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PURPOSE: Amide proton transfer-weighted (APTw) MRI at 3T provides a unique contrast for brain tumor imaging. However, APTw imaging suffers from hyperintensities in liquid compartments such as cystic or necrotic structures and provides a distorted APTw signal intensity. Recently, it has been shown that heuristically motivated fluid suppression can remove such artifacts and significantly improve the readability of APTw imaging. THEORY AND METHODS: In this work, we show that the fluid suppression can actually be understood by the known concept of spillover dilution, which itself can be derived from the Bloch-McConnell equations in comparison to the heuristic approach. Therefore, we derive a novel post-processing formula that efficiently removes fluid artifact, and explains previous approaches. We demonstrate the utility of this APTw assessment in silico, in vitro, and in vivo in brain tumor patients acquired at MR scanners from different vendors. RESULTS: Our results show a reduction of the CEST signals from fluid environments while keeping the APTw-CEST signal intensity almost unchanged for semi-solid tissue structures such as the contralateral normal appearing white matter. This further allows us to use the same color bar settings as for conventional APTw imaging. CONCLUSION: Fluid suppression has considerable value in improving the readability of APTw maps in the neuro-oncological field. In this work, we derive a novel post-processing formula from the underlying Bloch-McConnell equations that efficiently removes fluid artifact, and explains previous approaches which justify the derivation of this metric from a theoretical point of view, to reassure the scientific and medical field about its use.
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Neoplasias Encefálicas , Sustancia Blanca , Humanos , Protones , Amidas , Imagen por Resonancia Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Sustancia Blanca/patologíaRESUMEN
PURPOSE: Immunosuppression is a well-established risk factor for primary central nervous system lymphomas (PCNSLs), which present in this context distinct radiological characteristics. Our aim was to describe the radiological evolution of treated PCNSL in immunocompromised patients and suggest adapted MRI response criteria. METHODS: We conducted a multicenter retrospective study of patients from the French LOC, K-Virogref and CANCERVIH network databases and enrolled adult immunocompromised patients with newly diagnosed PCNSL. RESULTS: We evaluated the baseline, intermediate, end-of-treatment and follow-up MRI data of 31 patients (9 living with HIV, 16 with solid organ transplantation and 6 with an autoimmune disease under chronic immunosuppressive therapy). At baseline, 23/30 (77%) patients had necrotic lesions with ring enhancement and 28% of the lesions were hemorrhagic. At the end of the first-line treatment, 12/28 (43%) patients could not be classified according to the IPCG criteria. Thirteen of 28 (46%) patients still harbored contrast enhancement, and 11/28 (39%) patients had persistent large necrotic lesions with a median diameter of 15 mm. These aspects were not associated with a pejorative outcome and progressively diminished during follow-up. Six patients relapsed; however, we failed to identify any neuroimaging risk factors on the end-of-treatment MRI. CONCLUSION: In immunocompromised patients, PCNSLs often harbor alarming features on end-of-treatment MRI, with persistent contrast-enhanced lesions frequently observed. However, these aspects seemed to be related to the necrotic and hemorrhagic nature of the lesions and were not predictive of a pejorative outcome. Specific response criteria for this population are thereby proposed.
