RESUMEN
OBJECTIVE: This study involved very early post-mortem (PM) examination of human fetal anatomy at 8 weeks of gestation (WG) using whole-body multimodal micro-imaging: micro-CT and high-field MRI (HF-MRI). We discuss the potential place of this imaging in early first-trimester virtual autopsy. METHODS: We performed micro-CT after different contrast-bath protocols including diffusible iodine-based contrast-enhanced (dice) and HF-MRI with a 9.4 T machine with qualitative and quantitative evaluation and obtained histological sections. RESULTS: Nine fetuses were included: the crown-rump length was 10-24 mm and corresponded to 7 and 9 WG according to the Robinson formula. The Carnegie stages were 17-21. Dice micro-CT and HF-MRI presented high signal to noise ratio, >5, according to the Rose criterion, and for allowed anatomical phenotyping in these specimens. Imaging did not alter the histology, allowing immunostaining and pathological examination. CONCLUSION: PM non-destructive whole-body multimodal micro-imaging: dice micro-CT and HF-MRI allows for PM human fetal anatomy study as early as 8 WG. It paves the way to virtual autopsy in the very early first trimester. Obtaining a precision phenotype, even regarding miscarriage products, allows a reverse phenotyping to select variants of interest in genome-wide analysis, offering potential genetic counseling for bereaved parents.
Asunto(s)
Feto , Imagen por Resonancia Magnética , Embarazo , Femenino , Humanos , Microtomografía por Rayos X/métodos , Feto/diagnóstico por imagen , Edad Gestacional , Autopsia/métodos , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND AND OBJECTIVES: Meningioma is one of the most common neoplasm of the central nervous system. To describe the epidemiology of meningioma operated in France and, to assess grading and histopathological variability among the different neurosurgical centres. METHODS: We processed the French Brain Tumour Database (FBTDB) to conduct a nationwide population-based study of all histopathologically confirmed meningiomas between 2006 and 2015. RESULTS: 30,223 meningiomas cases were operated on 28,424 patients, in 61 centres. The average number of meningioma operated per year in France was 3,022 (SD ± 122). Meningioma was 3 times more common in women (74.1% vs. 25.9%). The incidence of meningioma increased with age and, mean age at surgery was 58.5 ± 13.9 years. Grade 1, 2, and 3 meningiomas accounted for 83.9%, 13.91% and, 2.19% respectively. There was a significant variability of meningioma grading by institutions, especially for grade 2 which spanned from 5.1% up to 22.4% (p < 0.001). Moreover, the proportion of grade 2 significantly grew over the study period (p < 0.001). There was also a significant variation in grade 1 subtypes diagnosis among the institutions (p < 0.001). 89.05% of the patients had solely one meningioma surgery, 8.52% two and, 2.43% three or more. The number of surgeries was associated to the grade of malignancy (p < 0.001). CONCLUSION: The incidence of meningioma surgery increased with age and, peaked at 58.5 years. They were predominantly benign with meningothelial subtype being the most common. However, there was a significant variation of grade 1 subtypes diagnosis among the centres involved. The proportion of grade 2 meningioma significantly grew over the study time, on contrary to malignant meningioma proportion, which remained rare and, stable over time around 2%. Likewise, there was a significant variability of grade 2 meningioma rate among the institutions.
Asunto(s)
Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/epidemiología , Meningioma/patología , Meningioma/cirugía , Francia/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Meníngeas/epidemiología , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/cirugía , Anciano , Adulto , Incidencia , Anciano de 80 o más Años , Clasificación del Tumor , Adulto Joven , Adolescente , Bases de Datos FactualesRESUMEN
PURPOSE: Meningeal solitary fibrous tumour (SFT) and haemangiopericytoma (HPC) are uncommon tumours that have been merged into a single entity in the last 2021 WHO Classification of Tumors of the Central Nervous System. To describe the epidemiology of SFT/HPC operated in France and, to assess their incidence. METHODS: We processed the French Brain Tumour Database (FBTDB) to conduct a nationwide population-based study of all histopathologically confirmed SFT/HPC between 2006 and 2015. RESULTS: Our study included 399 SFT/HPC patients, operated in France between 2006 and 2015, in one of the 46 participating neurosurgical centres. The incidence reached 0.062, 95%CI[0.056-0.068] for 100,000 person-years. SFT accounted for 35.8% and, HPC for 64.2%. The ratio of SFT/HPC over meningioma operated during the same period was 0.013. SFT/HPC are about equally distributed in women and men (55.9% vs. 44.1%). For the whole population, mean age at surgery was 53.9 (SD ± 15.8) years. The incidence of SFT/HPC surgery increases with the age and, is maximal for the 50-55 years category. Benign SFT/HPC accounted for 65.16%, SFT/HPC of uncertain behaviour for 11.53% and malignant ones for 23.31%. The number of resection progresses as the histopathological behaviour became more aggressive. 6.7% of the patients with a benign SFT/HPC had a second surgery vs.16.6% in case of uncertain behaviour and, 28.4% for malignant SFT/HPC patients. CONCLUSION: Meningeal SFT and HPC are rare CNS mesenchymal tumours which both share common epidemiological characteristics, asserting their merging under a common entity. SFT/HPC incidence is less that one case for 1 billion per year and, for around 100 meningiomas-like tumours removed, one SFT/HPC may be diagnosed. SFT/HPC are equally distributed in women and men and, are mainly diagnosed around 50-55 years. The more aggressive the tumour, the higher the probability of recurrence.
