the bone marrow findings and imaging tests. In some cases, the cells still produce light chains that can be detected by sensitive blood tests.

Plasma cell leukemia

This is a rare and aggressive form of myeloma in which large numbers of plasma cells are found in the bloodstream. It may occur on its own (primary) or as a late stage of myeloma (secondary). Treatment is more intensive and begins promptly after diagnosis.

How do doctors stage and assess risk?

Doctors use the Revised International Staging System (R-ISS) to group patients with multiple myeloma based on the following features:

  • Blood levels of beta-2 microglobulin, albumin, and LDH.

  • Presence of certain high-risk chromosome changes detected by FISH.

Patients are classified as stage I, II, or III. The stage helps predict outcomes and guides treatment decisions.

What is the prognosis?

Multiple myeloma varies greatly from person to person. Outcomes depend on the stage, genetic changes, kidney function, and how well the disease responds to therapy.

Although multiple myeloma is usually not curable, modern treatments—such as targeted drugs, immunotherapy, proteasome inhibitors, and stem-cell transplantation—have greatly improved survival and quality of life. Many patients live well for many years with ongoing treatment and monitoring.

Questions to ask your doctor

  • Which SLiM or CRAB features are present in my case?

  • What did my bone marrow biopsy and genetic tests show?

  • What type of M-protein or light chain is being produced?

  • What is my R-ISS stage and overall risk category?

  • How will my response to treatment be measured and monitored?

  • Are there clinical trials or new therapies that might benefit me?

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