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Posterior fossa group A ependymomas (EPN_PFA) are characterized by a loss of H3 K27 trimethylation due to either EZHIP overexpression or H3 p.K27M mutation, similar to H3 K27-altered diffuse midline gliomas (DMG), but in reverse proportions. Very little data is available in the literature concerning H3 K27M-mutant EPN_PFA. Here, we retrospectively studied a series of nine pediatric tumors initially diagnosed as H3 K27M-mutant EPN_PFA to compare them to EZHIP-overexpressing EPN_PFA in terms of radiology, follow-up, histopathology, and molecular biology (including DNA-methylation profiling). Seven tumors clustered within EPN_PFA by DNA-methylation analysis and t-distributed stochastic neighbor embedding. Among the two remaining cases, one was reclassified as a DMG and the last was unclassified. H3 K27M-mutant EPN_PFA cases were significantly older than their counterparts with an EZHIP overexpression. Radiological and histopathological central review of our seven H3 K27M-mutant EPN_PFA cases found them to be similar to their counterparts with an EZHIP overexpression. Sequencing analyses revealed HIST1H3B (n = 2), HIST1H3C (n = 2), H3F3A (n = 1), and HIST1H3D (n = 1) K27M mutations (no sequencing analysis available for the last case which was immunopositive for H3K27M). Consequently, HIST1H3C/D mutations are more frequently observed in EPN_PFA than in classic pontine DMG, H3K27-mutant. Overall survival and event-free survival of EZHIP-overexpressing and H3 K27M-mutant EPN_PFA were similar. After surgery and radiation therapy, 5/7 patients were alive at the end of the follow-up. In summary, the diagnosis of EPN_PFA must include tumor location, growth pattern, Olig2 expression, and DNA-methylation profiling before it can be differentiated from DMG, H3 K27-altered.

International audience; Dysplastic gangliocytoma of the cerebellum (DGC), also called Lhermitte-Duclos disease, is a rare lesion of the posterior fossa consisting of a diffuse hypertrophy of the cerebellar cortex. DGC frequently presents in young adults and rarely in childhood. Only 3 cases have been previously described in newborns. We present an uncommon case of DGC which was diagnosed in utero.The radiological presentation prenatally and at birth was similar to a heterotopic neuroglial brain tissue. MRI aspects evolved from T1/T2 isointense signals to hypoT1 and hyperT2 signals at the age of 1 year. The girl was then operated on total removal of the lesion which was performed with no postoperative complication. Genetics did not demonstrate any germline PTEN mutation or family history suggesting Cowden disease. Two years later, the child was doing well and MRI confirmed complete resection. This case illustrates the difficulties of diagnosing intracranial lesions in foetuses and newborns. Physicians caring for pregnant women and pediatrics should be aware that neoplasm-like lesions such as DGC may present as hamartomas. Surgical resection could then be discussed whenever possible.

OBJECTIVETumor-related edema of the optic tract (EOT) corresponds to a preferential posterior distribution of peritumoral edema along the white matter tract of the visual system. To date, the consequences of EOT have never been evaluated specifically in the pediatric population. In this study, the authors attempted to identify clinical and radiological features associated with the development of EOT and the specific influence of this edema on visual function.METHODSA retrospective review was performed of data collected from patients younger than 18 years who underwent surgery for a tumor in the sellar region at the authors’ institution between January 2005 and January 2016. Data were collected on patient characteristics, ophthalmological evaluations, and neuroimaging findings. To evaluate and compare visual function impairment, ophthalmological data were converted to a global visual function score, which took into account visual acuity, visual field evaluations, and laterality deficiencies. The visual acuity score was defined according to the International Classification of Diseases, 10th Revision. Visual field deficiencies were converted to a score of 0–2. Two opposing groups were then distinguished according to the presence or absence of EOT. Visual acuity, visual field results, and global scores were compared between groups before and after treatment.RESULTSTwenty-six patients were included in the study: 17 patients with craniopharyngioma, 3 patients with pilocytic astrocytoma, 2 patients with ganglioglioma, 2 patients with germ cell tumor, 1 patient with macroprolactinoma, and 1 patient with Rathke’s cleft cyst. There were 11 children in the group with edema and 15 children in the group without edema. None of the following criteria were statistically different between the 2 groups: age, sex, clinical symptoms at presentation (endocrine deficiency or intracranial hypertension signs), incidence of hydrocephalus, compression of the optic tracts and mass effect on the optic chiasm, tumor size and localization, presence of intratumoral cysts, treatment, type of tumor, or recurrence. The median global visual function and visual acuity scores were not significantly different between the groups either at presentation or at final evaluation. The visual field score was lower (i.e., more deficiency) in the group with edema than in the group without edema (p < 0.05); 89% of the patients with edema had severe or mild visual field impairment versus only 40% of the patients without edema. At the final examination after treatment, the visual field scores were not different between the 2 groups. Although not significant, the number of patients with optic disc pallor was greater in the group without edema both at diagnosis and at final examination.CONCLUSIONSThis study confirms that EOT in the context of sellar region tumor in children is not necessarily associated with a less-favorable visual prognosis.

