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Multiple myeloma symptoms, diagnosis, and staging

Multiple myeloma symptoms, diagnosis, and staging
S Vincent Rajkumar, MD
Section Editor
Robert A Kyle, MD
Deputy Editor
Rebecca F Connor, MD
Last literature review version 19.3: Fri Sep 30 00:00:00 GMT 2011 | This topic last updated: Mon Oct 10 00:00:00 GMT 2011 (More)

MULTIPLE MYELOMA OVERVIEW — Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow. Normally, plasma cells produce antibodies and play a key role in immune function. However, uncontrolled growth of these cells leads to bone pain and fractures, anemia, infections, and other complications.

In the United States, about four people per 100,000 are diagnosed with MM each year. This condition is slightly more common among men than women, and almost twice as common among blacks as among whites. The average age at diagnosis is 65 to 70 years.

The current treatment options for MM include watchful waiting (for asymptomatic or smoldering multiple myeloma), chemotherapy, treatment with immune modulating medications, and stem cell transplantation. Multiple myeloma is seldom cured, although treatment can relieve symptoms, induce remission, and prolong life.

The cause of MM is unknown. Exposure to radiation, organic chemicals (such as benzene), herbicides, and insecticides may play a role. Genetic factors and viral infection may also influence the risk of developing multiple myeloma.

This topic review discusses the signs and symptoms, diagnostic tests, and staging system used for people with multiple myeloma. The treatment of multiple myeloma is discussed in a separate topic review. (See “Patient information: Multiple myeloma treatment”.)

MULTIPLE MYELOMA FEATURES — Multiple myeloma can produce a wide variety of symptoms.

Bone symptoms — Most individuals develop bone pain in the back or chest, or less commonly, the arms and legs, at the time of diagnosis. The pain is usually triggered by movement and is absent at night, except when changing positions.

MM causes both generalized bone loss throughout the body as well as areas of bone destruction (called “lytic lesions” on x-ray) in specific areas. The bone loss and erosions can lead to osteoporosis and fractures. Many individuals with multiple myeloma experience fractures of the vertebrae (the bones of the spine), which can lead to a loss of height; about 30 percent of individuals experience fractures in other bones, often with little or no preceding trauma. For this reason they are called “pathologic fractures.”

High blood calcium levels — Because bones contain large amounts of calcium, the breakdown of bone in MM can lead to high blood calcium levels (called hypercalcemia). High blood calcium levels occur in 10 to 15 percent of individuals, and the symptoms may include loss of appetite, nausea, vomiting, frequent urination, increased thirst, constipation, weakness, confusion, stupor, or coma.

Anemia — About two-thirds of individuals have anemia (low red cell count) at the time of diagnosis, and anemia eventually occurs in almost all individuals. The signs and symptoms of anemia include paleness, weakness, and fatigue.

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Impaired kidney function — The excess proteins and high blood calcium levels associated with MM can damage the kidneys. Kidney function is abnormal at diagnosis in about half of individuals with multiple myeloma. Occasionally, kidney failure is the first sign of MM.

Thickened blood — The excessive production of proteins by the malignant plasma cells in MM can cause a thickening of the blood (called hyperviscosity syndrome). The symptoms may include bleeding from the nose and mouth, blurred vision, neurologic symptoms, and heart failure.

Neurologic symptoms — Fractures of the vertebrae can lead to increased pressure on the nerve roots where they exit the spine, causing neurologic symptoms (called radiculopathy). This complication of multiple myeloma most commonly affects the chest, lower back, or legs, and the symptoms may include odd sensations (numbness or tingling), pain, or muscle weakness.

Occasionally, neurologic symptoms occur because plasma cells grow within the spinal canal and press on the spinal cord. The symptoms may include severe back pain, muscle weakness, especially of the legs, numbness or tingling, and loss of control of bowel or bladder function (incontinence). Spinal cord compression is a medical emergency and requires immediate treatment to relieve the pressure and prevent permanent damage.

Generalized symptoms — The generalized symptoms of MM include an increased susceptibility to infections (especially during chemotherapy) and weight loss. Occasionally, it causes increased bleeding or tumors of the ribs. In individuals with advanced MM, tumor cells may accumulate beneath the skin, causing large purple-colored bumps.

MULTIPLE MYELOMA TESTING — The diagnosis of MM is based upon the presence of characteristic signs and symptoms of the disease and on the results of tests of the blood and bone marrow. Several tests are used to determine the presence and severity of MM. In some individuals with early MM or related conditions, it may be necessary to repeat these tests periodically until the diagnosis is certain.

After MM is confirmed, additional tests are used to check for the presence of impaired kidney function, anemia, thickening of the blood, and other complications of multiple myeloma.

Blood and urine tests for monoclonal protein — An abnormal protein produced by the plasma cells, called a monoclonal (M) protein (sometimes called a “paraprotein”), can be found in the blood or urine of almost all patients with MM, which helps establish the diagnosis. M proteins serve no useful function, and may be responsible for increases in the thickness of the blood, kidney damage, or bleeding problems.

