A Combined Biomarker of Bright CD38 and MYC ≥55% Is Highly Predictive of Double-/Triple-Hit High-Grade B-Cell Lymphoma

Abstract

Objectives Diagnosis of high-grade B-cell lymphoma with MYC and BCL2 or BCL6 rearrangements (double-/triple-hit lymphoma [DTHL]) appears to mandate fluorescence in situ hybridization (FISH) testing for all large B-cell lymphoma (LBCL). Given the low incidence of DTHL, we aimed to identify flow cytometry (FC) and immunohistochemistry (IHC) features of DTHL that could be used to develop an optimal screening strategy. This combined FC-IHC approach has not yet been studied. Methods We compared features of 40 cases of DTHL and 39 cases of diffuse LBCL (DLBCL) without MYC rearrangement. Results Bright CD38 expression (CD38bright) by FC, high MYC expression (≥55%), and double-expressor phenotype by IHC were significantly associated with DTHL. The biomarker combining FC and IHC, CD38bright and/or MYC ≥55%, was superior to FC and IHC markers alone in predicting DTHL. Restricting FISH testing to approximately 25% of LBCL based on CD38brightand/or MYC ≥55% would detect approximately 95% of DTHL-BCL2 and approximately 75% of DHL-BCL6. Conclusions Our study demonstrated that the novel biomarker of CD38bright and/or MYC ≥55% is highly predictive of DTHL. Awareness of the advantages and limitations of this screening strategy would facilitate development of a rational diagnostic workflow to provide high-quality patient care.

Clinicopathologic features of relapsed CD19(−) B‐ALL in CD19‐targeted immunotherapy: Biological insights into relapse and LILRB1 as a novel B‐cell marker for CD19(−) B lymphoblasts

“…Clinicopathological features including the flow cytometric immunophenotype and cytogenetics/fluorescence in situ hybridization (FISH) (performed on bone marrow aspirate/peripheral blood samples) were evaluated as previously described. 25,26 Flow cytometric study was performed on 10-color BD FACSCanto and analyzed by Cytopaint Classic Software. The B-cell panel included LILRB1 (PE, clone of HP-F1, eBiosciense), CD10, CD19, CD20, CD22, CD24, CD34, CD38, and CD45.…”

Genomic profile of TdTpositiveMYC/BCL2 rearranged high‐grade B‐cell lymphoma supporting its diagnosis as mature aggressive lymphoma

“…Blastoid lymphoma cells exhibited some features of immaturity suggestive of B-ALL, such as CD20 few positive /sIg negative /CD45 dim positive / TdT positive . However, awareness of this rare entity mostly associated with MYC rearrangement, immunophenotypic features of MYC rearranged double-hit lymphoma [bright CD38 expression at an intensity level comparable to or high than germinal center B cells (Alsuwaidan et al, 2022), dim to absent CD20, and CD34 negative ], and clinical F I G U R E 1 (a) Follicular lymphoma in groin lymph node. Low power shows complete effacement of the lymph node with back-to-back, nonpolarized follicles with attenuated or absent mantle zones.…”