Differentiation Of Primary Central Nervous System Lymphomas Research Articles

Multiparametric differentiation of intracranial central nervous system lymphoma and high-grade glioma using diffusion-, perfusion-, susceptibility-weighted magnetic resonance imaging, and spectroscopy

Aims and Objectives: To observe the characteristics of primary central nervous system lymphoma (PCNSL) and high-grade glioma (HGG) in diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), susceptibility-weighted imaging (SWI) and spectroscopy, and differentiate them based on these parameters. Materials and Methods: A total of 45 patients diagnosed with the central nervous system (CNS) neoplasm on magnetic resonance imaging (MRI) using 1.5 Tesla MRI Siemens Magnetom Avanto (Siemens, Germany) and with subsequent histopathological evidence as glioblastoma or CNS lymphoma were included. The study was completed over a period of 2 years. Results: It was found that DWI is effective in the differentiation of HGGs and PCNSLs. A total of 20 (57.1%) HGGs showed diffusion restriction, whereas 9 (90%) of the PCNSLs showed diffusion restriction. The mean apparent diffusion coefficient (ADC) (×10–6 mm2/s) in PCNSLs was 646 whereas, in HGGs, it was found to be 824.3. Thirty-one (88.6%) of the HGGs showed increased perfusion. The mean value of rCBVmean in HGG was found to be 4.06 and the mean value of rCBVmax was 3.63. None of the PCNSLs showed increased perfusion. The mean value of rCBVmean in PCNSLs was 0.097 and rCBVmax was 0.133. 30 (85.7%) of HGGs showed significant areas of blooming on SWI (in the form of intratumoral susceptibility signals [ITSS]). None of the PCNSLs showed blooming. All HGGs and PCNSLs showed increased choline and decreased N acetyl aspartate (NAA) on spectroscopy. Mean Choline/Creatine (Cho/Cr) in HGGs was found to be 3.06, whereas in PCNSLs, it was 1.84. Conclusion: It is important to make a distinction between HGG and PCNSL as the treatment modalities are different for both. Multiparametric evaluation of ADC, ITSS, and rCBVmean allows the differentiation of PCNSLs and solid glioblastoma which supports the integration of advanced MR imaging techniques including DSC-PWI, DWI, and SWI for the routine diagnostic workup of these tumors.

Conventional MR and DW imaging findings of cerebellar primary CNS lymphoma: comparison with high-grade glioma

Primary central nervous system lymphomas (PCNSLs) and high-grade gliomas (HGGs) arising in the cerebellum is extremely low, making the differential diagnosis difficult or even impossible. The purpose of this study was to define the MR features of cerebellar PCNSL in immunocompetent patients, and to determine whether a combination of conventional MR and DW imaging can assist in the differentiation of PCNSLs and HGGs. Twelve PCNSLs and 15 HGGs confirmed by pathological analysis were retrospectively identified. The apparent diffusion coefficient (ADC) and conventional MRI parameters were compared for differences between PCNSL and HGG groups using the independent sample t test or chi-square test. Both ADCmin and ADCtotal values were lower in the PCNSL group than those in the HGG group (ADCmin: 0.53 × 10−3 vs. 0.83 × 10−3 mm2/sec, P < 0.001; ADCtotal: 0.66 × 10−3 vs. 0.98 × 10−3 mm2/sec, P = 0.001). As for conventional MR features, there were significant difference in the tumor size, enhancement patterns, the presence of cystic changes, edema degree and streak-like edema (all P < 0.01); but there were no significant difference in lesion type, the presence of bleeding, and involvement of brain surface between two groups (P = 0.554, 0.657 and 0.157, respectively). The results revealed that several conventional MR features, including enhancement patterns, branch-like enhancement and streak-like edema may be useful for the differentiation of PCNSL and HGG in cerebellum and, when combined with ADC values, further improve the discriminating ability.

Permeability measurement using dynamic susceptibility contrast magnetic resonance imaging enhances differential diagnosis of primary central nervous system lymphoma from glioblastoma.

To test if adding permeability measurement to perfusion obtained from dynamic susceptibility contrast MRI (DSC-MRI) improves diagnostic performance in the differentiation of primary central nervous system lymphoma (PCNSL) from glioblastoma. DSC-MRI was acquired in 145 patients with pathologically proven glioblastoma (n = 89) or PCNSL (n = 56). The permeability metrics of contrast agent extraction fraction (Ex), apparent permeability (Ka), and leakage-corrected perfusion of normalized cerebral blood volume (nCBVres) and cerebral blood flow (nCBFres) were derived from a tissue residue function. For comparison purposes, the leakage-corrected normalized CBV (nCBV) and relative permeability constant (K2) were also obtained using the established Weisskoff-Boxerman leakage correction method. The area under the receiver operating characteristics curve (AUC) and cross-validation were used to compare the diagnostic performance of the single DSC-MRI parameters with the performance obtained with the addition of permeability metrics. PCNSL demonstrated significantly higher permeability (Ex, p < .001) and lower perfusion (nCBVres, nCBFres, and nCBV, all p < .001) than glioblastoma. The combination of Ex and nCBVres showed the highest performance (AUC, 0.96; 95% confidence interval, 0.92-0.99) for differentiating PCNSL from glioblastoma, which was a significant improvement over the single perfusion (nCBV: AUC, 0.84; nCBVres: AUC, 0.84; nCBFres: AUC, 0.82; all p < .001) or Ex (AUC, 0.80; p < .001) parameters. Analysis of the combined permeability and perfusion metrics obtained from a single DSC-MRI acquisition improves the diagnostic value for differentiating PCNSL from glioblastoma in comparison with single-parameter nCBV analysis. • Permeability measurement can be calculated from DSC-MRI with a tissue residue function-based leakage correction. • Adding Exto CBV aids in the differentiation of PCNSL from glioblastoma. • CBV and Exmeasurements from DSC-MRI were highly reproducible.

