In many cases, myeloma is discovered when blood tests, done as part of a routine physical examination or for some other reason, reveal anemia or a high level of protein. A urine test may show protein in the urine.It is important to do both a blood test and a urine test for proteins when testing for myeloma. Occasionally, a chest x-ray will identify significant osteoporosis in the vertebral (spine) bones, or even compression of a vertebral body. Such findings should prompt further testing to detect the underlying cause.
At some point in this testing process, the health care provider refers the person to a blood cancer specialist (hematologist-oncologist). Once the evaluation is completed and the presumptive diagnosis confirmed, the findings are usually presented to the patient in person and also to the patient’s health care provider in writing.
Blood and urine tests
The most important measures in the CBC are as follows:
- Hemoglobin and hematocrit: Hemoglobin is the amount of oxygen-carrying proteinin the blood. Hematocrit is the percentage of red blood cells in the blood. A low hemoglobin or hematocrit value indicates anemia.
- White blood cell count: This is usually abbreviated WBC count and is a measure of how many white blood cells there are in a certain volume of blood.
- Platelet count: Platelets are an important part of the clot that forms when a blood vessel is broken or torn. A low platelet count may indicate a tendency to bleed or bruise.
White blood cell differential: In addition to a CBC, most laboratories report a “white blood cell differential,” often abbreviated “diff.” This test, which may be performed either manually or with an automated counter, gives a breakdown by percentages of the different types of blood cells that make up the white blood cell count. The percentages should add up to be 100. Subclassifying the white blood cells can help determine if there are deficiencies in a particular type of cell.
Blood chemistry panel: This set of tests gives a broad look at levels of various substances in the blood that may indicate the severity of myeloma and myeloma-related complications.
- Protein: Two types of protein are commonly measured in the blood: albumin and globulins. A high level of total protein in the blood may be a clue to the presence of myeloma; a high level of globulins is even more suggestive.
- Calcium: A high level of calcium suggests activereabsorption of boneand thus active myeloma.
- Lactate dehydrogenase (LDH): A high level of this enzyme may indicate active myeloma.
- Blood urea nitrogen (BUN) and creatinine: These are indicators of kidney function. Elevated levels, particularly of creatinine,represent kidney dysfunction.
Immunoglobulin levels: Measuring levels of the immunoglobulins is one way of tracking the extent and progression of the disease. If the myeloma activelysecretes one form of immunoglobulin, then the levels of the other normal immunoglobulins will be suppressed.For example, if a patient has IgG myeloma, the IgG level will be high, and the IgA and IgM levels will be low.
Serum protein electrophoresis (SPEP): This test measures the levels of various proteins in the blood. It is the best test for detecting and measuring the abnormal monoclonal protein level associated with myeloma.
Urine protein electrophoresis (UEP): This test measures the levels of various proteins in the urine. In light-chain-only disease, the abnormal proteins are usually detectable only in urine, not in blood.
Immunofixation (or immunoelectrophoresis, IEP): This test can reveal the specific type of abnormal protein produced by the myeloma.
24-hour urine test for Bence-Jones or light chain proteins in the urine: This test measures the actual amount of myeloma protein being produced by the kidneys.
Serum free light chain measurement: This test measures the amount of light chain, a type of myeloma protein,in the blood.
Prognostic indicators: Various blood tests are used to predict the outcome (prognosis) for an individual. Some of these are simple tests done in every laboratory; others are done only in specialized labs or in research settings. Many of these are not yet used widely but may be in the future. Depending on the situation, these tests may or may not be performed.
- Beta2-microglobulin (B2M): A high level of this normal protein indicates extensive disease and a thus a poorer prognosis.
- C-reactive protein (CRP): A high level of this inflammatory marker may indicate a poor prognosis.
- Lactate dehydrogenase (LDH): A high level of this normal enzyme indicates extensive myeloma.
- In cases of IgM myeloma, a serum viscosity test may be performed.
Bone marrow examination
Examination of the bone marrow is necessary to make the diagnosis of myeloma and to estimate the extent of the disease. Abone marrow biopsy is the procedure to collect a sample of bone marrow.
- Two types of bone marrow samples are taken: Liquid bone marrow (an aspirate) and solid bone marrow within bone core (a biopsy). The biopsy is usually performed on the hip bone.
- The bone marrow is examined under a microscope by a pathologist, a physician who specializes in diagnosing diseases by examining cells and tissues.
- If plasma cells comprise 10-30% of the cells in the bone marrow, this supports the diagnosis of myeloma, in combination with M protein and X-ray findings.
- Bone marrow biopsymay be an uncomfortable, but relatively quick,procedure, so most patients receive some from of premedication to make them more comfortable. Itcan usually be performed in a medical office.