Asunto(s)
Hemangiopericitoma , Neoplasias Meníngeas , Tumores Fibrosos Solitarios , Humanos , Francia/epidemiología , Hemangiopericitoma/epidemiología , Hemangiopericitoma/patología , Hemangiopericitoma/cirugía , Hemangiopericitoma/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Meníngeas/epidemiología , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/diagnóstico , Tumores Fibrosos Solitarios/epidemiología , Tumores Fibrosos Solitarios/patología , Tumores Fibrosos Solitarios/cirugía , Tumores Fibrosos Solitarios/diagnóstico , Adulto , Anciano , Incidencia , Adulto Joven , Meningioma/epidemiología , Meningioma/patología , Meningioma/cirugía , Meningioma/diagnóstico , Adolescente , Anciano de 80 o más Años , NiñoAsunto(s)
Neoplasias Encefálicas , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos , Humanos , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/diagnóstico por imagen , Masculino , Femenino , AdultoRESUMEN
Background: Patients affected by Von Hippel-Lindau (VHL) are prone to develop central nervous system neoplasms such as hemangioblastomas (HBs). Myxopapillary ependymoma (MPE) is not commonly associated with VHL disease. Case Description: We present the first case of a VHL patient affected by simultaneous silent cauda equina MPE and a symptomatic conus medullaris HB. The patient was first operated for systemic tumors and followed for asymptomatic HBs. Simple surveillance was maintained until neurological symptoms appeared. Regular follow-up demonstrated objective growth of the cystic conus medullaris tumor while the cauda equina lesion remained stable. Surgery was performed to avoid further neurological worsening. Histopathological examination showed conus medullaris HB and a nearby cauda equina MPE. Conclusion: Simultaneous spinal HBs and isolated MPE may exceptionally occur in VHL patients.
RESUMEN
Background: The treatment timing and choice after neurosurgical resection in patients with newly diagnosed diffuse low-grade glioma (DLGG) remain controversial. Indeed, the effect of such treatments must be balanced with the possible side effects. This study evaluated the feasibility of longitudinal exhaustive quality of life (QoL) and neuropsychological assessments in patients with DLGG receiving first-line temozolomide. Methods: QoL, neurocognition, and psychological disorders were assessed prospectively until disease progression, using testing, clinician-reported, and self-reported questionnaires. The primary endpoint was the participation and adherence to this complete assessment at Baseline (before temozolomide initiation), months 6 and 12 of treatment, and month 6 post-treatment. The QoL and neuropsychological changes over time also were described. Results: Twenty-six of the twenty-nine eligible patients were enrolled (participation rate: 89.7%, 95% CI: 72.6-97.8). The adherence rate was 95.7% (95% CI: 78.1-99.9; nâ =â 23 because 3 patients progressed in the first 12 months of treatment). Up to month 6 post-treatment, QoL and fatigue remained stable (EORTC QLQC30 and BN20, MFI-20); some specific symptoms were transitory. Both subjective (FACT-Cog) and objective (Z-scores of neurocognitive tests) neurocognitive outcomes remained stable or tended to improve. The percentage of patients with severe depression (BDI-II), anxiety (STAI-Y), or anger (STAXI-II) was stable over time. Conclusions: This prospective study demonstrated the feasibility of an exhaustive and longitudinal evaluation of QoL, neurocognition, and psychological disorders, with high acceptability by patients with DLGG undergoing chemotherapy. First-line temozolomide seems to have limited short-term effects on QoL and neurocognition. These findings must be confirmed in the long term and in a larger cohort.
