Primary CNS Lymphoma (Dense Periventricular Mass & Steroid Washout)

• Seen in two distinct clinical populations (immunocompetent older adults aged 60–75 years and immunocompromised patients aged 30–50 years):
• (1)
  Immunocompetent Individuals: Older adults (peak age 60–80 years, male:female 1.5:1) presenting with subacute cognitive decline, personality changes, progressive lethargy, signs of elevated intracranial pressure (headache, vomiting), and focal neurological deficits.
• (2)
  Immunocompromised Hosts (HIV/AIDS, solid organ transplant recipients): Younger patients (peak age 30–50 years, CD4 count <50 cells/uL) presenting with multifocal necrotic masses, seizures, and rapid clinical deterioration.
• Caused by highly aggressive non-Hodgkin lymphoma arising within and confined strictly to the central nervous system (brain, leptomeninges, eyes, or spinal cord) without systemic disease:
• (1)
  Histopathological Entity: Diffuse Large B-Cell Lymphoma (DLBCL, >95% of cases), composed of monotonous sheets of densely packed malignant lymphoid cells with high nuclear-to-cytoplasmic ratio and brisk mitotic activity.
• (2)
  Anatomical Tropism: Characteristically exhibits 'angiocentric' growth, tracking along perivascular Virchow-Robin spaces, with a predilection for the deep periventricular white matter, corpus callosum, and basal ganglia.
• (3)
  Epstein-Barr Virus (EBV): EBV genome is detected in virtually 100% of immunocompromised CNS lymphomas, driving oncogenesis, whereas immunocompetent PCNSL is typically EBV-negative.

Imaging Findings

• Computed Tomography (CT Head - Non-Contrast & Contrast Protocol):
• –
  Non-Contrast CT Hallmark: Discrete, well-demarcated, single or multiple masses that appear characteristically hyper-attenuating / hyperdense (45–60 HU) relative to normal cerebral cortex, reflecting extreme cellularity, high nuclear-to-cytoplasmic ratio, and minimal interstitial water.
• –
  Contrast Enhancement: Intense, brilliant, homogeneous 'solid' enhancement in immunocompetent patients; irregular, peripheral, ring-like necrotic enhancement in immunocompromised/AIDS patients.
• Magnetic Resonance Imaging (Brain MRI - Diagnostic Gold Standard Framework):
• –
  Periventricular & Deep Gray Predilection: Mass centered directly in the periventricular white matter, corpus callosum, or basal ganglia, often abutting the ependymal lining.
• –
  Restricted Diffusion (High Cellularity Signature):
• 1.
  Uniform, intense restricted diffusion (markedly bright on DWI b=1000, profoundly dark on ADC maps), with ADC values characteristically lower than high-grade glioblastoma or metastases (typically <600–750 x 10^-6 mm2/s).
• –
  T1WI & T2WI Characteristics: Hypointense or isointense to gray matter on T1WI; isointense to slightly hypointense on T2WI (matching high cellular density), surrounded by moderate vasogenic edema on FLAIR.
• –
  Post-Contrast T1WI: Dense, solid, homogeneous 'cotton-wool' or 'sheet-like' enhancement, frequently with ependymal contact or contact with the subarachnoid space ('notch sign').
• –
  Advanced MR Spectroscopy (MRS): Enormous Choline peak, profound Choline/Creatine elevation, marked reduction of NAA, and prominent lipid-lactate peaks.
• –
  DWI / ADC (Diagnostic Hallmark): Demonstrates profound, homogeneous diffusion restriction with markedly low ADC values (typically ADC <600 × 10⁻⁶ mm²/s—lower than glioblastoma or metastasis) due to densely packed lymphoid cells with high nuclear-to-cytoplasmic ratio.
• –
  **SWI / T2* GRE: In immunocompetent patients, PCNSL classically shows absence of intratumoral blooming hemorrhage or calcification on SWI—the presence of prominent blooming microhemorrhages strongly favors glioblastoma** over immunocompetent PCNSL.

Differential Diagnosis

Important Points to Remember

• Diagnostic Pitfall: Administering systemic corticosteroids before obtaining stereotactic biopsy! Primary CNS lymphoma is exceedingly sensitive to corticosteroids ('the ghost tumor' phenomenon). Administration of Dexamethasone induces massive, rapid apoptosis and lysis of neoplastic B-cells, causing the mass to completely vanish on MRI within 48–72 hours. This produces false-negative, non-diagnostic biopsy specimens and delays life-saving chemotherapy. Systemic corticosteroids MUST be strictly withheld until stereotactic biopsy is safely completed, unless impending brain herniation threatens life.
• Crucial Review Areas:
• 1.
  Corpus callosum and periventricular ependymal margins on coronal contrast T1WI for subependymal infiltration and midline crossing.
• 2.
  ADC map: profoundly low ADC values (<750) confirming extreme cellularity (lymphoma signature).
• 3.
  Ophthalmic examination (slit-lamp) to rule out vitreous or retinal involvement (ocular lymphoma, present in 15–20%).
• 4.
  Whole-body CT or PET-CT to definitively exclude systemic systemic non-Hodgkin lymphoma.
• Radiologist Safe Practice & Management:
• 1.
  Strict Steroid-Withholding Protocol: Strictly withhold all systemic corticosteroids until diagnostic stereotactic biopsy has been performed, to prevent diagnostic tumor lysis.
• 2.
  Urgent Stereotactic Core Biopsy: CT-guided or neuronavigation-guided stereotactic needle biopsy to obtain tissue confirmation (avoiding radical surgical debulking, which carries zero survival benefit in PCNSL).
• 3.
  Complete Neuro-Oncological Staging: Contrast-enhanced MRI of the entire neuraxis (brain and whole spine), diagnostic lumbar puncture with CSF flow cytometry, and dedicated ophthalmological slit-lamp examination.
• 4.
  Systemic Body Staging: 18F-FDG PET/CT or contrast CT of the chest, abdomen, pelvis, and bone marrow biopsy to confirm primary CNS versus secondary systemic lymphoma.
• 5.
  High-Dose Methotrexate Induction Chemotherapy: First-line medical therapy with high-dose intravenous Methotrexate-based polychemotherapy (e.g. MATRix regimen), followed by autologous stem cell transplantation (ASCT) or whole-brain radiation therapy (WBRT).