Monoclonal gammopathy of undetermined significance (MGUS) is a common condition, occurring in 3% of individuals over the age of 70 years. It is characterized by the presence of a paraprotein secreted by a neoplastic but clinically benign clone of plasma cells or lymphoplasmacytic cells. Over a period of years, or even decades, multiple myeloma, light-chain-associated amyloidosis, chronic lymphocytic leukaemia or non-Hodgkin lymphoma develops in a proportion of individuals [1,2]. In others, there is no apparent progression. The 2016 WHO classification assigns cases to two categories: IgM MGUS (with lymphoplasmacytic cells) and non-IgM MGUS (with plasma cells). In most cases of non-IgM MGUS the paraprotein is immunoglobulin (Ig) G or IgA and rarely IgD or IgE with a concentration below 30 g/l. There is also a light-chain MGUS defined by an abnormal free light chain ratio and the presence of light chain in the urine of <0.5 g/24 h without heavy chain expression. In non-IgM MGUS, bone marrow plasma cells account for <10% of cells and there is absence of end-organ damage, amyloidosis, light and heavy chain deposition diseases and paraneoplastic syndromes . IgM MGUS is defined by the presence of an IgM paraprotein below 30 g/l with bone marrow clonal lymphoplasmacytic cells <10% and with no organomegaly, end-organ damage, anaemia or systemic symptoms attributable to an underlying lymphoproliferative disorder .
There are no clinical features, the diagnosis being an incidental one when serum protein electrophoresis or investigation of serum or urine light chains is performed in an individual who does not have signs or symptoms attributable to a lymphoid neoplasm.
Haematological and pathological features
The blood count is normal. The blood film may show some increase in rouleaux formation as a result of the presence of the paraprotein. In non-IgM MGUS a bone marrow aspirate shows an increase in plasma cells between 1% and 10%. These may be cytologically normal or may show minor atypical features such as the presence of a nucleolus or less chromatin condensation than in normal plasma cells. On trephine biopsy sections, there is either an interstitial infiltrate or small foci of plasma cells. In IgM MGUS, the bone marrow is infiltrated by small lymphocytes and lymphoplasmacytic clonal B cells accounting for <10% of cells in the aspirate or trephine biopsy. The paraprotein, detectable by serum protein electrophoresis and immune fixation in non-IgM MGUS, may be IgG, IgA, IgD or IgE (Figures 26.1 and 26.2) or there may be a urinary Bence Jones protein. The concentration of normal immunoglobulin is reduced in about one-third of patients.
Serum protein electrophoresis in a patient with non-IgM MGUS showing a paraprotein in the gamma region in a concentration of 8.3 g/l. With thanks to Miss Carol Hughes.