Defining and Treating High-grade B-cell lymphoma, NOS

Abstract

High-grade B-cell lymphoma, not otherwise specified (HGBL, NOS) is a recently introduced diagnostic category for aggressive B-cell lymphomas. It includes tumors with Burkitt-like or blastoid morphology that do not have double-hit cytogenetics and that cannot be classified as other well-defined lymphoma subtypes. HBCL, NOS are rare and heterogeneous; most have germinal center B-cell phenotype, and up to 45% carry a single-hit MYC rearrangement, but otherwise they have no unifying immunophenotypic or cytogenetic characteristics. Recent analyses utilizing gene expression profiling (GEP) revealed that up to 15% of tumors currently classified as diffuse large B-cell lymphoma display a HGBL-like GEP signature, indicating a potential to significantly expand the HGBL category using more objective molecular criteria. Optimal treatment of HGBL, NOS is poorly defined due to its rarity and inconsistent diagnostic patterns. A minority of patients have early-stage disease which can be managed with standard RCHOP-based approaches with or without radiation. For advanced-stage HGBL, NOS, which often presents with aggressive, disseminated disease, high lactate dehydrogenase, and involvement of extranodal organs (including the central nervous system [CNS]), intensified Burkitt lymphoma-like regimens with CNS prophylaxis may be appropriate. However, many patients diagnosed at age > 60 years are not eligible for intensive immunochemotherapy. An improved, GEP and/or genomic-based pathologic classification that could facilitate HGBL-specific trials is needed to improve outcomes for all patients. In this review, we discuss the current clinicopathologic concept of HGBL, NOS, existing data on its prognosis and treatment, and delineate potential future taxonomy enrichments based on emerging molecular diagnostics.