Multiple Myeloma Staging and Investigations


multiple myeloma staging

If a person is suspected to have multiple myeloma due to the presented signs and symptoms, some investigations are required to confirm the diagnosis of the disease. Further, these multiple myeloma diagnosis can help in staging and selecting an appropriate treatment approach.

Revised International Staging System (RISS) 

It is the most commonly used system for staging multiple myeloma.

Following table describes the characteristics of multiple myeloma according to different RISS stages:

Stage I

Serum beta-2 microglobulin <3.5 mg/L;
Serum albumin level >/=3.5 g/dL;
Absence of high-risk cytogenetic abnormalities; and
Serum LDH level </= Upper limit of normal

Stage II

Neither Stage I nor Stage III

Stage III

Serum beta-2 microglobulin >/=5.5 mg/L; and
Either Presence of high-risk cytogenetic abnormalities; or
Serum LDH level > Upper limit of normal

What are the Investigations for Diagnosis and Staging of Multiple Myeloma?

If a person is suspected to have multiple myeloma due to the presented signs and symptoms, some investigations are required to confirm the diagnosis of the disease. Further, these help in staging and selecting an appropriate treatment approach.

Blood Tests

blood tests

Blood tests can provide very important information that provides direction to the diagnostic workup of multiple myeloma and help in selecting an appropriate treatment approach.

Following are the commonly employed blood test for the diagnosis of the multiple myeloma.

Complete blood cells count (CBC)

This test provides information on the level of RBCs, WBCs, and platelets. In most cases of Multiple myeloma, low level of these formed elements is observed.

Serum protein electrophoresis (SPEP)

In this test, the type of M protein is determined in serum. About 70% of patients with multiple myeloma have elevated levels of monoclonal IgG, about 20% have IgA, and about 1% to 2% have no detectable M protein (non-secretory multiple myeloma).

Immunofixation is another test which helps in determining the class of heavy and light chain constituting the M protein.

Serum free light-chain (FLC) assay

In this test, the level of FLCs of M protein, that is kappa (k) and lambda (l), is estimated. These light chains are not firmly bound to intact (whole) M protein.

This test is very useful in some cases like light-chain only disease, non-secretory myeloma, renal disease, and amyloidosis.

Beta-2 microglobulin (b2M) level in blood

b2M is a protein expressed on the surface of abnormal myeloma cells and it keeps shedding into the blood. High level of b2M indicate worse prognosis and decreased renal function.

Apart from above blood tests, few blood analyses like the level of creatinine, blood urea nitrogen (BUN), calcium, albumin, C-reactive protein, lactate dehydrogenase (LDH), and erythrocyte sedimentation rate (ESR) tests may also be employed.

Bone Marrow Aspiration and Biopsy

Bone Marrow Aspiration

Biopsy samples contain a tiny piece of tissue collected from the bone with the help of a biopsy needle.

The biopsy sample is then tested in a laboratory and can provide very useful information about the myeloma cells such as percentage of plasma cells, clonality of plasma cells, and the presence of specific defective genes or proteins.

Following are various techniques used for collecting this information:


In this technique, a very thin portion of biopsy sample is first attached to a microscope glass slide. The sample is then treated with a specific antibody which gets attached to a protein specific to certain types of cancer cells. Some reagents are then added to the treated sample that causes the bound antibody to changes its color. The change in color of the antibody-protein complex can be observed under the microscope, which confirms the type of cancer cells.

Flow cytometry

In this technique, the biopsy sample is first treated with some fluorescent antibodies that get attached to certain specific proteins (antigens) on the surface of cells. The treated sample is then analyzed using a laser beam and a detector attached to a computer. This test can detect different types of cells in the biopsy sample along with the quantification of each type of cells.

Cytogenetic Testing

In this technique, chromosomes are evaluated for certain defects which are very common in multiple myeloma. The sample cells are first grown into the culture medium and are observed under a microscope after adding certain reagents that bind only to a specific portion of a chromosome. This test enables detection of chromosomal abnormalities like translocation, amplification, or deletion. The presence of certain chromosomal abnormalities is linked to the poor prognosis of the disease, for example, deletion: 17p13, translocations: t(4;14), t(14;16), and chromosome 1 amplification.

Fluorescent in situ hybridization (FISH)

In this technique, a fluorescent RNA probe is used which binds to a specific portion of a chromosome in the sample cells. Then, the sample can be examined under a microscope to determine the presence of certain chromosomal abnormalities like translocation, addition, or deletion. This technique is very sensitive, fast, and accurate. Thus, this technique is preferably used for detecting chromosomal abnormalities.

Imaging Tests

These tests help in scanning larger body area to diagnose the extent of involvement of bones. Alternatively, these tests are employed after treatment to evaluate the treatment efficacy and to detect any signs of disease progression/recurrence.

Radiographic Examination

Radiographic Examination

This is usually the first imaging test which is employed when a multiple myeloma (or any other bone abnormality) is suspected. In this test, x-rays (high energy radiations emitted by certain elements and x-ray generators) are directed towards the body part to be examined. These x-rays are reflected back or absorbed by different body tissues depending upon their density.

The reflected x-rays are collected on an x-ray sensitive film to produce an image of the internal body structures especially bones that reflect most of the x-rays. This test can provide information on the bone lesion compared to the nearby bone on x-ray film. Any abnormality observed during this test warrant detailed investigations to establish the diagnosis of multiple myeloma.

Computed tomography (CT) scan

CT Scan

In this technique, detailed cross-sectional images of body organs are generated using x-rays. This technique can also be utilized for scanning the complete body instead of simple radiography. This technique can sometimes be used to guide a biopsy needle to collect biopsy samples from the affected bone or soft tissue.

Magnetic resonance imaging (MRI) scan

MRI Scan

This technique provides detailed images of internal body structures using radio waves, strong magnetic field, and gadolinium-based contrast material (which is used via intravenous injection to improve the clarity of the MRI images). Whole body MRI is sometimes recommended for the diagnosis of any bone lesions in the skeletal system, which might be missed on plain radiography. This technique can be used when detailed imaging is required, for example in case of spinal cord compression.

Positron emission tomography (PET) scan

PET Scan

This technique uses a radioactive substance (known as fluorodeoxyglucose or FDG) that is given via intravenous injection prior to the procedure. Cancer cells absorb larger amounts of the radioactive substance than normal cells. The areas of higher radioactivity indicate cancerous tissue on the PET scan. Thus, this technique can diagnose unsuspected involvement of bones.

This technique is considered sensitive to diagnose multiple myeloma and to assess response to treatment. This technique can also be combined with CT scan (PET/CT) to accurately diagnose the extent of disease in distant body parts and soft tissue involvement.

Urine Tests

urine analysis

Similar to blood tests, some urine tests are also commonly employed in the diagnostic work-up of multiple myeloma. The most commonly employed urine tests include a 24-hour urine protein electrophoresis and immunofixation for the determination of M protein excreted in the urine. This can help in excluding/detecting non-secretory myeloma. These tests can also reveal renal damage, especially presence of glomerular versus tubular lesions. It can also be used for response assessment after starting treatment.


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