What is Monoclonal Gammopathy of Undetermined Significance?
Monoclonal gammopathy of undetermined significance (MGUS) is a condition that doesn’t present any symptoms. In medical terms, this condition is described as a “premalignant plasma cell disorder”, which essentially means it could potentially lead to cancer, but it doesn’t always do so. MGUS is characterized by several markers, such as the presence of a specific protein (M-protein) in the blood below certain levels, a limited number of particular plasma cells (a type of white blood cell) in the bone marrow and an absence of damage to the body from plasma cell myeloma (a type of cancer that forms in a type of white blood cell). In addition, there shouldn’t be any indication of B-cell lymphoma (a type of cancer) or any other disease that can also lead to the presence of M-protein.
There are three types of MGUS:
1. Non-IgM MGUS: This is the most common type of MGUS. It’s marked by a particular plasma cell.
2. IgM MGUS
3. Light-chain MGUS
These types of MGUS can develop into more serious conditions. Non-IgM MGUS can evolve into a cancerous plasma cell disorder. IgM MGUS can progress to Waldenstrom macroglobulinemia (a type of cancer that affects white blood cells), light chain amyloidosis (a disease where abnormal proteins build up in tissues and organs), or lymphoma (cancer of lymph nodes). Light-chain MGUS is marked by a specific protein that lacks an important component. This type of MGUS can develop into disorders characterized by abnormalities in proteins or lead to plasma cell myeloma. However, a study has shown that the risk of this type of MGUS progressing to multiple myeloma (a type of blood cancer) is relatively low (0.3%).
What Causes Monoclonal Gammopathy of Undetermined Significance?
The exact cause of non-IgM MGUS, a type of blood disorder, is unknown. However, it is thought to be linked to certain non-cancerous conditions. These include connective tissue disorders (diseases affecting tissues that support, bind, or separate different kinds of tissues and organs), peripheral neuropathies (conditions that cause nerve damage), skin conditions such as angioedema (swelling beneath the skin), hormonal diseases, and liver infections such as hepatitis C and HIV liver disease.
Research from northern Europe and the United States has indicated that people have a higher chance of developing MGUS if their close family members also have MGUS or a similar condition called myeloma. This suggests that the condition could either be caused by certain genes inherited from parents, common environmental factors, or a combination of both.
Risk Factors and Frequency for Monoclonal Gammopathy of Undetermined Significance
Monoclonal gammopathy of undetermined significance, also known as MGUS, is a condition that affects around 2% to 3% of adults over 50 years old, and 5% of adults over 70 years old. Men are more likely to have MGUS than women, with a ratio of 1.5 to 1. Additionally, MGUS is more common among African Americans, who have it 2 to 3 times more than Caucasians. Amongst all MGUS cases, up to 85% are Non-IgM MGUS, while up to 15% are IgM MGUS.
- MGUS is found in around 2% to 3% of adults over 50 and 5% of adults over 70.
- Men are more likely to have MGUS than women, with a ratio of 1.5:1.
- African Americans have MGUS 2 to 3 times more than Caucasians.
- Non-IgM MGUS represents up to 85% of all MGUS cases.
- IgM MGUS accounts for up to 15% of all MGUS cases.
Signs and Symptoms of Monoclonal Gammopathy of Undetermined Significance
Non-IgM MGUS, a medical condition related to the blood, often doesn’t cause any symptoms. This condition usually gets diagnosed incidentally, i.e., when doctors are testing for other ailments, such as peripheral neuropathy, vasculitis, hemolytic anemia, skin rashes, hypercalcemia, and elevated erythrocyte sedimentation rate. Non-IgM MGUS is typically not regarded as a cancerous process, and it only has an annual 1% risk of progressing. However, it can possibly develop into more severe conditions like PCM, solitary plasmacytoma, or amyloidosis. Two factors that can influence the progression of non-IgM MGUS are the size and type of M protein and the level of immunoglobulin.
