Detection of Circulating Tumor Plasma Cells in Monoclonal Gammopathies: Methods, Pathogenic Role, and Clinical Implications

Cancer dissemination and distant metastasis most frequently require the release of tumor cells into the blood circulation, both in solid tumors and most hematological malignancies, including plasma cell neoplasms. However, detection of blood circulating tumor cells in solid tumors and some hematological malignancies, such as the majority of mature/peripheral B-cell lymphomas and monoclonal gammopathies, has long been a challenge due to their very low frequency. In recent years, the availability of highly-sensitive and standardized methods for the detection of circulating tumor plasma cells (CTPC) in monoclonal gammopathies, e.g., next-generation flow cytometry (NGF), demonstrated the systematic presence of CTPC in blood in virtually every smoldering (SMM) and symptomatic multiple myeloma (MM) patient studied at diagnosis, and in the majority of patients with newly-diagnosed monoclonal gammopathies of undetermined significance (MGUS). These methods set the basis for further detailed characterization of CTPC vs. their bone marrow counterpart in monoclonal gammopathies, to investigate their role in the biology of the disease, and to confirm their strong impact on patient outcome when measured both at diagnosis and after initiating therapy. Here, we review the currently available techniques for the detection of CTPC, and determine their biological features, physiopathological role and clinical significance in patients diagnosed with distinct diagnostic categories of plasma cell neoplasms.