What is an M (monoclonal) spike?

What is an M Spike?

An M spike (monoclonal spike) is a narrow, distinct peak on serum protein electrophoresis that represents a monoclonal immunoglobulin (M-protein) produced by a clone of abnormal plasma cells or B cells. 1, 2

Definition and Detection

• The M spike appears as a sharp, homogeneous band on protein electrophoresis, representing the overproduction of a single type of immunoglobulin by clonal cells. 2, 3
• This finding is pathognomonic of a plasma cell dyscrasia, meaning it is a defining characteristic of disorders involving abnormal plasma cell proliferation. 3
• The monoclonal protein can be detected as either narrow peaks on protein electrophoresis or discrete bands on immunofixation electrophoresis. 2

Clinical Significance

The presence of an M spike indicates one of several conditions along a spectrum of plasma cell disorders:

Benign/Premalignant Conditions

• Monoclonal Gammopathy of Undetermined Significance (MGUS): Characterized by a serum monoclonal protein <3 g/dL (or <30 g/L), <10% bone marrow plasma cells, and no organ damage. 4, 5
• Smoldering Multiple Myeloma (SMM): Higher tumor burden than MGUS but still asymptomatic, with greater risk of progression. 3

Malignant Conditions

• Multiple Myeloma (MM): Defined by the presence of end-organ damage (CRAB criteria: hypercalcemia, renal insufficiency, anemia, bone lesions) or specific myeloma-defining events. 4
• Waldenström Macroglobulinemia (WM): Particularly when the M spike is IgM type. 4
• Other lymphoproliferative disorders: Including chronic lymphocytic leukemia with monoclonal protein production. 4

Types of M-Proteins

• IgG M-protein: Most common type, typically progresses to multiple myeloma if progression occurs. 4
• IgA M-protein: Higher risk of progression compared to IgG. 5
• IgM M-protein: Usually progresses to Waldenström macroglobulinemia or other lymphoproliferative disorders rather than multiple myeloma. 4
• Light chain only: Can occur without a heavy chain component, detected by abnormal free light chain ratio. 4

Diagnostic Workup Required

When an M spike is detected, comprehensive evaluation is mandatory:

• Serum protein electrophoresis (SPEP) with immunofixation (SIFE) to quantify and type the M-protein, as SPEP alone misses up to 50% of cases. 1
• 24-hour urine protein electrophoresis (UPEP) and urine immunofixation (UIFE) because some patients have negative serum but positive urine findings. 1
• Serum free light chain assay with κ:λ ratio for prognostic information and monitoring. 1
• Bone marrow aspiration and biopsy to quantify clonal plasma cells and perform cytogenetic studies. 1
• Imaging studies (whole-body low-dose CT or skeletal survey) to identify lytic bone lesions. 1

Clinical Implications by M-Spike Size

• M-spike <3 g/dL with <10% bone marrow plasma cells and no organ damage: Consistent with MGUS, which carries approximately 1% per year risk of progression to malignancy. 4, 5
• M-spike ≥3 g/dL or ≥10% bone marrow plasma cells without organ damage: Suggests smoldering multiple myeloma with higher progression risk. 5
• Any M-spike with CRAB features present: Diagnostic of symptomatic multiple myeloma requiring treatment. 5, 1

Monitoring Recommendations

• For MGUS, follow-up should include serum protein electrophoresis every 6-12 months, assessment of free light chain ratios, and clinical evaluation for development of CRAB features. 5
• An increase in M-spike by ≥0.5 g/dL from the lowest confirmed value should raise suspicion for progression to multiple myeloma. 5
• Serial M-protein measurements must use the same laboratory test consistently for accurate monitoring. 1

Special Considerations

• Monoclonal Gammopathy of Renal Significance (MGRS): The M-protein can cause kidney damage even without meeting criteria for malignancy, requiring kidney biopsy for diagnosis. 4
• Some M-proteins are transient and may disappear without treatment, particularly in cases where only immunofixation detects the protein without a quantifiable spike. 6
• In rare cases (4%), double monoclonal gammopathies can occur, where two different M-proteins are present. 7