- Occasionally more involved tests may be performed on the bone marrow.Not all tests listed are routinely performed by the pathologist, but they can be requested by the patient’s physician. These may be helpful in assessing prognosis and expected behavior of the myeloma.
- Chromosome analysis:This test identifies chromosome abnormalities in the abnormal plasma cells. Certain chromosome abnormalities are linked to poorer prognosis. Certain chromosomal abnormalities also imply that some specific treatments might be less effective. This test is therefore an important treatment guide.
The following bone marrow tests are under further evaluation and may not be standardly performed:
- Plasmablastic morphology:This test examines the abnormal plasma cells and determines their level of maturity.Fewer mature plasma cells indicate a poorer prognosis.
- Bone marrow microvessel density:A high degree of new blood vessel development in the bone marrow indicates active tumor growth and thus a poorer prognosis.
- Plasma cell labeling index: A high level of this indicator of active plasma cell growth may indicate a poorer prognosis.
- X-ray films: X-ray filmsgive a general overview of bone damage. A skeletal survey includes x-ray filmsfrom every part ofthe body. Osteolytic lesions look darkened, “punched out,” or mottled against the white bone substance on X-ray films. X-ray films can alsoreveal bone fractures or collapse, as in the vertebrae of the spine.
- MRI: MRI uses differences in magnetic vibrations between different types of tissue to give a detailed picture of body structures. MRI is a good choice to show greater detail of a site where myeloma is suspected of causing damage to nerves, blood vessels, or other soft tissues.
These tests are used not only to diagnose myeloma but also to monitor the disease’s progress over time and to measure response to treatment. Thus, the specialist regularly repeats all or most of these tests to keep track of how the disease is progressing. Tracking the levels of normal and abnormal proteins in the blood is particularly useful in this regard.
In most people, treating the plasma cell tumors stops damage to the bones and kidneys and reverses complications due to low blood cell counts, hypercalcemia, and hyperviscosity. Blood cell counts and hemoglobin, protein, calcium, and other indicators return to normal or near normal levels when the disease is under control.
Like most cancers, myeloma is classified into various groups based on the extent of disease, how fast it is progressing, the type and amount of abnormal protein produced, and the types of symptoms and complications. Staging is important because it helps the specialist determine the optimal timing of treatment, the best type of treatment, and the outlook for remission and survival for each individual with myeloma. The types of plasma cells disorders are as follows:
- Monoclonal gammopathy of undetermined significance, or MGUS: In this condition,a small amount of monoclonal protein is produced, but it does not fulfill criteria for the diagnosis of myeloma.There is no associated anemia, infections, bone disease, or lowering of normal immunoglobulin levels.It is unknown whether this disease will progress.Because MGUS involves no symptoms or complications, it does not require treatment. Instead, thepersonundergoes regular follow-up and testing so that any progression to malignant disease can be detected early and treated promptly. This type accounts for about 1% of people with plasma cell disorders.
- Smoldering multiple myeloma: This condition involves the findings of abnormal plasma cells that produce a monoclonal protein, but no symptoms or complications of myeloma are present. This condition accounts for about 5% of all cases of myeloma. The disease may remain stable without progressing to active myeloma for years. In some people, it never does. Because the disease is not active, it does not require treatment. Like MGUS, smoldering myeloma requires carefulfollow-up and testing so that any progression to active myeloma can be detected early and treated promptly.
- Indolent multiple myeloma: People with this type of myeloma have an elevated number of abnormal plasma cells in the bone marrow that may or may not produce monoclonal protein. They also have mild anemia or a few bone lesions, but they have no symptoms. The disease may remain stable for long periods. Treatment begins at the first sign of any disease progression.
- Symptomatic multiple myeloma: This is the full, active form of myeloma. The number of plasma cells in the bone marrow is generally more elevated, with production of monoclonal protein, except in the case of nonsecretory myeloma.Other specific diagnostic criteria must be met before making the diagnosis of myeloma, such as degree of anemia, depression of normal immunoglobulin levels, level of calcium, and presence of bone lesions.
As with all cancers, a system to define the extent of disease, which is important for making treatment decisions and predicting outcomes, has been designated as “staging.”
In myeloma, staging has traditionally been based upon the following criteria:level of hemoglobin (RBC level), degree of M protein elevation, serum calcium levels, and the presence of bone lytic lesions.Early stage disease is deemed to be stage I, while extensive disease is deemed stage III.Intermediate findings suggest stage II disease.Recently, a newer International Staging System has proposed the use of serum beta-2microglobulin and albumin levels to determine stages I-III, suggesting that such markers may more accurately define treatment decisions and, potentially, outcome.