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Neoplasias del Sistema Nervioso Central , Huésped Inmunocomprometido , Linfoma , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias del Sistema Nervioso Central/inmunología , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Estudios Retrospectivos , Huésped Inmunocomprometido/inmunología , Anciano , Adulto , Linfoma/diagnóstico por imagen , Linfoma/patología , Linfoma/inmunología , Estudios de SeguimientoRESUMEN
BACKGROUND: Dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-FDOPA) positron emission tomography (PET) is a valuable tool for managing high-grade gliomas (HGGs), but there is a lack of literature on its relationship with glioma subtypes since the 2021 reclassification of brain tumors. There is also debate surrounding the mechanism of 18F-FDOPA uptake, particularly after chemoradiation therapy. This study aimed to investigate the correlation between 18F-FDOPA uptake and histomolecular characteristics, particularly L-amino acid transporter 1 (LAT1) expression, in recurrent gliomas, and examine their impact on survival in HGGs. METHODS: Thirty-nine patients with recurrent HGGs (14 isocitrate dehydrogenase [IDH]-mutant, 25 IDH-wildtype) who underwent a brain 18F-FDOPA PET/computed tomography (CT) or PET/magnetic resonance imaging (MRI) followed by surgical resection of the 18F-FDOPA-avid lesion within 6 months, were retrospectively reviewed. PET results were compared with histological examination and for SCL7A5/LAT1 immunostaining. The study also examined the relationship between PET parameters, LAT1 expression, and survival outcomes. RESULTS: Astrocytoma IDH-mutant G4 had higher 18F-FDOPA uptake than glioblastoma IDH-wildtype G4 (maximum tumor-to-normal brain ratio [TBRmax] 5 [3.4-9] vs. 3.8 [2.8-5.9], p = 0.02). IDH-mutant gliomas had higher LAT1 expression than IDH-wildtype gliomas (100 [14-273] vs. 15.5 [0-137], p < 0.05) as well as higher TBRmax (5 [2.4-9] vs. 3.8 [2.8-6], p < 0.05). In survival analysis, LAT1 score >100 was a predictor for longer progression-free survival in IDH-mutant HGGs. CONCLUSIONS: To our knowledge, our study is the first to suggest a link between LAT1 expression and IDH mutation status. We showed that higher TBRmax was associated with higher LAT1 expression and IDH mutation status. Further studies are needed to better understand the mechanisms underlying amino acid PET tracers uptake, especially in the post-radiation and chemotherapy settings.
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Neoplasias Encefálicas , Glioma , Humanos , Estudios Retrospectivos , Glioma/diagnóstico por imagen , Glioma/genética , Dihidroxifenilalanina , Tomografía de Emisión de Positrones/métodos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologíaRESUMEN
Background Noninvasive identification of glioma subtypes is important for optimizing treatment strategies. Purpose To compare the in vivo neurochemical profiles between isocitrate dehydrogenase (IDH) 1-mutant 1p/19q codeleted gliomas and their noncodeleted counterparts measured by MR spectroscopy at 3.0 T with a point-resolved spectroscopy (PRESS) sequence optimized for D-2-hydroxyglutarate (2HG) detection. Materials and Methods Adults with IDH1-mutant gliomas were retrospectively included for this study from two university hospitals (inclusion period: January 2015 to July 2016 and September 2019 to June 2021, respectively) based on availability of 1p/19q codeletion status and a PRESS acquisition optimized for 2HG detection (echo time, 97 msec) at 3.0 T before any treatment. Spectral analysis was performed using LCModel and a simulated basis set. Metabolite quantification was performed using the water signal as a reference and correcting for water and metabolite longitudinal and transverse relaxation time constants. Concentration ratios were computed using total creatine (tCr) and total choline. A two-tailed unpaired t test was used to compare metabolite concentrations obtained in codeleted versus noncodeleted gliomas, accounting for multiple comparisons. Results Thirty-one adults (mean age, 39 years ± 8 [SD]; 19 male) were included, and 19 metabolites were quantified. Cystathionine concentration was higher in codeleted (n = 13) than noncodeleted (n = 18) gliomas when quantification was performed using the water signal or tCr as references (2.33 mM ± 0.98 vs 0.93 mM ± 0.94, and 0.34 mM ± 0.14 vs 0.14 mM ± 0.14, respectively; both P < .001). The sensitivity and specificity of PRESS to detect codeletion by means of cystathionine quantification were 92% and 61%, respectively. Other metabolites did not show evidence of a difference between groups (P > .05). Conclusion Higher cystathionine levels were detected in IDH1-mutant 1p/19q codeleted gliomas than in their noncodeleted counterparts with use of a PRESS sequence optimized for 2HG detection. Of 19 metabolites quantified, only cystathionine showed evidence of a difference in concentration between groups. Clinical trial registry no. NCT01703962 © RSNA, 2023 See also the editorial by Lin in this issue.