RESUMEN
OBJECTIVE: Systemic therapeutic advancements have improved the prognosis of cancer patients, leading to surgery more frequently being carried out for patients with multiple brain metastases (BM). The underlying evidence for the strategy is currently lacking. This study aimed to evaluate the prognostic significance of the number of BM and total tumor burden (TTB) on the overall survival (OS) of patients with resected BM of non-small cell lung cancer (NSCLC) in a modern series. METHODS: In this monocentric retrospective series, patients who underwent resection of BM of NSCLC between 2015 and 2021 were included. Demographic, clinical, and histological parameters were collected, and formal radiological volumetric analyses were performed. Prognostic biomarkers for cerebral progression-free survival (C-PFS) and OS were analyzed with univariate and multivariate Cox proportional hazards analysis. RESULTS: One hundred eighty-four patients were included in the study. Among these, 108 patients (58.7%) presented with a single brain metastasis, 36 patients (19.6%) with 2 BM, 22 patients (11.9%) with 3 BM, and 18 patients (9.8%) with more than 3 BM (maximum 15 BM). The mean ± SD (range) preoperative tumor burden was 23.1 ± 25.3 (1.1-145.3) cm3. The mean residual tumor burden after surgery was 0.3 ± 0.8 (0.0-6.3) cm3. By the time of the analysis, 128 patients (69.6%) had died. The median follow-up duration was 49.0 months (95% CI 39.6-63.6). The median OS was 19.2 months (95% CI 13.2-24.0), and the survival rates at 6 months, 1 year, and 2 years were 76% (95% CI 69%-82%), 61% (95% CI 53%-67%), and 43% (95% CI 35%-50%), respectively. The median C-PFS was 8.4 months (95% CI 7.2-12.0). In the Cox multivariate regression model, younger age (< 65 years), single brain metastasis, adjuvant brain radiation therapy, adjuvant use of targeted therapy, and TTB < 7 cm3 were all independent predictors of longer OS. CONCLUSIONS: In this era of modern systemic treatments for cancer, the number of BM and total cerebral tumor burden remain significant prognostic factors of OS. However, resection should be considered as an option even in those patients with multiple BM in order to enhance patient clinical status, enable further local and systemic treatment delivery, and improve their survival and quality of life.
Asunto(s)
Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carga Tumoral , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/secundario , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/cirugía , Masculino , Femenino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Pronóstico , Adulto , Anciano de 80 o más AñosRESUMEN
BACKGROUND AND OBJECTIVES: The aim of this study was to identify novel biomarkers for multiple sclerosis (MS) diagnosis and prognosis, addressing the critical need for specific and prognostically valuable markers in the field. METHODS: We conducted an extensive proteomic investigation, combining analysis of (1) CSF proteome from symptomatic controls, fast and slow converters after clinically isolated syndromes, and patients with relapsing-remitting MS (n = 10 per group) using label-free quantitative proteomics and (2) oligodendrocyte secretome changes under proinflammatory or proapoptotic conditions using stable isotope labeling by amino acids in cell culture. Proteins exhibiting differential abundance in both proteomic analyses were combined with other putative MS biomarkers, yielding a comprehensive list of 87 proteins that underwent quantification through parallel reaction monitoring (PRM) in a novel cohort, comprising symptomatic controls, inflammatory neurologic disease controls, and patients with MS at various disease stages (n = 10 per group). The 11 proteins that passed this qualification step were subjected to a new PRM assay within an expanded cohort comprising 158 patients with either MS at different disease stages or other inflammatory or noninflammatory neurologic disease controls. RESULTS: This study unveiled a promising biomarker signature for MS, including previously established candidates, such as chitinase 3-like protein 1, chitinase 3-like protein 2, chitotriosidase, immunoglobulin kappa chain region C, neutrophil gelatinase-associated lipocalin, and CD27. In addition, we identified novel markers, namely cat eye syndrome critical region protein 1 (adenosine deaminase 2, a therapeutic target in multiple sclerosis) and syndecan-1, a proteoglycan, also known as plasma cell surface marker CD138 and acting as chitinase 3-like protein 1 receptor implicated in inflammation and cancer signaling. CD138 exhibited good diagnostic accuracy in distinguishing MS from inflammatory neurologic disorders (area under the curve [AUC] = 0.85, CI 0.75-0.95). CD138 immunostaining was also observed in the brains of patients with MS and cultured oligodendrocyte precursor cells but was absent in astrocytes. DISCUSSION: These findings identify CD138 as a specific CSF biomarker for MS and suggest the selective activation of the chitinase 3-like protein 1/CD138 pathway within the oligodendrocyte lineage in MS. They offer promising prospects for improving MS diagnosis and prognosis by providing much-needed specificity and clinical utility. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that CD138 distinguishes multiple sclerosis from other inflammatory neurologic disorders with an AUC of 0.85 (95% CI 0.75-0.95).