However, it is important to remember that not everyone with a monoclonal protein has MM. The diagnosis also requires one or more abnormalities such as anemia, bone lesions (see ‘X-rays’ below), kidney failure, or high calcium levels in the blood (see ‘Criteria for diagnosis’ below).

Bone marrow examination — In most individuals with MM, a bone marrow aspiration and biopsy (a collection of a small sample of bone marrow for laboratory analysis, usually taken from the hip) shows that plasma cells comprise an abnormally high percentage of bone marrow cells (more than 10 percent). It may be necessary to collect samples from different areas because MM can affect the marrow of some bones but not others.

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X-rays — In about 80 percent of individuals, routine x-rays show distinct, round (lytic) areas of bone erosion; generalized thinning of the bones; and/or fractures at the time of diagnosis. The bones most commonly involved are the vertebrae, the ribs, the pelvic bones, and the bones of the thigh and upper arm.

Genetic and chromosomal tests — Specialized tests may reveal genetic or chromosomal abnormalities of the plasma cells in individuals with MM. The results of these tests are helpful for predicting the response to treatment and survival.

Plasma cell labeling index — The plasma cell labeling index (PCLI) determines how rapidly the abnormal plasma cells are growing and dividing. Patients in whom the labeling index is low tend to have slower disease progression than those with high values. This test is also useful for distinguishing MM from related conditions that generally have a better prognosis. A normal plasma cell labeling index suggests that MM is less likely, while an elevated index suggests that multiple myeloma is more likely. Although this test is not readily available in many centers, PLCI is a reliable marker of high risk disease. Thus, if it is available, it is recommended to help differentiate between high risk and standard risk MM.

Criteria for diagnosis — The diagnosis of multiple myeloma requires the following:


  • A bone marrow aspirate or biopsy showing that at least 10 percent of the cells are plasma cells or the presence of a plasma cell tumor (called a plasmacytoma), plus
  • M protein in the blood or urine, plus
  • Evidence of damage to the body as a result of the plasma cell growth, such as destructive bone lesions, kidney failure, anemia, or high calcium in the blood.


MULTIPLE MYELOMA STAGING AND PROGNOSIS — The simplest measure of prognosis in MM is based on blood levels of two markers: beta-2-microglobulin and albumin. In general, higher levels of beta-2-microglobulin and lower levels of albumin are associated with a poorer prognosis. This staging system is referred to as the International Staging System, or ISS.

The Durie-Salmon staging system is an older system that divides patients into three stages: Stages I, II, and III, corresponding to low, intermediate, and high cell mass, depending upon the severity of anemia, calcium level, kidney function, presence or absence of bone lesions, and the quantity of abnormal proteins. This staging system is best used as a measure of the overall amounts of malignant plasma cells present in the patient, and is less useful as a measure of prognosis.

Standard versus high-risk MM — Approximately 25 percent of people with MM have high-risk disease. This type of MM is aggressive and may shorten survival. As such, patients with high risk disease are treated with more aggressive therapy.

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Tests performed to distinguish between high and standard risk MM include studies looking for chromosomal abnormalities and the plasma cell labeling index (PLCI).

MULTIPLE MYELOMA TREATMENT — The treatment of multiple myeloma is discussed in a separate topic review. (See “Patient information: Multiple myeloma treatment”.)

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our website (

Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient Level Information:

Patient information: Multiple myeloma treatment

Professional Level Information:

Allogeneic hematopoietic cell transplantation in multiple myeloma
Autologous hematopoietic cell transplantation in multiple myeloma
Clinical features, laboratory manifestations, and diagnosis of multiple myeloma
Determination of initial therapy in patients with multiple myeloma
Diagnosis and management of solitary extramedullary plasmacytoma
Diagnosis and management of solitary plasmacytoma of bone
Clinical presentation, laboratory manifestations, and diagnosis of immunoglobulin light chain (AL) amyloidosis (primary amyloidosis)
Evaluating response to treatment of multiple myeloma
Initial chemotherapy for symptomatic multiple myeloma in patients who are candidates for transplantation
Initial chemotherapy for symptomatic multiple myeloma in patients who are NOT candidates for transplantation
Diagnosis of monoclonal gammopathy of undetermined significance
Pathobiology of multiple myeloma
Pathogenesis of immunoglobulin light chain (AL) amyloidosis and light and heavy chain deposition diseases
Pathogenesis and diagnosis of myeloma cast nephropathy (myeloma kidney)
Treatment of relapsed or refractory multiple myeloma
Treatment of kidney disease in multiple myeloma
Treatment of the complications of multiple myeloma
Types of renal disease in multiple myeloma
The use of bisphosphonates in patients with multiple myeloma

The following organizations also provide reliable health information.


  • National Library of Medicine




  • National Cancer Institute




  • American Cancer Society




  • The Leukemia & Lymphoma Society




  • National Marrow Donor Program




  • The American Society of Clinical Oncology





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