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Primary mediastinal large B-cell lymphoma (PMBCL) is an aggressive B-cell lymphoma arising from thymic B-cells having clinicopathologic features distinct from systemic diffuse large B-cell lymphoma (DLBCL). PMBCL comprises 2% to 4% of all non-Hodgkin lymphomas (NHL), 7% of DLBCL and seen predominantly in young females with a median age of 35 years at diagnosis. The annual incidence of PMBCL is 0.4 per million with a 5-year survival rate exceeding 70% with improving supportive care and genetic characterization of the disease. Pathogenesis involves dysregulation of Janus kinase-signal transducer and activator of transcription (JAK-STAT), nuclear factor-kB (NF-kB) pathways and amplification of the 9p24.1 region of chromosome 9. PMBCL patients have a prolonged life expectancy necessitating the need for treatment approaches that are based on maximizing cure with minimal long-term toxicity. Due to rarity and its recognition as a distinct entity, therapeutic decisions are guided by clinical presentation, clinician and center experience, and analysis of patients with PMBCL within DLBCL registries. Historically R-CHOP has been the usual first line treatment for PMBCL followed by involved site radiotherapy (ISRT), however clinical practice varies across centers with emerging consensus to avoid upfront RT by utilizing dose intense regimens (DA-EPOCH-R) in younger and fit patients. Prognosis of relapsed refractory PMBCL not responding to salvage chemotherapy is dismal, however there are many emerging options including Brentuximab Vedotin, immune check point inhibitors and chimeric antigen receptor T-cell therapy. In this article, we focus on the pathogenesis, current and evolving treatments, and provide recommendations for optimal management of patients with PMBCL., (Copyright © 2021. Published by Elsevier Inc.)

Background: Invasion of CNS in MM is an extremely rare occurrence that is associated with advanced disease with poor prognosis., Patients and Methods: Our MM database identified 35 CNS MM cases presenting between January 1996 and March 2012. Descriptive analyses were performed on available data on patient characteristics, disease course, and outcomes., Results: The mean age at diagnosis was 55.4 years; 23.5% (n = 8) patients had elevated levels of beta-2-microglobulin > 5.5 mg/L; 68.6% (n = 24) of patients had elevated lactate dehydrogenase (LDH) levels (≥ 2 times upper limit of normal); and 14% (n = 5) of patients had secondary plasma cell leukemia. Magnetic resonance imaging (MRI), which was performed in 34 patients, showed diffuse or localized leptomeningeal disease in 20 patients (58.8%). Monoclonal malignant plasma cells were found by CSF analysis in all 35 patients. In total, 31 patients received chemotherapy, including intrathecal chemotherapy as a part of their treatment, with a median survival of 4 months after CNS MM diagnosis., Discussion: In our experience, CNS MM is an aggressive terminal disease feature associated with high beta-2-microglobulin level, high LDH level, and secondary plasma cell leukemia. This study highlights an unmet need in this subset of patients with high-risk, relapsed or refractory MM., Conclusion: Achieving adequate CSF penetration while limiting the off-target effects needs to be considered in MM-specific novel drug development., (Copyright © 2014 Elsevier Inc. All rights reserved.)