Sainte-Anne Hospital Center

Medulloblastoma, the most common malignant brain tumor of childhood, exhibits significant biological complexity that demands deeper exploration. Here, we present a large multiomics dataset integrating data from 384 primary medulloblastoma patient samples across five omic layers: CpG methylome, transcriptome, proteome, phosphoproteome, and metabolome, paired with associated clinical metadata. Data integration revealed intertumoral heterogeneity of lipid metabolism across proteomic subtypes. Notably, while the MYC-FASN-SCD axis drives lipid biosynthesis, pathway inhibition elicits a compensatory escape mechanism in vivo through exogenous fatty acid uptake. Unexpectedly, we demonstrated that MYC triggers lipid storage, creating a unique dependency on lipid droplet-mitochondria communications to sustain tumor maintenance in vivo. Together, this comprehensive analysis reveals a targetable vulnerability downstream of MYC that constitutes a promising therapeutic approach to treat currently untreatable medulloblastoma subtypes.

The neuroepithelial tumor, PATZ1-fused (NET-PATZ1), has been recently isolated as a distinct methylation class by DNA-methylation profiling and is characterized by recurrent PATZ1 fusions, in association with the EWSR1 or MN1 genes and a chromosome 22 chromothripsis. The clinical phenotype is mainly pediatric and features circumscribed supratentorial tumors. However, the histopathology is vastly heterogeneous (glial, glioneuronal, sarcomatous, multiphenotypic) and a cell of origin has not yet been identified, explaining the previsionary imprecise terminology of “NET”. Moreover, extra-central nervous system (CNS) sarcomas also harboring the EWSR1::PATZ1 fusion have been reported and added to the current World Health Organization (WHO) Classification of Soft Tissue and Bone Tumors, in the chapter on undifferentiated small round cell sarcomas. However, their relationship to their CNS counterparts has not yet been studied. Herein, we analyzed a cohort of twelve CNS tumors with PATZ1 fusions in terms of clinical presentation, radiology, histopathology, immunohistochemistry, ultrastructure and DNA-methylation profiling and compared them to five extra-CNS sarcomas-PATZ1. Based on the reported GATA2 overexpression in NET-PATZ1, we also studied the potential interest of GATA2 immunoexpression as a diagnostic tool. We confirmed their distinct molecular characteristics and clinical phenotype but evidenced a morphological intratumoral heterogeneity with three recurrent morphological patterns (oligodendroglial-like, pleomorphic xanthoastrocytoma-like and spindle cells). Despite the unusual spindle and proliferative component in a CD34 + glioneuronal tumor (using electronic microscopy), these tumors present a favorable prognosis. Their histopathological features were all clearly distinct from their soft tissue counterparts. GATA2 immunostaining is highly specific for CNS tumors PATZ1-fused, but its sensitivity is perfectible and further studies are needed to confirm its use as a diagnostic tool. To conclude, our work highlights that CNS tumors, PATZ1-fused seem to represent a novel pediatric glioneuronal tumor type exhibiting a polymorphous morphology and provides new support for its addition as a provisional emerging pediatric circumscribed glioneuronal tumor type, low grade.

Middle meningeal artery (MMA) embolization has been proposed as a potential treatment for chronic subdural hematoma (CSDH). To assess the efficacy of MMA embolization in reducing the risk of CSDH recurrence at 6 months compared with standard care in patients who underwent an operation and were at high risk of CSDH recurrence. Multicenter, open-label, randomized clinical trial with blinded end point assessment. Patients who underwent an operation for CSDH recurrence or a first CSDH episode at high risk of recurrence were recruited from July 2020 to March 2023 in 12 French neurosurgical or comprehensive neurosurgical and interventional neuroradiology centers. Last follow-up took place on November 2, 2023. Participants were randomized 1:1 to undergo MMA embolization with microparticles within 7 days of surgery (171 patients, intervention group) or standard medical care alone (171 patients, control group). The primary end point was the rate of CSDH recurrence at 6 months assessed by an independent, blinded adjudication committee. There were 5 secondary end points, including rates of repeat surgery for homolateral CSDH recurrence during the 6-month follow-up period and embolization procedure–related complications. Among 342 randomized patients (median [IQR] age, 77 [68-83] years; 274 [80.1%] male), 308 (90.1%) completed the trial. The primary end point was observed in 24 of 162 (14.8%) and 33 of 157 (21.0%) patients in the intervention and control groups, respectively (after imputation: odds ratio, 0.64 [95% CI, 0.36-1.14]; adjusted absolute difference, −6% [95% CI, −14% to 2%]; P = .13). The groups did not significantly differ in any of the secondary end points. Repeat surgery was performed in 7 of 162 (4.3%) and 13 of 157 (8.3%) patients in the intervention and control groups (P = .14), respectively. Minor and major embolization procedure–related complications occurred in 3 of 171 (1.8%) and 1 of 171 (0.6%) patients, respectively. In this randomized clinical trial, among patients who underwent an operation for CSDH recurrence or a first CSDH episode at high risk of recurrence, MMA embolization did not lead to a significantly lower rate of recurrence at 6 months compared with standard medical care alone. However, the magnitude of the effect estimate is consistent with other recent trials, including some that demonstrated the benefit of MMA embolization with nonadhesive liquid embolic agents, and these findings considered together may inform future studies and potential use of this therapeutic approach for CSDH management. ClinicalTrials.gov Identifier: NCT04372147

According to the current World Health Organization classification of central nervous system tumors, the angiocentric glioma (AG) assigned a grade 1, characterized by recurrent MYB fusions. However, it also mentions that increased proliferative activity and other anaplastic features have been reported, but the clinical significance of such findings is unclear as an increased proliferative activity alone does not necessarily alter the benign behavior of AGs. Most cases with “anaplasia” were mainly described before the molecular era. Herein, we report the case of a 3-year-old female with epilepsy symptomatic of a left temporo-parietal tumor. Histopathologically, the initial tumor displayed atypical AG morphology and a proliferation index of 1

Diffuse leptomeningeal glioneuronal tumour (DLGNT) is rare a glioneuronal neoplasm of the central nervous system, which occurs mainly in children and adolescents characterized by the presence of MAPK pathway alteration and 1p deletion. Clinical, radiological and molecular data from 20 patients diagnosed with DLGNT from May 2001 to May 2023 were collected. Clinical presentation was polymorphous, with intracranial hypertension and back pain as most common symptoms. Patients underwent multiple lines of treatment (median of 4, range 1–8) in addition to surgery with a median follow up of 94 months (range 7–241). Radiotherapy and carboplatin-based chemotherapy were the 2 treatments with the higher number of partial response (PR) and stable disease (SD) of 7/10 and 2/10 for radiotherapy and 7/12 and 5/12 for carboplatin-based chemotherapy. All patients treated with trametinib progressed before 2 years, while 2-years PFS was of 52