Primary brain lymphomas, a type of primary central nervous system lymphoma, originate in neural tissue and are usually B-cell tumors. Diagnosis requires neuroimaging and sometimes cerebrospinal fluid analysis (including Epstein-Barr titers) or brain biopsy. Treatment includes glucocorticoids, chemotherapy, and radiation therapy.
Primary brain lymphomas account for only 3 to 4% of intracranial tumors, although incidence among older adults has been increasing over the past few decades; the median age of presentation is 65 years with a slightly greater incidence in men (1). Lymphomas tend to infiltrate the brain diffusely, often as multicentric masses adjacent to the ventricles, but may occur as solitary brain masses. Lymphomas may also occur in the meninges, uvea, or vitreous humor. Most are B-cell tumors, often immunoblastic. The Epstein-Barr virus may contribute to development of lymphomas in immunocompromised patients. Most patients do not develop subsequent systemic lymphoma.
General reference
1. de Koning ME, JJ, Jansen C, Doorduijn JK, Bromberg JEC, van der Meulen M. Primary central nervous system lymphoma. J Neurol. 2024;271(5):2906-2913. doi:10.1007/s00415-023-12143-w
Diagnosis of Primary Brain Lymphomas
MRI
Cerebrospinal fluid (CSF) analysis or biopsy
Magnetic resonance imaging can help differentiate primary CNS lymphoma from other intracranial pathology based on T2-weighted hyperintensity, diffuse contrast enhancement, and diffusion restriction. 18-FDG PET is used to differentiate primary CNS lymphoma from systemic lymphoma secondarily seeding the brain.
CSF must be examined to exclude lymphomatous meningitis if there is gadolinium enhancement on MRI or if clinical examination detects evidence of meningeal signs, particularly if cranial neuropathies are detected. Epstein-Barr virus DNA may be detected in CSF. If CSF does not contain lymphoma cells or Epstein-Barr virus DNA, guided-needle or open biopsy is required. Because lymphoma is initially highly sensitive to glucocorticoids, these medications should not be given to patients with suspected CNS lymphoma before biopsy (unless acute clinical deterioration requires it) because of the potential for a false negative biopsy.
Staging of primary brain lymphomas involves imaging of the chest, abdomen, and pelvis; slit-lamp examination of the eye; and bone marrow biopsy to determine if and where the tumor has spread.
Treatment of Primary Brain Lymphomas
Glucocorticoids
Chemotherapy
Radiation therapy
Glucocorticoids result in rapid improvement initially, but responses are not durable; primary brain lymphomas typically recur. There is no role for surgical excision except when herniation is impending. Multidrug chemotherapy regimens including high-dose IV methotrexate may result in long-lasting responses. The addition of consolidation chemotherapy, consolidation whole-brain radiation therapy, or high-dose chemotherapy with stem-cell rescue may improve survival (Glucocorticoids result in rapid improvement initially, but responses are not durable; primary brain lymphomas typically recur. There is no role for surgical excision except when herniation is impending. Multidrug chemotherapy regimens including high-dose IV methotrexate may result in long-lasting responses. The addition of consolidation chemotherapy, consolidation whole-brain radiation therapy, or high-dose chemotherapy with stem-cell rescue may improve survival (1).
Whole-brain radiation can cause clinically significant leukoencephalopathy, particularly in older patients. This effect may be exacerbated by methotrexate.Whole-brain radiation can cause clinically significant leukoencephalopathy, particularly in older patients. This effect may be exacerbated by methotrexate.
Median 5-year survival is approximately 30 to 38% (2). Survival is higher among younger than older patients (3).
Treatment references
1. de Koning ME, Hof JJ, Jansen C, Doorduijn JK, Bromberg JEC, van der Meulen M. Primary central nervous system lymphoma. J Neurol. 2024;271(5):2906-2913. doi:10.1007/s00415-023-12143-w
2. Lv C, Wang J, Zhou M, et al. Primary central nervous system lymphoma in the United States, 1975-2017. Ther Adv Hematol. 13:20406207211066166 2022. doi: 10.1177/20406207211066166
3. Tang D, Chen Y, Shi Y, et al. Epidemiologic characteristics, prognostic factors, and treatment outcomes in primary central nervous system lymphoma: A SEER-based study. Front Oncol. 12:817043, 2022. doi: 10.3389/fonc.2022.817043
Drug Information for the Topic
