Hepatic Stem-like Phenotype and Interplay of Wnt/β-Catenin and Myc Signaling in Aggressive Childhood Liver Cancer

SummaryHepatoblastoma, the most common pediatric liver cancer, is tightly linked to excessive Wnt/β-catenin signaling. Here, we used microarray analysis to identify two tumor subclasses resembling distinct phases of liver development and a discriminating 16-gene signature. β-catenin activated different transcriptional programs in the two tumor types, with distinctive expression of hepatic stem/progenitor markers in immature tumors. This highly proliferating subclass was typified by gains of chromosomes 8q and 2p and upregulated Myc signaling. Myc-induced hepatoblastoma-like tumors in mice strikingly resembled the human immature subtype, and Myc downregulation in hepatoblastoma cells impaired tumorigenesis in vivo. Remarkably, the 16-gene signature discriminated invasive and metastatic hepatoblastomas and predicted prognosis with high accuracy

Les méningiomes olfactifs (résultats à long terme d'une série chirurgicale consécutive de 62 patients)

Les méningiomes olfactifs s insèrent à la jonction ethmoïdo-sphenoïdale de l étage antérieur de la base du crâne. Leur exérèse complète pose le problème de l ouverture des cavités aériques de la face en cas d exérèse de l ostéome réactionnel ou tumoral. La surveillance au long cours justifie-t'elle de laisser en place cet ostéome ? Il s agit d une étude rétrospective d une série consécutive de 62 patients porteurs d un méningiome olfactif opérés le plus souvent par voie fronto-ptérionale unilatérale par un même opérateur dans une même institution. 62 patients (51 femmes, 11 hommes, ratio 1/5) de 30 à 75 ans (51,9ans de moyenne) ont été opérés d un méningiome olfactif entre 1978 et 2007 au sein d une même institution par un même opérateur. Une baisse de l acuité visuelle, des céphalées, des troubles du comportement, une anosmie et/ou des crises d épilepsies révélaient le méningiome dans respectivement 62,9%, 50%, 27,4%, 16,1% et 14,5% des cas. L examen clinique retrouvait une anosmie dans 66,1% des cas, un déficit neurologique dans 8% des cas, des troubles des fonctions supérieures dans 14,5% des cas, une atteinte visuelle dans 74,2% des cas et un score d atteinte visuelle moyen de 45,4 (2-100). Le plus grand diamètre moyen à l imagerie était de 4,865cm (2-8) avec la présence d un ostéome d insertion à la jonction ethmoïdo-sphenoïdale dans 80,3% des cas et un envahissement des cavités sinusiennes de la face dans 8,2% des cas. L exérèse chirurgicale, totale dans 90,2% des cas, subtotale dans 19,8% des cas a permis une amélioration de l état neurologique et ophtalmologique de 100% et 93,7% des patients. Le score de déficience visuelle post-opératoire était de 17,4 (2-81) avec 80,4% d anosmie. Le taux de récidives était de 9,6% avec un suivi moyen de 68 mois (1-285mois ; 5,6 ans en moyenne). 3 patients ont du être réopérés. En per-opératoire il a été rapporté 19 cas où la zone d insertion était étendue sur l étage antérieur jusqu aux gouttières optiques. Tous les patients ayant récidivé symptomatiquement sauf un présentaient ce type d insertion étendue. Ainsi, cette étude confirme que la voie fronto-ptérionale permet de faire l exérèse des méningiomes olfactifs avec un faible taux de complication et de récidive à long terme. D autre part, il faut bien distinguer les méningiomes dont la zone d insertion s étend aux gouttières optiques dont l exérèse est techniquement plus difficile et dont les récidives sont plus rapidement symptomatiques compte tenu des rapports anatomiques avec les nerfs optiques. Cependant dans ces cas la voie d abord proposée reste la plus adaptée pour appréhender les rapports vasculo-nerveux à risquePARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Does the left inferior longitudinal fasciculus play a role in language? A brain stimulation study.

