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eEdE -61 1ry CNS lymphomas: Review of imaging findings: MRS, DWI, perfusion-MRI and dynamic contrast enhanced studies. Lara A Brando a and Mauricio Castillo MD, FACR b Clinic a Felippe Mattoso Clinic- Barra Da Tijuca, Rio De Janeiro-RJ- Brazil and Fleury Group Diagnostic Medicine. b Division of Neuroradiology, Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7510, USA. Felippe Mattoso

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Disclosures: Lara A Brando MD: No disclosures. Mauricio Castillo MD: AJNR EIC, Book royalties (Elsevier, Thieme, Springer, Lippincott, Cambridge, Wiley.)

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Introduction: 1ry lymphoma involves the CNS without systemic disease. It is the 3rd most common CNS tumor after meningioma and glioma and typically is a non- Hodgkin b-cell lymphoma. Its prevalence is growing; it is more common in males. The only risk factor at the moment is immunodeficiency. Most common imaging findings are a solitary or multifocal solid brain lesions, especially supratentorial. Meningeal involvement is more common with 2ry lymphoma. Most times, conventional and advanced MRI are capable of distinguishing it from gliomas. Accurate preoperative differentiation between these 2 tumors is important for treatment. GBs are usually treated with maximal surgical resection plus radiation and chemotherapy, whereas lymphoma is not treated with surgery.

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Purpose: 1. Present the most common imaging findings of 1ry CNS lymphoma on conventional MRI as well as proton MRS, DWI, dynamic susceptibility contrast (DSC) MRI, and dynamic contrast enhanced (DCE) studies. 2. Emphasize some imaging aspects that may help distinguish between lymphoma and high grade glioma. Methods: Retrospective review of clinical and neuroimaging studies in 125 patients with 1ry CNS lymphoma (we excluded t-cell and other less common types of lymphomas). MRI was performed on a 1.5 or 3.0 T imagers, available sequences included sagittal T1 and T1 3D SPGR, axial T1, T2, FLAIR, GRE and DWI, as well as coronal T2. MRS, DSC and DCE studies were obtained in some patients, and gadolinium was administered in all. Diagnosis was confirmed by therapeutic response to therapy, biopsy and, in some cases, surgical resection.

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Findings: Our sample included 90 men and 35 women, age range: 32-79 years (median: 55.5 years). Most common neuroimaging features in 1ry CNS lymphomas were: 1. Supratentorial predilection. 2. Predilection for periventricular white matter, subependymal regions, deep gray nuclei and corpus callosum. 3. Presentation as round well-circumscribed solid lesions. 4. Hypo- to iso-intense to cortex on T2 sequences. 5. Solid contrast enhancement. 6. Restricted diffusion. 7. High choline and presence of lipids/lactate on MRS. 8. No elevation of blood volume on perfusion studies. 9. No significant elevation of permeability. 10. Significant reduction in size or disappearance after steroid therapy.

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Most common neuroimaging features were: 1. Predilection for supratentorial compartment. About 85% of lymphomas were located in the supratentorial compartment, while 15% were located in the posterior fossa. 2. Predilection for the periventricular white matter, subependymal regions, deep gray nuclei and corpus callosum. Among supratentorial lymphomas 95% were in the periventricular and subependymal regions and deep gray nuclei. Corpus callosum was infiltrated in 40%. Important differential diagnosis: Infiltration of the callosum is common in GBs. However, GBs tend to bleed and show necrosis, findings not common in lymphomas unless they occur in immunocompromised patients.

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Supratentorial location Series of corresponding post Gd T1 and DWIs show multifocal deeply located lymphomas with restricted diffusion (ADCs not shown). Patient 1 Patient 2

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Callosal involvement Patient 1 Patient 2 Series of MRIs in 2 different patients with lymphomas crossing the corpus callosum with typical dense and nearly homogeneous contrast enhancement and restricted DWI. These lesions may have similar appearance to GBs.

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Most common neuroimaging features were (cont.): 3-Presentation as round well circumscribed solid lesions instead of infiltrative form. In our series, 90% of patients presented with well circumscribed round or oval multifocal or less common solitary lesions. In 4% of patients the tumors presented with infiltrating patterns.

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Well circumscribed single lesions Patient 1 Patient 2 MRI studies in 2 patient with lesions (1: ependymal based, 2: dural based) show solid contrast enhancement, low perfusion, low ADC.

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Well circumscribed multiple lesions Patient 1 Patient 2 Multifocal well-defined lymphomas show homogeneous enhancement, high choline and lactate on MRS and restricted ADCs.

