Evaluation of Elevated Total Protein

Introduction to Monoclonal Gammopathies

The National Comprehensive Cancer Network recommends evaluating elevated total protein on a comprehensive metabolic panel (CMP) to identify monoclonal gammopathies, such as Waldenström macroglobulinemia or multiple myeloma, which have significant implications for morbidity and mortality 1

The National Comprehensive Cancer Network suggests performing bone marrow aspirate and biopsy with immunohistochemistry to diagnose monoclonal gammopathies 1
The National Comprehensive Cancer Network recommends MYD88 (L265P) mutation testing, especially if IgM paraprotein is present, to aid in the diagnosis of Waldenström macroglobulinemia 1
The National Comprehensive Cancer Network advises using CT scans of chest, abdomen, and pelvis with IV contrast and/or PET-CT to evaluate the extent of disease in patients with suspected monoclonal gammopathies 1
Consider serum protein electrophoresis (SPEP), serum immunofixation electrophoresis, and serum quantitative immunoglobulins (IgG, IgA, IgM) to characterize the type of protein elevation, as recommended by the National Comprehensive Cancer Network 1

Elevated total protein can be caused by various conditions, including monoclonal gammopathies (multiple myeloma, Waldenström macroglobulinemia), polyclonal gammopathies, chronic infections (HIV, hepatitis, TB), autoimmune disorders (rheumatoid arthritis, SLE), and chronic liver disease, as noted by the American College of Rheumatology 2

The National Comprehensive Cancer Network recommends treatment for Waldenström macroglobulinemia based on clinical presentation, with options including BTK inhibitors, anti-CD20 antibodies, or chemotherapy 1
For multiple myeloma, treatment should follow established myeloma guidelines, as recommended by the National Comprehensive Cancer Network 1
The American Academy of Pediatrics suggests considering multisystem inflammatory syndrome in children (MIS-C) if elevated protein is accompanied by fever, inflammatory markers, and history of COVID-19 exposure, and completing a diagnostic evaluation for MIS-C if suggestive clinical features are present 2

The National Comprehensive Cancer Network recommends follow-up per hematology/oncology recommendations for patients with monoclonal gammopathies 1
For polyclonal gammopathies, repeat protein studies every 3-6 months until normalized or stable, as suggested by the American College of Physicians 3
For unexplained elevations, repeat CMP and SPEP in 3-6 months to monitor for changes or development of underlying conditions, as recommended by the National Comprehensive Cancer Network 1