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Cistationina , Glioma , Adulto , Humanos , Masculino , Creatina , Glioma/diagnóstico por imagen , Glioma/genética , Espectroscopía de Resonancia Magnética , Receptores de Antígenos de Linfocitos T , Estudios Retrospectivos , Agua , Femenino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Mesial Temporal Lobe Epilepsy-associated Hippocampal Sclerosis (MTLE-HS) is a syndrome associated with various aetiologies. We previously identified CD34-positive extravascular stellate cells (CD34+ cells) possibly related to BRAFV600E oncogenic variant in a subset of MTLE-HS. We aimed to identify the BRAFV600E oncogenic variants and characterise the CD34+ cells. METHODS: We analysed BRAFV600E oncogenic variant by digital droplet Polymerase Chain Reaction in 53 MTLE-HS samples (25 with CD34+ cells) and nine non-expansive neocortical lesions resected during epilepsy surgery (five with CD34+ cells). Ex vivo multi-electrode array recording, immunolabelling, methylation microarray and single nuclei RNAseq were performed on BRAFwildtype MTLE-HS and BRAFV600E mutant non-expansive lesion of hippocampus and/or neocortex. RESULTS: We identified a BRAFV600E oncogenic variant in five MTLE-HS samples with CD34+ cells (19%) and in five neocortical samples with CD34+ cells (100%). Single nuclei RNAseq of resected samples revealed two unique clusters of abnormal cells (including CD34+ cells) associated with senescence and oligodendrocyte development in both hippocampal and neocortical BRAFV600E mutant samples. The co-expression of the oncogene-induced senescence marker p16INK4A and the outer subventricular zone radial glia progenitor marker HOPX in CD34+ cells was confirmed by multiplex immunostaining. Pseudotime analysis showed that abnormal cells share a common lineage from progenitors to myelinating oligodendrocytes. Epilepsy surgery led to seizure freedom in eight of the 10 patients with BRAF mutant lesions. INTERPRETATION: BRAFV600E underlies a subset of MTLE-HS and epileptogenic non-expansive neocortical focal lesions. Detection of the oncogenic variant may help diagnosis and open perspectives for targeted therapies.
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Epilepsias Parciales , Epilepsia del Lóbulo Temporal , Epilepsia , Neocórtex , Humanos , Epilepsia del Lóbulo Temporal/patología , Neocórtex/patología , Proteínas Proto-Oncogénicas B-raf/genética , Hipocampo/patología , Epilepsias Parciales/genética , Epilepsias Parciales/complicaciones , Epilepsias Parciales/patología , Epilepsia/patología , Esclerosis/patología , Imagen por Resonancia MagnéticaRESUMEN
In this review focused on lymphoma and the central nervous system (CNS), we summarize recent developments in the management of primary (PCNSL) and secondary CNS lymphoma (SCNSL), treatment of CNS lymphoma in the older population, the neuroradiological assessment of CNS lymphoma and finally highlight the ongoing debate on optimal CNS prophylaxis. The section on PCNSL focuses on the different approaches available for frontline treatment in Europe and the United States and discusses consolidation strategies. We then highlight available strategies to treat PCNSL in the elderly population, an area of unmet need. New therapies aiming at minimizing toxicity and prioritizing quality of life are emerging for these patients. Secondary CNS lymphoma, especially in the relapsed/refractory setting is another area of unmet need, and the efficacy of CAR-T cell therapy is being explored. We provide an overview of the imaging challenges in the neuroradiological assessment of CNS lymphoma. Finally, the section on CNS prophylaxis summarizes recent findings from large retrospective studies challenging the efficacy of present approaches to prophylaxis in higher-risk patients with lymphoma.
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PURPOSE OF REVIEW: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal diffuse large B cell lymphoma. Despite its apparent immunopathological homogeneity, PCNSL displays a wide variability in outcome. Identifying prognostic factors is of importance for patient stratification and clinical decision-making. The purpose of this review is to focus on the clinical, neuroradiological and biological variables correlated with the prognosis at the time of diagnosis in immunocompetent patients. RECENT FINDINGS: Age and performance status remain the most consistent clinical prognostic factors. The current literature suggests that neurocognitive dysfunction is an independent predictor of poor outcome. Cumulating data support the prognostic value of increased interleukin-10 level in the cerebrospinal fluid (CSF), in addition to its interest as a diagnostic biomarker. Advances in neuroimaging and in omics have identified several semi-quantitative radiological features (apparent diffusion restriction measures, dynamic contrast-enhanced perfusion MRI (pMRI) pattern and 18F-fluorodeoxyglucose metabolism) and molecular genetic alterations with prognostic impact in PCNSL. SUMMARY: Validation of new biologic and neuroimaging markers in prospective studies is required before integrating future prognostic scoring systems. In the era of radiomic, large clinicoradiological and molecular databases are needed to develop multimodal artificial intelligence algorithms for the prediction of accurate outcome.
