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Rajkumar SV et al Monoclonal gammopathy of undetermined significance, Waldenstrom macroglobulinemia, AL amyloidosis and related plasma cell disorders: diagnosis and treatment Mayo Clin Proc 2006 May;81(5):693 703 [PMID: 16706268]
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sequence of the variable (V) regions is fixed, and only one type ( or ) of light chain is produced Polyclonal gammopathies result from proliferation of many B cell clones, resulting in a diffuse increase of immunoglobulins
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1 Monoclonal Gammopathy of Uncertain Significance
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2 Multiple Myeloma (See 13) 3 Waldenstr m s Macroglobulinemia (See 13) 4 Amyloidosis
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M protein in the serum without symptoms or signs of multiple myeloma, macroglobulinemia, amyloidosis, or lymphoma Less than 10% plasma cells in the bone marrow
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The diagnosis is based on clinical suspicion, family history, and preexisting long-standing infection or debilitating illness Microscopic examination of biopsy (eg, gingival, renal, rectal) or surgical specimens is diagnostic Fine-needle biopsy of subcutaneous abdominal fat is a simple and reliable method for diagnosing secondary systemic amyloidosis
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The incidence of monoclonal gammopathy of uncertain significance (MGUS) increases with age, and the prevalence may approach 5% in persons 70 years of age or older Lymphoid malignancies, amyloidosis, macroglobulinemia, or multiple myeloma will develop in as many as one-third of patients with apparently benign monoclonal gammopathies (1% per year) No specific therapy is necessary, but close observation is required Patients with MGUS should be periodically monitored for changes in serum M proteins, urinary Bence Jones proteins, evidence of renal failure, anemia, hypercalcemia, lytic bone lesions, or bone marrow plasmacytoses Parameters that suggest a favorable prognosis include: (1) concentrations of homogeneous immunoglobulin less than 2 g/dL, (2) no increase in concentration of the immunoglobulin from the time of diagnosis, (3) no decrease in the concentration of normal immunoglobulins, (4) absence of a homogeneous light chain in the urine, and (5) normal hematocrit and serum albumin
General Considerations
Amyloidosis is a group of disorders manifested by impaired organ function due to infiltration with insoluble protein fibrils Different fibrils can be correlated with the clinical syndromes In primary amyloidosis (AL), the protein fibrils are monoclonal immunoglobulin light chains, whereas in secondary amyloidosis (AA), protein deposits are derived from acute phase reactant apolipoprotein precursors Familial amyloidosis syndromes commonly cause infiltrative neuropathies Other types of amyloidosis may also be hereditary Over 20 types of fibrils have been identified in amyloid deposits Amyloidosis due to deposition of 2-microglobulin in carpal ligaments occurs in long-term hemodialysis patients
Clinical Findings
A Symptoms and Signs
No clinical symptoms are associated with MGUS In patients with MGUS, the quantity of M protein is stable, and the lymphadenopathy, splenomegaly, or bony lesions seen with multiple myeloma are absent
Clinical Findings
A Symptoms and Signs
The symptoms and signs of primary amyloidosis are due to amyloid infiltration and subsequent malfunction of the infiltrated organ (eg, nephritic syndrome and renal failure, cardiomyopathy and cardiac conduction defects, Alzheimer s disease, intestinal malabsorption and pseudo-obstruction, carpal tunnel syndrome, macroglossia, peripheral neuropathy, endorgan insufficiency of endocrine glands, respiratory failure, capillary damage with ecchymosis) Secondary amyloidosis is more often limited to the liver, spleen, and adrenals Familial syndromes commonly cause infiltrative neuropathies
B Laboratory Findings
The diagnosis of MGUS is made upon finding of a monoclonal spike on serum protein electrophoresis, confirmed by immunoelectrophoresis to be a homogeneous immunoglobulin with either or light chains
Kyle RA et al Prevalence of monoclonal gammopathy of undetermined significance N Engl J Med 2006 Mar 30;354(13):1362 9 [PMID: 16571879] Landgren O et al Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States Blood 2006 Feb 1;107(3):904 6 [PMID: 16210333]
B Laboratory Tests
The diagnosis of primary amyloidosis is based on clinical suspicion with corroboration provided by detection of a monoclonal gammopathy on serum protein electrophoresis and
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microscopic examination of abdominal fat pad aspirates; rectal or gingival biopsies reveal amyloid protein (green birefringence under polarizing microscope after Congo red staining) In systemic disease, rectal or gingival biopsies show a sensitivity of about 80%, bone-marrow biopsy about 50%, and abdominal fat aspiration between 70% and 80% The latter is a simple and reliable method for diagnosing systemic amyloidosis
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