Molecular Profiling of Extramedullary and Medullary Plasmacytomas

Abstract

Plasmacytomas are rare plasma cells disorders and are potentially cured with local approaches such as radiation treatment. Extramedullary plasmacytomas usually progress slowly, can recur locally, and develop into multiple myeloma (MM) less frequently (8–36%) compared to solitary medullary plasmacytomas (60%). Biologically these cells are independent of bone marrow microenvironment for their growth and survival and the understanding of the differences in their underlying molecular characteristic can provide crucial insights into the pathogenesis of progression to MM. To investigate the differences between extramedullary and medullary plasmacytomas, we sought to molecularly profile these tumors by tissue microarrays, gene expression, microRNA, and FISH. We identified 78 patients from our data base with a pathological diagnosis of plasmacytoma. Of the 78 patients, 11 patients presented with extramedullary plasmacytomas, and 50 had medullary plasmacytomas. Seventeen patients who had been previously identified as having plasmacytomas were later confirmed to have MM. Among the patients with extramedullary plasmacytomas (n=11), 1 patient presented with multiple lesions. Three of 11 (27%) patients progressed to develop MM at a median of 12 months. Fifty patients presented with medullary plasmacytomas, of which 23 had solitary lesions and 27 (54%) progressed to MM at a median of 20.5 months. There was a male preponderance (76% vs 34%) and the median age at diagnosis was 59.6 years (range 30.4–84.3). Tissue microarrays were performed on 52 patients (7: extramedullary, 29: medullary, 16: MM) in whom paraffin-embedded tissue was available. Samples were stained for CD138, CD27, CD56, cyclin D1, Bcl-2, Ki-67 and light chain restriction by immunohistochemistry and/or in situ hybridization. Both paraffin and fresh frozen tissue was available for 12 medullary, 3 extramedullary, and 2 MM samples at diagnosis for comparison. FISH for del 13q, t(4;14), t(11;14), and t(14;16) was performed on these samples. Gene and microRNA profiling was also performed. The differential profile of gene and microRNA expression between the two subtypes of plasmacytomas and MM will be presented. Differential expression patterns of factors involved in proliferation, survival, adhesion, and stroma-cancer cell interactions may help explain plasmacytoma biology and identify factors responsible for progression to multiple myeloma. These insights may help identify new therapeutic approaches and targets in the treatment of plasma cell disorders.