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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. Over a period of years or even decades, multiple myeloma, light-chain-associated amyloidosis, chronic lymphocytic leukaemia or non-Hodgkin's lymphoma develops in a proportion of individuals with MGUS [1, 2]. In others there is no apparent progression.

Clinical features

There are no clinical features, the diagnosis being an incidental one when serum protein electrophoresis 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. A bone marrow aspirate shows an increase in plasma cells to 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 of plasma cells or there are small foci. The paraprotein, detectable by serum protein electrophoresis and immune fixation, may be immunoglobulin (Ig) G, IgA or IgM (Figures 22.1 and 22.2). Its concentration does not exceed 20-30 g/l. The concentration of normal Igs is not reduced. If a Bence-Jones protein is present in the urine it is at a low concentration.

Figure 22.1

Serum protein electrophoresis in a patient with MGUS showing a paraprotein in the gamma region in a concentration of 8.3 g/l. With thanks to Miss Carol Hughes.

Figure 22.2

Serum protein electrophoresis in a patient with MGUS (left) showing a paraprotein in the gamma region; on immune fixation (right) this is identified as an IgG λ paraprotein. With thanks to Miss Carol Hughes.


The clonal plasma cells show light chain restriction of cytoplasmic Ig, i.e. they express either kappa (κ) or lambda (λ) light chains but not both. They express CD79a but do not usually express other pan-B markers. They express CD38 and CD138. They resemble myeloma cells in being CD19 negative but are usually CD56 negative, whereas normal plasma cells are CD19 positive and CD56 negative. In MGUS, polyclonal plasma cells usually co-exist with immunophenotypically aberrant clonal cells, in contrast to multiple myeloma, where only a minority of patients have polyclonal plasma cells detectable by flow cytometry and then only as a low percentage.

Cytogenetic and molecular genetic abnormalities

Fluorescence in situ hybridization (FISH) analysis ...

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