Why does primary central nervous system (CNS) lymphoma appear hypointense on T1-weighted magnetic resonance imaging (MRI) and hyperintense on T2-weighted MRI?

MRI Characteristics of Primary CNS Lymphoma

Primary CNS lymphoma (PCNSL) typically appears hypointense on T1-weighted MRI and hyperintense on T2-weighted MRI due to its dense cellularity, high nuclear-to-cytoplasmic ratio, and disruption of normal brain architecture.

Key MRI Features of PCNSL

Signal Characteristics

• T1-weighted images: Hypointense or isointense 1, 2, 3
• T2-weighted images: Variable appearance, but often hyperintense 4
  • Approximately 40% are hyperintense on T2-weighted images 2
  • Some lesions may appear isointense to hypointense on T2 due to high cellularity 1, 5

Other Imaging Characteristics

• Diffusion-weighted imaging (DWI): Shows restricted diffusion with reduced ADC values due to high cellularity 1, 3
• Enhancement pattern: Strong homogeneous enhancement after contrast administration 1
• Edema: Variable surrounding edema 1
• Location: Most commonly found in:
  • Frontal lobe and brain hemispheres (38%)
  • Periventricular regions (12%)
  • Thalamus or basal ganglia (16%)
  • Corpus callosum (14%) 1

Pathophysiological Basis for MRI Appearance

The hypointense appearance on T1-weighted images occurs because:

• High cellular density of lymphoma cells
• Disruption of normal brain parenchyma
• Relatively low fat content in lymphoma tissue

The hyperintense appearance on T2-weighted images is due to:

• Increased water content in the tumor
• Disruption of normal tissue architecture
• Associated vasogenic edema

Differential Diagnosis

Several conditions may have similar MRI appearances:

• High-grade gliomas: Usually more heterogeneous with irregular enhancement 3
• Tumefactive demyelinating lesions: Typically have incomplete ring enhancement 3
• Brain metastases: Often multiple, located at gray-white matter junction 4
• Progressive multifocal leukoencephalopathy: Typically non-enhancing 4

Diagnostic Pitfalls

1. Prior corticosteroid administration: Can dramatically reduce enhancement and lead to false-negative biopsies 1
2. Atypical presentations: Occur in approximately 25% of cases, leading to diagnostic delays 1
3. Immunocompromised patients: May present with multiple lesions, hemorrhage, and necrosis 3

Diagnostic Recommendations

• Contrast-enhanced cranial MRI is the recommended imaging modality for patients with suspected PCNSL 1
• The International PCNSL Collaborative Group (IPCG) protocol using 3T or 1.5T MRI is recommended 1
• Avoid corticosteroid administration before biopsy whenever clinically possible 1
• Stereotactic biopsy remains the gold standard for definitive diagnosis 1, 3

Advanced MRI techniques such as MR spectroscopy, perfusion imaging, and metabolic imaging (FDG-PET) may provide additional diagnostic information in challenging cases 6.