Monoclonal gammopathy of clinical significance (MGCS): when monoclonal gammopathy of undetermined significance (MGUS) is no longer undetermined

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) is a condition characterized by the presence of a monoclonal immunoglobulin (mIg) without its organ- or tissue-damaging effect. In recent years, attention has been paid to patients who show a MGUS-like condition, but at the same time present damage to the kidneys, peripheral nerves, or skin, resulting from the deposit of mIg. These disorders do not meet the criteria for smoldering myeloma or multiple myeloma. In 2018, the term ‘monoclonal gammopathy of clinical significance’ (MGCS) was introduced for this group of patients. The dysfunction associated with MGCS is the result of the toxic activity of a monoclonal protein produced by dangerous, small clones of B cells and plasmocytes. Taking this into account, the term ‘MGUS’ should be limited to those cases where no association with mIg organ or tissue damage can be demonstrated, whereas the term ‘MGCS’ (monoclonal gammopathy of clinical significance) should be used in patients in whom the monoclonal protein plays a direct role in damage, especially to the kidneys, skin, and nervous system. This article summarizes the current state of knowledge of the main syndromes and symptoms of MGCS.