In multiple myeloma and related conditions, one type of white blood cell called a lymphocyte is overproduced. For this reason, these conditions are known as lymphoproliferative disorders. Specifically, multiple myeloma and its related disorders involve the overproduction of a lymphocyte called the plasma B cell. Some lymphoproliferative disorders are cancerous conditions, while others are not. In myeloma, abnormal versions of plasma B cells are overproduced. They crowd out healthy cells and form tumors. Most tumors form in bone marrow, causing pain, weakening the bones, and limiting the production of healthy blood cells. In some people, tumors form in soft tissues such as the throat, sinuses, lung, or muscle.

Normal plasma B cells secrete proteins called immunoglobulins – also known as Ig or antibodies – that recognize and destroy specific viruses and other threats. Antibodies produced by healthy plasma B cells are an important part of the immune system. In some cases of lymphoproliferative disorders, abnormal plasma B cells secrete ineffective antibodies that do not provide protection, weakening the immune system and leaving the body unprotected from 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 lymphoproliferative disorders are mild and asymptomatic – they do not cause any symptoms, do not require treatment, and may never progress to cancer. Other types and stages can be life-threatening and must be treated urgently. Once someone has been diagnosed with a lymphoproliferative disorder, they must be monitored regularly for progression.

Read about how types of myeloma are diagnosed.

Types of lymphoproliferative disorders

Researchers believe that mild asymptomatic types of lymphoproliferative disorders always precede cancer such as multiple myeloma, although they are not caught and diagnosed in every person. However, the precancerous conditions only progress to cancer in a small fraction of people. Many people never progress from a milder disorder to multiple myeloma. Being diagnosed with a mild lymphoproliferative disorder does not mean that you will definitely develop multiple myeloma. Being diagnosed with a mild disorder means that if your condition does progress, regular screenings will ensure that you receive a new diagnosis and treatment as early as possible.

Monoclonal gammopathy of undetermined significance (MGUS)

MGUS is diagnosed when fragments of abnormal antibodies – called monoclonal protein or M protein – are found in the blood, usually during blood tests for unrelated conditions. MGUS is not a cancerous condition and does not involve a tumor. Each year, about 1 percent of those with MGUS experience progression to a more serious lymphoproliferative disorder such as smoldering multiple myeloma or multiple myeloma, or a condition related to abnormal antibodies such as amyloidosis or light chain deposition disease. MGUS is usually asymptomatic, but it can cause skin rash or neuropathy (pain, tingling, or numbness in the extremities).

Most doctors recommend watchful waiting instead of treatment for MGUS. People diagnosed with MGUS should undergo blood and urine testing once every six or 12 months to monitor for progression. If routine monitoring shows evidence of progression, your doctor may recommend beginning treatment. Those diagnosed with both MGUS and osteoporosis may be recommended to begin taking a bisphosphonate medication such as Aredia or Zometa to help maintain bone mineral density.

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

Smoldering multiple myeloma (SMM)

Like MGUS, SMM is also a precancerous disorder involving abnormal antibody fragments in the blood but no tumor. In some people, smoldering myeloma progresses to multiple myeloma. However, people with SMM have a higher risk for progression – 10 percent – than those with MGUS. SMM is asymptomatic in most people. Rarely, when the abnormal B plasma cells of someone with smoldering myeloma are tested, they show specific genetic characteristics that carry a risk of progression much higher than the average. In this subset of high-risk SMM cases, doctors may recommend beginning treatment to delay the progression to cancer. SMM is much less common than MGUS.

Researchers believe that either MGUS or SMM precede all cases of multiple myeloma.

Solitary plasmacytoma

If one cancerous tumor formed by abnormal B plasma cells is present, it is known as a solitary plasmacytoma. Solitary plasmacytomas most frequently develop in bone. A single plasmacytoma that occurs in bone may be known as solitary bone plasmacytoma or solitary medullary plasmacytoma. Symptoms of solitary bone plasmacytoma depend on where it is located, but it may cause pain, fracture, or compression of the spinal cord. Some cases of solitary bone plasmacytoma are cured with treatment. Between 50 and 70 percent of people diagnosed with solitary bone plasmacytoma progress to multiple myeloma within 10 years.