Primary central nervous system lymphoma in immunocompetent patients: Spectrum of findings and differential characteristics

Primary central nervous system lymphomas (PCNSL) are rare and their management varies significantly from that of other malignant tumors involving the CNS. This article discusses how the imaging findings often suggest the diagnosis early in time. The typical findings in immunocompetent patients consist of one supratentorial intra-axial mass of homogeneous enhancement. Other findings that should be assessed include multifocality and incomplete ring enhancement. The differential diagnosis of PCNSL should mainly consider other malignant tumors of the CNS such as glioblastomas or metastases. PCNSLs tend to have less edema and less mass effect; they also tend to spare the adjacent cortex. Necrosis, hemorrhage, and calcification are rare in PCNSLs. Although the findings in the morphologic sequences are characteristic, they are not completely specific and atypical types can sometimes be found. Advanced imaging techniques such as diffusion-weighted images and, above all, perfusion-weighted images provide qualitative and quantitative data that play an important role in the differentiation of PCNSLs from other brain tumors.

Differentiation of primary central nervous system lymphoma and high-grade glioma with dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging

Preoperative differentiation of primary central nervous system lymphomas (PCNSLs) from other tumors is important for presurgical staging, intraoperative management, and postoperative treatment. Dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging (DSC perfusion MRI) can provide in vivo assessment of the microvasculature in intracranial mass lesions. To determine the utility of DSC perfusion MRI in the differentiation of PCNSLs and high-grade gliomas, as well as their pathological and physiological differences. Nine patients with pathologically proven PCNSLs and 11 patients with high-grade gliomas were examined using a 1.5 T MRI scanner. DSC perfusion MRI was performed by gradient-echo echo-planar imaging (GE-EPI). The maximum rCBV ratio, the signal intensity-time curves, and the percentage of signal intensity recovery were obtained. The maximum relative cerebral blood volume (rCBV) ratio and the percentage of signal intensity recovery of PCNSLs were compared with those of high-grade gliomas by using Student's t test. Microvessel density (MVD) was evaluated using immunohistochemical staining of surgical specimens with anti-CD34, and MVDs of the two tumor groups were compared by using Student's t test. The maximum rCBV ratio of primary intracranial lymphomas was 1.72+/-0.59, while that of high-grade gliomas was 4.86+/-2.18. PCNSLs tended to have relatively low perfusion compared to high-grade gliomas (P=0.001), and the MVD labeled by anti-CD34 of PCNSLs was much lower than that of gliomas (P<0.001). The signal intensity-time curve of primary intracranial lymphomas was different from that of high-grade gliomas. The percentage of signal intensity recovery was significantly greater in PCNSLs compared with that of high-grade gliomas (P<0.001). The difference in DSC perfusion MRI characteristics between PCNSLs and high-grade gliomas is determined by their different vascularities and different patterns of contrast agent leakage. This difference may be helpful in the diagnosis and preoperative differentiation between PCNSLs and high-grade gliomas, which sometimes may have similar conventional MR imaging appearance.

Implications of the blood–brain barrier in primary central nervous system lymphoma

The optimal treatment of primary central nervous system lymphoma (PCNSL), a rare form of extranodal non-Hodgkin lymphoma, has yet to be defined. Whole-brain radiation therapy (WBRT) has limited efficacy as a single therapeutic modality and is associated with a high risk of delayed neurotoxicity. Methotrexate-based chemotherapy regimens yield poor drug penetration across the blood-brain barrier (BBB), thus necessitating administration of high doses with the concomitant risk of increased systemic and neurological toxicity. Combined-modality therapy (WBRT plus chemotherapy) can improve response and survival rates, yet it is associated with a high risk of neurotoxicity. The aim of chemotherapy in conjunction with BBB disruption is to maximize drug delivery to the brain and improve the agent's efficacy, while preserving neurocognitive function and minimizing systemic toxicity. Methotrexate-based chemotherapy regimens administered in conjunction with BBB disruption have shown promising results in PCNSL. Animal models of central nervous system lymphoma and drug neurotoxicity offer new possibilities to study the effects of various treatments on PCNSL and normal brain and can also help understand biological and pathophysiological aspects of this disease. Because the intact BBB is even less permeable to antibodies than it is to drugs, preclinical and clinical studies of monoclonal antibody delivery (for example, rituximab and 90Y ibritumomab tiuxetan) to the brain in conjunction with BBB disruption offer a new possibility to make these novel treatments more efficient against PCNSL. Regarding the evaluation of more sensitive and specific diagnostic imaging tools, iron oxide-based contrast agents for magnetic resonance imaging have shown promise for better differentiation of PCNSL from other white matter diseases.