Although advances in diffusion tensor imaging have enabled us to better study the anatomy of the inferior longitudinal fasciculus (ILF), its function remains poorly understood. Recently, it was suggested that the subcortical network subserving the language semantics could be constituted, in parallel with the inferior occipitofrontal fasciculus, by the left ILF, joining the posterior occipitotemporal regions to the temporal pole, then relayed by the uncinate fasciculus connecting the anterior temporal pole to the frontobasal areas. Nevertheless, this hypothesis was solely based on neurofunctional imaging, allowing a cortical mapping but with no anatomofunctional information regarding the white matter. Here, we report a series of 12 patients operated on under local anaesthesia for a cerebral low-grade glioma located within the left temporal lobe. Before and during resection, we used the method of intraoperative direct electrostimulation, enabling us to perform accurate and reliable anatomofunctional correlations both at cortical and subcortical levels. In order to map the ILF. Using postoperative MRI, we correlated these functional findings with the anatomical locations of the sites where language disturbances were elicited by stimulations, both at cortical and subcortical levels. Our goal was to study the potential existence of parallel and distributed language networks crossing the left dominant temporal lobe, subserved by distinct subcortical pathways--namely the inferior occipitofrontal fasciculus and the ILF. Intraoperative stimulation of the anterior and middle temporal cortex elicited anomia in four patients. At the subcortical level, semantic paraphasia were induced in seven patients during stimulation of the inferior occipitofrontal fasciculus, and phonological paraphasia was generated in seven patients by stimulating the arcuate fasciculus. Interestingly, subcortical stimulation never elicited any language disturbances when performed at the level of the ILF. In addition, following a transient postoperative language deficit, all patients recovered, despite the resection of at least one part of the ILF, as confirmed by control MRI. On the basis of these results, we suggest that the "semantic ventral stream" could be constituted by at least two parallel pathways within the left dominant temporal lobe: (i) a direct pathway, the inferior occipitofrontal fasciculus, that connects the posterior temporal areas and the orbitofrontal region, crucial for language semantic processing, since it elicits semantic paraphasia when stimulated; (ii) and also possibly an indirect pathway subserved by the ILF, not indispensable for language, since it can be compensated both during stimulation and after resection

Superficial middle cerebral vein connection to the cavernous sinus is not infrequent in brain arteriovenous malformations: an argument against their congenital origin?

International audienceIntroductionThe aim of this study was to test the hypothesis that the superficial middle cerebral vein (SMCV) is frequently absent or fails to connect with the cavernous sinus (CS) in the presence of brain arteriovenous malformations (AVMs), a frequently reported argument for the congenital origin of brain AVMs.MethodsThe SMCV was retrospectively compared between patients with a brain AVM and a control group. The presence or absence of the SMCV, its direct or indirect connection to the CS and its termination in a laterocavernous sinus (LCS), paracavernous sinus (PCS), or directly in the CS was studied on digital subtraction angiography.ResultsOne hundred twenty-five left or right side carotid angiograms from 70 patients with a brain AVM were compared to 125 angiograms from 74 controls. The SMCV was present in 88 (70.4 %) cases in the brain AVM group and 96 (76.8 %) cases in controls (p = 0.25). The SMCV was connected directly or indirectly to the CS in 65 (52 %) cases in the brain AVM group and 65 (52 %) cases in controls (p = 1). When comparing the subgroup of carotid angiograms ipsilateral to a supratentorial AVM, no statistically significant difference was found with controls. In three of six cases in which a SMCV drained an AVM, the vein terminated directly or indirectly in the CS.ConclusionsNo difference of SMCV presence and direct or indirect connection to the CS was found between patients with AVM and a control group. SMCV anatomy does not support the congenital origin of brain AVMs

Teaching neuroimages: Burkitt dural lymphoma mimicking a subacute subdural hematoma.

International audienceA 59-year-old woman with no history of trauma presented with severe headaches and right-sided weakness. A CT scan showed a left hemispheric isodense subdural collection thought to be consistent with a subacute subdural hematoma (figure 1A). The patient underwent a single parietal burr hole for evacuation, but the neurosurgeon found subdural fleshy tissue and performed a biopsy. Immediate postoperative MRI showed a homogeneous hypercellular subdural mass (figure 1, B–F).1 Pathology was consistent with Burkitt lymphoma (figure 2). Retrospectively, the homogeneous density of the collection argued against hematoma. In nonemergent situations, an atypical radiologic appearance of a subdural hematoma may suggest the need for further radiologic investigations before surgical evacuation.

