To differentiate between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma in a patient with elevated monoclonal protein levels, a comprehensive clinical, laboratory, and imaging assessment is essential. Initial laboratory tests should include serum protein electrophoresis and serum-free light-chain assay to confirm the presence of a monoclonal protein, followed by serum immunofixation to characterize the paraprotein type NICE NG35. MGUS is characterized by a lower level of monoclonal protein (usually <30 g/L), less than 10% clonal plasma cells in the bone marrow, and absence of myeloma-defining events such as end-organ damage (CRAB criteria: hyperCalcaemia, Renal impairment, Anaemia, Bone lesions) [1, Bird et al. 2009].
In contrast, multiple myeloma diagnosis requires ≥10% clonal plasma cells in the bone marrow or biopsy-proven plasmacytoma, plus evidence of myeloma-related organ damage or biomarkers of malignancy such as a serum free light-chain ratio >100, more than one focal lesion on MRI, or involved/uninvolved serum free light-chain ratio abnormalities NICE NG35. Bone marrow aspirate and trephine biopsy with morphology and flow cytometry are used to determine plasma cell percentage and phenotype NICE NG35.
Imaging is critical to differentiate the two conditions: whole-body MRI or low-dose CT is preferred to detect myeloma-related bone disease or extramedullary plasmacytomas, which are absent in MGUS NICE NG35. Skeletal surveys are less sensitive and not recommended as first-line imaging NICE NG35.
Additional laboratory markers such as full blood count, renal function, calcium levels, and bone profile help identify end-organ damage indicative of myeloma NICE NG35. Urine Bence-Jones protein testing may support diagnosis but should not be used alone to exclude myeloma NICE NG35.
MGUS requires regular monitoring every 3–6 months initially, focusing on stability of monoclonal protein and absence of progression signs, whereas multiple myeloma requires prompt referral and treatment [1, Merlini & Palladini 2012].
Key References
- NG35 - Myeloma: diagnosis and management
- NG12 - Suspected cancer: recognition and referral
- (Bird et al., 2009): UK Myeloma Forum (UKMF) and Nordic Myeloma Study Group (NMSG): guidelines for the investigation of newly detected M-proteins and the management of monoclonal gammopathy of undetermined significance (MGUS).
- (Merlini and Palladini, 2012): Differential diagnosis of monoclonal gammopathy of undetermined significance.