How is Multiple Myeloma diagnosed?

Introduction to Multiple Myeloma Diagnosis

Multiple myeloma is a cancer that affects plasma cells in the bone marrow. Plasma cells make antibodies that help kill germs. When they become cancerous, the cells rapidly grow and create an abnormal antibody known as M protein. 
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With no prominent risk factors and varied symptoms, determining if you have multiple myeloma is an extensive process, but a timely and accurate diagnosis is crucial. 
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To confirm multiple myeloma healthcare teams perform blood tests, urine tests, bone marrow biopsies, and imaging. 
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Understanding the Diagnostic Process for Multiple Myeloma

Like any diagnostic process for an illness, the first step is an evaluation of symptoms and medical history. 

Then, a doctor will perform laboratory tests to assess blood cell count and urine levels, which signify two symptoms: low blood cell count and kidney damage.
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Finally, the patient undergoes a bone marrow biopsy and imaging tests to confirm the diagnosis and determine the spread of the cancerous cells. 

Learn more about multiple myeloma here.

Initial Evaluation of Symptoms and Medical History

Not every patient who has multiple myeloma will experience symptoms, but there are some common ones, including: 

• Bone pain or weakness primarily in the back, hips, and skull. 
• Fatigue as a result of anemia or high levels of calcium.
• Back pain or numbness in legs due to spinal cord compression.
• Recurrent inflections.

Diagnosing multiple myeloma is challenging because there are no apparent risk factors, but age, sex, race, family history with myeloma, and other plasma cell diseases are all reviewed.

Laboratory Tests for Multiple Myeloma Diagnosis

Various blood tests help determine the presence of cancerous plasma cells, including:

• Complete blood count (CBC) tests count the number of red blood cells, white blood cells, and platelets. A doctor will compare your results to those of a healthy person.
• Blood chemistry profiles measure different enzymes and materials in the blood to determine liver and kidney function. This test measures specific blood markers to assess disease severity. 
• Serum protein electrophoresis (SPEP) separates proteins in blood samples to determine the levels of M protein, which is the abnormal antibody present in multiple myeloma patients.
• Serum free light chains: quantify the levels of kappa and lambda light chains in the blood
• Lactic Dehydrogenase (LDH) and Beta-2 microglobulin: provide prognostic information.

Urine tests are also performed, including urine protein electrophoresis (UPEP) which measures M protein, and antibody light chains levels in the urine. 

Imaging Studies in the Diagnostic Process

A bone marrow biopsy will help determine the number of myeloma cells and how extensive the disease is. Imaging tests will also help inform you about the status of the disease.

These tests include:

• X-rays help identify lytic bone lesions (small holes in bones), fractures, or bone density changes characteristic of multiple myeloma.
• Magnetic resonance imaging (MRI) provides detailed visualization of bone and soft tissue abnormalities, including tumor growth and spinal cord compression.
• Positron emission tomography (PET) scans help detect active myeloma lesions and assess disease spread or response to treatment.

Blood and Urine Tests for Multiple Myeloma Diagnosis

Let’s break down some of the diagnostic blood and urine tests:

Serum Protein Electrophoresis (SPEP)

A SPEP test is one of the initial tools used for suspected multiple myeloma. 
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The test measures antibodies in the blood sample and detects abnormal proteins, such as M protein. M protein is also called monoclonal immunoglobulin or antibody. 

The overproduction of M protein is known as monoclonal gammopathy, which is an increase of antibodies from just one cell type. This condition differs from polyclonal gammopathy, also known as hypergammaglobulinemia, which means elevated levels of antibodies using multiple cells. Polyclonal gammopathy doesn’t usually indicate cancer.

Urine Protein Electrophoresis (UPEP)

UPEP tests are complementary to SPEP tests and provide a comprehensive evaluation. 
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This test examines protein levels in the patient's urine,  detecting abnormal M proteins and Bence Jones proteins.
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An antibody is made of four protein chains, and Bence Jones proteins are the light chain proteins that make up an antibody. M proteins are the entire antibody. Excessive amounts of either protein can denote multiple myeloma.

Measurement of Specific Proteins

Blood chemistry profiles will also help identify and quantify beta-2 microglobulin levels, and lactate dehydrogenase (LDH) enzymes.
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High levels of beta-2 microglobulin indicate multiple myeloma as it is a protein made by the cancerous cell. High levels also reveal extensive kidney disease, which is a cause of myeloma. 
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LDH is an enzyme that aids energy creation and is present in all cells. But, when its levels are high, the myeloma cells may be rapidly reproducing and spreading. 
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Another test for specific proteins is serum-free light chains which measures light chains and the ratio of different types of chains. There are kappa and lambda light chains, and a healthy person will have the same number as both. Someone with multiple myeloma will have a high level of one of the light chains. Monitoring this ratio helps physicians determine the effectiveness of treatment. 

