High-grade B-cell lymphomas: high difficulties to diagnose and treat?

The high-grade B-cell lymphomas represent a pathologically and clinically heterogeneous group of mature B-cell malignancies. With modern molecular diagnostics and genomic studies, they are becoming increasingly resolved as we understand more of their shared oncogenic mechanisms. The result has been a realignment of the classification of these tumors, which may initially appear baffling. These tumors are most commonly of large cell morphology but can be of variable high-grade morphology. The double-hit high-grade B-cell lymphomas (HGBLs) that harbor dual translocations of MYC and BCL2 are of a germinal center phenotype and have a homogeneous biology. By contrast, those with dual MYC and BCL6 translocations do not appear to have such a unifying biology. The group of HGBLs not otherwise specified is poorly resolved and not characterized by distinct oncogenic aberrations. Together, the HGBLs may present with aggressive features; respond poorly to R-CHOP, ie, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; and may benefit from intensified induction regimens. However, clinical interpretation is hampered by a paucity of prospective studies. In the relapsed and refractory setting, chimeric antigen receptor T-cell therapy has demonstrated significant efficacy, and there is much expectation for other novel therapeutic approaches, including bispecific antibodies. By understanding the biology and a commitment to collaborative prospective evaluation, their high diagnostic and treatment challenges may be resolved.