Development of tumours such as adrenocortical carcinomas (ACC), choroid plexus tumours (CPT) or female breast cancers before age 31 or multiple primary cancers belonging to the Li-Fraumeni (LFS) spectrum is, independently of the familial history, highly suggestive of a germlineAmong 328 unrelated patients harbouring a germlineThis study performed on a large series of

International audience; PURPOSE: Presence of metastases in newly diagnosed pediatric posterior fossa tumors (PFT) is not a rare situation, but optimal treatment of associated hydrocephalus in these children has remained undetermined. METHODS: Twenty-nine children treated between January 2005 and December 2015 for a metastatic PFT associated with hydrocephalus constituted the study cohort. Patients were divided into three groups: ventriculoperitoneal shunt (VPS), endoscopic third ventriculostomy (ETV), and temporary ventricular drainage before or during tumor resection (PVD). RESULTS: There were 4 VPS, 18 ETV, and 7 PVD. The global incidence of CSF diversion failure was 52%. No case of dysfunction or dissemination of metastatic cells occurred in the VPS group. Recurrence of hydrocephalus occurred in 55% of the ETV group. Presence of multiple macroscopic metastases and CSF metastatic cells after tumor surgery was associated with ETV failure. Fifty-seven percent of the children in the PVD group were reoperated after an average time of 53 days. Specific oncologic treatment was initiated earlier in the VPS group (11 days) compared to ETV (27 days) and PVD (23 days) groups. CONCLUSIONS: ETV should be avoided in cases of multiple macroscopic metastases, and children who underwent ETV must be followed carefully when metastatic cells are present in CSF after tumor surgery. External ventricular drainage before or during surgical removal should not be considered as a final option to treat hydrocephalus. VPS remains a safe alternative in this situation and allows an early specific oncologic treatment.

International audience; Ifosfamide and methotrexate are widely used for the treatment of pediatric osteosarcoma. However, both these chemotherapeutic drugs can cause encephalopathy. A 17-year-old girl presented with profound hearing loss and dizziness during a postoperative course of ifosfamide, 20 days after a course of methotrexate. Cerebral magnetic resonance imaging (MRI) showed bilateral white matter hypersignal in Fluid Attenuated Inversion Recovery sequences. The clinical evolution was rapidly favorable after methylene blue infusion. This is the second reported case of acute deafness, possibly associated with ifosfamide, whereas MRI data revealed unnoticed chronic methotrexate toxicity. Systematic MRI screening and hearing evaluation may be useful in such cases.

Pediatric cortical glioneuronal benign tumors mainly include gangliogliomas (GG) [differential diagnoses pilocytic astrocytomas (PA) and pleomorphic xanthoastrocytomas (PXA)] and dysembryoplastic neuroepithelial tumor (DNT). DNT include the specific form and the controversial non‐specific form that lack the specific glioneuronal element. Our aims were to search for BRAF(V600E) mutation and CD34 expression in DNT, PXA, GG and PA to correlate BRAF(V600E) mutation with BRAF(V600E) expression and to evaluate their diagnostic and prognostic values. Ninety‐six children were included. BRAF(V600E) mutation was studied by sequencing and immunohistochemistry; CD34 expression was analyzed by immunohistochemistry. BRAF(V600E) mutation was detected in PXA (60%), GG (38.7%), DNT (30%, including 3/11 specific and 3/9 non‐specific forms) and PA (12.5%). BRAF(V600E) expression was recorded in PXA (60%), GG (45.2%) and DNT (30%). CD34 expression was recorded in PXA (60%), GG (58.1%), DNT (25%) and PA (12.5%). Neither CD34 expression nor BRAF(V600E) status was predictive of prognosis, except for PA tumors where CD34 expression was associated with a shorter overall survival. In conclusion, DNT shared with PXA and GG, BRAF(V600E) mutation and/or CD34 expression, which represent molecular markers for these tumors, and we recommend searching for CD34 expression and BRAF(V600E) mutation in all DNT, especially the non‐specific forms.

Gliomatosis cerebri (GC) is a rare neoplasm including a variety of tumors, with extremely variable evolution and heterogeneity of prognosis. It may appear either de novo or after a focal glioma, involve predominantly the white or the gray matter, and concern either pediatric or adult patients. We focused on primary GC involving exclusively gray matter in a pediatric population in order better to define the presentation and outcome of this disease.We reviewed the databases of seven Departments of Pediatric Oncology to identify pediatric cases of GC between 1990 and 2007. Patients were included if they demonstrated a diffuse infiltrative process involving gray matter in magnetic resonance imaging (MRI) and histological tissue analyses, confirming a proliferative glial disorder.Fourteen patients with a median age of 8 years were identified. Epilepsy was the main presenting symptom. Brain MRI showed a lesion of the temporal and insular cerebral cortex associated with tumoral infiltration of the thalami and the basal ganglia. Histological examination confirmed the diagnosis of high-grade glioma. Prognosis was always very gloomy in the short term, with a median survival of less than a year.This rare entity, whose prognosis is appalling whatever the treatment proposed, should be clearly identified within the heterogeneous group of GC in the same way as diffuse intrinsic pontine gliomas have been identified among brain stem tumors. Systematic biopsies appear essential to permit the molecular studies which will assist in guiding the choice of future targeted treatments.