Monoclonal Gammopathies, Beyond Multiple Myeloma. A Narrative Review

Monoclonal gammopathies (MG) comprise a spectrum of entities that share a common feature: The pathological production of a monoclonal immunoglobulin (Ig). The paradigmatic disorder within this group is multiple myeloma (MM). A knowledge gap persists regarding the differential diagnosis of the remaining conditions that present with MG.

To characterize the spectrum of diseases associated with MG, emphasizing their pathophysiological and clinical features.

A database search was performed. An inductive approach was applied for the critical analysis of the scientific literature. Information extracted from the selected publications was organized into thematic categories to construct a narrative review.

Of the 53 initially screened articles, 32 were included for analysis and grouped into two major thematic categories. The first was subdivided into two sections and the second into three. These categories were used to structure the narrative review.

MG are classified into three groups: MG associated with overt neoplasms, monoclonal gammopathies of clinical significance (MGCS), and monoclonal gammopathies of undetermined significance (MGUS). The first group includes MM, plasma cell leukemia, solitary plasmacytoma, and mature B-cell lymphoproliferative neoplasms with a monoclonal component. MGCS are defined by organ damage attributable to a "small but dangerous" clone and are categorized as systemic or localized. MGUS is defined by the presence of MG with <10% clonal plasma cells or B lymphocytes in bone marrow, without associated clinical impact. The evaluation of a patient with MG requires ruling out overt neoplasms and MGCS to establish a diagnosis of MGUS.

The spectrum of MG encompasses entities ranging from various neoplasms (not only MM) to strictly asymptomatic conditions. MGUS is, by definition, a diagnosis of exclusion.