Extramedullary plasmacytoma

A plasmacytoma may also grow in soft tissues such as the nose, throat, lung, bladder, skin, or muscle. A plasmacytoma that occurs in soft tissue is called an extramedullary plasmacytoma. Symptoms of extramedullary plasmacytoma depend on the location, but may include pain or obstruction – for instance an obstruction of the respiratory, urinary, or digestive tract. An extramedullary plasmacytoma may occur alone, as a solitary plasmacytoma. A solitary extramedullary plasmacytoma has a lower risk of progressing to multiple myeloma – approximately 10 percent. About 80 percent of solitary extramedullary plasmacytomas occur in the upper respiratory tract – nose, sinuses, or throat. Extramedullary plasmacytomas may also occur in addition to bone tumors in those with multiple myeloma.

Localized myeloma

In cases of a plasmacytoma that is spreading locally to neighboring sites, the term localized myeloma may be used. Localized myeloma differs from multiple myeloma because the cancer is still confined to one area of the body rather than widespread.

Multiple myeloma

Multiple myeloma is diagnosed when cancerous tumors have developed in multiple sites throughout the body. Bones are the most common site for tumors in multiple myeloma, but tumors in soft tissue (extramedullary plasmacytomas) can also develop. Symptoms of multiple myeloma can be severe and include fatigue, weakness, frequent infections, bone pain, fractures, spinal cord compression, neuropathy, kidney damage or failure, and problems with bleeding or the heart.

Multiple myeloma is the most dangerous form of lymphoproliferative disorder. Multiple myeloma is not curable in most cases, and it can be fatal. However, multiple myeloma is highly treatable. New treatments are making multiple myeloma a manageable chronic condition for many people.

When multiple myeloma is diagnosed, a stage is assigned. The stage of myeloma reflects how far the myeloma has progressed. Read more about stages of multiple myeloma.

Relapsed myeloma

Multiple myeloma that has returned after a previous effective treatment is known as relapsed myeloma. Relapsed myeloma may be treated with the same treatments that were effective before, or doctors may recommend different treatments after a relapse.

Refractory myeloma

Multiple myeloma that has progressed despite treatment is called refractory myeloma. Refractory myeloma may be subtyped as primary refractory myeloma if it has not responded to any treatment yet. If a previous treatment was effective, but the myeloma is not responding to a second round of treatment, it may be referred to as secondary refractory myeloma.

Refractory myeloma is by definition more difficult to treat. After safer, first-line treatments have failed, doctors may suggest trying treatments with a higher risk of serious side effects. Some people with refractory myeloma participate in a clinical trial for a chance to access experimental treatments.

Light chain myeloma

In almost all cases of multiple myeloma, cancerous plasma B cells secrete fragments of abnormal antibodies. In about 20 percent of myeloma cases, plasma B cells secrete only fragments of antibodies known as light chain proteins. This is known as light chain myeloma. Light chain myeloma can be further subtyped by the type of light chain protein it secretes as either kappa light chain myeloma or lambda light chain myeloma. People with light chain myeloma are significantly more likely to experience kidney failure than those with non-light chain myeloma.

Resources

External references

• Myeloma Staging – Leukemia & Lymphoma Society
• Multiple Myeloma: Stages – Cancer.net
• Early treatment of smoldering multiple myeloma – Multiple Myeloma Research Foundation
• Smoldering Multiple Myeloma – Blood
• The Risk of MGUS Progression to Multiple Myeloma – NEJM Group
• Monoclonal gammopathy of undetermined significance (MGUS) – Mayo Clinic
• Understanding MGUS and Smoldering Multiple Myeloma (PDF) – International Myeloma Foundation
• Solitary or Extramedullary Plasmacytoma – Memorial Sloan Kettering Cancer Center
• Solitary Plasmacytoma – Leukaemia Foundation
• Diagnosis and management of solitary extramedullary plasmacytoma – UpToDate
• About Multiple Myeloma – UCSF Helen Diller Comprehensive Cancer Center
• Clinical features, laboratory manifestations, and diagnosis of multiple myeloma – UpToDate

Internal resources

• Multiple Myeloma – An Overview
• Multiple Myeloma – The Path to Diagnosis
• Symptoms of Multiple Myeloma
• Treatments for Multiple Myeloma
• What Causes Multiple Myeloma?
• Stages of Multiple Myeloma
• Myeloma Treatments A-Z