Multiple Myeloma Differential Diagnosis
Following are some disorders that arise from uncontrolled proliferation of plasma cells, and thus, these are closely related to multiple myeloma:
- Solitary Plasmacytoma: It involves single bone lesion with the presence of abnormal plasma cells but the absence of any symptoms and end-organ damage. In case a single lesion is detected in soft tissue the condition is termed as an extramedullary plasmacytoma. M protein may be present in some cases with absence of any end-organ damage indication.
- Monoclonal gammopathy of undetermined significance (MGUS): MGUS is an asymptomatic benign condition with abnormal plasma cells in bone marrow (<10%) and M protein is present in serum (<3 g/dL) but indications of end-organ damage are absent. It is postulated that virtually all cases of myeloma arise from MGUS. However, all cases of MGUS do not ultimately progress to multiple myeloma. MGUS do not require a treatment but patients with MGUS are followed-up closely for progression of the condition to multiple myeloma or any other aggressive disease.
- Smoldering multiple myeloma: It is an asymptomatic pre-malignant condition characterized by the abnormal plasma cells in bone marrow (>/=10%) and presence of M protein in serum (>/=3 g/dL) but the absence of any indication of end-organ damage.
- Light chain amyloidosis: Similar to secretion of antibodies by normal plasma cells. Abnormal plasma cells secrete M protein with a heavy and a light chain. Sometimes, the abnormal plasma cells secrete more light chain than the heavy chain. These light chain proteins can build-up in different organs and known as amyloid. This amyloid deposition in different organs may cause their enlargement and/or organ dysfunction. The most commonly affected organs by amyloidosis are the heart, kidneys, and peripheral nerves.
Investigations for Multiple Myeloma Diagnosis
Following tests can provide very important information that provides direction to the diagnostic workup of multiple myeloma and help in selecting an appropriate treatment approach.
Complete blood cells count (CBC)
This test provides information on the level of RBCs, WBCs, and platelets. In many cases of myeloma, one or more of these may be reduced. Anemia, thrombocytopenia and/or neutropenia may be 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)
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
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, 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.
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.
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.
This is usually the first imaging test which is employed when a multiple myeloma (or any other bone abnormality) is suspected. 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
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
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
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 Protein Electrophoresis and Immunofixation
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.