A series of tests may be necessary to diagnose multiple myeloma. A doctor may order blood, urine, and imaging tests. A biopsy can help confirm a diagnosis. For some people, genetic testing may be beneficial.

Multiple myeloma, or simply myeloma, occurs when plasma cells grow uncontrollably and become cancerous. Usually, routine blood tests can initially lead a doctor to suspect that someone may have multiple myeloma.

Detecting M-protein in blood or urine samples can also be a sign of multiple myeloma. M-protein is an abnormal monoclonal antibody.

However, a doctor will likely order several different tests to help the diagnostic process.

This article covers what these tests involve and how doctors use them to diagnose multiple myeloma. It also briefly covers how doctors stage multiple myeloma.

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Multiple myeloma causes an atypical antibody to circulate in the blood. It can alter the levels of blood components. Doctors can use blood tests to assess for either the antibody, blood components, or both. The results can usually indicate whether someone has multiple myeloma and, if so, the stage of the disease.

Complete blood count

Doctors use a complete blood count to measure the levels of certain components of blood, including:

Multiple myeloma can cause these levels to become low — most commonly the level of red blood cells.

Blood chemistry tests

Doctors may measure several chemicals and proteins when diagnosing multiple myeloma. These include:

  • Albumin: Albumin is a protein the liver produces. Myeloma can cause albumin levels to be low.
  • Beta-2 microglobulin: Beta-2 microglobulin is a protein usually found in small amounts in the body. Elevated levels of beta-2 microglobulin can indicate myeloma.
  • Lactic dehydrogenase (LDH): LDH is an enzyme the body uses to make energy. LDH levels can be beneficial in determining a person’s outlook. Elevated LDH levels can be a sign of advanced myeloma.
  • Creatinine and blood urea nitrogen (BUN): Creatinine and BUN are chemicals the kidneys filter out of the blood. People with multiple myeloma commonly have elevated levels of both. Elevated levels usually indicate that the kidneys are not functioning adequately.
  • Calcium: Elevations in blood calcium levels can be an indicator of myeloma. Myeloma causes damage to the bones, leading to the release of calcium into the blood.

Liver function tests

Liver function tests can assess the levels of proteins and enzymes the liver typically makes or filters out of the body. They can assess the levels of various enzymes, such as:

  • alanine aminotransferase (ALT)
  • alkaline phosphatase (ALP)
  • aspartate aminotransferase (AST)

Multiple myeloma can cause the liver not to function properly. In turn, this causes enzyme levels to be too high or low.

Myeloma cells create a monoclonal antibody, which is unusual. Detecting this in the blood can be the first sign of multiple myeloma.

Quantitative immunoglobulin tests

These tests can measure the levels of different antibodies, or immunoglobulins, in the blood, including:

  • IgA
  • IgD
  • IgE
  • IgM

When someone has multiple myeloma, it can cause the level of one antibody to be higher than others.

Serum protein electrophoresis (SPEP)

SPEP is a test doctors use to measure antibodies in the blood and locate the atypical monoclonal antibody that myeloma cells produce. M-protein is one name for this atypical antibody.

Immunofixation is another type of electrophoresis test doctors use to identify any other atypical proteins in the blood.

Serum-free light chain (SLFC) assay

Antibodies are made of protein chains: two heavy chains and two light chains. The SLFC assay measures the level of light chains in the blood.

This is useful in rare cases when only the light chain in the antibody is affected, known as light chain myeloma. Also, SLFC may be beneficial when SPEP detects no M-protein, likely because the latter only detects whole antibodies (with both heavy and light chains).

The SLFC assay also measures the ratio of different light chains in the blood, which is typically equal. Myeloma sometimes produces more of one light chain than another, making the ratio unequal.

A doctor can use urine tests to look for the atypical protein myeloma cells produce. Two kinds of urine tests can be helpful: urine protein electrophoresis (UPEP) and urine immunofixation.

UPEP uses a routine urine sample. Urine immunofixation uses a sample collected over 24 hours.

Doctors use biopsy procedures to take tissue samples and assess them for multiple myeloma. Samples can come from:

Bone marrow biopsy

In this procedure, a doctor uses a local anesthetic to numb the back of the pelvic bone. They then insert a needle into the bone and use a syringe to take a small sample of liquid bone marrow.

People with multiple myeloma have atypical plasma cells in their bone marrow. When doctors examine bone marrow samples, they look for abnormalities in the cells’ shape, size, appearance, and arrangement.

Cytogenetics can also be used to examine the DNA in bone marrow samples. In cytogenetic testing, a doctor compares the DNA of normal bone marrow cells and myeloma cells. Myeloma cells often have abnormalities in their DNA, some of which are high risk and others low risk. This information can indicate a person’s outlook.

Fine needle aspiration biopsy

In this procedure, a doctor uses an extremely thin needle and a syringe to remove a tissue sample from a tumor or lymph node. The doctor feels around or uses an imaging test called a CT scan to find the enlarged lymph node.

Core needle biopsy

This procedure is similar to a fine needle biopsy but uses a bigger needle to remove a larger tissue sample. A needle biopsy (core or fine) can help confirm a multiple myeloma diagnosis.

Imaging technology can generate pictures of the inside of the body. Doctors can use imaging tests to:

  • look for cancer
  • monitor cancer spread
  • check whether the treatment is working

Tests that doctors may use when diagnosing myeloma include:

Bone X-ray

X-rays can produce pictures of bones. Doctors can use this to check whether the bones display signs of damage caused by myeloma cells.

CT scan

CT scans use X-rays taken from several angles to produce comprehensive images of organs. Doctors can sometimes use CT scans to check whether the bones show signs of damage from myeloma cells.

Also, CT scans can help guide the needle during a fine needle aspiration biopsy.

MRI scan

MRI scans use powerful magnets and radio waves to produce images of bones and organs. They are useful because images can detect plasma cell tumors that other tests, such as X-rays, may not.

Also, MRI scans can help assess the bone marrow in people with multiple myeloma.

PET scan

PET scans use radioactivity to locate tumors that X-rays cannot. A doctor injects a kind of radioactive sugar, which the cancer cells absorb. A scanner can then detect where the radioactivity accumulates.

PET scans are sometimes combined with CT scans.

Learn more about how multiple myeloma appears on imaging scans.

A doctor diagnoses multiple myeloma based on the tests mentioned above, a person’s symptoms, and the results of a physical examination.

Once a doctor collects all the necessary information and the criteria are met, they can confirm a diagnosis of multiple myeloma.

Staging the cancer is next. Multiple myeloma staging is based on four factors:

  • albumin levels in the blood
  • beta-2 microglobulin levels in the blood
  • LDH levels in the blood
  • gene abnormalities of the myeloma cells and whether they are low or high risk

The Revised International Staging System (RISS) outlines the following stages:

stage 1• albumin level is 3.5 (g/dL) or more, and
• beta-2 microglobulin level is less than 3.5 (mg/L), and
• gene abnormalities are not high risk, and
• LDH levels are normal
stage 2not stage 1 or 3
stage 3• beta-2 microglobulin level is 5.5 (mg/L) or more, and
• gene abnormalities are high risk, and/or
• LDH levels are high

Staging is complex. Many factors influence this process.

Learn more about the stages of multiple myeloma.

A doctor may order several tests to determine whether a person has multiple myeloma. These tests include blood, antibody, urine, and imaging tests. A doctor either assesses the levels of components in samples, such as M-protein, or looks for the presence of myeloma cells.

Using these tests, doctors can stage the cancer and provide information on a person’s outlook.