Primary central nervous system lymphoma

Abstract

Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy that affects the brain, spinal cord, leptomeninges, or vitreoretinal space, without evidence of systemic involvement. The diagnosis of PCNSL requires a high level of suspicion because clinical presentation varies depending upon involved structures. Initiation of treatment is time sensitive for optimal neurologic recovery and disease control. In general, the prognosis of PCNSL has improved significantly over the past few decades, largely as a result of the introduction and widespread use of high-dose methotrexate (MTX) chemotherapy, which is considered the backbone of first-line polychemotherapy treatment. Upon completion of MTX-based treatment, a consolidation strategy is often required to prolong duration of response. Consolidation can consist of radiation, maintenance therapy, nonmyeloablative chemotherapy, or myeloablative treatment followed by autologous stem cell transplant. Unfortunately, even with consolidation, relapse is common, and 5-year survival rates stand at only 30% to 40%. Novel insights into the pathophysiology of PCNSL have identified key mechanisms in tumor pathogenesis, including activation of the B-cell receptor pathway, immune evasion, and a suppressed tumor immune microenvironment. These insights have led to the identification of novel small molecules targeting these aberrant pathways. The Bruton tyrosine kinase inhibitor ibrutinib and immunomodulatory drugs (lenalidomide or pomalidomide) have shown promising clinical response rates for relapsed/refractory PCNSL and are increasingly used for the treatment of recurrent disease. This review provides a discussion of the clinical presentation of PCNSL, the approach to work-up and staging, and an overview of recent advancements in the understanding of the pathophysiology and current treatment strategies for immunocompetent patients.

Graphical abstract

Figure 1.

PCNSL imaging pattern on MRI. Characteristic PCNSL imaging features on MRI. (A) T1 sequence with gadolinium contrast (T1c) demonstrates homogenously enhancing lesions affecting the deep white matter. (B) Fluid-attenuated inversion recovery (FLAIR) sequence demonstrates moderate edema surrounding the lesion. (C) Diffusion-weighted imaging sequence (DWI) demonstrates restricted diffusion within the lesions.

Figure 2.

Effects of corticosteroids on imaging in PCNSL and histopathologic features of PCNSL. (A) Hematoxylin and eosin (H&E) staining (10× magnification) of PCNSL demonstrating angiocentric growth pattern and diffusely infiltrating PCNSL cells invading the brain parenchyma. (B) Cells are positive for the B-cell surface marker CD20 (40× magnification).