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Primary CNS lymphoma

Summary

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  • Rare, aggressive non-Hodgkin lymphoma confined to the CNS
  • Typically presents with focal neurological deficits, cognitive changes, or seizures
  • Characteristic imaging findings include homogeneous enhancement and restricted diffusion1

Pathophysiology

  • Most cases are diffuse large B-cell lymphomas (DLBCL)
  • Arises from malignant transformation of lymphocytes within the CNS
  • Exact etiology unknown, but associated with immunosuppression (e.g., HIV, organ transplantation)
  • Disruption of blood-brain barrier allows for tumour growth and invasion

Demographics

  • Accounts for 1-2% of all non-Hodgkin lymphomas
  • Median age at diagnosis: 65 years
  • Male to female ratio: 1.2-1.7:1
  • Higher incidence in immunocompromised individuals

Diagnosis

  • Clinical presentation:
    • Focal neurological deficits (70%)
    • Neuropsychiatric symptoms (43%)
    • Increased intracranial pressure (33%)
    • Seizures (14%)
  • Laboratory findings:
    • CSF analysis: elevated protein, low glucose, lymphocytic pleocytosis
    • Serum LDH often elevated
  • Definitive diagnosis:
    • Stereotactic brain biopsy
    • Flow cytometry and immunohistochemistry to confirm B-cell origin

Imaging

  • CT:
    • Hyperdense lesions with moderate to marked enhancement
    • Minimal surrounding oedema
  • MRI:
    • T1: hypointense to isointense
    • T2/FLAIR: iso to hyperintense
    • Diffusion-weighted imaging: restricted diffusion
    • Contrast-enhanced T1:
    • Homogeneous enhancement
    • "Butterfly" pattern in corpus callosum lesions
  • PET/CT:
    • High FDG uptake in lesions
    • Useful for staging and treatment response assessment

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  • 70-year-old patient presented with a 3 week history of headaches.
  • CT showed a grossly enlarged and subtly hyperattenuating splenium.
  • On MRI, the lesion enhanced homogeneously with diffusion restriction.

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  • A 70-year-old patient presented with confusion and visual disturbance.
  • CT showed a hyperdense lesion involving the parietal white matter and corpus callosum.
  • Relative hypointensity on T2 and low values on ADC also indicated hypercellularity.
  • Alongside confluent avid enhancement, the imaging was typical for the final diagnosis of PCNSL.

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  • A 40-year-old patient presented with agitation and aggressive behaviour.
  • MRI showed multiple lesions, some of which caused diffusion restriction (internal capsules) and some of which enhanced (right hemipons).
  • A diagnosis was not secured even after extensive investigation. The lesions responded to a trial of steroid therapy.
  • 3 years later, the patient presented following a seizure. MRI showed marked progression with an infiltrative and enhancing lesion in the brainstem and new frontal lobe lesions.
  • Biopsy of a right frontal lesion revealed a diffuse large B-cell lymphoma, which again showed a response to therapy.

Treatment

  • High-dose methotrexate-based chemotherapy (± rituximab). Crucially, corticosteroids can transiently "melt away" the lesion, so biopsy should ideally precede steroids

Differential diagnosis

Differential Diagnosis Differentiating Feature
Glioblastoma Typically has more heterogeneous enhancement and necrosis on MRI
Metastatic brain tumour Often multiple lesions at the grey-white matter junction; ring or nodular enhancement; surrounding vasogenic oedema
Toxoplasmosis Ring-enhancing lesions in basal ganglia and at grey-white matter junction; restricted diffusion in centre
Multiple sclerosis Typically smaller lesions, periventricular distribution
Acute disseminated encephalomyelitis More diffuse, bilateral, asymmetric white matter involvement; grey matter involvement common; no restricted diffusion typically
Cerebral abscess Ring-enhancing lesion with restricted diffusion on DWI
Subacute infarct Follows arterial vascular territory; gyral enhancement pattern; no restricted diffusion in subacute phase
Tumefactive demyelination Incomplete ("open ring") enhancement pattern; less mass effect relative to lesion size; no DWI restriction
Neurosarcoidosis Leptomeningeal and perivascular enhancement; cranial nerve involvement; no corpus callosum or periventricular predilection
Progressive multifocal leukoencephalopathy Asymmetric subcortical white matter lesions without enhancement; U-fibre involvement; no mass effect

  1. Calimeri et al. Molecular diagnosis of primary CNS lymphoma in 2024 using MYD88(Leu265Pro) and IL-10. 2024. The Lancet. Haematology - Open in new tab. ↩