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How should I interpret serum protein electrophoresis results in the context of suspected multiple myeloma?

Answer

Guideline-Aligned (High Confidence)
Generated by iatroX. Developer: Dr Kola Tytler MBBS CertHE MBA MRCGP (General Practitioner).
Last reviewed: 16 August 2025

Interpreting serum protein electrophoresis (SPE) results in suspected multiple myeloma involves identifying a monoclonal (M) protein spike, typically in the gamma or beta region, which indicates clonal plasma cell proliferation. The presence of a sharp, well-defined M band on SPE is a key diagnostic feature suggestive of multiple myeloma 1. Quantification of the M protein concentration helps assess disease burden and guides further diagnostic steps. Additionally, the absence or reduction of normal immunoglobulin bands (immunoparesis) supports the diagnosis 1. Serum immunofixation electrophoresis (IFE) should be performed to confirm the isotype of the monoclonal protein and to detect small or hidden clones not clearly visible on SPE. This is essential for accurate diagnosis and monitoring (Dejoie et al., 2016).

In the context of suspected multiple myeloma, SPE results must be integrated with clinical features, full blood count, calcium levels, renal function, and imaging findings. A significant M protein level combined with CRAB features (hyperCalcaemia, Renal impairment, Anaemia, Bone lesions) supports the diagnosis and need for specialist referral 1. Serial SPE measurements are important for monitoring disease progression or response to therapy. The IFM recommendations emphasize uniform interpretation criteria, including recognizing oligoclonal patterns post-treatment and differentiating them from relapse (Dejoie et al., 2016).

In summary, a monoclonal spike on SPE, confirmed by immunofixation, with associated clinical and laboratory abnormalities, strongly suggests multiple myeloma and warrants urgent haematology referral. SPE is a screening tool but must be interpreted in the broader clinical context to avoid misdiagnosis or delayed treatment 1 (Dejoie et al., 2016).

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