Primary central nervous system lymphoma

Abstract

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal non-Hodgkin lymphoma (NHL), confined to the brain, eyes, spinal cord or leptomeninges without systemic involvement. Overall prognosis, diagnosis and management of PCNSL differ from other types of NHL. Prompt diagnosis and initiation of treatment are vital to improving clinical outcomes. PCNSL is responsive to radiation therapy, however whole-brain radiotherapy (WBRT) inadequately controls the disease when used alone and its delayed neurotoxicity causes neurocognitive impairment, especially in elderly patients. High-dose methotrexate (HD-MTX)-based induction chemotherapy with or without autologous stem cell transplantation (ASCT) or reduced-dose WBRT leads to durable disease control and less neurotoxicity. The optimal treatment has yet to be defined, however HD-MTX-based induction chemotherapy is considered standard for newly diagnosed PCNSL. Ongoing randomized trials address the role of rituximab, and of consolidative treatment using ASCT or reduced-dose WBRT. Despite high tumor response rates to initial treatment, many patients have relapsing disease with very poor prognosis. The optimal treatment for refractory or relapsed PCNSL is poorly defined. The choice of salvage treatment depends on age, previous treatment and response, performance status and comorbidities at the time of relapse. Novel therapeutics targeting underlying tumor biology include small molecule inhibitors of B-cell receptor, cereblon, and mammalian target of rapamycin signaling, and immunotherapy programmed cell death 1 receptor inhibitors and chimeric antigen receptor T cells.

Keywords: autologous stem cell transplantation; methotrexate primary central nervous system lymphoma; rituximab; whole brain radiation therapy.

Figure 1.

Brain magnetic resonance imaging (MRI) of two patients (a–c, d and e) with primary central nervous system lymphoma (PCNSL): (a) axial fluid-attenuated inversion recovery (FLAIR) sequence demonstrating a hypointense lesion surrounded by hyperintense edema; (b) axial, T1-weighted, contrast-enhanced sequence with intense homogeneous contrast enhancement; (c) diffusion-weighted axial sequence showing bright signal in the lesion, indicating restricted diffusion. (d, e) Axial and coronal T1-weighted, contrast-enhanced sequences revealing multifocal contrast-enhanced PCNSL lesions. (Courtesy of Martin Bendszus, M.D., Division of Neuroradiology, University of Heidelberg.)