Multiple myeloma is a cancer of the bone marrow that arises when plasma cells become malignant, invade the marrow, multiply uncontrollably, and disrupt normal bone function. These abnormal cells can also cause a number of other serious problems throughout the body. Patients with this condition develop malignant tumors in more than one spot, thus the name “multiple” myeloma.
According to the American Cancer Society, nearly 19,920 people in the United States will be diagnosed with multiple myeloma in 2008 (11,190 men and 8,730 women). The number of new cases diagnosed each year has increased over the past decades for reasons not well understood. This increase may be a result of improved methods of detection rather than an actual increase in the number of cases. Multiple myeloma is more common in men than women, and more common in African Americans. The median age at the time of diagnosis is 63.
The Origins of Disease
Plasma cells are the final product in the life cycle of B lymphocytes (B cells), a type of white blood cell that originates in the bone marrow and helps constitute the immune system. When a person develops an infection, B cells respond by rapidly maturing into plasma cells. These cells produce antibodies called immunoglobulins that help destroy infectious agents. Plasma cells are found in the tonsils, lymph nodes, abdomen, and bone marrow.
Multiple myeloma develops when a normal plasma cell is transformed into a malignant cell and begins to grow and spread uncontrollably. This transformation results from genetic mutations — changes in a cell’s DNA — that can occur as plasma cells divide. The malignant cell begins producing identical copies of itself, called clones, which bind to stromal cells, a type of connective tissue cell. Once bound to the bone marrow, myeloma cells multiply.
Normal plasma cells produce one of five types of antibodies or immunoglobulins — IgG, IgA, IgM, IgE, or IgD. Each of these proteins has a slightly different function in the body. Myeloma cells also produce these immunoglobulins, but myeloma cells make them in excessive amounts. About half of myeloma patients produce very high levels of IgG, 20 percent produce high levels of IgA, and a few patients produce excessive levels of IgD or IgE. Most people with myeloma also have protein in their urine, a condition called Bence-Jones proteinuria. One percent of myeloma patients have a form of the disease called nonsecretory myeloma in which there is no protein in their blood or urine, but malignant plasma cells are present in the bone marrow.
Over time, as myeloma cells divide and increase in number, they affect the patient in a number of ways. Myeloma cells interfere with the body’s ability to build bone and instead cause bones to weaken and break down — especially those in the spine, skull, ribs, and pelvis. Eventually myeloma cells permeate the interior of the bone (the medullary cavity) and also erode the outer layer of the bone (the cortex). Minor stresses and injuries are more likely to fracture weakened bones; these are called pathologic fractures. As bones break down, calcium is released into the bloodstream, often leading to a condition called hypercalcemia, which can cause pain, nausea, vomiting, altered mental states, depression, headache, and, in severe cases, coma.
As myeloma cells take over the marrow space, they prevent bone marrow from producing essential blood cells, including red and other white blood cells. Patients with multiple myeloma are therefore prone to anemia, which is caused by low levels of red (oxygen-carrying) blood cells, and to infections because of the lack of white (infection-fighting) blood cells.
In a condition sometimes called “myeloma kidney,” high levels of calcium and/or protein in the blood can interfere with the way kidneys function and diminish their ability to filter the blood properly. Over time, this can lead to permanent kidney damage and, ultimately, kidney failure.
Risk factors for different types of cancer are those traits that increase the likelihood that an individual will develop disease. Risk factors include certain kinds of behavior such as cigarette smoking for lung cancer, inherited (genetic) traits, and exposure to cancer-causing agents in the environment. The few known risk factors for multiple myeloma are outlined below. In most cases, though, there are no known risk factors for multiple myeloma.
Several studies have pointed to links between multiple myeloma and environmental exposure to certain kinds of chemicals. Slightly higher rates of multiple myeloma are found among agricultural workers (who are exposed to pesticides and fertilizers), petrochemical and sheet metal workers, and those exposed on the job to wood dust. In rare cases, multiple myeloma or MGUS can affect more than one person in a family. There is no reliable evidence that bacterial or viral infections cause myeloma.
The symptoms of multiple myeloma usually develop from the organs damaged by the disease. They can include:
- Bone pain and skeletal fractures, including compression fractures of the spine, which can cause severe pain and neurologic symptoms
- Frequent infections, especially bacterial infections of the respiratory and urinary tracts, which occur because the immune system is weakened
- Anemia, causing fatigue, weight loss, and general discomfort
- Abnormally high calcium levels (hypercalcemia), resulting in nausea, vomiting, altered mental states, depression, headache, and in severe cases, coma
- Loss of kidney function, leading to fatigue, a buildup of fluid in the lower limbs, and excessive thirst
- High levels of protein in the blood, causing blood to thicken (a condition called hyperviscosity), which can lead to bruising, rashes, nosebleeds, vision loss, headache, dizziness, and peripheral neuropathy (numbness, tingling, and burning pain in the extremities)
In about a third of patients, multiple myeloma is detected before symptoms appear by routine blood tests that pick up elevated levels of immunoglobulin proteins.