Myeloma is a form of blood cancer caused by the excessive production of abnormal plasma cells in the bone marrow, the spongy tissue inside some bones where blood cells are generated.
Plasma cells typically play an important role in protecting the body against infections by producing antibodies, but these abnormal cells produce an abnormal antibody instead, which can cause multiple symptoms.
Diagnosing myeloma involves reviewing a patient’s symptoms as well as the results of physical examination and tests that can include blood and urine tests, bone marrow tests, and different kinds of imaging scans.
Blood tests
Due to the rapid accumulation of myeloma cells in the bone marrow, the generation of other blood cells is often impaired, which can be detected by a complete blood count test. This test measures the levels of red blood cells, white blood cells, and platelets. Low counts of these cells may be indicative of myeloma, with the most common finding being anemia, or low counts of red blood cells.
A blood sample can also be used to measure the levels of M protein, the abnormal antibody produced by myeloma cells. In cases where the M protein is not detected, the presence of a small segment of this antibody, known as light chain, in the blood can help diagnose myeloma.
Measuring the blood levels of beta-2-microglobulin is also useful to diagnose myeloma. This protein is present at the surface of most cells, but its levels are raised in myeloma, and that helps doctors determine how advanced the disease is.
Additionally, blood tests to examine calcium levels — which can be abnormally increased in myeloma patients due to excessive bone breakdown — and kidney function can provide further relevant information on a potential myeloma diagnosis.
Levels of albumin, the most abundant protein in the blood, may also be measured, as they can be lower than normal in myeloma patients.
Urine tests
Urine tests are mainly used to measure the levels of M protein’s light chain, which is referred to as Bence Jones protein when detected in the urine. These specific tests commonly require the collection of urine over a 24-hour period, not just a single urine sample.
Bone marrow tests
Given that myeloma cells develop and grow in the bone marrow, its examination, either through bone marrow aspiration or biopsy, is commonly used to diagnose myeloma.
These invasive procedures, often done at the same time, use long specialized needles to collect either a fluid sample (bone marrow aspiration) or a small, solid piece (bone marrow biopsy) from the bone marrow. Samples are usually collected from the pelvic bone, located in the lower back by the hip.
The samples are then analyzed through several tests to confirm the presence of myeloma cells, as well as genetic abnormalities, which can help predict disease course.
Imaging tests
Imaging tests can be used to detect bone problems associated with multiple myeloma, including changes in their structure and the presence of myeloma masses, as well as to assess how far cancer has spread. These noninvasive tests include X-rays, computerized tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET) scans.
X-rays, where a single-dimensional image of the bones is taken, can detect bone damage that may be caused by myeloma, while CT scans combine X-rays taken from different angles to provide detailed three-dimension (3D) images of soft tissue and bones.
MRI, which uses radio waves to produce detailed 3D images of soft tissue and bones, can show if normal bone marrow has been replaced by myeloma cells or masses. MRI can also be used to measure a tumor’s size and to assess whether a mass is pressing spinal cord nerves.
PET scans, often combined with CT scans, involve the delivery of a harmless amount of a radioactive sugar directly into the bloodstream before scanning. Because cancer cells use sugar at a higher rate than normal cells, they absorb more of the radioactive sugar, being easily detected in the resulting three-dimensional color images. These scans can be used to detect myeloma masses that can’t be seen on regular X-rays.
Diagnostic criteria
The criteria for a positive myeloma diagnosis include the biopsy-proven presence of myeloma masses in or outside the bone or at least 10% of plasma cells in the bone marrow, and one or more of the following:
- Higher than normal levels of calcium in the blood
- Impaired kidney function, as assessed with blood tests
- Anemia
- Bone lesions, or holes, seen on imaging tests
- Having one type of light chain (a natural fragment of antibodies) that is 100 times more common than the other, suggesting the presence of M protein’s light chain.
- 60% or more plasma cells in the bone marrow
Staging
Some people have abnormal plasma cells producing M protein, but no signs or symptoms of the disease. In these cases, the presence of low levels of M protein is classified as a monoclonal gammopathy of undetermined significance, while high M protein levels and plasma cells accounting for 10% to 60% of all cells in bone marrow are classified as smoldering multiple myeloma.
Since these people have an increased risk of developing full-blown myeloma, they are usually monitored closely, and treatment is only initiated when symptoms appear.
Diagnosed myeloma is classified based on its prognosis. Multiple myeloma is commonly staged using the Revised International Staging System (RISS) based on blood levels of albumin, beta-2-microglobulin, and lactic dehydrogenase (LDH), as well as specific genetic abnormalities in myeloma cells.
LDH, an enzyme involved in energy production, is released into the blood when cells are damaged or destroyed, and higher than normal levels are associated with worse disease course and survival.
RISS divides myeloma into three stages. Stage I is the less aggressive form — characterized by normal levels of all three molecules and no high-risk genetic changes in myeloma cells — and stage III the most aggressive, with abnormally high beta-2-microglobulin levels, plus high-risk genetic abnormalities and/or high LDH. Stage II is given to patients whose results do not fit in either stage I or III.
Last updated: Dec. 17, 2021, by Marta Figueiredo PhD
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