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Productos Biológicos , Neoplasias del Sistema Nervioso Central , Linfoma de Células B Grandes Difuso , Inteligencia Artificial , Biomarcadores , Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Humanos , Interleucina-10/líquido cefalorraquídeo , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/genética , PronósticoRESUMEN
PURPOSE: To evaluate the ability of the PRESS sequence (TE = 97 ms, optimized for 2-hydroxyglutarate detection) to detect cystathionine in gliomas and the effect of the omission of cystathionine on the quantification of the full neurochemical profile. METHODS: Twenty-three subjects with a glioma were retrospectively included based on the availability of both MEGA-PRESS and PRESS acquisitions at 3T, and the presence of the cystathionine signal in the edited MR spectrum. In eight subjects, the PRESS acquisition was performed also in normal tissue. Metabolite quantification was performed using LCModel and simulated basis sets. The LCModel analysis for the PRESS data was performed with and without cystathionine. RESULTS: All subjects with glioma had detectable cystathionine levels >1 mM with Cramér-Rao lower bounds (CRLB) <15%. The mean cystathionine concentrations were 3.49 ± 1.17 mM for MEGA-PRESS and 2.20 ± 0.80 mM for PRESS data. Cystathionine concentrations showed a significant correlation between the two MRS methods (r = 0.58, p = .004), and it was not detectable in normal tissue. Using PRESS, 19 metabolites were quantified with CRLB <50% for more than half of the subjects. The metabolites that were significantly (p < .0028) and mostly affected by the omission of cystathionine were aspartate, betaine, citrate, γ-aminobutyric acid (GABA), and serine. CONCLUSIONS: Cystathionine was detectable by PRESS in all the selected gliomas, while it was not detectable in normal tissue. The omission from the spectral analysis of cystathionine led to severe biases in the quantification of other neurochemicals that may play key roles in cancer metabolism.
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Neoplasias Encefálicas , Glioma , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Cistationina , Glioma/patología , Humanos , Espectroscopía de Resonancia Magnética/métodos , Estudios RetrospectivosRESUMEN
INTRODUCTION: The corpus callosum (CC) is frequently involved in primary central nervous system lymphomas (PCNSLs). In this cohort study, we described the neurocognition of patients with PCNSL-CC and its posttherapeutic evolution. METHODS: Immunocompetent patients with PCNSL-CC were identified retrospectively at the Pitié-Salpêtrière Hospital. We described their clinical presentation. Neuropsychological test scores (MMSE; digit spans; Free and Cued Selective Reminding Test; Image Oral Naming Test; Frontal Assessment Battery; Trail Making Test; Stroop and verbal fluency tests; Rey's Complex Figure test) and factors impacting them were analyzed. RESULTS: Twenty-seven patients were included (median age: 67 years, median Karnofsky Performance Status: 70); cognitive impairment and balance disorders were present in 74% and 59%, respectively. At diagnosis, neuropsychological test results were abnormal for global cognitive efficiency (63% of patients), memory (33-80% depending on the test) and executive functions (44-100%). Results for visuospatial and language tests were normal. All patients received high-dose methotrexate-based polychemotherapy, followed in one patient by whole-brain radiotherapy; 67% of patients achieved complete response (CR). With a median follow-up of 48 months (range 6-156), patients in CR had persistent abnormal test results for global cognitive efficiency in 17%, executive function in 18-60%, depending on the test, and memory in 40-60%. Splenium location and age ≥ 60 years were significantly associated with worse episodic memory scores throughout the follow-up. CONCLUSIONS: PCNSL-CC is associated with frequent cognitive dysfunctions, especially memory impairment, which may recover only partially despite CR and warrant specific rehabilitation. Older age (≥ 60) and splenium location are associated with worse neurocognitive outcomes.
