Primary CNS Lymphoma

Patho/Etiology
- Rare, aggressive extranodal non-Hodgkin lymphoma confined to the brain, spinal cord, meninges, or eyes.
- Most are Diffuse Large B-cell Lymphoma (DLBCL).
- Strong association with immunosuppression (e.g., HIV/AIDS, post-transplant).
- In immunocompromised patients, it is almost always associated with Epstein-Barr virus (EBV).
Clinical Presentation
- Symptoms depend on tumor location.
- Focal neurologic deficits (e.g., hemiparesis, aphasia) are common (70% of patients).
- Neuropsychiatric symptoms (e.g., personality changes, confusion, memory loss) occur in about 43% of cases.
- Seizures are less common than in other brain tumors.
- Ocular symptoms (e.g., blurry vision, floaters) can occur with intraocular involvement.
Diagnosis
- MRI with contrast is the imaging modality of choice.
  - Immunocompetent: Typically a solitary, intensely and homogeneously enhancing periventricular mass. May cross the corpus callosum.
  - Immunocompromised: Often multiple, ring-enhancing lesions, making it hard to distinguish from toxoplasmosis.
- Stereotactic brain biopsy is the gold standard for definitive diagnosis. Corticosteroids should be withheld before biopsy as they are lymphocytotoxic and can lead to a non-diagnostic ("disappearing") lesion.
- CSF analysis may show malignant lymphocytes; in immunocompromised patients, CSF PCR for EBV DNA is highly specific.
DDx (of a Ring-Enhancing Lesion)
- Brain Abscess: Often has a smoother, thinner ring and a central area of high signal (pus) on DWI.
- Toxoplasmosis: Key differential in HIV+ patients. Usually multiple lesions, often in basal ganglia. Empiric anti-toxo therapy (pyrimethamine/sulfadiazine) is often tried first in this population.
- Glioblastoma: Typically occurs in older, immunocompetent patients; shows irregular, thick-walled ring enhancement with central necrosis.
- Metastases: Often multiple lesions located at the gray-white matter junction; patient usually has a known primary cancer.
Management/Treatment
- High-dose Methotrexate (HD-MTX)-based chemotherapy is the cornerstone of treatment. Rituximab is often added.
- Whole-brain radiation therapy (WBRT) may be used as consolidation but is associated with significant long-term neurotoxicity, especially in older patients.
- Corticosteroids (e.g., dexamethasone) are used to reduce peritumoral edema and symptoms but are not a long-term treatment.
- In younger, fit patients, high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT) may be used for consolidation.
Key Associations/Complications
- Prognosis is generally poor, though it has improved with modern therapies; median survival is now 30-60 months. Untreated, survival is only a few months.
- WBRT-induced neurotoxicity is a major complication, causing dementia, gait instability, and incontinence, particularly in patients >60 years old.
- Relapse is common, occurring in up to 50% of patients within the first two years.