According to specific criteria given in 2014 by the International Myeloma Working Group, doctors make a non-IgM MGUS diagnosis based on three factors:
- Monoclonal protein in serum is less than 30 g/L (3 g/dL)
- Less than 10% of plasma cells in the bone marrow are clonal
- No CRAB symptoms are present (these include hypercalcemia, renal insufficiency, anemia, and bone lesions that could possibly indicate PCM)
Testing for Monoclonal Gammopathy of Undetermined Significance
For a condition known as “Non-IgM MGUS”, a variety of tests are required to ensure it’s not confused with other similar diseases. These tests may include a complete count of your blood cells, a bone marrow biopsy, marker tests for specific cells, kidney and bone health tests, and specialized urine and blood tests to understand the precise structure of the proteins involved in this condition.
In most cases, the blood tests yield normal results, although some unusual patterns may emerge. The bone marrow biopsy often shows a small amount of normal-looking plasma cells. A major sign of Non-IgM MGUS is the presence of an abnormal protein, known as a “M” protein, in your blood and urine tests. The nature of the plasma cells and their proteins can reveal if the condition is present.
Advanced molecular testing hasn’t yet linked certain genetic alterations in plasma cells to the development of Non-IgM MGUS.
For imaging scans, an international group of experts in 2019 advised the following approach:
Scans that take images of your entire body are recommended only for tend to progress to a disease known as Waldenstrom macroglobulinemia, routine bone scans are not recommended.
For cases where Non-IgM MGUS could be high risk, a CT scan is often recommended to help rule out another condition called multiple myeloma. If a CT scan cannot be performed, a skeletal survey or a scan using MRI are suggested.
If the results from CT scan are uncertain, then MRI scans of the whole body (or just the spine and pelvis, if a full-body scan is not possible) are recommended.
If the CT scan results are positive, then experts suggest a PET/CT scan, which combines a CT scan with a test to observe the cellular activity in your body. Further bone scans are not recommended unless there are signs that the disease is progressing and causing symptoms such as pain or an increase in unusual proteins in the body.
If your scans show unusual areas of bone damage, further tests may be needed to ensure that other kinds of cancer are not present. Sometimes, a biopsy (a test where a small sample of body tissue is taken for further examination) may be required.
Treatment Options for Monoclonal Gammopathy of Undetermined Significance
Generally, doctors do not recommend treatment for patients with a condition known as Monoclonal Gammopathy of Undetermined Significance, or MGUS for short. However, since it has the potential to develop into a more serious condition, such as a type of cancer affecting our cells that helps fight disease, it’s suggested to have regular check-ups.
If a patient with MGUS has a specific type of protein in their blood called IgM, some additional tests may be helpful. These include a bone marrow biopsy, where a small amount of bone marrow is taken for testing, and a CT scan of the abdomen. These tests can aid in detecting the presence of a rare type of cancer known as Waldenström macroglobulinemia or other similar conditions.
Nerve disorders associated with MGUS usually do not require treatment unless severely disabling in case of an IgM protein cell, or if it’s connected to a nerve condition known as Chronic Inflammatory Demyelinating Neuropathy (CIDP) and associated with the IgG/IgA type of proteins. Most patients with these conditions experience positive effects from standard treatments for nerve disorders and some might even stabilize without treatment. Patients with MGUS who also have weak or brittle bones might benefit from IV medication known as bisphosphonates.
The frequency of check-ups for patients with MGUS depends on the potential risk of it developing into more serious conditions. Usually, an initial check-up six months after diagnosis is suggested, followed by further visits depending on how high the risk is. High risk patients should think about participating in preventive clinical trials if available.
What else can Monoclonal Gammopathy of Undetermined Significance be?
Identifying non-IgM MGUS from other severe plasma cell diseases is crucial as it can lead to different treatment plans. There are other conditions that may appear similar to non-IgM MGUS, which include:
- Plasma cell myeloma (smoldering or symptomatic): This is not diagnosed as non-IgM MGUS if the patient’s non-IgM protein in serum is equal to or more than 30 g/L, or if more than 10% of plasma cells in their bone marrow are clonal. Many doctors view smoldering PCM as a step between non-IgM MGUS and symptomatic PCM, and it is identified based on the size of the M protein and the percent of clonal plasma cells in the bone marrow.
