Diagnostic applications of nuclear medicine: Multiple myeloma

Multiple myeloma (MM) represents about 1.8% of all cancers and 10% of all hematologic malignancies. MM is the most common primary bone cancer. The clonal proliferation of malignant plasma cells in the bone marrow may result both in local growth and in systemic effects due to the overproduction of a monoclonal protein (M-protein). Plasma cell proliferation is linked to a variety of clinical presentations of the disease, ranging from simple monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM) to full-blown "malignant" MM. MM differs from MGUS and SMM by the presence of the end-organ damage associated with a complex syndrome named CRAB. However, in the updated version of the criteria for the diagnosis of plasma cell proliferative disorders established by the International Myeloma Working Group (IMWG), more specific criteria have been established to define MM, MGUS, and SMM. Excess bone marrow plasma cells, M-protein, osteolytic bone lesions, renal disease, and immunodeficiency constitute the pathophysiologic bases of the clinical manifestations of MM. Severe bone pain, pathologic fractures, spinal cord compression, and hypercalcemia are caused by lytic bone lesions. The course of MM is highly variable, and the clinical behavior is remarkably heterogeneous. Many studies have identified prognostic factors capable of predicting this heterogeneity in survival (serum β2-microglobulin, albumin, C-reactive protein, and lactate dehydrogenase). The standard workup of MM is based on a number of laboratory tests that are utilized for risk stratification. The International Staging System (ISS) is a powerful and reproducible three-stage classification in which the ISS3 class is associated with the poorest outcome. Imaging studies demonstrate the extent and severity of bone involvement (intramedullary/extramedullary, site and number of lesions) at baseline, including disease-related complications, such as pathologic fractures; they also serve to assess response to treatment and provide follow-up surveillance. The ISS introduced over 25 years ago is mainly based on serum β2-microglobulin and albumin levels, without any reference to the presence of bone lesions or to the methodology employed for their evaluation. Although the ISS serves as a prognostic indicator rather than as an accurate scoring system, it adequately estimates tumor burden and risk stratification, allowing differentiation of MGUS and SMM from MM. In 1975, Durie and Salmon introduced a clinical staging system based on the presence of bone lesions to grade the severity of the disease. While the original Durie and Salmon system was essentially based on the use of planar X-ray for evaluating bones, a newer version, the PLUS system, was released in 2005 to improve the accuracy of staging with advanced imaging modalities such as [18F]FDG-PET/CT and MRI.