Asunto(s)
Biomarcadores , Esclerosis Múltiple Recurrente-Remitente , Sindecano-1 , Humanos , Biomarcadores/líquido cefalorraquídeo , Adulto , Femenino , Masculino , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Persona de Mediana Edad , Sindecano-1/líquido cefalorraquídeo , Estudios de Cohortes , Proteómica , Esclerosis Múltiple/líquido cefalorraquídeo , Esclerosis Múltiple/diagnóstico , Oligodendroglía/metabolismoRESUMEN
Pilocytic astrocytomas (PA) typically exhibit distinct clinical, radiological, histopathological, and genetic features. DNA-methylation profiling distinguishes PA according to their location (infratentorial, midline, hemispheric, or spinal). In the hemispheric location, distinguishing PA from glioneuronal tumors remains a common diagnostic challenge for neuropathologists. Furthermore, the current version of the DKFZ classifier seems to have difficulty separating them from gangliogliomas. In this study, after central radiological review, we identified a histopathologically defined set of PA (histPA, n = 11) and a cohort of DNA-methylation defined PA (mcPA, n = 11). Nine out of the 11 histPA matched the methylation class of hemispheric PA, whereas 2 cases were classified at the end of the study as dysembryoplastic neuroepithelial tumors. Similarly, the mcPA cohort contained tumors mainly classified as PA (7/11), but 4 cases were classified as glioneuronal. The analysis of the 16 tumors with an integrated diagnosis of PA revealed that they affect mainly children with a wide spectrum of radiological, histopathological (i.e. a predominantly diffuse growth pattern), and genetic characteristics (large range of mitogen-activated protein kinase alterations). Based on these results, we consider hemispheric PA to be different from their counterparts in other locations and to overlap with other glioneuronal tumors, reinforcing the necessity of interpreting all data to obtain an accurate diagnosis.
Asunto(s)
Ácido 2-Metil-4-clorofenoxiacético , Astrocitoma , Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Glioma , Neoplasias Neuroepiteliales , Niño , Humanos , Astrocitoma/patología , Glioma/genética , Neoplasias Neuroepiteliales/genética , Neoplasias Neuroepiteliales/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , ADNRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with short- and long-term neurological complications. The variety of symptoms makes it difficult to unravel molecular mechanisms underlying neurological sequalae after coronavirus disease 2019 (COVID-19). Here we show that SARS-CoV-2 triggers the up-regulation of synaptic components and perturbs local electrical field potential. Using cerebral organoids, organotypic culture of human brain explants from individuals without COVID-19 and post-mortem brain samples from individuals with COVID-19, we find that neural cells are permissive to SARS-CoV-2 to a low extent. SARS-CoV-2 induces aberrant presynaptic morphology and increases expression of the synaptic components Bassoon, latrophilin-3 (LPHN3) and fibronectin leucine-rich transmembrane protein-3 (FLRT3). Furthermore, we find that LPHN3-agonist treatment with Stachel partially restored organoid electrical activity and reverted SARS-CoV-2-induced aberrant presynaptic morphology. Finally, we observe accumulation of relatively static virions at LPHN3-FLRT3 synapses, suggesting that local hindrance can contribute to synaptic perturbations. Together, our study provides molecular insights into SARS-CoV-2-brain interactions, which may contribute to COVID-19-related neurological disorders.
Asunto(s)
Encéfalo , COVID-19 , Homeostasis , Organoides , SARS-CoV-2 , Sinapsis , Humanos , SARS-CoV-2/fisiología , COVID-19/virología , COVID-19/metabolismo , COVID-19/patología , Encéfalo/virología , Sinapsis/virología , Sinapsis/metabolismo , Organoides/virología , Virión/metabolismo , Neuronas/virología , Neuronas/metabolismo , Receptores de Péptidos/metabolismo , Receptores de Péptidos/genéticaRESUMEN
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.