Myeloma diagnosis

An accurate diagnosis is one of the most important aspects of a person’s medical care. Obtaining a precise diagnosis will help your doctor to estimate how the disease will progress and determine the appropriate treatment.

The results of blood tests that accompany periodic medical examinations may indicate the need for further evaluation for myeloma. These include an elevated protein level, anemia, and abnormalities in kidney function or calcium levels.

Tests used to diagnosed myeloma

Blood and urine tests: Myeloma cells make too much of a protein called “M protein.” Tests can measure the amount of M protein in the blood and urine. Abnormal levels of M protein in the blood and urine may be a sign of myeloma. A test called a complete blood cell count is used to count the number or red blood cells, white blood cells and platelets in a sample of blood. People with myeloma have low blood cell counts. The most common is a low red blood cell count. 

Bone marrow tests: Myeloma usually starts in the bone marrow. If a blood or urine test is abnormal, your doctor may recommend a test of your bone marrow to look for malignant plasma cells. Bone marrow testing involves two steps usually done at the same time in a doctor's office or a hospital: 

• A bone marrow aspiration to remove a liquid marrow sample
• A bone marrow biopsy to remove a small amount of bone filled with marrow 

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Fluorescence in situ hybridization (FISH): FISH is a laboratory test to see if there are changes to the chromosomes of the myeloma cells taken from the bone marrow. Chromosomes are the parts of a cell that contain genetic information. Normal human cells contain 23 pairs of chromosomes, each of which are a certain size, shape and structure. In some cases of myeloma, the chromosomes of the myeloma cells have abnormal changes. The results of the FISH test help your doctor plan your treatment.

Next-generation sequencing (NGS): This test looks for mutations in the genes of the myeloma cells. Next-generation sequencing is currently being done in research but may soon become part of routine practice.

Imaging tests: Bone problems are common in people with myeloma. Imaging tests make images (pictures) of the inside of the body and can help show bone problems such as bone lesions, breaks or thinning of the bones. Because myeloma can be in any bone in the body, it is important to receive a whole-body scan. Imaging tests are a very important part of the diagnosis, staging and management of myeloma. These tests include:

• Whole body low-dose computed tomography (CT) scan: CT scans take many pictures of areas inside the body from different angles using x-rays. A computer combines all the images to create a single, clear and detailed picture. The amount of radiation used in a low-dose CT scan is much lower than that used for standard CT scans.
• Positron emission tomography (PET)-computed tomography (CT) scan: A PET-CT scanner combines the techniques of both PET and CT in one machine. A PET scan is a procedure in which a small amount of radioactive glucose (sugar) is injected into a vein, and a scanner is used to make detailed, computerized pictures of areas inside the body where the glucose is taken up. Because cancer cells often take up more glucose than normal cells, the pictures can be used to find cancer cells in the body. A PET-CT scan provides a more detailed picture of where the cancer is located in the body than either test alone.
• Magnetic resonance imaging (MRI): This test is done in select cases. It uses radio waves, a powerful magnet and a computer to make a series of detailed pictures of areas inside the body.
• Bone/Skeletal survey: X-rays of all the bones in the body are taken and examined. Bone surveys have mostly been replaced by low-dose CT scans, which show bone damage better than regular x-rays.

Learn more about lab and imaging tests.

Tracking your myeloma tests 

These tips may help you save time and learn more about your health:

• Ask your doctor why certain tests are being done and what to expect.
• Discuss test results with your doctor.
• Ask how to get copies of your lab reports, such as print copies or access to an online patient portal.
• Find out if and when you need follow-up tests.
• Mark upcoming appointments on your calendar.

Diagnostic criteria for myeloma

A myeloma diagnosis requires:

1. A plasmacytoma proven by a biopsy or at least 10 percent of bone marrow made up of cancerous plasma cells
2. At least one of the following findings:
   • High calcium levels in the blood (hypercalcemia)
   • Kidney damage
   • Low red blood cell count (anemia)
   • Bone lesions
   • Bone marrow where at least 60 percent of the cells are cancerous plasma cells
   • A large ration between kappa and lambda free light chains, whereby one is over 100 times higher than the other
   • More than one focal lesion on a MRI (A focal lesion is an abnormal area that shows the development of a small hole in the bone within 18 to 24 months.)

