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Multiple myeloma is a cancer of plasma cells. Normal plasma cells are found in the bone marrow (the soft, inner parts of certain bones where new blood cells are made) and are an important part of the immune system.

Your immune system is made up of several types of cells that work together to fight infections and other diseases. Lymphocytes are one of the main types of white blood cells in the immune system. They include T cells and B cells. Lymphocytes are in many areas of the body, such as lymph nodes, the bone marrow, the intestines, and the bloodstream.

When B cells respond to an infection, they mature and change into plasma cells. Plasma cells make the antibodies (also called immunoglobulins) that help the body attack and kill germs.

In general, when plasma cells become cancerous and grow out of control, this is called multiple myeloma. The plasma cells make an abnormal antibody (immunoglobulin) known by several different names, including monoclonal immunoglobulin, monoclonal protein (M-protein), M-spike, or paraprotein.

There are, however, other plasma cell disorders that have abnormal plasma cells but do not meet the criteria to be called active multiple myeloma. These other plasma cell disorders include:

• Monoclonal gammopathy of uncertain significance (MGUS)
• Smoldering multiple myeloma (SMM)
• Solitary plasmacytoma
• Light chain amyloidosis

These conditions are described below. To learn more about the criteria used to diagnose the different plasma cell disorders, see Tests for Multiple Myeloma.

Multiple myeloma features

Low blood counts

In multiple myeloma, the overgrowth of plasma cells in the bone marrow can crowd out normal blood-forming cells, leading to low blood counts.

• Anemia (a shortage of red blood cells) can cause a person to feel weak, fatigued (tired), or short of breath.
• A low level of platelets in the blood (called thrombocytopenia) can lead to increased bleeding and bruising.
• Leukopenia (a shortage of normal white blood cells) can lead to an increased risk of infections.

Bone and calcium problems

Myeloma cells also interfere with cells that help keep bones strong. Bones are constantly being remade to keep them strong. Two kinds of bone cells work together to keep bones healthy and strong:

• Osteoclasts break down old bone.
• Osteoblasts lay down new bone.

Myeloma cells make a substance that tells the osteoclasts to speed up dissolving the bone. So old bone is broken down without new bone to replace it, making the bones weak and easy to break. Fractured bones are a major problem in people with myeloma. This increase in bone breakdown can also raise calcium levels in the blood. Problems caused by high calcium levels are discussed in Signs and Symptoms of Multiple Myeloma.

Infections

Abnormal plasma cells cannot protect your body from infections. As mentioned before, normal plasma cells make antibodies that attack germs. In multiple myeloma, the myeloma cells crowd out the normal plasma cells, so that antibodies to fight the infection can’t be made.

Kidney problems

The antibod?y made by myeloma cells can harm the kidneys, leading to kidney damage or even kidney failure.

Other plasma cell disorders

Monoclonal gammopathy of undetermined significance (MGUS)

In monoclonal gammopathy of undetermined significance (MGUS), abnormal plasma cells make many copies of the same antibody (called a monoclonal protein). However, these plasma cells do not form an actual tumor or mass and do not cause any of the problems seen in multiple myeloma.

MGUS usually does not affect a person’s health. It doesn’t cause weak bones, high calcium levels, kidney problems, or low blood counts. It’s most often found when a routine blood test finds a high level of protein in the blood and further testing shows the protein is a monoclonal antibody. In MGUS, the number of plasma cells may be increased, but they still make up less than 10% of the cells in the bone marrow.

MGUS is not considered cancer, but some people with MGUS will eventually develop cancers such as multiple myeloma or lymphoma. They might also develop amyloidosis, a condition associated with blood cancers. Each year, about 1% of people with MGUS develops one of these diseases. The risk is higher in people whose protein levels are particularly high.

People with MGUS don’t need treatment, but they are watched closely to see if they get a disease that does need to be treated, such as multiple myeloma.

Solitary plasmacytoma

A plasmacytoma is a type of plasma cell tumor. Rather than many tumors in different locations as in multiple myeloma, there is only one tumor, hence the name solitary plasmacytoma.

A solitary plasmacytoma often develops in a bone. When a plasmacytoma starts in other body tissues (such as the lungs or other organs), it is called a solitary extramedullary (or extraosseous) plasmacytoma.

Solitary plasmacytomas can usually be treated with radiation therapy and/or surgery. As long as no other plasmacytomas are found later on, the person’s outlook is usually excellent. However, since people with a solitary plasmacytoma might develop multiple myeloma, these people are watched closely for signs of this disease.

Smoldering multiple myeloma ?(SMM)

Smoldering multiple myeloma (SMM) is an early or asymptomatic (no symptoms) myeloma that is not causing any problems. People with smoldering myeloma have some signs of multiple myeloma, such as any of the following:

• A large amount of plasma cells in the bone marrow
• A high level of monoclonal immunoglobulin (monoclonal protein) in the blood
• A high level of light chains (also called Bence Jones protein) in the urine

However, they have normal blood counts, normal calcium levels, normal kidney function, no bone or organ damage, and no signs of amyloidosis.

Most people with smoldering multiple myeloma do not need treatment right away, because the disease can take anywhere from many months to years to become active (symptomatic) myeloma. Some people may have very slow disease that never becomes active myeloma, but for others the risk is higher, so earlier treatment might be helpful. To learn more, see Treatment Options for Multiple Myeloma and Other Plasma Cell Disorders.

Light chain amyloidosis

Light chain amyloidosis (also known as AL amyloidosis or primary amyloidosis) is also a disorder of abnormal plasma cell growth, but with lower amounts of abnormal plasma cells in the bone marrow compared to multiple myeloma.

Monoclonal proteins (antibodies) are made up of joined protein chains – 2 short light chains and 2 longer heavy chains. In light chain amyloidosis, abnormal plasma cells make too many light chains, which are shorter and weigh less than the heavy chains. The light chains build up in tissues as an abnormal protein known as amyloid.

The buildup of amyloid in certain organs can enlarge them and affect the way they work. For example:

• W?hen amyloid builds up in the heart, it can cause an irregular heart beat and can make the heart larger and weaker. A weak heart can lead to a condition called congestive heart failure, with symptoms like shortness of breath and swelling in the legs.
• Amyloid in the kidneys can cause them to work poorly. This may not cause symptoms early on, but the poor kidney function may be found on blood tests. If it gets worse, it can lead to kidney failure.

To learn more, see Signs and Symptoms of Multiple Myeloma.

Light chain amyloidosis is only one of the diseases where amyloid builds up and causes problems. Amyloidosis can also be caused by a genetic (hereditary) disease called familial amyloidosis. Long-standing (chronic) infection and/or inflammation can also cause amyloidosis. This is known as secondary or AA amyloidosis. These other kinds of amyloidosis are not covered here.

Waldenstrom macroglobulinemia (WM)

The cancer cells in people with WM are similar to those in multiple myeloma and non-Hodgkin lymphoma (NHL). Multiple myeloma is considered a cancer of plasma cells, and non-Hodgkin lymphoma is a cancer of lymphocytes. WM cells have features of both plasma cells and lymphocytes.

Even though WM is sometimes grouped into other plasma cell disorders, it is considered a type of NHL.

To learn more, see Waldenstrom Macroglobulinemia.