Pattern-Based Identification Of Normal And Aberrant Plasma Cell Compartment Across A Spectrum Of Plasma Cell Proliferative Disorders Using Multiparametric Flow Cytometry

Context The discriminative power of various antigens for delineating normal plasma cells (NPC) from aberrant plasma cells (APC) is variable; thus, understanding of the multiparametric flow cytometry (MFC)-based PC compartment is crucial for reliable PC characterization across various PC proliferative disorders (PCPD). Objective The expression profile and patterns of currently used immunophenotypic (IPT) markers were assessed for their ability to differentiate NPC from APC across the spectrum of PCPDs. Design This is a prospective analysis of patients diagnosed with PCPD (per standard IMWG criteria). Setting Tertiary care cancer center. Patients A total of 900 patients with diagnosis of PCPD were evaluated (MM: 724, PCL: 15, SMM: 12, MGUS: 42, Plasmacytoma: 54, Amyloidosis: 31, POEMS: 22). Interventions Bone marrow aspirate from cases (n=900) and controls (n=30) were processed per consensus guidelines from the Euro-flow protocol. An aberrant PC cluster was defined by >30 plasma cells with light chain expression beyond the range of control samples (0.26 to 3.08) and/or aberrant immunophenotypes (≥3). Main Outcomes Measures 1. Utility of cytoplasmic light chain restriction and 2. Most useful combination of markers to discriminate NPC from APC. Results All cases were segregated into three groups: cases with 1. only APC (n=181); 2. with both NPC and APC (n=574); or 3. only NPC (n=145). The PC compartment was solely characterized by light chain expression and IPT aberrancy in 36.22% (n=326) and 21.88% cases (n=197), respectively (p Conclusions Assessment of cytoplasmic light chain expression by MFC is essential for demonstrating clonality in cases with all normal or all aberrant PC. Pattern-based recognition is a useful parameter that identifies aberrant PC reliably in the majority of cases with co-existing NPC and APC, especially in setting of smaller clones of APC, which are likely to be missed by light chain assessment alone.