Primary central nervous system (CNS) lymphoma is an aggressive non-Hodgkin lymphoma arising from the brain parenchyma, leptomeninges, eyes, or spinal cord without systemic involvement. Over 95% of cases are diffuse large B-cell lymphoma (DLBCL) subtype. In immunocompetent patients, it typically occurs between ages 50-70 with characteristic periventricular involvement. In immunosuppressed patients (HIV, transplantation), it may present at younger ages with multiple lesions. The triad of homogeneous enhancement, marked DWI restriction (high cellularity), and periventricular location on MRI are the most characteristic findings. Transient dramatic regression with corticosteroid treatment ('ghost tumor' phenomenon) is a diagnostic clue.
Age Range
50-80
Peak Age
65
Gender
Male predominant
Prevalence
Uncommon
The pathogenesis of primary CNS lymphoma is based on clonal proliferation of B lymphocytes within the brain parenchyma that are not normally present in the CNS. Tumor cells accumulate in periventricular regions and subependymal areas — this location preference stems from periventricular lymphatic drainage pathways and vascular permeability characteristics of the subependymal area. High nuclear-to-cytoplasmic ratio and dense cellular packing form the basis of marked diffusion restriction on DWI — tightly packed tumor cells narrow the extracellular space, restricting water diffusion. The dramatic response to corticosteroids (ghost tumor phenomenon) results from lymphocyte susceptibility to glucocorticoid receptor-mediated apoptosis; cell death and repair of the blood-brain barrier with steroid treatment leads to transient loss of enhancement. However, tumor cells are not completely eliminated and the lesion becomes visible again when steroids are discontinued.
The triad of intensely homogeneously enhancing periventricular lesion + marked diffusion restriction on DWI (low ADC) + low-intermediate rCBV on perfusion MRI (enhancement-perfusion dissociation) is considered diagnostic with high specificity for primary CNS lymphoma. This triad provides >90% accuracy in differentiating from the most important differential diagnoses including glioblastoma (high rCBV), metastasis (heterogeneous enhancement), and toxoplasmosis (ring enhancement, DWI negative center).
On non-contrast CT, primary CNS lymphoma typically appears hyperdense relative to brain parenchyma. This hyperdensity reflects the tumor's high cellularity (high nuclear-to-cytoplasmic ratio, dense cellular packing). Located in periventricular or deep brain structures (basal ganglia, thalamus, corpus callosum). Calcification and significant necrosis are rare in immunocompetent patients. Moderate vasogenic edema may be seen in surrounding parenchyma. Hypodense center (necrosis) may be present in immunosuppressed patients.
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On non-contrast CT, a hyperdense mass relative to brain parenchyma is identified in the periventricular region with mild-moderate vasogenic edema in the surrounding parenchyma.
On T1-weighted images, primary CNS lymphoma appears isointense or slightly hypointense relative to gray matter. Signal tends to be homogeneous due to dense cellular structure. Internal structure is homogeneous as necrosis is rare in immunocompetent patients. In immunosuppressed patients, intratumoral necrosis may create heterogeneous signal on T1. Corpus callosum involvement and ependymal spread can be evaluated on T1.
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On T1-weighted sequence, a homogeneous iso- to hypointense mass relative to gray matter is identified in the periventricular region.
On T2-weighted images, primary CNS lymphoma appears isointense or slightly hypointense relative to gray matter — showing lower T2 signal unlike most other brain tumors (generally T2 hyperintense). This finding reflects the tumor's high cellularity and dense cellular packing (low free water content) and is an important clue for differentiating lymphoma from high-grade tumors like glioblastoma. Perilesional vasogenic edema appears hyperintense on T2. Necrotic areas may appear hyperintense on T2 in immunosuppressed patients.
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On T2-weighted sequence, the periventricular mass shows iso- to hypointense signal relative to gray matter suggesting high cellularity, with accompanying vasogenic edema in surrounding parenchyma.
On DWI, primary CNS lymphoma shows marked diffusion restriction: high signal on DWI and low signal on ADC map. ADC values are typically 0.4-0.7 × 10⁻³ mm²/s and significantly lower than other intracranial tumors (glioblastoma ADC: 0.8-1.2 × 10⁻³ mm²/s). This finding reflects the tumor's high cellularity and dense cellular packing. DWI is the most valuable sequence for differentiating lymphoma from glioblastoma, toxoplasmosis, and metastasis. Minimum ADC values correlate with tumor grade and treatment response.
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On DWI, the periventricular mass shows marked diffusion restriction with low signal on ADC map, consistent with high cellularity and characteristic for lymphoma.
On contrast MRI, primary CNS lymphoma shows intense homogeneous enhancement in immunocompetent patients — one of the most prominent enhancement patterns of cellular tumors. Enhancement pattern reflects the tumor's disrupted blood-brain barrier and high vascular permeability. In immunosuppressed patients (HIV/AIDS), ring enhancement is more common (due to central necrosis). Ependymal spread may appear as subependymal enhancing linear pattern. Multifocal lesions are seen in 20-40% of cases. Enhancement may dramatically decrease or disappear after steroids (ghost tumor).
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On post-contrast T1-weighted sequence, the periventricular mass shows intense homogeneous enhancement, characteristic for primary CNS lymphoma.
On FLAIR, primary CNS lymphoma shows iso- to hyperintense signal. Perilesional vasogenic edema appears markedly hyperintense on FLAIR and is valuable for delineating tumor margins. Ependymal spread and subependymal infiltration may be detected more sensitively on FLAIR compared to contrast sequences. Spread along the corpus callosum and periventricular infiltration are prominent on FLAIR.
