Monoclonal gammopathy of unknown significance
Monoclonal gammopathy of unknown significance (MGUS) is an asymptomatic, premalignant plasma cell disorder defined by a serum monoclonal protein under 3 g/dL, clonal marrow plasma cells under 10%, and no myeloma-defining end-organ damage. It is the most common plasma cell dyscrasia, progresses to multiple myeloma or a related malignancy at about 1% per year, and requires no treatment, only periodic surveillance.
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What this article covers
- Overview
Definition: monoclonal gammopathy of unknown significance (MGUS) is an asymptomatic, premalignant clonal plasma cell disorder in which a small population of plasma cells secretes a monoclonal…
- Epidemiology
Age-dependent prevalence: MGUS occurs in approximately 3% of persons older than 50 years and approximately 5% of persons older than 70 years.
- Risk factors
Older age: the dominant risk factor for having MGUS, with prevalence roughly doubling from the sixth to the eighth decade of life.
- Pathophysiology
Clonal plasma cell expansion: a genetically altered clone of plasma cells, arising in the bone marrow, secretes a monoclonal immunoglobulin or fragment (the M protein), producing a spike on serum or urine protein electrophoresis.
- Clinical features
Asymptomatic by definition: any hypercalcemia, kidney failure, anemia, or bone disease excludes MGUS and points toward multiple myeloma instead.
- Differential diagnosis
Multiple myeloma: M protein of any size with clonal marrow plasma cells at or above 10% (or a biopsy-proven plasmacytoma) plus at least one CRAB feature or a SLiM biomarker; end-organ damage is the discriminator (multiple myeloma).
- Diagnosis
Establish MGUS with the defining laboratory criteria, all three required: a serum monoclonal protein level less than 3 g/dL (or, for the light-chain subtype, urinary monoclonal free light chains less…
- Management
No treatment is indicated for MGUS itself: the plasma cell clone is not treated because MGUS is premalignant, not malignant; therapy is reserved for patients who progress to multiple myeloma…
- Complications
Progression to multiple myeloma: the principal long-term risk for non-IgM MGUS, approximately 1% per year and never disappearing (Multiple myeloma).
- Prognosis
Progression risk never disappears: the roughly 1% per year risk of transformation to multiple myeloma is lifelong and does not decline with years of prior stability.
- Prevention
No modifiable risk factor prevents MGUS itself: age, sex, race, and family history are non-modifiable, so prevention targets early detection of progression rather than the clone.
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Multiple myeloma is a clonal plasma cell neoplasm that produces a monoclonal immunoglobulin and end-organ damage summarized by CRAB (hypercalcemia, renal failure, anemia, bone lesions), diagnosed by marrow clonal plasma cells of 10% or more plus a CRAB or SLiM myeloma-defining event. Treatment combines a proteasome inhibitor, an immunomodulatory drug, and dexamethasone, followed by autologous stem cell transplant and maintenance in eligible patients.
- Amyloidosis
Amyloidosis is extracellular deposition of misfolded protein fibrils that stain apple-green with Congo red under polarized light, most often AL (clonal light chains, linked to plasma cell dyscrasias), AA (chronic inflammation), or ATTR (transthyretin, hereditary or wild-type). Diagnosis requires tissue biopsy for Congo red birefringence plus typing of the amyloid protein, and treatment targets the underlying source, plasma-cell-directed therapy for AL, inflammatory disease control for AA, and transthyretin stabilizers or silencers for ATTR.
- Cardiac amyloidosis
Cardiac amyloidosis is myocardial infiltration by misfolded amyloid fibrils, chiefly transthyretin (ATTR) or light-chain (AL) type, causing a restrictive, thick-walled cardiomyopathy with heart failure, conduction disease, and low-voltage ECG despite increased wall thickness. Diagnosis distinguishes AL (light chains plus biopsy) from ATTR (a positive bone-tracer scan without a plasma cell disorder), and treatment is type-specific plus supportive heart-failure care.