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Cuerpo Calloso , Linfoma , Anciano , Estudios de Cohortes , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Humanos , Linfoma/tratamiento farmacológico , Linfoma/terapia , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estudios RetrospectivosRESUMEN
BACKGROUND: Mucosae-associated lymphoid tissue (MALT) lymphomas are a rare and poorly understood form of primary central nervous system lymphoma (PCNSL). The aim of this study was to better describe these tumors, their management and their long-term prognosis. METHODS: Patients with primary CNS MALT lymphoma (PCNSML) were retrospectively selected from the database on PCNSL of the Pitié-Salpêtrière Hospital. RESULTS: Of 662 PCNSL, 11 (1.7%) PCNSML (9 females and 2 males, median age: 56 years) were selected. The median time from first symptoms to diagnosis was 13 months. Location was dural in 8 cases and parenchymal in 3 cases. The disease was multifocal/diffuse in 7 cases. In first line, all patients received chemotherapy (high-dose methotrexate (HD-MTX) based chemotherapy (n = 4) and non-HD-MTX-based chemotherapy (n = 7)), preceded by surgery in 4 cases. None received radiotherapy. According to the IPCG (International PCNSL Collaborative Group) criteria, the overall response rate was 7/11 (64%). At latest news, 5 patients had persistent contrast enhancement, stable with no treatment since a median of 57 months, raising the question of complete response despite persisting contrast enhancement. No patient developed neurotoxicity except for one patient who subsequently received radiotherapy. The median follow-up was 109 months. The median progression-free survival was 78.0 months and the 10-year overall survival rate was 90%. CONCLUSION: This is the largest series demonstrating that chemotherapy is an efficient treatment in PCNSML, with an excellent long-term outcome and the absence of neurotoxicity, and calling into question the relevance of the IPCG criteria for the evaluation of response.
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Neoplasias del Sistema Nervioso Central , Linfoma de Células B de la Zona Marginal , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Femenino , Humanos , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/etiología , Masculino , Metotrexato , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
PURPOSE: This study aimed to assess the benefit-risk ratio by determining diagnostic yield and safety of brainstem biopsies in adult patients. The secondary objectives were (i) to compare brainstem biopsy safety and postbiopsy patients' outcomes and survival with those of patients biopsied for a brain or cerebellar lesion, and (ii) to assess the impact of brainstem biopsy on final diagnosis and further therapeutic management. METHODS: Among 1784 stereotactic biopsies performed in adult patients at a tertiary center between April 2009 and October 2020, we retrospectively examined 50 consecutive brainstem biopsies. We compared variables regarding diagnostic yield, safety and post-biopsy outcomes between brainstem biopsy patients and brain/cerebellum biopsy patients. RESULTS: Brainstem biopsy led to a diagnosis in 86% of patients (94.6% in patients with suspected tumor). Lesion contrast enhancement on imaging was the sole predictor of obtaining a diagnosis. Rates of symptomatic complications and mortality were significantly higher in brainstem biopsy patients compared to brain/cerebellum biopsy patients (20% vs 0%; p < 0.001 and 6% vs 0%; p = 0.01, respectively). Transfrontal trajectory and prebiopsy swallowing disorders were predictors of brainstem biopsy-related symptomatic complications. Brainstem biopsy findings led to diagnostic change in 22% of patients. CONCLUSIONS: Stereotactic biopsy in adult patients with brainstem lesion has a high diagnostic yield. Although stereotactic brainstem biopsy is associated with more functional and fatal complications than biopsies targeting the brain/cerebellum, its safety profile appears acceptable. Thus, the benefit-risk ratio of stereotactic biopsy in patients with brainstem lesion is favorable but should nevertheless be carefully weighted on a case-by-case basis.