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Well circumscribed multiple lesions 2 well defined lymphoma lesions are T2 dark, enhance, have low ADC and loss of anisotropy on DTI directionality map (arrows).

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Infiltrative pattern Lymphoma infiltrating midbrain show high choline and lactate on MRS. Its T2 signal is nearly identical to that of the cortex.

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Infiltrative pattern Lymphoma infiltrating left basal ganglia shows little contrast enhancement but ependymal involvement (arrows) clearly enhances.

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Infiltrative pattern Lymphoma infiltrating left basal ganglia and deep white mater shows no contrast enhancement with an appearance simulating gliomatosis cerebri.

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Most common neuroimaging features were (cont.): 5. Solid contrast enhancement. Enhancement was demonstrated in most focal and multifocal lymphomas (95%). Among these, 63% presented with solid homogeneous enhancement. Non-homogeneous enhancement was demonstrated in 10% being more common in immunocompromised ones. Subependymal enhancement was demonstrated in 14 patients. In patients presenting with infiltrative lymphoma (4%) subtle subependymal enhancement was seen in half of them. 4. Isointense to cortex on T2. Solid tumors were typically isointense to cortex on T2 in all patients. Infiltrative lymphomas were T2 bright. Signal intensity on T2 is related to high cell density and high nuclear/cytoplasm ratio and is a characteristic finding but can also be seen in aggressive gliomas.

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Isointense to cortex on T2 Despite significant contrast enhancement some lymphomas can be nearly isointense to cortex on T2.

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Most common neuroimaging features (cont.): 6. Restricted diffusion In our series, 90% of focal and multifocal tumors presented with restricted diffusion. Restricted diffusion was occasionally demonstrated in infiltrative lymphomas. Another situation in which restricted diffusion may be absent in lymphomas is after steroids.

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Restricted diffusion 4 patients with lymphoma show very low ADC.

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Note restricted diffusion before treatment and less restriction after steroids (last picture). Restricted diffusion

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Most common neuroimaging features (cont.): 7. High choline along with presence of lipids/lactate in MRS. Spectral pattern of lymphomas is similar to that of other malignant tumors and characterized by increase in Cho, reduction in myo-inositol and prominent lipids. When lipids and lactate are demonstrated in a solid lesion, lymphoma should be suggested.

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3 different lymphomas on long TE MRS show similar findings: high Cho, low NAA, lipids and lactate. MRS pattern

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Most common neuroimaging features (cont.): 8. No elevation of cerebral blood volume. Angiogenesis is not prominent in lymphomas, thus perfusion is low which helps to distinguish them from gliomas grades III and IV. If high cellular density is suggested by ADC and no elevation of rCBV is seen, consider lymphoma. Rarely, rCBV of lymphomas may be high overlapping with that of aggressive gliomas. In this case, ADC maps may be valuable to distinguish between these lesions as lymphoma usually shows very restricted diffusion. 9. No significant elevation of permeability. Lymphomas may present with no or minimal elevation of permeability, a finding that may help distinguish them from GB.

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Multifocal lymphoma (left case) shows no increase in rCBV. Minimal peripheral perfusion was thought to be related to choroid plexus and veins. Butterfly type lymphoma (right case) shows no increase in perfusion. Low perfusion

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This rare lymphoma (with calvarial extension) shows increased perfusion. High perfusion

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Despite contrast enhancement, permeability map and curve show no significant and fast contrast change percentage as expected for a high grade glioma. Low permeability

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Most common neuroimaging features (cont.): 10. Significant reduction in size or disappearance after steroids. Lymphomas typically respond well to steroids, reducing size and sometimes disappearing completely; because of this, they are also known as ghost tumors. Steroids do not treat lymphomas and tumors will come back after their discontinuation. Be aware that after steroids, ADC maps and perfusion studies also may change. After steroids, restricted ADC may resolve and perfusion may be reduced.

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Disappearance after steroids. Left: patient with lymphoma before steroids. Right: same patient after steroids. T2 abnormalities and enhancement have disappeared.

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Left and center: treatment-naive lymphoma shows high perfusion. Right: after steroid, perfusion has decreased. Low perfusion after steroids

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Summary: Remember the following features of lymphomas. Supratentorial predilection. Predilection for periventricular white matter, subependymal regions, deep gray nuclei and corpus callosum. Presentation as round well-circumscribed solid lesions. Hypo- to iso-intense to cortex on T2 sequences. Solid contrast enhancement. Restricted diffusion. High choline and presence of lipids/lactate on MRS. No elevation of blood volume on perfusion studies. No significant elevation of permeability. Significant reduction in size or disappearance after steroid therapy

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