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On FLAIR, the periventricular mass shows iso- to hyperintense signal with prominent vasogenic edema in the surrounding parenchyma.
On perfusion MRI (DSC), primary CNS lymphoma shows low to intermediate rCBV values — this characteristic dissociation (enhancement-perfusion dissociation) showing low perfusion despite intense enhancement is one of lymphoma's most distinguishing findings. While glioblastoma and metastasis show high rCBV with intense enhancement, lymphoma shows low rCBV because the tumor does not exhibit neoangiogenesis (new vessel formation) — it uses existing brain vasculature with only increased permeability. This dissociation is the most valuable perfusion MRI finding for differentiating lymphoma from glioblastoma, with >90% diagnostic accuracy.
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On perfusion MRI, the periventricular mass shows low-intermediate rCBV values despite intense enhancement, and this 'enhancement-perfusion dissociation' is characteristic for primary CNS lymphoma.
On MR spectroscopy, primary CNS lymphoma shows prominent choline elevation (increased membrane turnover), decreased NAA (neuronal damage), and elevated lipid/lactate peaks. Cho/Cr ratio is typically >2.5. Lipid peaks reflect cell membrane destruction, lactate reflects anaerobic metabolism. High choline + high lipid combination may overlap with glioblastoma, but Cho/Cr ratio is generally higher in lymphoma.
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On MR spectroscopy, prominent choline elevation (Cho/Cr >2.5), decreased NAA, and elevated lipid/lactate peaks are detected within the mass, consistent with high-grade tumor.
Criteria
In HIV-negative, immunocompetent patient. Typically age 50-70. Single or few (1-3) lesions. Periventricular, basal ganglia, or corpus callosum location. Homogeneous enhancement, marked DWI restriction. Necrosis is rare.
Distinct Features
Corticosteroid response is pronounced (ghost tumor). Standard treatment: high-dose methotrexate-based chemotherapy + rituximab. Radiotherapy may be used for consolidation. 5-year survival 50-70%.
Criteria
In setting of HIV/AIDS, organ transplantation, or chronic immunosuppression. Strong EBV association (80-90%). Younger age (30-40). Multiple lesions are common. Ring enhancement and central necrosis are characteristic. Differentiation from toxoplasmosis is critical.
Distinct Features
Toxoplasma differentiation: Lymphoma shows central DWI restriction, toxoplasmosis does not show central restriction. Thallium-201 SPECT or FDG-PET positive in lymphoma, negative in toxoplasmosis. Trial treatment: anti-toxoplasmosis therapy 2 weeks → biopsy if no response. Prognosis worse than immunocompetent type.
Criteria
Rare variant. Tumor cells proliferate within vascular lumens (does not form extravascular mass). MRI shows multifocal, bilateral, nonspecific white matter lesions. Multiple small foci of diffusion restriction on DWI (tumor emboli in microvasculature). Enhancement pattern is variable.
Distinct Features
Clinical presentation is atypical — encephalopathy, stroke-like episodes, cognitive impairment. Imaging findings are nonspecific; diagnosis is usually made by biopsy. May be confused with vasculitis, demyelinating disease, and ischemic lesions. Prognosis is poor.
Distinguishing Feature
Glioblastoma shows heterogeneous enhancement (ring pattern, necrotic center), high rCBV (neoangiogenesis). Lymphoma enhances homogeneously, shows low rCBV (enhancement-perfusion dissociation). T2 signal is heterogeneous in glioblastoma, iso- to hypointense in lymphoma.
Distinguishing Feature
Toxoplasmosis shows ring enhancement in immunosuppressed patient (similar to lymphoma), but does not show central diffusion restriction on DWI (central restriction is positive in lymphoma). Thallium-201 SPECT and FDG-PET negative in toxoplasmosis, positive in lymphoma. 'Eccentric target sign' may be seen in toxoplasmosis.
Distinguishing Feature
Metastasis is typically at gray-white matter junction, multiple, with heterogeneous enhancement and prominent perilesional edema. Lymphoma is periventricular with homogeneous enhancement and relatively less edema. Known primary malignancy history in metastasis. Metastasis shows high rCBV on perfusion MRI.
Distinguishing Feature
Brain abscess shows ring enhancement and bright central signal on DWI (viscous purulent content) — lymphoma also has central DWI restriction but abscess ADC values are lower. Prominent vasogenic edema surrounding abscess and 'dual rim sign' on SWI are distinguishing. Clinical infection findings (fever, leukocytosis) accompany abscess.
Urgency
urgentManagement
chemotherapy (high-dose methotrexate-based)Biopsy
NeededFollow-up
MRI every 2-3 months during treatment; every 3-6 months for 2 years post-treatmentTreatment of primary CNS lymphoma is high-dose methotrexate-based chemotherapy + rituximab. Surgical resection has no role — biopsy is sufficient for diagnosis confirmation. CRITICAL: Corticosteroids should NOT be given before biopsy — steroids shrink the tumor transiently through lymphocyte apoptosis (ghost tumor) and may render biopsy results non-diagnostic. In immunosuppressed patients, initiation of antiretroviral therapy (HIV) or reduction of immunosuppression is part of treatment. Whole-body PET-CT should exclude systemic lymphoma. Ophthalmologic examination is needed to assess ocular involvement. Prognosis: 5-year survival 50-70% in immunocompetent patients, worse in immunosuppressed.
Primary CNS lymphoma responds to radiotherapy and high-dose methotrexate-based chemotherapy. Steroid administration before biopsy can mask the diagnosis (ghost tumor). Tissue diagnosis via stereotactic biopsy is essential. Surgical resection is not indicated.