Central Nervous System Lymphoma: Characteristic Findings on Traditional and Advanced Imaging
TL;DR: New CT and MR imaging techniques and metabolic imaging have demonstrated characteristic findings in CNS lymphoma, aiding in its differentiation from other CNS lesions, and advanced imaging techniques may, in the future, substantially improve the diagnostic accuracy of imaging, ultimately facilitating a noninvasive method of diagnosis.
Abstract: CNS lymphoma consists of 2 major subtypes: secondary CNS involvement by systemic lymphoma and PCNSL. Contrast-enhanced MR imaging is the method of choice for detecting CNS lymphoma. In leptomeningeal CNS lymphoma, representing two-thirds of secondary CNS lymphomas, imaging typically shows leptomeningeal, subependymal, dural, or cranial nerve enhancement. Single or multiple periventricular and/or superficial contrast-enhancing lesions are characteristic of parenchymal CNS lymphoma, representing one-third of secondary CNS lymphomas and almost 100% of PCNSLs. New CT and MR imaging techniques and metabolic imaging have demonstrated characteristic findings in CNS lymphoma, aiding in its differentiation from other CNS lesions. Advanced imaging techniques may, in the future, substantially improve the diagnostic accuracy of imaging, ultimately facilitating a noninvasive method of diagnosis. Furthermore, these imaging techniques may play a pivotal role in planning targeted therapies, prognostication, and monitoring treatment response.
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TL;DR: An overview of the updated CT and PET response criteria for lymphoma staging and response assessment is provided to familiarize the radiologist with the most important and clinically relevant aspects of lymphoma imaging.
Abstract: Lymphoma comprises a heterogeneous group of diseases; remarkable advances have been made in diagnosis and treatment. Diagnostic imaging provides important information for staging and response assessment in patients with lymphoma. Over the years, staging systems have been refined, and dedicated criteria have been developed for evaluating response to therapy with both computed tomography (CT) and fluorine-18 fluorodeoxyglucose positron emission tomography (PET)/CT. The most recent system proposed for staging and response assessment, known as the Lugano classification, applies to both Hodgkin and non-Hodgkin lymphoma. The use of standardized criteria for staging and response assessment is important for making accurate treatment decisions and for determining the direction of further research. This review provides an overview of the updated CT and PET response criteria to familiarize the radiologist with the most important and clinically relevant aspects of lymphoma imaging. It also provides a short clinical update on lymphoma and the associated spectrum of imaging findings.
129 citations
TL;DR: Combined evaluation of mean ADC, mean rCBV, and presence of ITSS allowed reliable differentiation of PCNSL and atypical glioblastoma in most patients, and these results support an integration of advanced MR imaging techniques for the routine diagnostic workup of patients with these tumors.
Abstract: Multiparametric assessment of mean apparent diffusion coefficients, relative cerebral blood volume, and intratumoral susceptibility signals significantly increased the probability for differentiation of primary central nervous system lymphoma and atypical, solid enhancing glioblastoma when compared with the evaluation of one or two imaging parameters.
123 citations
TL;DR: A combined stepwise systematic approach outlined here may facilitate an expeditious, comprehensive presurgical evaluation for cases of suspected CNS lymphoma.
Abstract: Central nervous system (CNS) lymphoma can present a diagnostic challenge. Currently, there is no consensus regarding what presurgical evaluation is warranted or how to proceed when lesions are not surgically accessible. We conducted a review of the literature on CNS lymphoma diagnosis (1966 to October 2011) to determine whether a common diagnostic algorithm can be generated. We extracted data regarding the usefulness of brain and body imaging, serum and cerebrospinal fluid (CSF) studies, ophthalmologic examination, and tissue biopsy in the diagnosis of CNS lymphoma. Contrast enhancement on imaging is highly sensitive at the time of diagnosis: 98.9% in immunocompetent lymphoma and 96.1% in human immunodeficiency virus-related CNS lymphoma. The sensitivity of CSF cytology is low (2%-32%) but increases when combined with flow cytometry. Cerebrospinal fluid lactate dehydrogenase isozyme 5, β2-microglobulin, and immunoglobulin heavy chain rearrangement studies have improved sensitivity over CSF cytology (58%-85%) but have only moderate specificity (85%). New techniques of proteomics and microRNA analysis have more than 95% specificity in the diagnosis of CNS lymphoma. Positive CSF cytology, vitreous biopsy, or brain/leptomeningeal biopsy remain the current standard for diagnosis. A combined stepwise systematic approach outlined here may facilitate an expeditious, comprehensive presurgical evaluation for cases of suspected CNS lymphoma.
123 citations
Cites background from "Central Nervous System Lymphoma: Ch..."
...encephalopathy.(22) Specialized imaging may help to discriminate between these entities....
