Chapter 2 – Diagnosis and staging

Contributors: Carlos Fernández de Larrea and Joan Bladé

1 – Diagnostic criteria

Multiple myeloma (MM) is a plasma cell disorder characterized by a clonal proliferation of cells producing a homogeneous plasma protein of monoclonal character (M-protein or paraprotein), restricted by kappa or lambda light chains, which are detected in the serum and/or urine [1]. In fact, MM is the prototypical malignant monoclonal gammopathy, where the amount of paraprotein produced by the plasma cell proliferation and immunodeficiency gives rise to the clinical and biological features of the disease. Diagnostic criteria from the International Myeloma Working Group (IMWG) have recently been updated to reflect a paradigm shift in the approach to myeloma by including validated biomarkers in addition to the existing requirements of ‘CRAB’ (hypercalcemia, renal failure, anemia, and bone lesions) features. These biomarkers are associated with near inevitable development of CRAB features in patients who may have previously been diagnosed with smoldering MM (Table 2.1) [2]. The main clinical manifestations at diagnosis of MM are shown in Table 2.2 [3].

Initial diagnostic workup in patients with MM is summarized in Table 2.3 [4]. Particular attention should be focused on: (1) baseline values (serum and/or urine M-protein, plasma cell infiltration, serum free light chain [FLC], and extramedullary involvement) for follow-up during treatment; (2) presence and degree of end-organ damage, mainly summarized under the acronym CRAB (Table 2.1), and other clinical myeloma-related manifestations; and (3) risk-stratification.

Table 2.1 International Myeloma Working Group (IMWG) updated criteria for the diagnosis of multiple myeloma.

CT, computed tomography; Hb, haemoglobin; MRI, magnetic resonance imaging; ULN, upper limit of normal. All rights reserved. Rajkumar et al [2].

Table 2.2 Clinical and laboratory findings in multiple myeloma.

*Non-infectious fever is extremely infrequent (<1%). IgA/D/E/G/M, immunoglobulin A/D/E/G/M. Adapted from © Mayo Foundation for Medical Education and Research, 2003. All rights reserved. Kyle et al [3].

Table 2.3 Initial studies for patients with multiple myeloma.

CT, computed tomography; FISH, fluorescence in situ hybridization; LDH, lactate dehydrogenase; MRI, magnetic resonance imaging; PET, positron emission tomography. Adapted from © Informa PLC, 2014. All rights reserved. Fernández de Larrea et al [4].