According to the 2022 WHO classification, High-grade B-cell lymphoma with 11q aberration (HGBCL-11q) is a MYC-negative lymphoma with 11q duplication and terminal deletion as specific chromosomal aberrations for this neoplasm. However, there are a growing number of reports defying this definition describing cases with the co-occurrence of 11q aberration and MYC rearrangement (HGBCL-11q,MYCR). This research has two aims. First, to compare the unique HGBCL-11q,MYCR group of 9 cases with 26 HGBCL-11q cases on chromosomal, mutational and clinicopathological level. The second objective is to investigate the association of the new HGBCL-11q,MYCR group with HGBCL-11q and two other closely related MYC-positive aggressive lymphoma subtypes: Burkitt lymphoma (BL) (n=17) and High-grade B-cell lymphoma, not otherwise specified with MYC rearrangement (n=10). Genetic results were obtained by classical cytogenetics, fluorescence in situ hybridization, microarrays, and whole exome sequencing. In parallel histopathological/ immunohistochemical analyses (HP/IHC) with flow cytometry(FCM), in conjunction with clinical presentation and treatment outcomes are presented. Our findings reveal that HGBCL-11q,MYCR, exists as an independent nosological entity, distinct from BL and HGBCL-11q at the cytogenetic, molecular, and clinicopathological levels, although it contains common features of both lymphoma subtypes. Common features with BL include: MYC rearrangement with the immunoglobulin genes, patterns of secondary chromosomal aberrations like dup(1q), del(17p), high number of MYC and CCND3 mutations. Other BL features are: frequent extranodal abdominal presentation, morphology, GCB cell of origin determined by IHC and FCM, immunophenotypical features such as MYC(+)/LMO2(-) detected by flow cytometric features: CD45(+)weaker, more cases with CD43(+) and CD44(-) expression, only expression of IgD and IgM heavy chain and CD38(+)higher overexpression, which correlates with MYC rearrangement assessed by FCM. Similarity to HGBCL-11q includes the existence of 11q aberration, presence of DDX3X, ETS1, GNA13, NFRKB, KMT2D, and the lack of TCF3 and ID3 mutations. Additionally, frequent nodal and tonsillar presentation, morphology, GCB cell of origin, immunophenotypical features with flow cytometry measured CD56(+) expression, associated with NCAM duplication/amplification on 11q, and pathogenesis not associated with Epstein-Barr virus infection. The distinctive chromosomal change of HGBCL-11q,MYCR was the gain or amplification of 3q29. Our cohort of patients with HGBCL-11q,MYCR had similar relapse-free survival to that of patients with HGBCL-11q and BL, if treated with BL-directed regimens.
