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Multiple Myeloma/Plasmacytoma

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Multiple myeloma (also known as “myeloma”) is the most common primary bone cancer. It accounts for about 1% of all cancers, occurring in more than 20,000 people in the United States each year.

This disease generally occurs in older adults. Very few cases occur in people younger than 40 years of age. Multiple myeloma tends to be more common in men than women. It is twice as common in African Americans as it is in Caucasians. 

Description

Multiple myeloma is named for the "clock face" appearance of the cancer cells when seen under a microscope. They infiltrate virtually all of a patient's bone marrow. In x-ray images of multiple myeloma, it looks like holes have been "punched out" of the bone. 

X-ray of multiple myeloma in skull

A skull x-ray taken from the side shows typical findings of multiple myeloma and multiple "punched-out" holes. The arrow is pointing at one of the larger holes. 

Multiple myeloma cells come from changed plasma cells. Plasma cells are white blood cells that secrete antibodies as part of the immune response. The changed plasma cells produce abnormal amounts of an antibody protein. No one knows the exact cause or location of the cellular change.

Multiple myeloma is not confined to a specific bone or location within a bone. It tends to involve the entire skeleton. When only one lesion is found it is called a “plasmacytoma.” Most doctors believe that plasmacytoma is simply an early, isolated form of multiple myeloma. 

Cause

Multiple myeloma occurs spontaneously. Patients exposed to ionizing radiation and the pesticide dioxin may develop the disease. Infection with some viruses (HIV and human herpesvirus 8) has also been associated with multiple myeloma. No known risk factors are inherited. 

Symptoms

Patients usually complain of bone pain. Other symptoms include:

  • Fatigue
  • Feeling ill
  • Fever
  • Night sweats

Weight loss is not common in the early stages.

Physically, patients are pale with diffuse bone tenderness, especially around the sternum (breastbone) and pelvis (hips).

Pathologic fractures (fractures caused by tumors) occur frequently. Patients will often have their multiple myeloma first discovered when they develop this kind of fracture. The spine is the most common location for a pathologic fracture to occur. It can also happen in the ribs and pelvis. 

X-rays of multiple myeloma and a pathologic fracture

This x-ray, taken from the side, shows the lower end of a patient’s femur (thighbone) near the knee. Multiple myeloma has weakened the bone and resulted in a pathologic fracture (black arrow). The white arrow is pointing at one of the “punched out” holes typically seen on x-ray. 

Reproduced from Johnson TR, Steinbach LS (eds.):  Essentials of Musculoskeletal Imaging. Rosemont, IL. American Academy of Orthopaedic Surgeons, 2004, p. 145.

Compression of the spinal cord occurs in up to 5% of patients. This causes pain in the back and legs and numbness and weakness in the legs.

Patients who have high levels of calcium in their blood may experience nausea, fatigue, confusion, constipation, and frequent urination.

Patients with anemia may experience fatigue, weakness, and shortness of breath with exercise.

In advanced cases, patients typically have recurrent infections and can have kidney failure. 

Doctor Examination and Tests

Several tests are used to confirm a diagnosis of multiple myeloma, including x-rays, bone scans, a bone biopsy, and a blood test.

Multiple myeloma appears on x-rays as decreased bone density with a lot of "punched out" holes in the bone. These destructive lesions are not surrounded by the white rim of bone typically seen in other types of destructive lesions. A bone scan may show which bones are involved with multiple myeloma, but often the lesions cannot be seen. If a bone scan is negative, a skeletal survey is usually performed. This consists of x-rays of many different parts of the skeleton. 

X-rays of multiple myeloma in leg

These x-rays show typical lesions caused by multiple myeloma. (Left) A lesion in the tibia (shinbone). (Right) Two lesions at the lower end of the femur (thighbone) near the knee. 

The diagnosis is made when a large number of abnormal plasma cells are found in the patient's bone marrow. The doctor obtains this marrow through a bone biopsy.

A blood test can confirm the diagnosis. The patient's blood is checked for abnormal antibodies produced by myeloma cells.

Some forms of multiple myeloma produce proteins that can be detected with a urine analysis.

Patients may also have:

  • Anemia (low red blood cell count)
  • Leukopenia (low white blood cell count)
  • Thrombocytopenia (low platelet count)
  • Hypercalcemia (high calcium level in the blood) 

Treatment

Multiple myeloma is currently not curable. Chemotherapy may prolong life expectancy and decrease symptoms.

Chemotherapy

Chemotherapy is the use of medications or drugs to treat cancer. The standard treatment medications for multiple myeloma are melphalan and prednisone.

For patients in whom this therapy is ineffective, alternatives include:

  • VBMCP (vincristine, carmustine, melphalan, cyclophosphamide and prednisone)
  • VAD (vincristine, adriamycin and dexamethasone)

These treatments may cause severe muscle weakness. They may also increase the chance of infections.

Thalidomide and interferon are also sometimes used.

Fortunately, a recent advancement in the treatment of multiple myeloma has increased response and survival rates. This treatment consists of high-dose chemotherapy, followed by autologous stem cell transplantation. This stem cell transplantation involves:

  • Harvesting a patient's own blood cells
  • Conditioning them with very high doses of melphalan
  • Re-infusing the blood cells back into the patient 

Radiation Therapy

Radiation therapy is reserved for decreasing the size of symptomatic bone lesions.

Supportive Care

Supportive care is critical. This includes comfort measures, pain control, and interventions that maintain function. Supportive care includes managing the bone disease, anemia, infections, kidney failure, and pain associated with multiple myeloma.

  • Bisphosphonate medications can prevent destructive bone lesions and spine fractures.
  • Erythropoietin or occasional blood transfusions can manage anemia.
  • Antibody infusions and vaccinations can help patients with recurrent infections.
  • Corticosteroids and hydration can be used to treat high blood calcium concentrations (from bone loss) and dehydration.
  • Narcotics can address the pain associated with bone lesions. 

Surgical Treatment

Surgery will not cure multiple myeloma, but is used to treat fractures and impending fractures. The goal of these surgeries is to decrease pain and maintain function.

Internal fixation augmented with cement is frequently recommended, as are joint replacements and vertebroplasties (for spine fractures). Surgery does not alter the survival rate, but it does improve the quality of life. 

Research on the Horizon

Research in multiple myeloma has been evolving rapidly. Currently, there are a number of new biologic agents entering various stages of clinical studies. 

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Last Reviewed

February 2018

Contributed and/or Updated by

Rajiv Rajani, MD

Peer-Reviewed by

Stuart J. Fischer, MD

AAOS does not endorse any treatments, procedures, products, or physicians referenced herein. This information is provided as an educational service and is not intended to serve as medical advice. Anyone seeking specific orthopaedic advice or assistance should consult his or her orthopaedic surgeon, or locate one in your area through the AAOS Find an Orthopaedist program on this website.