MOLECULAR ANALYSES AND AN INNOVATIVE DIAGNOSTIC ALGORITHM IN MYC -NEGATIVE BURKITT-LIKE LYMPHOMA WITH 11Q ABERRATION: A SINGLE INSTITUTION EXPERIENCE

Burkitt-like lymphoma with 11q aberration (BLL,11q) is a new entity of a germinal center (GCB)-derived, highly aggressive B-cell lymphoma. Clinically and pathomorphologically, BLL,11q resembles Burkitt lymphoma (BL), but it lacks MYCrearrangements and presents proximal gains and distal losses in chromosome 11. In the updated 2017 WHO classification, BLL,11q has been recognized as a provisional entity. BLL,11q could be promoted to definite lymphomas but for this purpose it is necessary to publish as many new cases as possible, and more molecular studies are expected to add to an understanding and managing of this very rare malignancy. Still, the recognition of BLL,11q entity is clinically relevant because a favorable outcome is observed after BL-directed therapy. Unfortunately, the routine diagnosis of BLL,11q is difficult, and BLL,11q is often misdiagnosed by histopathology and due to the lack of MYC rearrangement it is inappropriately treated. To the best of our knowledge, we have so far published the largest cohort of BLL,11q and of BL cases carrying both MYC rearrangement and 11 aberration. Our initial RT-qPCR-based miRNA studies showed similarities of BLL,11q (n = 12) to BL (n = 34), but not to DLBCL (n = 49) in miR-155, miR-21 and mir-26a expression Next, a detailed immunohistochemical and flow cytometry analysis of 10 BLL,11q and 23 MYC-positive BL cases revealed similarities along with subtle but essential differences in BLL,11q and BL immunophenotypes. We also correlated the occurrence of bulky tumors in BLL,11q with amplification of the 11q23.3 region, where KMT2A is located. Most recently, by next generation sequencing of 10 BL and 7 BLL,11q, we identified 49 microRNAs and 2572 mRNA transcripts differentially expressed between BL and BLL,11q. Accumulating data show significant differences between sporadic BL and BLL,11q in mRNA and microRNA profiles, and point to different chromosomal and mutational profiles of BLL,11q from BL, and additionally from other aggressive GCB-lymphomas. Thus, BLL,11q seems indeed to be a molecularly distinct category. Still, BLL,11q patients, if treated with BL-directed regimen, have a relapse-free outcome similar to BL patients. We proposed an original and practical flow cytometry- and immunohistochemistry-based diagnostic algorithm for the differential diagnosis of BLL,11q vs. BL and other aggressive lymphomas which enables BLL,11q diagnosis within 1.5 hours following fine needle aspiration biopsy procedure. Keywords: Burkitt lymphoma (BL); fine-needle aspirate (FNA); flow cytometry. Disclosures: Rymkiewicz, G: Other Remuneration: Roche, fee, travel expenses.