Multiple myeloma is a kind of cancer that develops when white blood cells called lymphocytes become abnormal and grow out of control. This blood cancer and its related disorders affect plasma cells, a type of lymphocyte also known as plasma B cells. Some plasma cell disorders are cancerous conditions, while others are not.

In myeloma, the body makes too many abnormal plasma cells, which crowd out healthy cells and form tumors. Most tumors develop in the bone marrow (soft, spongy tissue in the center of bones), causing pain, weakening bones, and lowering the production of healthy blood cells. In some people, tumors form in soft tissues such as the throat, sinuses, lungs, or muscles.

Normal plasma cells secrete proteins called immunoglobulins (Igs) — also known as antibodies — that recognize and destroy specific viruses and other threats. Antibodies produced by healthy plasma cells are an important part of the immune system. In plasma cell disorders, abnormal plasma cells make ineffective antibodies that don’t provide protection. This weakens the immune system and makes it harder for the body to fight infection. In some cases, so many abnormal antibodies are present in the bloodstream that they interfere with blood flow and damage the kidneys.

Some types and stages of plasma cell disorders are mild and asymptomatic. They don’t cause any symptoms or require treatment, and they may never progress to cancer. Other types and stages can be life-threatening and must be treated right away. Once someone has been diagnosed with a plasma cell disorder, they need to be monitored regularly to check for changes or progression.

Read more about how myeloma is diagnosed.

Types of Plasma Cell Disorders

Researchers believe that mild, asymptomatic types of plasma cell disorders often occur before cancers like multiple myeloma, but these early stages aren’t always caught and diagnosed. However, only a small number of people with these precancerous conditions go on to develop cancer. Many people with milder disorders never progress to multiple myeloma.

Being diagnosed with a mild plasma cell disorder doesn’t mean you’ll definitely develop multiple myeloma. It just means that if your condition does progress, regular checkups will ensure that you get a new diagnosis and treatment as soon as possible.

Monoclonal Gammopathy of Undetermined Significance

Monoclonal gammopathy of undetermined significance (MGUS) is diagnosed when abnormal antibodies, called monoclonal proteins or M proteins, are found in the blood. This usually happens during blood tests for other conditions. MGUS isn’t a cancerous condition and doesn’t involve a tumor. People with MGUS have a 1 percent chance each year of their condition progressing to multiple myeloma, according to the International Myeloma Foundation. MGUS can also lead to other serious plasma cell disorders, such as smoldering multiple myeloma, or conditions related to abnormal antibodies, such as amyloidosis or light chain deposition disease. MGUS usually doesn’t cause symptoms.

For most people with MGUS, doctors recommend watchful waiting — having blood and urine tests every six or 12 months to check for changes, rather than immediately starting treatment. Doctors classify MGUS as low, intermediate, or high risk for turning into myeloma. However, the risk of progression can increase over time. Doctors now recommend that everyone with MGUS, including those with few risk factors, get screened regularly for myeloma.

If routine monitoring shows that MGUS is progressing, your doctor may recommend beginning treatment. People diagnosed with both MGUS and osteoporosis (a disease that weakens bone) may receive a bisphosphonate medication such as pamidronate (Aredia) or zoledronic acid (Zometa) to help maintain bone mineral density.

Subtypes of MGUS include IgM MGUS, non-IgM MGUS, and light chain MGUS.

Smoldering Multiple Myeloma

Like MGUS, smoldering multiple myeloma (SMM) involves abnormal antibodies in the blood with no myeloma signs or symptoms. Some doctors now call this condition asymptomatic myeloma. In some people, SMM progresses to multiple myeloma. People with SMM have a higher risk of disease progression than those with MGUS, but this risk decreases over time:

• In the first five years after being diagnosed with SMM, there’s a 10 percent chance each year of developing myeloma.
• During the next five years, this risk drops to 3 percent a year.
• After 10 years, the risk is about 1 percent per year.

Rarely, testing of the abnormal plasma cells in someone with SMM shows specific genetic traits that increase the risk of developing myeloma much more than average. Some people with SMM also have more abnormal cells, which can be measured with blood tests and a bone marrow biopsy. In high-risk cases like these, doctors may recommend beginning treatment to slow down the progression to cancer.

Ongoing clinical trials are helping doctors learn more about which treatments can best improve outcomes for people with SMM. Researchers believe that either MGUS or SMM comes before all cases of multiple myeloma.

