A Combined Biomarker of Bright CD38 and MYC [greater than or equal to]55% Is Highly Predictive of Double-/Triple-Hit High-Grade B-Cell Lymphoma: Implication on Diagnostic Workup

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 ([CD38.sup.bright]) by FC, high MYC expression ([greater than or equal to]55%), and double-expressor phenotype by IHC were significantly associated with DTHL. The biomarker combining FC and IHC, [CD38.sup.bright] and/or MYC [greater than or equal to]55%, was superior to FC and IHC markers alone in predicting DTHL. Restricting FISH testing to approximately 25% of LBCL based on [CD38.sup.bright] and/or MYC [greater than or equal to]55% would detect approximately 95% of DTHL-BCL2 and approximately 75% of DHL-BCL6. Conclusions: Our study demonstrated that the novel biomarker of [CD38.sup.bright] and/or MYC [greater than or equal to]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. KEY WORDS High-grade B-cell lymphoma; Double-/triple-hit lymphoma; MYC; CD38; Flow cytometry; Immunohistochemistry