Bright CD38 Expression by Flow Cytometric Analysis Is a Biomarker for Double/Triple Hit Lymphomas with a Moderate Sensitivity and High Specificity

Background: High-grade B-cell lymphomas (HGBCL) with MYC and BCL2 or/and BCL6 rearrangements (R), so-called double/triple-hit lymphomas (DH/THL), are uncommon, clinically aggressive lymphomas that require a prompt diagnosis. We aim to identify flow cytometric immunophenotypic (IP) features of DH/THL that may aid in triaging these cases followed by a timely confirmatory cytogenetic study. Methods: We compared the IP features of 43 cases of DH/THL to those of 55 cases of single-hit lymphoma (SHL) and 59 cases of diffuse large B-cell lymphoma (DLBCL) without MYC-R (MYC^neg DLBCL). We analyzed the expression patterns of CD10, CD19, CD20, CD38, and surface immunoglobulin light chain in lymphoma cells. Results: Bright CD38 expression (CD38^bright) analyzed either qualitatively or semi-quantitatively was more common in DH/THL (56%) than in MYC^neg DLBCL (17%) but less common compared to SHL (82%), indicating that CD38^bright can serve as a biomarker for DH/THL. Additionally, CD38^bright may be a better indicator for predicting DH/THL-BCL2 than DHL-BCL6, and very bright CD38 expression was exclusive to MYC rearranged lymphomas. The expression patterns of other markers were similar among these lymphoma groups. Conclusions: CD38^bright is a biomarker associated with DH/THL with a moderate sensitivity (~50%) and high specificity (~90%). While this marker cannot be used as a screening tool, awareness of this correlation may aid in expediting the diagnosis and prioritizing FISH testing in resource limited settings or situations when samples are limited. Future studies to combine immunohistochemical markers are needed to further enhance the predictive power of CD38^bright in diagnosing DH/THL.