14. A novel cytogenomic approach to diagnosis of plasma cell neoplasms

Abstract

Plasma cell neoplasm (PCN) is characterized by specific chromosomal aberrations with diagnostic and prognostic significance. Low percentage of neoplastic cells is a drawback in application of karyotyping and fluorescence in situ hybridization (FISH) for evaluation of bone marrow aspirates. Enrichment techniques to isolate the CD138+ cells have improved the detection rates. However, a complete FISH analysis for various abnormalities may not be achieved due to limited number of isolated cells. In 2017, we validated and implemented a novel approach for a whole genome profiling of plasma cells in PCN. The protocol consisted of isolation of CD138+ cells, whole genome DNA amplification and microarray comparative genomic hybridization. Separate FISH analysis was performed for detection of balanced IGH rearrangements. Of 412 clinical cases to date, 234 (56.8%) had morphologic and immunohistochemical studies indicative of PCN with 0.5–90% plasma cells in a bone marrow aspirates. Among PCN patients, chromosomal abnormalities were identified in 223 (95.2%) demonstrated by both microarray and FISH (n = 76, 32.9%), microarray (n = 116, 50.2%) or FISH only (n = 31, 13.9%). The most common findings included IGH rearrangement (49%), 13q deletion (45%), hyperdiploidy (41%), and 1q duplication (38%). Tetraploidy and MYC rearrangements were observed in 2.1% (5/234) and 1.7% (4/234) of patients, respectively. Interestingly, microarray revealed characteristic deletions involving the 6q21q25 region in 4/7 patients with Waldenström Macroglobulinemia. Our diagnostic approach to PCN is a cost-efficient replacement of multiple FISH assays that provides a superior detection rate and additional information for disease classification, prognosis, treatment and differentiation from other B cell malignancies.