A comprehensive flow-cytometry-based immunophenotypic characterization of Burkitt-like lymphoma with 11q aberration

Abstract

We previously described a subset of MYC translocation-negative aggressive B-cell lymphomas resembling Burkitt lymphoma, characterized by proximal gains and distal losses in chromosome 11. In the 2016 WHO classification, these MYC-negative lymphomas were recognized as a new provisional entity, 'Burkitt-like lymphoma with 11q aberration'. Here we present an immunophenotype analysis of Burkitt-like lymphomas with 11q aberration. Cells were acquired by fine needle aspiration biopsy from 10 young adult patients, 80% of whom presented recurrence-free 5-year survival. Twenty-three MYC-positive Burkitt lymphomas, including three carrying both MYC rearrangement and 11q aberration, served as controls. By immunohistochemistry, all Burkitt-like lymphomas with 11q aberration were CD20+/CD10+/BCL6+/BCL2-/MUM1-/MYC+/EBV-, usually LMO2+/CD44-/CD43- and sometimes CD56+, and showed high proliferation rate. By flow cytometry, Burkitt-like lymphoma with 11q aberration immunophenotypically resembled MYC-positive Burkitt lymphoma, except for significantly (adjusted P<0.001) more frequent CD38 expression in Burkitt lymphoma (91% MYC-positive Burkitt lymphoma vs 10% Burkitt-like lymphoma with 11q aberration), more frequently diminished CD45 expression in Burkitt lymphoma (74% vs 10%), an exclusive CD16/CD56 and highly restricted CD8 expression in Burkitt-like lymphoma with 11q aberration (60% vs 0% and 40% vs 4%, respectively). We showed high diagnostic accuracy and effectiveness of flow cytometry in Burkitt lymphoma. CD16/CD56 expression without CD38 and the lack of CD16/CD56 with CD38 expression proves to be a reliable, fast, and cost-effective method for diagnosing 11q aberration and MYC rearrangements in CD10(+) aggressive lymphomas, respectively. In addition, we confirmed a pattern of an inverted duplication with telomeric loss of 11q, as a recurrent 11q abnormality, but one case presented alternative changes, possibly resulting in an equivalent molecular effect. Our findings reveal similarities along with subtle but essential differences in the immunophenotype of Burkitt-like lymphoma with 11q aberration and MYC-positive Burkitt lymphoma, important for the differential diagnosis, but also for understanding the pathogenesis of Burkitt-like lymphoma with 11q aberration.

Comprehensive histopathological diagnostics of aggressive B-cell lymphomas based on the updated criteria of the World Health Organisation’s 2017 classification

“…That characteristics may contribute to the differential diagnosis of BLL, 11q and BL [49]. The 11q aberrations in BLL, 11q (11q-gain/loss) were described as an inverted duplication of a part of the long arm of chromosome 11 with mono-or biallelic telomeric deletion of 11q ( Figure 6) [45,46,47,49]. Coincidence of duplication and deletion of 11q (11q23 and 11q24-qter, respectively) suggests a possibility of simultaneous up-regulation of oncogenes and down-regulation of tumour suppressor genes.…”

“…BLL,11q usually express CD43/LMO2/CD56 in IHC and CD16/CD56/CD38/CD45/CD8/CD43 in FCM. That characteristics may contribute to the differential diagnosis of BLL, 11q and BL [49]. The 11q aberrations in BLL, 11q (11q-gain/loss) were described as an inverted duplication of a part of the long arm of chromosome 11 with mono-or biallelic telomeric deletion of 11q ( Figure 6) [45,46,47,49].…”

“…5). MYC-negative BLL,11q shows a number of clinico-pathological similarities to MYC-positive BL, but also harbour some significant differences in immunoprofile [1,45,46,47,48,49,50]. BLL,11q usually express CD43/LMO2/CD56 in IHC and CD16/CD56/CD38/CD45/CD8/CD43 in FCM.…”

The mutational landscape of Burkitt-like lymphoma with 11q aberration is distinct from that of Burkitt lymphoma

“…Recently, a subgroup of germinal center-derived B-cell (GCB) lymphomas has been described that resembles Burkitt lymphoma (BL) with regard to morphology, immunophenotype, and gene-expression profile but it lacks the IG-MYC translocation typical for BL. [1][2][3][4][5] Instead, these cases are cytogenetically characterized by a peculiar pattern of an 11q aberration consisting of a gain in 11q23.2-23.3 followed by a telomeric loss in 11q24.1-qter. According to the revised 4th edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue, these lymphomas have been described as a new provisional entity called "Burkitt-like lymphoma with 11q aberration" (abbreviated herein as "mnBLL,11q,").…”

Clinical Interest of LMO2 Testing for the Diagnosis of Aggressive Large B-Cell Lymphomas

“…Moreover, recent studies suggest that LMO2 also appears to be useful for the differential diagnosis of BL and the provisional category of Burkitt-like lymphoma with 11q aberration. Two independent studies characterizing Burkitt-like lymphoma with 11q aberration, noted LMO2 protein expression in 7/10 (70%) and 5/11 (46%) cases [31,32]. An additional study including 75 BL observed absent expression of LMO2 in 74 (99%) cases, whereas three out of three Burkitt-like lymphomas with 11q aberration were positive [33].…”