Simple Karyotype and BCL-6 Expression Predict a Diagnosis of Burkitt Lymphoma and Better Survival in IG-MYC Rearranged High-Grade B-Cell Lymphomas
AC Seegmiller, R Garcia, R Huang, A Maleki, N Karandikar, W Chen. The University of Texas Southwestern Medical Center, Dallas, TX
Background: Rearrangement (R) of MYC with immunoglobulin genes (IG) is a hallmark of Burkitt lymphoma (BL). However, it is not entirely specific and is often accompanied by varying numbers of additional cytogenetic abnormalities (ACA). This study assessed the impact of ACA detected by karyotype, in correlation with immunophenotype (IP), on the diagnosis and outcomes of MYC-IG rearranged lymphomas.
Design: An institutional database was searched for B-cell lymphomas with karyotypes including MYC-IG R, IP by flow cytometry (FC) and immunohistochemistry, and clinical data, which yielded 34 cases that included 22 BLs, 3 diffuse large B-cell lymphomas (DLBCL), 6 unclassifiable B-cell lymphomas with features intermediate between DLBCL and BL (INT), and 3 plasmablastic lymphomas (PBL), using the 2008 WHO classification scheme.
Results: MYC R cases exhibited bright CD38 expression by FC (mean MFI of 2009) compared to DLBCL without MYC R (MFI of 880 in our previous study). Twenty-six cases showed ACA (mean 5.5/case). Four cases (12%) harbored dual R involving BCL-2 or BCL-6. BL cases had significantly fewer ACA (mean of 1.7), compared with INT (3.3), DLBCL (21.7) and PBL (6.7). Cases with few ACA (defined as ≤2) were more likely to be BL and express bcl-6. There was a significant inverse correlation between bcl-6 expression and ACA. BL diagnosis, bcl-6 expression, and low ACA were individual predictors for better overall survival (OS). In multivariate analysis, only bcl-6 expression remained an independent predictor, although survival could be further stratified by ACA within bcl-6(+) patients. Expression of other markers, including CD10, bcl-2, TCL-1, CD44 and MUM-1, had no impact on diagnosis and survival.
|ACA ≤ 2 (n=19)||29 (2-62)||18 M, 1 F||18/19(95%)||17/19(89%)||undefined|
|ACA >2 (n=15)||50 (3-66)||10 M, 5 F||7/15(47%)||5/15(33%)||7.0 months|