Systemic lymphoma spreads to the CNS in about 10% of cases, most commonly in the setting of advanced or relapsing disease . Certain sites of systemic disease are more likely to seed the CNS: the testis, bone marrow, bone, orbit, peripheral blood and paranasal sinuses.
Propensity to spread to the CNS also varies with histologic subtype. Low-grade lymphomas rarely metastasize to the brain. Most metastases are diffuse large-cell or high-grade lymphomas. High-grade histology, elevated LDH levels, advanced disease and symptoms such as fever, sweats and weight loss are predictive of CNS relapse.
CNS involvement by secondary lymphoma is usually leptomeningeal; the parenchyma is rarely involved. The clinical presentation of secondary CNS lymphoma reﬂects the predominantly leptomeningeal disease. Symptoms and signs typically include headache, altered mental status, meningismus and cranial or spinal neuropathy.
Leptomeningeal involvement by lymphoma is best visualized with contrast-enhanced MRI. Given the common meningeal involvement in secondary CNS lymphoma, CSF cytology is more frequently positive than in primary CNS lymphoma. CSF may be positive in up to 70% of cases . The combination of abnormal brain imaging and CSF findings in the setting of progressive or relapsing systemic lymphoma makes biopsy for diagnosis unnecessary.
Choice of therapy for secondary cerebral lymphoma must consider both the systemic and cerebral disease. Frequently, the combination of systemic and intrathecal chemotherapy is chosen. Whole-brain radiation and the drugs given for primary CNS lymphoma are also used frequently. Response to therapy, as reﬂected by clinical remission of CNS disease, is a favorable prognostic sign .
The prognosis for patients with secondary cerebral lymphoma is poor. Fewer than 15% survive for 1 year. Progressive systemic disease is the usual cause of death. Cerebral involvement is often used as an indicator of the extent of systemic disease. It rarely independently worsens the outcome.
Patients at high risk for CNS involvement, such as those with high-grade lymphomas, warrant prophylactic treatment. Intrathecal methotrexate (the agent most frequently used) reduces the incidence of cerebral metastasis .