SOHO State of the Art Updates and Next Questions| Mediastinal Gray-zone Lymphoma: Novel Biologic Insights and Updates on How Best to Approach This Rare Entity.

Abstract

Mediastinal gray zone lymphoma (MGZL) is a very rare aggressive B-cell non-Hodgkin lymphoma characterized by clinical, pathologic, and molecular features that overlap between nodular sclerosis Hodgkin lymphoma (NSHL) and primary mediastinal B-cell lymphoma (PMBL). While these are clinically related lymphomas, recent molecular profiling studies demonstrated similarities between these 3 entities, including alterations in the nuclear factor-κB pathway, JAK2/STAT signaling, copy number alterations in 9p24.1, and immune evasion. In the most recent WHO-5 and ICC classifications, the definition of GZL was restricted to mediastinal GZL (MGZL), which remains as a separate entity between NSHL and PMBL; however, non-mediastinal GZL was classified under diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS). Given the rarity of the disease, evolving definition, and diagnostic challenges, few prospective studies have been undertaken to evaluate treatment outcomes. Response rates and survival with frontline chemotherapy are inferior compared to PMBL, and retrospective studies suggest superiority of dose-intensive regimens compared to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in MGZL. Despite recent therapeutic advancements in PMBL and classical Hodgkin lymphoma (cHL), most clinical trials have excluded patients with MGZL, leading to uncertainty regarding the best therapeutic strategy in both the frontline and relapsed/refractory settings.