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Biopsia , Neoplasias del Tronco Encefálico , Técnicas Estereotáxicas , Adulto , Humanos , Biopsia/efectos adversos , Biopsia/métodos , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patología , Neoplasias del Tronco Encefálico/diagnóstico , Neoplasias del Tronco Encefálico/patología , Estudios Retrospectivos , Técnicas Estereotáxicas/efectos adversos , Enfermedades del Sistema Nervioso Central/diagnóstico , Enfermedades del Sistema Nervioso Central/etiología , Enfermedades del Sistema Nervioso Central/patología , Medición de Riesgo , Resultado del TratamientoRESUMEN
PURPOSE OF REVIEW: This review aims to cover current MRI techniques for assessing treatment response in brain tumors, with a focus on radio-induced lesions. RECENT FINDINGS: Pseudoprogression and radionecrosis are common radiological entities after brain tumor irradiation and are difficult to distinguish from real progression, with major consequences on daily patient care. To date, shortcomings of conventional MRI have been largely recognized but morphological sequences are still used in official response assessment criteria. Several complementary advanced techniques have been proposed but none of them have been validated, hampering their clinical use. Among advanced MRI, brain perfusion measures increase diagnostic accuracy, especially when added with spectroscopy and susceptibility-weighted imaging. However, lack of reproducibility, because of several hard-to-control variables, is still a major limitation for their standardization in routine protocols. Amide Proton Transfer is an emerging molecular imaging technique that promises to offer new metrics by indirectly quantifying intracellular mobile proteins and peptide concentration. Preliminary studies suggest that this noncontrast sequence may add key biomarkers in tumor evaluation, especially in posttherapeutic settings. SUMMARY: Benefits and pitfalls of conventional and advanced imaging on posttreatment assessment are discussed and the potential added value of APT in this clinicoradiological evolving scenario is introduced.
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Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Traumatismos por Radiación/diagnóstico por imagen , Neoplasias Encefálicas/patología , Progresión de la Enfermedad , Humanos , Traumatismos por Radiación/etiología , Traumatismos por Radiación/patologíaAsunto(s)
Astrocitoma , Neoplasias Encefálicas , Sistema de Señalización de MAP Quinasas , Humanos , Astrocitoma/genética , Astrocitoma/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Sistema de Señalización de MAP Quinasas/fisiología , Sistema de Señalización de MAP Quinasas/genética , Adulto , Masculino , Femenino , Persona de Mediana Edad , Mutación/genéticaAsunto(s)
Neoplasias Encefálicas/genética , Glioblastoma/genética , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Neoplasias Encefálicas/patología , Receptores ErbB/genética , Femenino , Glioblastoma/patología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Primary meningeal melanocytic tumors are ultra-rare entities with distinct histological and molecular features compared with other melanocytic or pigmented lesions, such as brain and leptomeningeal metastases from metastatic melanoma. METHODS: The European Network for Rare Cancers (EURACAN) Task Force on Ultra-Rare Brain Tumors (domain 10, subdomain 10) performed a literature review from January 1985 to December 2023 regarding the epidemiologic and clinical characteristics, histological and molecular features, radiological findings, and efficacy of local treatments (surgery and radiotherapy) and systemic treatments for these entities. RESULTS: Molecular analysis can detect specific mutations, including GNAQ, GNA11, SF3B1, EIF1AX, BAP1, that are typically found in circumscribed primary meningeal melanocytic tumors and not in other melanocytic lesions, whereas NRAS and BRAF mutations are typical for diffuse primary meningeal melanocytic tumors. The neuroimaging of the whole neuroaxis suggests a melanocytic nature of a lesion, depicts its circumscribed or diffuse nature, but cannot predict the tumor's aggressiveness. Gross-total resection is the first choice in the case of circumscribed meningeal melanocytoma and melanoma; conversely, meningeal biopsy may be reserved for patients with diffuse and multinodular leptomeningeal spread to achieve a definitive diagnosis. High-dose radiotherapy is rarely indicated in diffuse melanocytic tumors except as palliative treatment to alleviate symptoms. Last, a definitive advantage of a specific systemic treatment could not be concluded, as most of the data available derive from case reports or small cohorts. CONCLUSIONS: As primary meningeal melanocytic tumors are extremely rare, the correlations between the clinical characteristics, molecular profile, radiological findings at diagnosis and progression are weak, and poor evidence on the best therapeutic approach is available. There is a need to develop shared platforms and registries to capture more knowledge regarding these ultra-rare entities.
