Molecular Profiling of Extramedullary and Medullary Plasmacytomas.

Abstract 1806

Poster Board I-832

Plasmacytomas are rare clonal proliferations of plasma cells that though cytologically identical to plasma cell myeloma, present with osseous or extraosseous growth pattern. Understanding their molecular characteristics can provide crucial insights into their pathogenesis and risk of progression to multiple myeloma (MM). To investigate the differences between extramedullary (EMP) and medullary plasmacytomas (MP) and MM without plasmacytomas, we sought to molecularly profile these tumors by tissue microarrays, gene expression, microRNA, and FISH.

We identified 85 patients from our data base with a pathological diagnosis of plasmacytoma. Of the 85 patients, 13 patients presented with EMP, and 72 had MP. Among the patients with EMP (n=13), 2 patients presented with multiple lesions. Three of 13 (23%) patients progressed to develop MM at a median of 12 months. 72 patients presented with MP, of which 21 had solitary lesions and 27 (37%) progressed to MM at a median of 20.5months. There was a male preponderance (67% vs 33%) and the median age at diagnosis was 60.5 years (range 27.7-87.6). The mean overall survival for patients with EMP was 121 months (95% confidence interval[CI] 97-144 months) and for patients with MP was 102 months (95% CI 93-128 months) { p=0.025}

MicroRNA (miRNAs) profiling was performed on MP (n=19) and MM samples (n=66). Data was normalized using U6 endogenous control. Three hundred and one miRNAs out of a total 665 were significantly differentially expressed between MP vs MM samples. Gene expression profiling performed on MP will be correlated with the miRNA data to identify genes and transcripts of interest which will be functionally validated. Tissue microarrays were performed on 52 patients (8: EMP, 44: MP,) in whom paraffin-embedded tissue was available. Of samples analyzed, CD56 positivity was observed in 55% MP and 71% EMP samples (p=0.67). Additional staining for cyclin D1, Bcl 2 and FISH analysis will be reported.

Differential expression patterns of factors involved in proliferation, survival, adhesion, and stroma-tumor cell interactions may help explain plasmacytoma biology and identify factors responsible for progression to MM. These insights may help identify new therapeutic approaches and targets in the treatment of these plasma cell disorders.