Primary central nervous system lymphoma !

A lymphoma that starts inside the brain, spinal cord, their fluid or the eye, without disease elsewhere; more common when the immune system is weak.

Updated 2026-11-01

Structures involved

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Why it happens

What it is

An aggressive extranodal non-Hodgkin lymphoma confined to the brain, spinal cord, leptomeninges and the vitreous and retina of the eye, with no lymphoma elsewhere in the body. More than 95% of cases are diffuse large B-cell lymphomas, and it typically forms deep masses next to the ventricles.

Who gets it

Rare: it accounts for a few per cent of primary brain tumours and about 1–2% of non-Hodgkin lymphomas. In immunocompetent people it mostly affects adults aged 45 to 70, and its incidence in older adults is rising. In people with advanced HIV it used to be much more frequent and has fallen with antiretroviral therapy; in Colombia and Latin America, late HIV diagnosis keeps the HIV-associated, EBV-driven form relevant, where it competes with cerebral toxoplasmosis in the differential.

Causes

Clonal B cells, usually of the activated B-cell type, that home to the central nervous system; frequent MYD88 and CD79B mutations
Epstein–Barr virus drives almost all cases linked to immunosuppression
Cause unknown in immunocompetent patients

Risk factors

HIV infection with a low CD4 count
Solid organ transplantation and other long-term immunosuppressive therapy
Congenital immunodeficiency and autoimmune disease treated with immunosuppressants
Age over 50–60 in immunocompetent people

Pathophysiology

Malignant B cells cluster around small blood vessels (an angiocentric pattern) in the deep white matter, corpus callosum, basal ganglia and periventricular regions, and can spread along the cerebrospinal fluid and into the vitreous. The masses cause oedema and raise intracranial pressure. Lymphoma cells are very sensitive to glucocorticoids, which kill them quickly: lesions can shrink or vanish on imaging after steroids, and a biopsy taken afterwards may show no tumour.

Classification

Immunocompetent versus immunosuppression-related (HIV, transplant), which is EBV-positive
By compartment: brain parenchyma, leptomeningeal, vitreoretinal (primary intraocular lymphoma) and spinal cord
Histology: diffuse large B-cell lymphoma in nearly all cases; T-cell forms are rare

Symptoms and signs

Subacute focal deficits such as weakness, speech or visual problems
Personality change, confusion, apathy or memory loss (frontal and deep lesions)
Headache, nausea and vomiting from raised intracranial pressure
Seizures, less common than with cortical tumours
Floaters or blurred vision from vitreous involvement
Unsteady gait and incoordination

Diagnosis

Clinical: Suspect it in a patient with weeks of cognitive or focal neurological change and one or more deep, periventricular or callosal enhancing lesions, especially with HIV or a transplant. Steroids are withheld until tissue is obtained unless herniation threatens.
Tests: Stereotactic brain biopsy is the diagnostic test (diffuse large B-cell lymphoma). HIV test; CSF cytology, flow cytometry and protein if a lumbar puncture is safe; EBV DNA in CSF supports the diagnosis in HIV. Slit-lamp and fundus examination, with vitreous sampling if the eye is involved. LDH, blood count and, sometimes, bone marrow biopsy and testicular ultrasound for staging.
Imaging: Contrast MRI of the brain: homogeneously enhancing mass or masses in deep white matter, corpus callosum or around the ventricles, often with restricted diffusion; in HIV lesions are more often multiple and ring-enhancing. MRI of the spine and body PET-CT or CT to exclude systemic lymphoma.

Differential diagnosis

Cerebral toxoplasmosis
Glioblastoma, including butterfly glioma of the corpus callosum
Brain metastases
Brain abscess and progressive multifocal leukoencephalopathy
Tumefactive multiple sclerosis
Secondary CNS involvement by systemic lymphoma

Goal of treatment

Obtain tissue quickly, then induce remission with chemotherapy that crosses the blood–brain barrier and consolidate it, while limiting late neurotoxicity.

Treatment

Medical: Induction with high-dose methotrexate-based combination chemotherapy, usually with rituximab and other agents such as cytarabine or thiotepa; surgical removal is not the treatment because the disease is diffuse.
Procedure: Consolidation with high-dose chemotherapy and autologous stem cell transplantation in fit patients; whole-brain radiotherapy is now used less often because of late cognitive damage.
Medical: In HIV-associated disease, start or optimise antiretroviral therapy; in transplant recipients, reduce immunosuppression where possible.
Follow-up: Nursing priorities during high-dose methotrexate: intravenous hydration, urine alkalinisation, close renal function and drug level monitoring, folinic acid rescue, and neurological checks.

Complications

Raised intracranial pressure and herniation
Relapse in the brain or eye, often within two years
Late leukoencephalopathy and dementia, especially after whole-brain radiotherapy in older adults
Methotrexate toxicity: acute kidney injury, mucositis and myelosuppression
Opportunistic infections

Prognosis

Untreated, survival is only a few months. With methotrexate-based chemotherapy, median survival in trials is several years and a substantial fraction of patients have long remissions; older age, poor performance status, high LDH and CSF protein, deep lesions and HIV worsen the outlook.

Test yourself

Think of the answer, then tap the question to see it.

What is the histological type of most primary CNS lymphomas?

Diffuse large B-cell lymphoma.

Why should glucocorticoids be withheld before biopsy of a suspected primary CNS lymphoma?

They kill lymphoma cells quickly, so lesions may shrink and the biopsy may be non-diagnostic.

Which virus is linked to primary CNS lymphoma in people with HIV?

Epstein–Barr virus.

What is the backbone of induction chemotherapy for primary CNS lymphoma?

High-dose methotrexate.

What is the main differential of a ring-enhancing brain lesion in a person with advanced HIV?

Cerebral toxoplasmosis.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: Primary Central Nervous System Lymphoma Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2025); Primary lymphoma of the brain (MedlinePlus (U.S. National Library of Medicine), 2025).

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Representative model, for educational purposes only.

White matter highlighted on the Durgical 3D model