Solitary Plasmacytoma

When just one cancerous tumor made up of abnormal plasma cells is present, it’s called a solitary plasmacytoma. Solitary plasmacytomas usually develop in bone, where they’re known as solitary bone plasmacytomas or solitary medullary plasmacytomas. Symptoms depend on where the tumor is located but may include pain, fractures, or compression of the spinal cord. Some cases of solitary bone plasmacytoma can be cured with radiation therapy. Between 50 percent and 70 percent of people diagnosed with solitary bone plasmacytoma progress to multiple myeloma within 10 years.

Extramedullary Plasmacytoma

A plasmacytoma can also grow in soft tissues such as the nose, throat, lung, bladder, or muscle. These are called extramedullary plasmacytomas. About 80 percent of solitary extramedullary plasmacytomas form in the upper respiratory tract — the nose, sinuses, or upper throat.

Signs and symptoms of extramedullary plasmacytoma depend on the tumor’s location but may include pain or blockages. For example, tumors in the airways, digestive system, or urinary tract can cause obstructions. The risk of progressing to multiple myeloma is lower with these types of tumors — around 8 percent. Extramedullary plasmacytomas may also occur along with bone tumors in people with multiple myeloma.

Localized Myeloma

A plasmacytoma that spreads to just a few neighboring sites is called localized myeloma. Unlike multiple myeloma, in which cancer is widespread, the cancer is still confined to one area of the body.

Multiple Myeloma

Multiple myeloma is diagnosed when cancerous plasma cells cause problems throughout the body. These cancer cells usually build up in the bones, but tumors can also form in soft tissues (called extramedullary plasmacytomas). Signs and symptoms of multiple myeloma can be severe and may include:

• Bone pain, weakness, or breaks
• Spinal cord compression (weakened or broken bones in the spine pressing on nerves), causing back pain and leg numbness or weakness
• Anemia (low red blood cell levels), leading to fatigue and weakness
• Leukopenia (low white blood cell counts), making infections more likely
• Thrombocytopenia (low platelet counts), which can cause bleeding problems
• Hypercalcemia (high calcium levels), which may cause dehydration, extreme thirst, frequent urination, constipation, abdominal pain, tiredness, and confusion
• Kidney damage or failure, which can lead to reduced urine, fluid buildup in the lungs (causing shortness of breath), itching, and leg swelling

Myeloma cells produce large amounts of abnormal antibodies. Doctors sometimes classify cases of multiple myeloma into subtypes based on the type of immunoglobulin being made — IgA, IgD, IgE, IgG, or IgM. Rarely, myeloma cells don’t make any (or very few) antibodies. Doctors call this nonsecretory myeloma.

Multiple myeloma is a serious plasma cell disorder. Although it usually can’t be cured and can be fatal, it can be managed for a long time with treatment. New treatments can help control the disease and improve quality of life.

When multiple myeloma is diagnosed, doctors assign it a stage, which shows how far the disease has progressed. Read more about the stages of multiple myeloma.

Relapsed Myeloma

Multiple myeloma that returns after a previous effective treatment is known as relapsed myeloma. In some cases, the same treatments that worked before may be used again, or doctors may recommend different treatments after a relapse.

Refractory Myeloma

When multiple myeloma progresses despite treatment, it’s called refractory myeloma. This type of myeloma is harder to treat. Some people with refractory myeloma choose to participate in clinical trials, which offer a chance to access experimental cancer treatments.

Light Chain Myeloma

In about 15 percent of multiple myeloma cases, cancerous plasma cells make only pieces of antibodies, known as light chain proteins or Bence-Jones proteins. This condition is called light chain myeloma, and it can be further categorized based on the type of protein — either kappa light chain myeloma or lambda light chain myeloma. People with light chain myeloma are significantly more likely to develop kidney failure than those with other types of myeloma.

AL Amyloidosis

AL amyloidosis is a condition in which plasma cells make too much abnormal light chain protein, but it’s not considered cancer. Instead of forming tumors, these proteins stick together, forming clumps called amyloid deposits. The deposits build up in tissues throughout the body and can damage organs. Symptoms include kidney problems, heart issues, digestive problems, and nerve damage. AL amyloidosis is treated with many of the same therapies that are used for multiple myeloma.

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