From the Guidelines
Yes, non-Hodgkin's lymphoma (NHL) can metastasize to the brain, and this is a significant concern in patients with high-risk NHL subtypes. This is known as secondary central nervous system (CNS) lymphoma and occurs in approximately 5-10% of NHL cases [ 1 ]. Certain NHL subtypes have a higher risk of CNS involvement, particularly aggressive variants like diffuse large B-cell lymphoma (especially with high-risk features), Burkitt lymphoma, lymphoblastic lymphoma, and mantle cell lymphoma. The metastasis typically occurs through direct spread via the bloodstream or through the cerebrospinal fluid. Symptoms of brain metastasis may include headaches, neurological deficits, seizures, personality changes, or cognitive impairment.
For patients with high-risk NHL subtypes, CNS prophylaxis with intrathecal chemotherapy (such as methotrexate or cytarabine) or systemic agents that cross the blood-brain barrier may be recommended [ 1 ]. The appropriate intravenous (IV) methotrexate dose to achieve therapeutic levels in the CNS is controversial, but IV methotrexate doses ≥3 g/m² appear to produce therapeutic levels in CSF and parenchyma [ 1 ]. Treatment for established CNS lymphoma typically involves high-dose methotrexate-based regimens, often in combination with other CNS-penetrating agents, and sometimes radiation therapy.
Early detection through cerebrospinal fluid analysis or brain imaging is important in high-risk patients, as CNS involvement significantly impacts prognosis and treatment approach [ 1 ]. The integration of systemic therapies with appreciable activity in the CNS should be considered in all patients with CNS involvement, either in addition to or in lieu of treatment with radiotherapy and intrathecal therapies [ 1 ]. However, the optimal timing for systemic therapy change vis-à-vis local therapies is less clear, and a better understanding of which combinations of intrathecal, radiation, and systemic therapies will achieve maximal synergistic antitumor activity while minimizing toxicities is a critically important question that warrants further investigation [ 1 ].
From the Research
Non-Hodgkin's Lymphoma and Brain Metastasis
- Non-Hodgkin's lymphoma can metastasize to the brain, with studies indicating that central nervous system (CNS) involvement occurs in a significant proportion of patients 2, 3, 4, 5.
- The incidence of CNS involvement varies depending on the histology of the lymphoma, with diffuse histology having a higher incidence than nodular lymphoma 4.
- CNS involvement can occur at any time during the course of the disease, including at initial diagnosis, during relapse, or while the patient is in clinical remission 2, 3, 4, 5.
- The risk of CNS invasion is greatest for patients with lymphoblastic lymphoma, and those with involvement of the testes, peripheral blood, or epidural space of the spinal cord 5.
- Cerebrospinal fluid (CSF) cytology is an important diagnostic tool for detecting CNS involvement, with a positive CSF cytology indicating the presence of malignant cells in the CNS 2, 3, 4.
Treatment and Prognosis
- Treatment of CNS lymphoma typically involves a combination of chemotherapy and radiation therapy, with intrathecal chemotherapy and whole-brain irradiation being common approaches 2, 3, 5.
- The prognosis for patients with CNS lymphoma is generally poor, with a median survival time of several months 3, 4, 5.
- However, some patients may achieve long-term disease-free survival with aggressive treatment, and CNS prophylaxis may be beneficial for high-risk patients 2, 3, 4, 5.
- A case study of primary central nervous system lymphoma (PCNSL) highlights the importance of extensive workup and diagnosis, as well as the use of high-grade methotrexate-based chemotherapy as a treatment option 6.