Monoclonal Immunoglobulins (M Protein) and light chains (Bence Jones Protein)

Healthy plasma cells make immunoglobulins (abbreviated as Ig) to fight infections. Immunoglobulins are antibodies (proteins) that attach to foreign substances entering the body. Immunoglobulins identify germs and help the immune system destroy them.

In healthy individuals, plasma cells normally produce proteins called “polyclonal immunoglobulins.” These are antibodies that protect the body against all kinds of different invading viruses, bacteria or other infectious agents (antigens).

Each type of plasma cell makes a single type of immunoglobulin, which is made of two larger pieces (heavy chains) and two smaller pieces (light chains) that are attached to each other. There are five types of heavy chains, and each type is represented by a specific letter: IgG, IgA, IgM, IgD and IgE. There are two types of light chains, kappa (k) and lambda (λ).

Myeloma cells, which are cancerous plasma cells, make large numbers of a single abnormal immunoglobulin. Unlike a normal immunoglobulin, the abnormal immunoglobulin does not help fight infection. This abnormal immunoglobulin is known by several different names, including M protein, monoclonal immunoglobulin, M spike and paraprotein.

Like normal immunoglobulins, M proteins are also made of a pair of heavy chains and a pair of light chains. The most common type of myeloma immunoglobulin is IgG kappa. In IgG kappa myeloma, the myeloma cells produce an immunoglobulin made from two IgG heavy chains bound to two kappa light chains.

Immunoglobulins can be measured in the following ways: (1) an SPEP (serum protein electrophoresis) assay looking for the M protein in the blood, (2) serum free light chain assay that looks for the abnormal kappa or lambda light chains in the blood, or (3) UPEP (urine protein electrophoresis) that looks for light chains from the M protein in the urine.

In some people with myeloma, the immunoglobulin components get distorted or do not fully join together: in these cases, the M protein test may be normal but the abnormal light chain (kappa or lambda) is detectable. 

In other myeloma patients, the myeloma cells only produce light chains, either kappa or lambda. These unattached “free” light chains enter the blood and are excreted in the urine where they can be detected. Light chains in the urine are referred to as “Bence Jones proteins.” In both cases, SPEP or UPEP tests for M proteins may not detect M proteins, but the abnormal light chains (kappa or lambda) are detectable in the blood.

A small number of patients have “oligosecretory myeloma,” in which the tests above are only slightly abnormal, or “non-secretory myeloma,” in which no monoclonal protein can be detected. 

About 2 to 3 percent of patients have non-secretory myeloma. In these cases, bone marrow biopsies can be used to look for the cancerous myeloma cells and to see if treatment is working. Even more rare, “macrofocal myeloma” means that plasmacytomas (masses of myeloma cells) occur in several bones without any bone marrow biopsy abnormalities. Here, imaging tests like MRI scans are the best way to track the disease.

Myeloma staging

Once doctors diagnose cancer, they need to know how much cancer is in the body and where it is located. This process is called staging. Figuring out the stage of the cancer helps doctors determine how best to treat it.

Myeloma has three stages numbered from 1 to 3. Often doctors write the stage in Roman numerals. You may see stage 1 written as Stage I, stage 2 written as Stage II and stage 3 written as Stage III. 

The stage tells your doctor how quickly your myeloma is growing. Stage 1 myeloma typically grows slowly. As the stages get higher, the myeloma typically grows more quickly. Knowing the stage can help your doctor predict your prognosis (likely outcome of the disease). Doctors use the results of blood, bone marrow and imaging tests to stage myeloma. These tests look at:  

• Hemoglobin levels in the blood, which may be lower than normal
• The amount of M protein found in the blood and urine (M protein is made by myeloma cells)
• The calcium level in the blood, which may be higher than normal
• The Beta-2 microglobulin level in the blood, which may be higher than normal
• The albumin level in the blood, which may be lower than normal
• The bones, to see if there are any bone lesions
• The presence of high-risk cytogenetic (chromosome) abnormalities in the myeloma cells
• The lactate dehydrogenase level in the blood, which may be higher than normal

There are two staging systems that are commonly used in myeloma. One is called the Durie-Salmon Staging System, and the other is called the Revised International Staging System (R-ISS) for Multiple Myeloma.