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TL;DR: Large-scale radiomics with a machine-learning algorithm can be useful for differentiating PCNSL from atypical GBM, and yields a better diagnostic performance than human radiologists and ADC values.
Abstract: To evaluate the diagnostic performance of magnetic resonance (MR) radiomics-based machine-learning algorithms in differentiating primary central nervous system lymphoma (PCNSL) from non-necrotic atypical glioblastoma (GBM). Seventy-seven patients (54 individuals with PCNSL and 23 with non-necrotic atypical GBM), diagnosed from January 2009 to April 2017, were enrolled in this retrospective study. A total of 6,366 radiomics features, including shape, volume, first-order, texture, and wavelet-transformed features, were extracted from multi-parametric (post-contrast T1- and T2-weighted, and fluid attenuation inversion recovery images) and multiregional (enhanced and non-enhanced) tumour volumes. These features were subjected to recursive feature elimination and random forest (RF) analysis with nested cross-validation. The diagnostic abilities of a radiomics machine-learning classifier, apparent diffusion coefficient (ADC), and three readers, who independently classified the tumours based on conventional MR sequences, were evaluated using receiver operating characteristic (ROC) analysis. Areas under the ROC curves (AUC) of the radiomics classifier, ADC value, and the radiologists were compared. The mean AUC of the radiomics classifier was 0.921 (95 % CI 0.825–0.990). The AUCs of the three readers and ADC were 0.707 (95 % CI 0.622–0.793), 0.759 (95 %CI 0.656–0.861), 0.695 (95 % CI 0.590–0.800) and 0.684 (95 % CI0.560–0.809), respectively. The AUC of the radiomics-based classifier was significantly higher than those of the three readers and ADC (p< 0.001 for all). Large-scale radiomics with a machine-learning algorithm can be useful for differentiating PCNSL from atypical GBM, and yields a better diagnostic performance than human radiologists and ADC values. • Machine-learning algorithm radiomics can help to differentiate primary central PCNSL from GBM.
• This approach yields a higher diagnostic accuracy than visual analysis by radiologists.
• Radiomics can strengthen radiologists’ diagnostic decisions whenever conventional MRI sequences are available.
101 citations
Cites background from "Central Nervous System Lymphoma: Ch..."
...In many cases, GBM and PCNSL can be adequately discriminated based on their different features on MRI [1, 6, 7]....
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TL;DR: The diffusion radiomics model had good generalizability and yielded a better diagnostic performance than conventional radiomics or single advanced MRI in identifying atypical PCNSL mimicking glioblastoma.
Abstract: Background Radiomics is a rapidly growing field in neuro-oncology, but studies have been limited to conventional MRI, and external validation is critically lacking. We evaluated technical feasibility, diagnostic performance, and generalizability of a diffusion radiomics model for identifying atypical primary central nervous system lymphoma (PCNSL) mimicking glioblastoma. Methods A total of 1618 radiomics features were extracted from diffusion and conventional MRI from 112 patients (training set, 70 glioblastomas and 42 PCNSLs). Feature selection and classification were optimized using a machine-learning algorithm. The diagnostic performance was tested in 42 patients of internal and external validation sets. The performance was compared with that of human readers (2 neuroimaging experts), cerebral blood volume (90% histogram cutoff, CBV90), and apparent diffusion coefficient (10% histogram, ADC10) using the area under the receiver operating characteristic curve (AUC). Results The diffusion radiomics was optimized with the combination of recursive feature elimination and a random forest classifier (AUC 0.983, stability 2.52%). In internal validation, the diffusion model (AUC 0.984) showed similar performance with conventional (AUC 0.968) or combined diffusion and conventional radiomics (AUC 0.984) and better than human readers (AUC 0.825-0.908), CBV90 (AUC 0.905), or ADC10 (AUC 0.787) in atypical PCNSL diagnosis. In external validation, the diffusion radiomics showed robustness (AUC 0.944) and performed better than conventional radiomics (AUC 0.819) and similar to combined radiomics (AUC 0.946) or human readers (AUC 0.896-0.930). Conclusion The diffusion radiomics model had good generalizability and yielded a better diagnostic performance than conventional radiomics or single advanced MRI in identifying atypical PCNSL mimicking glioblastoma.
96 citations
Cites background from "Central Nervous System Lymphoma: Ch..."
...Feature selection and classification Registered on ADC maps ADC maps Volume and shape (7) ROC analysis...
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References
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TL;DR: This European survey provides a reasonable basis for the treatment of primary intracerebral lymphoma with the following sequence: stereotactic biopsy sampling, chemotherapy with a methotrexate- and anthracycline-based regimen, followed by cranial irradiation.
