Plasma Cell Myeloma with MYC Rearrangement Involving Immunoglobulin Genes
M Almiski, A Maleki, R Garcia, W Chen. UT Southwestern Medical Center at Dallas, Dallas, TX
Background: Rearrangement (R) of the MYC gene has been suggested as a secondary oncogenetic event in the pathogenesis of plasma cell myeloma (PCM). While this aberration was reported in 15% of PCM, a comprehensive clinicopathologic study of cases with MYC R involving the immunoglobulin (Ig) partner genes is largely absent. We describe the morphologic, immunophenotypic and cytogenetic features of this subtype of PCM.
Design: An institutional database was searched for cases of PCM with abnormal karyotypes that included MYC R involving Ig genes, which yielded 18 bone marrow cases. Immunophenotype (IP) was analyzed by flow cytometry (FC). These results were correlated with available morphologic and clinical data for 4 cases. In addition, IP of 17 cases without MYC R was analyzed for comparison.
Results: Patients were 6 males and 12 females, median age 58 years (range 37-90). Neoplastic cells expressed CD19 in 1 case (5.6%), CD20 in 2 (11%), CD38 in all, CD45 in 5 (28%), CD56 in 11 (61%); dim surface and intracellular Ig restriction in 10 (55%) and all cases, respectively. This IP was not different from the cases without MYC R that expressed CD19, CD20, CD38, CD45, CD56, surface and intracellular Ig restriction in 5.9%, 5.9%, 100%, 35%, 65%, 53% and 100% of cases, respectively. Most common MYC R was t(8;22) [12 cases, 67%] followed by t(8;14)  and t(2;8) . The MYC R occurred in the context of a complex karyotype in all cases, with an average of 8.81.0 additional cytogenetic aberrations including recurrent abnormalities such as t(11;14)(3 cases) and -13(5). Most cases (15/18) had single but complex clone, and only 3 cases had 2 or 3 related clones that all had MYC R. Clinical and morphologic data were available in 4 cases. All had a de novo diagnosis. Neoplastic cells had intermediate-grade cytology. Patients presented at various clinical stages (IA in 1, IB in 1, IIIA in 2 cases), and beta-2 microglobuin level was from normal (1 case) to higher than 3.5 mg/L in 2. All patients received treatment; 2 are alive and 2 have died of disease.
Conclusions: The overall features of PCM with MYC R are similar to those without MYC R with respect to morphology, immunophenotype, and clinical presentation. These data combined with a predominance of single complex clone do not appear to support the view of MYC R as a secondary oncogenetic event. However, a large cohort of patients is needed to determine the place of MYC aberrations in PCM pathogenesis. Interestingly, most MYC rearranged cases had t(8;22), in contrast to common t(8;14) in high grade B-cell lymphomas.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 205, Wednesday Morning