Monoclonal gammopathy of undetermined significance
Other names
Benign monoclonal gammopathy, monoclonal gammopathy of unknown significance, monoclonal gammopathy of renal significance,[1]unknown or uncertain may be substituted for undetermined
Schematic representation of a normal
protein electrophoresis gel. A small spike would be present in the gamma (γ) band in MGUS
Monoclonal gammopathy of undetermined significance (MGUS) is a
plasma cell dyscrasia in which
plasma cells or other types of antibody-producing cells secrete a
myeloma protein, i.e. an abnormal
antibody, into the
blood; this abnormal protein is usually found during standard laboratory
blood or
urine tests. MGUS resembles
multiple myeloma and similar diseases, but the levels of antibodies are lower,[2] the number of
plasma cells (
white blood cells that secrete antibodies) in the
bone marrow is lower, and it rarely has symptoms or major problems. However, since MGUS can lead to multiple myeloma, which develops at the rate of about 1.5% a year, or other symptomatic conditions, yearly monitoring is recommended.
The progression from MGUS to multiple myeloma usually involves several steps. In rare cases, it may also be related with a slowly progressive symmetric distal sensorimotor
neuropathy.[3]
Signs and symptoms
People with monoclonal gammopathy generally do not experience signs or symptoms.[1] Some people may experience a rash or nerve problems, such as numbness or tingling.[1] MGUS is usually detected by chance when the patient has a blood test for another condition or as part of standard screening.[1]
Pathophysiology
Pathologically, the lesion in MGUS is in fact very similar to that in multiple myeloma. There is a predominance of
clonalplasma cells in the
bone marrow with an abnormal
immunophenotype (
CD38+
CD56+
CD19−) mixed in with cells of a normal phenotype (CD38+ CD56− CD19+);[4][5] in MGUS, on average more than 3% of the clonal plasma cells have the normal phenotype, whereas in multiple myeloma, less than 3% of the cells have the normal phenotype.[6]
Diagnosis
MGUS is a common, age-related medical condition characterized by an accumulation of bone marrow plasma cells derived from a single abnormal clone. Patients may be diagnosed with MGUS if they fulfill the following four criteria:[7]
A monoclonal paraprotein band less than 30 g/L (< 3g/dL);
No evidence of another B-cell proliferative disorder.
Differential diagnosis
Several other illnesses can present with a
monoclonal gammopathy, and the monoclonal protein may be the first discovery before a formal diagnosis is made:
MGUS occurs in over 3 percent of the White population over the age of 50, and is typically detected as an incidental finding when patients undergo a protein electrophoresis as part of an evaluation for a wide variety of clinical symptoms and disorders (eg, peripheral neuropathy, vasculitis, hemolytic anemia, skin rashes, hypercalcemia, or elevated erythrocyte sedimentation rate). Although patients with MGUS have sometimes been reported to have
peripheral neuropathy, a debilitating condition which causes bizarre sensory problems to painful sensory problems,[13] no treatment is indicated.[citation needed]
The
protein electrophoresis test should be repeated annually, and if there is any concern for a rise in the level of monoclonal protein, then prompt referral to a
hematologist is required. The hematologist, when first evaluating a case of MGUS, will usually perform a
skeletal survey (X-rays of the proximal skeleton), check the blood for
hypercalcemia and deterioration in
renal function, check the urine for
Bence Jones protein and perform a
bone marrow biopsy. If none of these tests are abnormal, a patient with MGUS is followed up once every 6 months to a year with a blood test (serum protein electrophoresis).[citation needed]
Prognosis
At the Mayo Clinic, MGUS transformed into multiple myeloma or similar
lymphoproliferative disorders at the rate of about 1-2% a year, or 17%, 34%, and 39% at 10, 20, and 25 years, respectively, of follow-up—among surviving patients. However, because they were elderly, most patients with MGUS died of something else and did not go on to develop multiple myeloma. When this was taken into account, only 11.2% developed lymphoproliferative disorders.[14]
Kyle et al. studied the prevalence of myeloma in the population as a whole (not clinic patients) in
Olmsted County, Minnesota. They found that the prevalence of MGUS was 3.2% in people above 50, with a slight male predominance (4.0% vs. 2.7%). Prevalence increased with age: of people over 70 up to 5.3% had MGUS, while in the over-85 age group the prevalence was 7.5%. In the majority of cases (63.5%), the paraprotein level was <1 g/dL, while only a very small group had levels over 2 g/dL.[15]
A study of monoclonal protein levels conducted in
Ghana showed a prevalence of MGUS of approximately 5.9% in African men over the age of 50.[16]
In 2009, prospective data demonstrated that all or almost all cases of multiple myeloma are preceded by MGUS.[17]
^Larking-Pettigrew M, Ranich T, Kelly R (1999). "Rapid onset monoclonal gammopathy in cutaneous lupus erythematosus: interference with complement C3 and C4 measurement". Immunol. Invest. 28 (4): 269–276.
doi:
10.3109/08820139909060861.
PMID10454004.