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BACKGROUND AND PURPOSE: Isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion classify adult-type diffuse gliomas into three tumor subtypes with distinct prognosis. We aimed to evaluate the performance of edited magnetic resonance spectroscopy (MRS) for glioma subtyping in a clinical setting, via the quantification of D-2-hydroxyglutarate (2HG) and cystathionine. The delay between this noninvasive classification and the integrated histomolecular analysis was also quantified. MATERIALS AND METHODS: Subjects with presumed low-grade glioma, eligible for surgery (cohort 1), and subjects with IDH-mutant glioma, previously treated and with progressive disease (cohort 2) were prospectively examined with a singlevoxel Mescher-Garwood point-resolved spectroscopy sequence at 3 T. Spectra were quantified using LCModel. The Cramér-Rao lower bounds (CRLB) threshold was set to 20%. Integrated histomolecular analysis according to the 2021 WHO classification was considered as a ground truth. RESULTS: Thirty-four consecutive subjects were enrolled. Due to poor spectra quality and lack of histological specimen, data from 26 subjects was analyzed. Twenty-one belonged to cohort 1 [11 females; median age: 42 years] and 5 to cohort 2 [3 females; median age: 48 years]. Edited MRS showed 100% specificity for detection of IDH mutation and 91% specificity for prediction of 1p/19q codeletion status. Sensitivities for prediction of IDH and 1p/19q codeletion were 62% and 33%, respectively. The median CRLB values were 14% (13 - 32) for IDH-mutant and 572% (554 - 999) for IDH-wild-type tumors. The time between MRS and surgery was longer for low-grade than high-grade gliomas (p = .03), yet the time between MRS and WHO diagnosis did not differ between grades (p = .07), possibly reflecting molecular analyses induced delays in high-grade gliomas. CONCLUSIONS: Our results, acquired in a clinic setting, confirmed that edited MRS is highly specific for both IDH mutation and 1p/19q codeletion predictions and can provide a faster prognosis stratification. In the upcoming IDH-inhibitor treatment era, incorporation of edited MRS into clinical workflow is desirable. ABBREVIATIONS: 2HG = D-2-hydroxyglutarate; Cth = cystathionine. CRLB: Cramér-Rao lower bound; IDH: isocitrate dehydrogenase.
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OBJECTIVES: Despite a high response rate at the first evaluation during induction chemotherapy, the risk of early relapse remains high and unpredictable in primary CNS lymphomas (PCSNLs). We aimed to assess the prognostic value of early IL-10 levels in CSF (e-IL-10) after 2 months of induction chemotherapy. METHODS: We retrospectively selected from the LOC (Lymphomes Oculo-Cérébraux) network database patients with PCSNLs who had complete or partial response at the 2-month evaluation of a high-dose methotrexate-based first-line chemotherapy for whom e-IL-10 was available. RESULTS: Thirty patients (median age: 62 years, brain involvement in 30/30, CSF involvement in 10/30, median baseline CSF IL-10: 27.5 pg/mL) met the selection criteria. e-IL-10 was undetectable in 22 patients and detectable in 8 patients. At the end of induction treatment, 7 of 8 and 4 of 22 of the patients with detectable and undetectable e-IL-10 had experienced progressive disease, respectively (p = 0.001, OR: 26.8, 95% CI 2-1,478). The median progression-free survival times were 5.8 months (95% CI 2.8-8.8) and 28.7 months (95% CI 13.4-43.9) in the groups with detectable and undetectable e-IL-10, respectively (p < 0.001). DISCUSSION: Our results suggest that despite an objective response, the persistence of detectable e-IL-10 is associated with a high risk of early relapse in PCNSL. A closer follow-up of such patients is warranted.
