In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS and smoldering myeloma represents an ongoing challenge, one that must be approached via prospective clinical monitoring and extensive correlative science. improving personalized management of patients with MGUS or smoldering myeloma, as well as the potential for developing early treatment strategies designed to delay and prevent development of multiple myeloma. CASE PRESENTATION The patient is a healthy 72-year-old white man with smoldering myeloma diagnosed 6 months ago and an 11-year history of monoclonal gammopathy of undetermined significance (MGUS) undergoing interval follow-up (Figure 1). His diagnosis of MGUS was first detected in 1999 during an annual physical when serum protein electrophoresis (SPEP) was ordered as part of a broad panel of blood Rabbit Polyclonal to GIMAP2 tests; all other results were within their normal ranges. Open in a separate window Figure 1. Case Patients M-Protein Levels Over TimeDiagnosis showed monoclonal gammopathy of undetermined significance (MGUS), and an M protein level that remained relatively stable for approximately 10 years before rapidly increasing in 2009 2009. aBone marrow biopsy performed in November 2009. bBone pain reported in January 2010. In 2009 2009, during a follow-up visit, laboratory values included creatinine 1.22 mg/dL, calcium 8.80 mg/dL, hemoglobin 12.6 g/dL, and albumin 4.3 g/dL (to convert values to SI units multiply creatinine by 88.4 for mol/L; calcium by 0.25 for mmol/L; hemoglobin by 10 for g/L; and albumin by 10 for g/L, respectively). The patients values, as revealed by SPEP were 4.4 g/dL for monoclonal protein (M protein), 5780 mg/dL for a highly elevated IgG, 47 mg/dL for a decreased level of IgA, and less than 21 mg/dL for a decreased level of IgM (to convert values to SI units multiply IgG by 0.01 for g/L; and IgA and IgM by 10 for mg/L, respectively). The ratio of serum free light chains (FLC) to FLC was 2.44 (normal range, 0.26-1.65). Bone marrow biopsy demonstrated AB-680 40% CD138+ -restricted plasma cells (Figure 2). Flow cytometry of the aspirate revealed almost all plasma cells were immunophenotypically abnormal (Figure 3). Skeletal survey showed negative results for lytic lesions, although an outside fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) displayed mild FDG uptake in the sacrum. Open in a separate window Figure 2. Case Patients Bone Marrow BiopsyThe diagnosis of smoldering myeloma was determined from a bone marrow biopsy. A, Hematoxylin-eosin AB-680 staining shows 30% to AB-680 50% marrow cellularity. B, Immunostaining for CD138 (brown chromagen; hematoxylin counterstain) shows 40% CD138+ cells. Based on the 2010 International Myeloma Working AB-680 Group criteria,1 CD138 staining of the marrow core is the reference standard for determining percentage of plasma cells. C and D, Immunostaining for free light chains (C) and free light chains (D) using a brown chromagen and hematoxylin counterstain shows a light chain restriction pattern with almost no -positive plasma cells. Immunohistochemistry for CD138 (B-A38; Cell Marque) and and light chains (DAKO, Carpinteria, California) was performed on Ventana using an Ultra View DAB detection kit (Ventana Medical Systems, Tucson, Arizona). CD138 staining of the marrow core was used as the criterion standard for determining percentage of plasma cells (original magnification 100 for all photomicrographs). Open in a separate window Figure 3. Immunophenotype Analysis of Case Patients Bone Marrow BiopsyA, Plasma cells were gated for analysis (indicated by blue border) based upon characteristically bright (increased) CD38 expression; plasma cell differentiation was further confirmed by the expression of CD138 in this population (C). By flow cytometry, 12% of cells were plasma cells compared with 40% plasma cells by immunohistochemistry. This much lower percentage of plasma cells was due to hemodilution, precluding the use of flow cytometry to quantitatively analyze the percentage of plasma cells. B and C, Antigen-negative populations are located in the 1-to-10 region of the scales. B, Analysis for and light chains demonstrated light-chain restriction. C, Almost all plasma cells were found to be immunophenotypically abnormal: CD38-positive, CD45-negative, CD19-negative, and dim (decreased) CD27 expression. At a follow-up visit 2 months later, the patient expressed concern of lower back pain located in the sacrum and left iliac bone areas. M-protein level was 4.9 g/dL. The back pain increased and magnetic resonance imaging (MRI) was conducted to rule out cord compression. Furthermore, a repeat FDG PET/CT revealed focal lesions in the sacrum and left iliac bone with a standard uptake value of 3.4 and 2.8, respectively (Figure 4). A diagnosis of multiple myeloma was made and treatment options were explained. The patient began treatment with lenalidomide/dexamethasone with partial.