How can I differentiate between MGUS and multiple myeloma in a patient presenting with elevated monoclonal protein levels?

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 ¹. 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 ¹. Bone marrow aspirate and trephine biopsy with morphology and flow cytometry are used to determine plasma cell percentage and phenotype ¹.

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 ¹. Skeletal surveys are less sensitive and not recommended as first-line imaging ¹.

Additional laboratory markers such as full blood count, renal function, calcium levels, and bone profile help identify end-organ damage indicative of myeloma ¹. Urine Bence-Jones protein testing may support diagnosis but should not be used alone to exclude myeloma ¹.

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 and Palladini, 2012)].