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Neoplasias del Sistema Nervioso Central , Quimioterapia de Inducción , Interleucina-10 , Humanos , Persona de Mediana Edad , Femenino , Masculino , Interleucina-10/líquido cefalorraquídeo , Neoplasias del Sistema Nervioso Central/líquido cefalorraquídeo , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Anciano , Estudios Retrospectivos , Pronóstico , Adulto , Linfoma/líquido cefalorraquídeo , Linfoma/tratamiento farmacológico , Metotrexato/uso terapéutico , Metotrexato/administración & dosificaciónRESUMEN
BACKGROUND AND OBJECTIVES: Epilepsy is a common comorbidity of brain tumors; however, little is known about the prevalence, onset time, semiology, and risk factors of seizures in primary CNS lymphoma (PCNSL). Our objectives were to determine the prevalence of epilepsy in PCNSL, to identify factors associated with epilepsy, and to investigate the prognostic significance of seizures in PCNSL. METHODS: We performed an observational, retrospective single-center study at a tertiary neuro-oncology center (2011-2023) including immunocompetent patients with PCNSL and no history of seizures. We collected clinical, imaging, and treatment data; seizure status over the course of PCNSL; and oncological and seizure outcome. The primary outcome was to determine the prevalence of epilepsy. Furthermore, we aimed to identify clinical, radiologic, and treatment-related factors associated with epilepsy. Univariate analyses were conducted using the χ2 test for categorical variables and unpaired t test for continuous variables. Predictors identified in the unadjusted analysis were included in backward stepwise logistic regression models. RESULTS: We included 330 patients, 157 (47.6%) were male, median age at diagnosis was 68 years, and the median Karnofsky Performance Status score was 60. Eighty-three (25.2%) patients had at least 1 seizure from initial diagnosis to the last follow-up, 40 (12.1%) as the onset symptom, 16 (4.8%) during first line of treatment, 27 (8.2%) at tumor progression and 6 (1.8%) while in remission. Focal aware seizures were the most frequent seizure type, occurring in 43 (51.8%) patients. Seizure freedom under antiseizure medication was observed in 97.6% patients. Cortical contact (odds ratio [OR] 8.6, 95% CI 4.2-15.5, p < 0.001) and a higher proliferation index (OR 5.7, 95% CI 1.3-26.2, p = 0.02) were identified as independent risk factors of epilepsy. Patients with PCNSL and epilepsy had a significantly shorter progression-free survival (median progression-free survival 9.6 vs 14.1 months, adjusted hazard ratio 1.4, 95% CI 1.0-1.9, p = 0.03), but not a significantly shorter overall survival (17 vs 44.1 months, log-rank test, p = 0.09). DISCUSSION: Epilepsy affects a quarter of patients with PCNSL, with half experiencing it at the time of initial presentation and potentially serving as a marker of disease progression. Further research is necessary to assess the broader applicability of these findings because they are subject to the constraints of a retrospective design and tertiary center setting.
Asunto(s)
Neoplasias del Sistema Nervioso Central , Epilepsia , Humanos , Masculino , Femenino , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Factores de Riesgo , Prevalencia , Pronóstico , Epilepsia/epidemiología , Neoplasias del Sistema Nervioso Central/epidemiología , Neoplasias del Sistema Nervioso Central/complicaciones , Linfoma/epidemiología , Linfoma/complicaciones , Adulto , Anciano de 80 o más AñosRESUMEN
A novel methylation class, "neuroepithelial tumor, with PLAGL1 fusion" (NET-PLAGL1), has recently been described, based on epigenetic features, as a supratentorial pediatric brain tumor with recurrent histopathological features suggesting an ependymal differentiation. Because of the recent identification of this neoplastic entity, few histopathological, radiological and clinical data are available. Herein, we present a detailed series of nine cases of PLAGL1-fused supratentorial tumors, reclassified from a series of supratentorial ependymomas, non-ZFTA/non-YAP1 fusion-positive and subependymomas of the young. This study included extensive clinical, radiological, histopathological, ultrastructural, immunohistochemical, genetic and epigenetic (DNA methylation profiling) data for characterization. An important aim of this work was to evaluate the sensitivity and specificity of a novel fluorescent in situ hybridization (FISH) targeting the PLAGL1 gene. Using histopathology, immunohistochemistry and electron microscopy, we confirmed the ependymal differentiation of this new neoplastic entity. Indeed, the cases histopathologically presented as "mixed subependymomas-ependymomas" with well-circumscribed tumors exhibiting a diffuse immunoreactivity for GFAP, without expression of Olig2 or SOX10. Ultrastructurally, they also harbored features reminiscent of ependymal differentiation, such as cilia. Different gene partners were fused with PLAGL1: FOXO1, EWSR1 and for the first time MAML2. The PLAGL1 FISH presented a 100% sensitivity and specificity according to RNA sequencing and DNA methylation profiling results. This cohort of supratentorial PLAGL1-fused tumors highlights: 1/ the ependymal cell origin of this new neoplastic entity; 2/ benefit of looking for a PLAGL1 fusion in supratentorial cases of non-ZFTA/non-YAP1 ependymomas; and 3/ the usefulness of PLAGL1 FISH.