Recommendations for use of tumor markers in monoclonal gammopathies

Monoclonal gammopathies constitute a group of disorders characterized by the clonal proliferation of plasma cells. The M protein is a tumor marker specific for monoclonal gammopathies because it reflects the clonal production of immunoglobulin. The monoclonal gammopathies include: multiple myeloma, Waldenström macroglobulinemia (WM), nonsecretory myeloma, smoldering multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS) primary systemic amyloidosis and heavy-chain diseases. The diagnosis of multiple myeloma is based on detection of M protein in serum and/or urine infiltration of plasma cells in the bone marrow, and lytic bone lesions on radiography of the skeleton. According to NACB (National Academy of Clinical Biochemistry) recommendations, the tumor markers for diagnosis, screening identification of clonality, follow up of disease and prognostic evaluation in monoclonal gammopathies are: serum and/or urine protein electrophoresis serume and/or urine immunofixation, serum and/or urine free light chains (FLC), serum viscosity and β2-microglobulin. Immunofixation is used to identify the clonality (type) of M protein observed on electrophoresis and when suspicion persists despite a normal protein electrophoretogram. It is particularly useful for the recognition and distinction of biclonal or triclonal gammopathies. The viscosity of serum should be measured if the patient has sings or symptoms of hyperviscosity syndrome. WM is the most common cause of hyperviscosity, but it can also occur in patients with large levels of monoclonal IgA or IgG. Serum FLC automated immunoassays are more sensitive for the detection of monoclonal light-chain myeloma, nonsecretory myeloma and AL amyloidosis than traditional electophoretic and immunofixation methods. Furthermore, serum FLC ration is an independent risk factor for malignant progression in MGUS patients. The determination of serum FLC and serum electrophoresis as first-line tests for investigating possible B-cell disorders gains additional diagnostic information.