Primary central nervous system (CNS) lymphoma is a rare, aggressive extranodal non-Hodgkin lymphoma confined to the brain, eyes, CSF, or spinal cord without systemic, non-CNS involvement. This article reviews the clinical presentation, imaging characteristics, diagnostic workup, novel pathophysiologic insights, and treatment of immunocompetent patients with primary CNS lymphoma.
The prognosis of primary CNS lymphoma has significantly improved over the past few decades because of the introduction of and widespread use of high-dose methotrexate, which is now the backbone of all first-line combination chemotherapy treatments. Despite this progress, durable remission is still observed in only approximately 50% of patients. Novel insights into the pathophysiology of primary CNS lymphoma have identified the B-cell receptor pathway as well as the suppressed tumor immune microenvironment and immune evasion as key mechanisms in the pathogenesis of primary CNS lymphoma. Novel, small molecules and agents targeting these aberrant pathways have been introduced into clinical trials of recurrent/refractory primary CNS lymphomas. Agents such as the Bruton tyrosine kinase (BTK) inhibitor ibrutinib or immunomodulatory drugs such as lenalidomide and pomalidomide have shown promising response rates in the relapsed setting.
Diagnosis of primary CNS lymphoma requires a high level of suspicion because clinical signs and deficits can vary and depend on the involved CNS compartments. Rapid initiation of therapy is essential for recovery and prognosis. The optimal treatment regimen has not been defined, but methotrexate-based chemotherapy regimens are considered the standard treatment approach for induction treatment. Novel, targeted agents have recently been introduced into the therapeutic arsenal.