Multiple myeloma is a cancer originating from abnormal plasma cells, specialized white blood cells found in the bone marrow. While healthy plasma cells produce antibodies to fight infection, cancerous cells multiply uncontrollably. Diagnosis involves a multi-step investigation, starting with fluid analysis and progressing through advanced imaging and bone marrow examination. This testing confirms the presence of cancerous plasma cells, assesses the damage they have caused, and determines the disease’s characteristics.
Initial Blood and Urine Screening
The first step involves laboratory tests on blood and urine to look for specific protein markers and signs of organ damage. Abnormal plasma cells typically produce excessive amounts of a single, non-functional antibody, known as a monoclonal protein or M-protein. This M-protein is a hallmark of the disease and is detected using specialized techniques.
Serum Protein Electrophoresis (SPEP) separates blood proteins, revealing a distinct spike (M-spike) if the M-protein is present in high concentrations. Urine Protein Electrophoresis (UPEP) is also used because some myeloma cells produce only light chains, often called Bence-Jones proteins, which are small enough to pass into the urine. The Serum Free Light Chain (SFLC) assay provides a sensitive measurement by quantifying free kappa and lambda light chains in the blood and calculating their ratio.
Basic blood chemistry panels are performed to look for organ impairment, often summarized by the CRAB criteria. This includes checking for high calcium levels (hypercalcemia), which results from bone breakdown. Kidney function is assessed by measuring creatinine and blood urea nitrogen (BUN), as excess proteins can cause damage. A complete blood count checks for anemia, which occurs when malignant plasma cells suppress the bone marrow’s ability to produce normal blood cells.
Imaging Tests for Myeloma Detection
Cancerous plasma cells frequently cause destruction of surrounding bone tissue, leading to lesions that must be visualized. Imaging tests are required to determine the extent of bone involvement, which is a key part of diagnosis and staging. These tests look for lytic lesions, which are areas where the bone has been broken down.
The traditional method was the skeletal survey, a series of plain X-rays covering the skull, spine, pelvis, and long bones. While X-rays reveal larger, established lytic lesions, they are limited in detecting smaller or early-stage bone damage. Advanced imaging techniques are now routinely used due to the need for greater sensitivity.
Whole-body low-dose Computed Tomography (CT) scans offer improved sensitivity for detecting bone destruction throughout the skeleton. Magnetic Resonance Imaging (MRI) is the most sensitive test for visualizing the bone marrow and detecting early, focal lesions in the spine and pelvis. Positron Emission Tomography (PET) scans combined with CT (PET-CT) are also common. These scans show lytic lesions and indicate the metabolic activity of the plasma cells, providing a measure of disease aggressiveness. The presence of more than one focal lesion measuring at least 5 millimeters on an MRI or PET-CT defines active myeloma.
Definitive Diagnosis via Bone Marrow Testing
Although blood, urine, and imaging tests suggest multiple myeloma, a definitive diagnosis requires direct examination of the bone marrow. This is achieved through a bone marrow aspiration and biopsy, typically performed on the posterior iliac crest (hip bone). This dual procedure is necessary because the bone marrow has both liquid and solid components.
The aspiration uses a hollow needle to withdraw a sample of the liquid bone marrow. The biopsy uses a larger needle to extract a core of the solid bone tissue and marrow. Both samples are analyzed by a pathologist to determine the percentage of plasma cells present.
In a healthy person, plasma cells make up less than 5% of bone marrow cells. The International Myeloma Working Group (IMWG) criteria for diagnosing active multiple myeloma requires finding at least 10% clonal (cancerous) plasma cells in the sample. This procedure confirms the malignant nature of the cells, quantifies their burden, and provides material for specialized genetic testing needed for prognosis.
Assessing Disease Risk and Prognosis
After diagnosis is confirmed, further testing assesses the disease’s aggressiveness and stage to determine the most effective treatment. This risk stratification relies heavily on genetic analysis of the cancerous plasma cells obtained during the bone marrow biopsy.
Cytogenetic analysis and Fluorescence In Situ Hybridization (FISH) testing identify specific chromosomal abnormalities. FISH is important because it uses fluorescent probes to detect subtle changes that standard genetic tests might miss. Certain changes are associated with a higher risk of early relapse or resistance to therapies. Examples include the deletion of chromosome 17p or specific translocations like t(4;14) or t(14;16). Identifying these high-risk features allows doctors to tailor the initial treatment plan.
Blood tests are also used to determine the disease stage using the International Staging System (ISS). This system relies on the levels of two proteins: Beta-2 Microglobulin (\(\beta_2M\)) and albumin. High \(\beta_2M\) and low albumin levels are associated with a higher tumor burden and a less favorable prognosis. Combining this genetic and protein analysis allows doctors to classify the myeloma into standard, intermediate, or high-risk categories, guiding personalized therapeutic decisions.