- Waldenström macroglobulinemia (smoldering or symptomatic): This disorder is defined by a lymphoplasmacytic lymphoma (LPL) in the bone marrow and an IgM monoclonal gammopathy. Symptoms can include high blood viscosity, swollen lymph nodes, or an enlarged spleen.
- Monoclonal gammopathy of renal significance: This condition is diagnosed if the patient has diagnostic criteria for MGUS as well as kidney insufficiency and monoclonal immunoglobulin deposits in the kidney.
- Light chain smoldering multiple myeloma (also known as idiopathic Bence Jones proteinuria): For this condition to be diagnosed, there must be monoclonal light chains in the urine (a condition known as Bence Jones proteinuria), no immunoglobulin heavy chain in the serum or urine, and no symptoms of PCM, WM, or light chain amyloidosis.
- Primary (amyloid light chain) amyloidosis and light chain deposition disease: This type of plasma cell disease involves the abnormal deposition of monoclonal light chains in tissue.
- B cell lymphoproliferative disorder
A correct diagnosis is essential in order to devise an effective treatment plan.
What to expect with Monoclonal Gammopathy of Undetermined Significance
Non-IgM MGUS is understood to be a condition that could potentially lead to cancer, with roughly a 1% risk of progression each year. The risk can increase when there is a higher than normal level of M protein or an abnormal free light chain ratio, which is a type of blood test. Treatment isn’t usually required for Non-IgM MGUS. However, managing this condition relies on knowing the chance of the disease advancing. Regular check-ups are generally recommended.
Many doctors are of the belief that everyone with Non-IgM MGUS should undergo a medical exam and laboratory testing for signs of disease progression each year. Those who are more likely to see their condition progress to advanced stages can be determined through several criteria:
1. Higher than normal levels of serum monoclonal protein (the protein that increases when plasma cells grow too much)
2. A type of MGUS that isn’t IgG – This would be IgA, IgM, or IgD MGUS
3. An abnormal ratio of serum free light chains, which involve proteins made by plasma cells
Patients are classified into different risk categories depending on the number of these risk factors present. Those with all three risk factors are seen as high risk, while those with two are seen as a high-intermediate risk. Patients with one risk factor are classified as a low-intermediate risk, and those with none of the risk factors are seen as low risk. Despite careful monitoring, some patients with Non-IgM MGUS might suddenly show signs of disease progression to a condition known as PCM.
Possible Complications When Diagnosed with Monoclonal Gammopathy of Undetermined Significance
The condition called Monoclonal gammopathy of undetermined significance (MGUS) can potentially develop into more serious health problems. These problems can range from disorders where the body makes too many blood cells to diseases that affect our bones or blood. Here’s a list of some of these serious conditions that might result from MGUS:
- Multiple myeloma: a type of blood cancer
- Light chain amyloidosis: a disorder that causes abnormal protein buildup
- Waldenstrom macroglobulinemia: a rare type of non-Hodgkin’s lymphoma
- Lymphoma: a group of blood cancers
- Osteoporosis: a condition that weakens bones
- Venous thromboembolism: a condition where blood clots form in the vein
Preventing Monoclonal Gammopathy of Undetermined Significance
People with a condition called monoclonal gammopathy of undetermined significance (MGUS) won’t necessarily need specific treatment. However, they should regularly check in with their doctor every six to twelve months for thorough health examinations, alongside certain blood and urine tests. This is to monitor any possible changes or progress in their condition.
MGUS is when there is an abnormal protein, called a monoclonal protein, found in your blood. This protein doesn’t typically cause problems, but it can lead to more serious conditions, hence the need for regular check-ups.
For patients experiencing bone thinning (osteopenia) or bone weakening (osteoporosis), a type of treatment known as bisphosphonate therapy might be beneficial. This therapy helps to slow down or prevent bone damage.