Extensive basal ganglia edema caused by a traumatic carotid-cavernous fistula: a rare presentation related to a basal vein of Rosenthal anatomical variation

International audienceThe authors report a very rare presentation of traumatic carotid-cavernous fistula (CCF) with extensive edema of the basal ganglia and brainstem because of an anatomical variation of the basal vein of Rosenthal (BVR). A 45-year-old woman was admitted to the authors' institution for left hemiparesis, dysarthria, and a comatose state caused by right orbital trauma from a thin metal rod. Brain MRI showed a right CCF and vasogenic edema of the right side of the brainstem, right temporal lobe, and basal ganglia. Digital subtraction angiography confirmed a high-flow direct CCF and revealed a hypoplastic second segment of the BVR responsible for the hypertension in inferior striate veins and venous congestion. Endovascular treatment was performed on an emergency basis. One month after treatment, the patient's symptoms and MRI signal abnormalities almost totally disappeared. Basal ganglia and brainstem venous congestion may occur in traumatic CCF in cases of a hypoplastic or agenetic second segment of the BVR and may provoke emergency treatment

Molecular Profiling Reclassifies Adult Astroblastoma into Known and Clinically Distinct Tumor Entities with Frequent Mitogen‐Activated Protein Kinase Pathway Alterations

International audienceBACKGROUND: Astroblastoma (ABM) is a rare glial brain tumor. Recurrent meningioma 1 (MN1) alterations have been recently identified in most pediatric cases. Adolescent and adult cases, however, remain molecularly poorly defined.MATERIALS AND METHODS: We performed clinical and molecular characterization of a retrospective cohort of 14 adult and 1 adolescent ABM.RESULTS: Strikingly, we found that MN1 fusions are a rare event in this age group (1/15). Using methylation profiling and targeted sequencing, most cases were reclassified as either pleomorphic xanthoastrocytomas (PXA)-like or high-grade glioma (HGG)-like. PXA-like ABM show BRAF mutation (6/7 with V600E mutation and 1/7 with G466E mutation) and CD34 expression. Conversely, HGG-like ABM harbored specific alterations of diffuse midline glioma (2/5) or glioblastoma (GBM; 3/5). These latter patients showed an unfavorable clinical course with significantly shorter overall survival (p = .021). Mitogen-activated protein kinase pathway alterations (including FGFR fusion, BRAF and NF1 mutations) were present in 10 of 15 patients and overrepresented in the HGG-like group (3/5) compared with previously reported prevalence of these alterations in GBM and diffuse midline glioma.CONCLUSION: We suggest that gliomas with astroblastic features include a variety of molecularly sharply defined entities. Adult ABM harboring molecular features of PXA and HGG should be reclassified. Central nervous system high-grade neuroepithelial tumors with MN1 alterations and histology of ABM appear to be uncommon in adults. Astroblastic morphology in adults should thus prompt thorough molecular investigation aiming at a clear histomolecular diagnosis and identifying actionable drug targets, especially in the mitogen-activated protein kinase pathway.IMPLICATIONS FOR PRACTICE: Astroblastoma (ABM) remains a poorly defined and controversial entity. Although meningioma 1 alterations seem to define a large subset of pediatric cases, adult cases remain molecularly poorly defined. This comprehensive molecular characterization of 1 adolescent and 14 adult ABM revealed that adult ABM histology comprises several molecularly defined entities, which explains clinical diversity and identifies actionable targets. Namely, pleomorphic xanthoastrocytoma-like ABM cases show a favorable prognosis whereas high-grade glioma (glioblastoma and diffuse midline gliome)-like ABM show significantly worse clinical courses. These results call for in-depth molecular analysis of adult gliomas with astroblastic features for diagnostic and therapeutic purposes