Primary CNS Lymphoma: Diagnosis, Treatment and Prognosis — Overview, Diagnosis & Treatment Options | MyMedicPlus

Primary CNS lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma confined to the brain, spinal cord, eyes (vitreoretinal lymphoma), or leptomeninges without systemic involvement. Approximately 1,500 new cases occur per year in the US. DLBCL subtype accounts for approximately 95% of immunocompetent patients.

Immunosuppression is the primary risk factor: HIV/AIDS, post-transplant immunosuppression (EBV-driven lymphomagenesis), and congenital immunodeficiency syndromes. In immunocompetent patients, MYD88 L265P and CD79B mutations are the dominant oncogenic drivers. Peak incidence occurs in the sixth and seventh decades.

Focal neurological deficits (hemiparesis, aphasia, cerebellar ataxia), cognitive decline, personality changes, seizures, headache, and visual disturbances (in ocular involvement, approximately 20% of cases). Symptoms progress rapidly over days to weeks, unlike slower-growing primary brain tumors.

MRI brain shows homogeneously enhancing periventricular mass (often multiple). CSF cytology, flow cytometry, and IL-10 level (elevated in PCNSL). Slit-lamp examination for vitreoretinal lymphoma. Stereotactic brain biopsy for tissue — critically, avoid corticosteroids before biopsy as they cause rapid lymphoma lysis and may render biopsy non-diagnostic. HIV testing. MYD88/CD79B testing on biopsy or CSF.

Induction: high-dose methotrexate (HD-MTX at 3-3.5 g/m2) plus rituximab, with or without temozolomide, cytarabine, or thiotepa in various regimens (MR, MATRix, CALGB). Consolidation for fit patients: autologous SCT (preferred over whole-brain radiotherapy to avoid neurotoxicity). WBRT reserved for patients ineligible for SCT. Maintenance: temozolomide or rituximab in some protocols.

With HD-MTX-based induction and autologous SCT consolidation: median OS approximately 5-10 years in younger patients. CR to induction: 5-year OS approximately 40-50%. WBRT as consolidation causes significant neurotoxicity (dementia, gait disturbance) especially in patients over 60 years. HIV-positive PCNSL: prognosis markedly worse, dependent on antiretroviral response.