Bone Marrow Biopsy and Aspirate Procedures

The bone marrow then undergoes analysis to identify the percentage of myeloma calls. Additional bone marrow tests also help determine genetic mutations, which guide healthcare teams when creating treatment plans. 

These tests are:

• Flow cytometry. This laser-based technique determines and identifies abnormal cells.
• Cytogenetics. This test compares the chromosomes between normal cells and myeloma cells to determine abnormalities. This test helps predict prognosis.
• Fluorescent in situ hybridization (FISH). This test reveals slight chromosome changes in myeloma cells that cannot be identified by cytogenetics.

Imaging Techniques Used in Multiple Myeloma Diagnosis

There are serval imaging techniques used to identify cancerous areas and determine how far the cancer has spread.

These techniques are:

• Skeletal surveys are a series of x-rays that gather comprehensive information about bone damage. 
• Magnetic resonance imaging (MRI) shows detailed bone and soft tissue evaluation.
• Positron emission tomography (PET) scans identify active myeloma lesions.

Read more about multiple myeloma.

Interpreting Test Results and Formulating a Diagnosis

Arriving at a multiple myeloma diagnosis usually requires the collaboration of oncologists, hematologists, and pathologists. These physicians administer the tests essential to diagnosis. 
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An official diagnosis requires both:

• One of the following:  

• High calcium levels
• Poor kidney function
• Anemia
• Bone damage or holes in the bones
• 60% or more myeloma cells
• An increase in one type of light chain proteins to over 100mg/dl
• More than one area of localized abnormality on a MRI scan

Diagnostic Challenges and Considerations for Multiple Myeloma Diagnosis

The presence of some of these symptoms or test results does not confirm multiple myeloma. It is a complex disease that is hard to diagnose without a comprehensive evaluation.

There are also similar plasma cell disorders that may act like multiple myeloma.

Differentiating Multiple Myeloma from Similar Conditions

There are many plasma cell disorders congruent with the symptoms of multiple myeloma, so undergoing extensive testing can help avoid misdiagnosis.
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You should advocate for all blood tests, biopsies, and imaging to ensure the correct results. 

Here are some of the similar conditions:

• Monoclonal Gammopathy of Undetermined Significance (MUGS). MUGS is usually a precursor to myeloma, but its progression risk is only 1%/year. The condition is asymptomatic but does involve an elevated level of M protein in the blood. Smoldering Multiple Myeloma: A stage between MGUS and smoldering myeloma characterized by a 10%/yr risk for progression to myeloma over the first 5 years after diagnosis.
• Monoclonal Gammopathy of Renal Significance (MGRS). A subset of MUGS, this condition requires treatment for kidney damage.Waldenström Macroglobulinemia (WM). This disease is a rare subtype of non-Hodgkin lymphoma that results in the overproduction of immunoglobin M (IgM). In multiple myeloma, the overproduction of M protein is any class of immunoglobulin, not just IgM. WM presents with bleeding and neurological symptoms instead of bone and kidney issues. 

Addressing False-Positive and False-Negative Test Results

Incorrect test results, whether false-positive or false-negative, are always possible.
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 Minimizing the possibilities of both results is helped by:

• Comprehensive initial screenings that provide context and adequate reasoning for testing.
• Multiple and repeat tests. Undergoing blood testing, urine testing, biopsies, and imaging ensures a throughout examination, while repeating these tests when necessary can minimize false results.
• Advanced genomic testing, like FISH or cytogenetics, can identify mutations before advanced symptoms. 

Recognizing the Importance of Comprehensive Evaluation

Multiple myeloma has few common risk factors and initial symptoms. There are also many similar diseases, so receiving a correct diagnosis is a laborious process. 
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Undergoing all testing available and meeting with multiple healthcare professionals is essential for your future health.

Early Detection Is Crucial in Multiple Myeloma

To effectively treat multiple myeloma, early detection is crucial, as is accurate diagnosis. These help determine disease staging and prognosis assessment, which inform treatment plans. 
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Routine blood testing can help catch multiple myeloma early. And diagnostic accuracy and outcomes are enhanced by a collaborative approach among healthcare professionals. 
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Learn more about multiple myeloma and contact My Cancer Haven to join a cancer care community.

Frequently Asked Questions