Abstract: Object. The authors present a retrospective analysis of 248 immunocompetent patients with primary intracerebral lymphoma treated at 19 French and Belgian medical centers between January 1980 and December 1995. Methods. This study involved 127 female and 121 male patients with a median age of 61 years (range 2–88 years). All tumors available for review were classic diffuse non-Hodgkin's lymphoma, for which the phenotype was determined in 220 patients: 212 (96.4%) were B-cell and eight (3.6%) were T-cell type tumors. According to the Revised European—American classification of lymphoid neoplasms, most lesions were diffuse large cell tumors (62%). A total of 196 tumors were reviewed in 127 patients for whom preoperative computerized tomography and magnetic resonance studies were available. There was a single lesion in 66% of the cases, with a supratentorial location in 87%. Tumor location in the basal ganglia, corpus callosum, or fornix, infiltration of the periventricular ependyma, or a mirror pattern, were...
491 citations
"Central Nervous System Lymphoma: Ch..." refers background in this paper
...Frontal lobe location is reported in 20%– 43% of PCNSLs, whereas the basal ganglia are affected in 13%–20%.(14,26,32,35)...
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TL;DR: The differential diagnosis of PCNSL includes central nervous system gliomas, metastatic tumors, demyelinating disorders, subacute infarcts, and space-occupied lesions due to an infectious etiology.
Abstract: Primary central nervous system lymphoma (PCNSL) is an uncommon extranodal non-Hodgkin lymphoma. Its incidence has increased during the last 3 decades and has been reported in both immunocompromised and immunocompetent patients. Immunocompromised patients are affected at a younger age compared with immunocompetent patients. It presents with raised intracranial pressure and focal neurologic and neuropsychiatric symptoms. The lesions are typically solitary. The majority of the lesions are located in the periventricular area, whereas in a few cases they are located in the supratentorial area. Diffuse large B-cell lymphomas constitute most PCNSLs, whereas T-cell, low-grade, anaplastic, and Hodgkin lymphomas are rarely encountered. The morphology of PCNSL shows a characteristic angiocentric pattern and is positive for B-cell markers by immunohistochemistry. The differential diagnosis of PCNSL includes central nervous system gliomas, metastatic tumors, demyelinating disorders, subacute infarcts, and space-occupying lesions due to an infectious etiology. The understanding of the molecular mechanisms involved in the pathogenesis of PCNSL and the identification of molecular biomarkers have lagged behind that of systemic nodal lymphomas. Primary central nervous system lymphomas are treated with combined radiotherapies and chemotherapies. The prognosis for PCNSL is worse than for other extranodal lymphomas.
448 citations
"Central Nervous System Lymphoma: Ch..." refers background in this paper
...enhancement is reported in up to 75% of cases.(28,31,39)...
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...Immunodeficient patients with PCNSL are often diagnosed with multifocal lesions, which are reported in 30%– 80% of patients with AIDS-related PCNSL (Fig 5).(28,31,39)...
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...Multiple lesions are reported in 20%– 40% of non-AIDS PCNSLs,(14,15,27,29,31) and ringlike enhancement, in 0%–13% (Figs 2 and 3).(14,29,31,32) Linear enhancement along perivascular spaces is highly suggestive of PCNSL....
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TL;DR: This work states that IO nanoparticles possess unique paramagnetic properties, which and generate significant susceptibility effects resulting in strong T2 and T2* contrast, as well as T1 effects at very low concentrations for magnetic resonance imaging (MRI), which is widely used for clinical oncology imaging.
Abstract: Magnetic iron oxide (IO) nanoparticles with a long blood retention time, biodegradability and low toxicity have emerged as one of the primary nanomaterials for biomedical applications in vitro and in vivo. IO nanoparticles have a large surface area and can be engineered to provide a large number of functional groups for cross-linking to tumor-targeting ligands such as monoclonal antibodies, peptides, or small molecules for diagnostic imaging or delivery of therapeutic agents. IO nanoparticles possess unique paramagnetic properties, which generate significant susceptibility effects resulting in strong T2 and T*2 contrast, as well as T1 effects at very low concentrations for magnetic resonance imaging (MRI), which is widely used for clinical oncology imaging. We review recent advances in the development of targeted IO nanoparticles for tumor imaging and therapy.
407 citations
TL;DR: The findings suggest that primary central nervous system lymphoma in patients with AIDS has a significantly different natural history than it does in immunocompetent persons.
Abstract: Objective: To compare the pathogenesis, clinical presentation, therapy, and prognosis of primary central nervous system lymphoma in immunocompetent persons with these characteristics of the disease...
393 citations
TL;DR: The profile of ARL has changed since the era of HAART, with a lower incidence of systemic and brain ARL, and the prognosis of systemic ARl has improved.
361 citations
"Central Nervous System Lymphoma: Ch..." refers background in this paper
...However, with the introduction of HAART during the past decade, the incidence of PCNSL in the HIV population has declined.(10,11)...
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