Diagnosis of haematological diseases with monoclonal gammopathy

Abstract

AbstractDespite the complexity of lymphoproliferative disorders, the presence of monoclonal immunoglobulins has been providing diagnostic guidance to the haematologist for more than a century. Clinicians may be alerted for the possible presence of serum monoclonal immunoglobulins produced in excess by increased erythrocyte sedimentation rate. Thereafter the diagnosis of monoclonal gammopathy could be proven by serum protein electrophoresis followed by immunofixation to properly identify the M‐protein. In a quarter of the cases, no intact monoclonal immunoglobulin could be detected in the sera, however, free light chains produced in excess may be identified using specialized immunoassays, so called free light chain analysis.Idiopathic monoclonal gammopathy of unknown significance (MGUS) may be present in 1% of the population above age 50 and up to 10% for individuals over 80 years of age. Due to the high frequency of MGUS, between 50‐65% of all monoclonal proteins detected fall into this category and most asymptomatic patients remain undetected for many years. MGUS patients have a 1% per year chance for transformation into malignant monoclonal gammopathies. Presently, it is accepted that most multiple myeloma and amyloidosis patients have their disease developed by transformation from preexisting MGUS. Additionally, some nonmalignant hematological disease also frequently exhibit monoclonal immunoglobulin synthesis, most notably Gaucher’s disease.From the field of neoplastic hematological diseases, smouldering and symptomatic multiple myeloma as well as Waldenström’s macroglobulinaemia almost always exhibit significant amounts of serum M‐protein and/or monoclonal free light chain excess. In case of solitary plasmocytoma, primary AL amyloidosis, cryoglobulinaemia and plasma cell leukemia, the correlation with gammopathy is less strict. Monoclonal gammopathy is less common in different types of non‐Hodgkin lymphoma. Within lymphomas lymphoplasmocytic lymphoma and marginal zone lymphoma more commonly secrete monoclonal immunoglobulins, while other B‐cell lymphomas have 14% cumulative chance for specific gammopathy. In the case of B‐cell chronic lymphocytic leukemia (the most common leukemia), intact monoclonal gammopathy has a 2% appearance, while abnormal free light chains may be detected in a third of the cases. Sporadically monoclonal gammopathy may be detected in chronic myelomonocytic leukemia, refractory anaemia, large granular cell leukemia and angioimmunoblastic lymphoma. Notably, in many of these diseases, the amount of secreted monoclonal immunoglobulin and/or free light chains correlate with the tumor burden and could be used for disease monitoring, especially in indolent hematological neoplasias.