Primary mediastinal Large B-cell Lymphoma

Abstract

Primary mediastinal large B-cell lymphoma (PMBCL) is a separate entity in the WHO classification based on clinico-pathologic features and a distinct molecular signature which overlaps with nodular sclerosis classical Hodgkin lymphoma (NScHL). Molecular classifiers can distinguish PMBCL from diffuse large B-cell lymphoma (DLBCL) using RNA derived from paraffin-embedded tissue and are integral to future studies. However, given that ~5% of DLBCL can have a 'molecular' PMBCL phenotype in the absence of mediastinal involvement, clinical information will remain critical for diagnosis. Studies over the last 10-20 years have elucidated the biologic hallmarks of PMBCL which are reminiscent of cHL, including the importance of JAK-STAT and NFKB signaling pathways as well as an immune evasion phenotype through multiple converging genetic aberrations. The outcome of PMBCL has improved in the modern rituximab era, however controversies remain whether there is a single standard treatment for all patients and when to integrate radiotherapy. Regardless of the frontline therapy, refractory disease can occur in up to 10% of patients and correlates with poor outcome. With emerging data supporting high efficacy of PD1 inhibitors in PMBCL, studies are underway integrating them into the up-front setting.