Significance of a Critical Set of 11q Chromosome Aberrations for Diagnosis of MYC Negative Burkitt Lymphoma

• Published in: Blood 2015-12, Vol.126 (23), p.2679-2679
• Main Authors: Rymkiewicz, Grzegorz, Chechlinska, Magdalena, Grygalewicz, Beata, Pienkowska-Grela, Barbara, Blachnio, Katarzyna, Bystydzienski, Zbigniew, Romejko-Jarosinska, Joanna, Sledz-Gawronska, Beata, Zajdel, Michalina, Domanska-Czyz, Katarzyna, Woroniecka, Renata, Sikorska-Mali, Kinga, Siwicki, Jan Konrad, Prochorec-Sobieszek, Monika, Walewski, Jan
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V126.23.2679.2679

Background: Burkitt lymphoma (BL) is characterized by a non-specific morphology and immunophenotype, a high proliferation rate, MYC rearrangements (MYC +), and by a simple karyotype. However, 5% of BL cases have no MYC rearrangements (MYC -) detectable by FISH. It is a matter of debate whether a true MYC (-) BL does exist.The WHO 2008 classification does not clearly define MYC (-) BL cases, and such cases are often misdiagnosed and treated as diffuse large B-cell lymphoma (DLBCL). We have previously described a provisional category of aggressive B-cell lymphoma unclassifiable (BCLU) with recurrent chromosome 11q aberrations, referred to as B-NHL(11q), with clinical, pathomorphological, and gene expression profile features typicalof BL,but MYC (-). B-NHLs(11q) carry proximal gains and telomeric losses of 11q. Karyotyping (CC) and FISH defined the gain region as dup(11)(q23q13) involving CCND1, ATM and KMT2A. As we have recently shown, BL and B-NHL(11q) express different levels of CD38 and CD16&CD56, and both have lower levels of miRNA-155, -21 and -26a than DLBCL. Here we describe a series of BL patients with a set of critical 11q aberrations and propose a diagnostic algorithm for a rapid work-up. Methods: Within a group of 82 BL cases diagnosed and treated with the BL protocol at our institution, we identified 15 cases of B-NHL(11q) with BL features and 11q aberrations: MYC (-) in 11(male/female 10/1, median age [range] 24 [18-62]) and MYC (+) in 4 cases (male/female 3/1, median age [range] 36.5 [20-82]). In MYC (-) pts, the disease was confined to a single site in 82%, was bulky (>7 cm) in 64% with diameter >20 cm in 45% of cases. BL, BCLU and DLBCL diagnosis according to WHO 2008 classification was based on histopathological/immunohistochemical examination (HP/IHC), CC, FISH, and clinical characteristics in all pts. For the final evaluation, the flow cytometry (FCM) immunophenotype, array comparative genomic hybridization (aCGH) data, and miRNA expression was assessed on samples obtained by the fine needle aspiration biopsy (FNAB). In the B-NHL(11q) cases we identified 11q duplication, dup(11q), with an inversion (inv) of the duplicated region and a deletion of its telomeric region, referred to as critical set of 11q aberrations, as opposed to non-critical aberration set that did not involve all three changes. B-NHL(11q) cells were evaluated with the panel of antibodies by IHC (CD20/CD10/BCL6/ BCL2/MUM1/MYC/Ki-67/CD43/CD44), and by FCM with CD (19, 20, 2