Cytogenomic and Clinicopathologic Comparison of MYC-Positive and MYC-Negative High-Grade B-Cell Lymphoma With 11q Aberration in the Context of Other Aggressive Lymphomas With MYC Rearrangement

According to the 2022 World Health Organization 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 is 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 2 aims. First, to compare the unique HGBCL-11q,MYCR group of 9 cases with 26 HGBCL-11q cases on chromosomal, mutational, and clinicopathological levels. The second objective was to investigate the association of the new HGBCL-11q,MYCR group with HGBCL-11q and 2 other closely related MYC-positive aggressive lymphoma subtypes: Burkitt lymphoma (BL) (n = 17) and HGBCL, not otherwise specified with MYCR (n = 10). Genetic results were obtained by classical cytogenetics, fluorescence in situ hybridization, microarrays, and whole exome sequencing. In parallel histopathologic/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 nosologic 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 following: MYCR with the immunoglobulin (Ig) genes, patterns of secondary chromosomal aberrations like dup(1q), del(17p), and high number of MYC and CCND3 mutations. Other BL features are: frequent extranodal abdominal presentation, morphology, germinal center B-cell-like cell of origin determined by IHC and FCM, immunophenotypical features such as MYC(+)/LMO2(–) detected by following 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 MYCR assessed by FCM. Similarity to HGBCL-11q includes the existence of 11q aberration, presence of DDX3X, ETS1, GNA13, NFRKB, and KMT2D, and the lack of TCF3 and ID3 mutations. Additionally, frequent nodal and tonsillar presentation, morphology, germinal center B-cell-like cell of origin, and immunophenotypical features, including CD56(+) expression measured using FCM, are observed, which are 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.