Monoclonal gammopathy of uncertain significance (MGUS) (BSH 2009)
MGUS Definition – presence of a monoclonal protein in the serum or urine of an individual with no evidence of myeloma, AL amyloidosis, Waldenstrom’s or other related disorders.
M-protein Definition – monoclonal immunoglobulin secreted by an abnormally expanded clone of plasma cells in an amount that can be visualized by immunofixation of serum or urine.
Detectable in 1% of population overall
SFLC ratio can be used as a surrogate for secretion of monoclonal free light chains.
Ratio may be abnormal even when renal threshold for reabsorption of FLC has not been reached, meaning that monoclonal SFLC has not been detected on immunofixation of urine.
Causes for M-proteins
DDx – MGUS, Myeloma, SBP/SEP, AL Amyloidosis, Waldenstroms
Abnormal SFLC ratio can occur with any other immune dysregulation – e.g. SLE, HIV, HSCT
Of newly detected M-proteins:
- 72% MGUS, 19% Myeloma, 6% Other LPD, 2% Waldenstroms, 1% Amyloidosis
M-Proteins and Associated disorders
Light chain cast nephropathy
Light-chain deposition disease
Adult Fanconi Syndrome
Type 1 Cryoglobulinaemia
M-Protein Antibody Activity
Mixed Cryoglobulinaemia Type 2
Prognosis of MGUS
Cumulative risk of progression to malignancy (MM or WM)
10% at 10 years, 21% at 21 years, 26% at 25 years
i.e. risk does not change with time
Risk factors for malignant transformation include:
Type of M-protein – IgA and IgM higher risk than IgG
Level of M-protein – Transformation rate increases steadily with level of M-protein
Presence of an abnormal SFLC ratio
Patterns of disease progression vary
Stable from diagnosis then gradual or sudden rise
Gradual or sudden increase from diagnosis
Stable M-protein level but myeloma ROTI start to occur.
Who should be referred to clinic?
IgD or IgE M-protein at any concentration
IgG M-protein >15g/l
IgA or IgM M-protein >10g/l
Significant BJP >500mg/l
Symptoms suggesting Myeloma, LPD or amyloidosis
Asymptomatic but with unexplained abnormal investigations – calcium, creatinine etc
Remaining patients (the majority) can be monitored in the community 3-4 monthly for the first year and then 6-12 monthly long-term.
Patients should be educated about vigilance for symptoms of Myeloma / WM etc.