Mieloma

THE SPECTRUM OF PLASMA CELL DYSCRASIAS

Differential diagnosis of monoclonal gammopathy of undetermined significance
Giampaolo Merlini1,2 and Giovanni Palladini1,2
Research and Treatment Center, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; and 2Department of Molecular Medicine, University of Pavia, Pavia, Italy
1Amyloidosis

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic plasma cell disorder occurring in 4.2% of adults 50 years of age, which can progress into symptomatic diseases either through proliferation of the plasma cell clone, giving rise to multiple myeloma and other lymphoplasmacellular neoplasms, or through organ damage caused by the monoclonal protein, as seen in light-chain amyloidosis and related conditions. Differential diagnosis of asymptomatic and symptomatic monoclonal gammopathies is the determinant for starting therapy. The criteria for determining end-organ damage should include markers of organ injury caused by the monoclonal protein. Patient assessment and optimal follow-up are now performed using risk stratification models that should also take into account the risk of developing AL amyloidosis. Patients with low-risk MGUS (approximately 40% of all MGUS patients) need limited assessment and very infrequent follow-up. The ongoing development of novel molecular biomarkers and advanced imaging techniques will improve the identification of high-risk patients who may benefit from early therapeutic intervention through innovative clinical trials.

Introduction
Robert Kyle coined the term monoclonal gammopathy of undetermined significance (MGUS) in 1978 after the observation that asymptomatic patients with a monoclonal protein (M-protein) had higher risk of developing multiple myeloma (MM), Waldenstrom ¨ macroglobulinemia (WM), light-chain amyloidosis (AL), or related conditions. MGUS is a premalignant clonal disorder that is present in more than 4% of the general white