From the Guidelines
A high globulin workup should begin with a serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE) to identify the specific protein abnormality, as recommended by the NCCN Guidelines for multiple myeloma 1. This initial step is crucial in distinguishing between polyclonal gammopathy, which may suggest inflammation or infection, and monoclonal gammopathy, which could indicate potential plasma cell disorders.
- Additional testing should include:
- Complete blood count
- Comprehensive metabolic panel
- Quantitative immunoglobulins (IgG, IgA, IgM)
- If a monoclonal protein is detected, a free light chain assay should be ordered to assess kappa and lambda light chains and their ratio, as this provides high sensitivity for screening and monitoring plasma cell disorders, including multiple myeloma and related conditions 1.
- Depending on the initial results, further diagnostic procedures such as bone marrow biopsy, skeletal survey, or advanced imaging like PET-CT may be indicated, particularly if multiple myeloma is suspected.
- Specific organ function tests may be needed based on symptoms, such as cardiac biomarkers for amyloidosis concerns. The importance of a thorough workup lies in the fact that elevated globulins can indicate a range of conditions, from chronic inflammation and infections to hematologic malignancies like multiple myeloma, lymphoma, or amyloidosis, and early identification of the underlying cause allows for appropriate treatment and management of potential complications.
- The approach to patients with suspected Waldenström macroglobulinemia or other lymphoproliferative disorders should also consider the Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) guidelines, which emphasize the role of serum IgM level, age, and other clinical and laboratory variables in determining the need for treatment and predicting outcome 1.
From the Research
High Globulin Workup
- A high globulin level can be an indicator of multiple myeloma or other serum protein disorders 2
- Serum protein electrophoresis (SPE) is a diagnostic tool used to identify patients with multiple myeloma and other serum protein disorders 2
- Immunofixation electrophoresis (IFE) is a more sensitive technique than SPE for detecting M protein in patients with atypical multiple myeloma 3
Diagnostic Techniques
- SPE separates proteins based on their physical properties and is used to identify homogeneous spike-like peaks in the gamma-globulin zone, which can indicate a monoclonal gammopathy 2
- IFE can detect M protein in patients with atypical multiple myeloma and can increase diagnosis accuracy in these patients 3
- Mass spectrometry (EXENT&FLC-MS) is a more sensitive method than IFE for detecting M protein in patients with multiple myeloma, especially after treatment 4
- Serum free light chain (sFLC) analysis can be used as an adjunct to SPE and IFE to detect multiple myeloma and other B-cell malignancies 5
Diagnostic Criteria
- The Revised International Staging System combines data from serum biomarkers, including β2 microglobulin, albumin, and lactate dehydrogenase, to assess estimated progression-free survival and overall survival in patients with multiple myeloma 6
- Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels, as well as SPE with IFE, 24-hour urine protein electrophoresis, and full-body skeletal imaging 6