The genomic landscape of dysembryoplastic neuroepithelial tumours and a comprehensive analysis of recurrent cases.

Aims: Dysembryoplastic neuroepithelial tumour (DNT) is a glioneuronal tumour that is challenging to diagnose, with a wide spectrum of histological features. Three histopathological patterns have been described: specific DNTs (both the simple form and the complex form) comprising the specific glioneuronal element, and also the non-specific/diffuse form which lacks it, and has unclear phenotype-genotype correlations with numerous differential diagnoses.

Methods: We used targeted methods (immunohistochemistry, fluorescence in situ hybridisation and targeted sequencing) and large-scale genomic methodologies including DNA methylation profiling to perform an integrative analysis to better characterise a large retrospective cohort of 82 DNTs, enriched for tumours that showed progression on imaging.

The Use of Pro-Angiogenic and/or Pro-Hypoxic miRNAs as Tools to Monitor Patients with Diffuse Gliomas.

IDH (isocitrate dehydrogenase) mutation, hypoxia, and neo-angiogenesis, three hallmarks of diffuse gliomas, modulate the expression of small non-coding RNAs (miRNA). In this paper, we tested whether pro-angiogenic and/or pro-hypoxic miRNAs could be used to monitor patients with glioma. The miRNAs were extracted from tumoral surgical specimens embedded in the paraffin of 97 patients with diffuse gliomas and, for 7 patients, from a blood sample too.

[Analysis of interference criteria for the validation of a method file: HPS staining after fixation with zinc-formalin in comparison to fixation with the classical 4% buffered formalin solution].

Introduction: The department of neuropathology of Sainte-Anne Hospital uses zinc-formalin as the fixative agent for its samples. No publication referenced in Pubmed has proven the validity of this fixative agent. In the context of the accreditation of our standard staining (HPS for Hemalun-Phloxin-Saffron), we started a file for the validation of this method in which the fixative agent constitutes an « interfering » substance which can modify the quality of the technique.

Meningioangiomatosis: Multimodal Analysis and Insights From a Systematic Review.

Background: Meningioangiomatosis is a poorly studied, rare, benign, and epileptogenic brain lesion.

Objective: To demonstrate that surgical resection and a short-time interval to surgery improves epileptic seizure control, we performed a systematic review and meta-analysis of meningioangiomatosis cases.

Methods: Using PRISMA-IPD guidelines, the authors performed a systematic review and meta-analysis of histopathologically-proven meningioangiomatosis cases.

Postoperative intracerebral haematomas following stereotactic biopsies: Poor planning or poor execution?

Background: Postoperative intracerebral haematomas represent a serious complication following stereotactic biopsy. We investigated the possible underlying causes - poor planning or poor execution - of postoperative intracerebral haematomas following stereotactic biopsies.

Methods: We performed a technical investigation using a retrospective single-centre consecutive series of robot-assisted stereotactic biopsies for a supratentorial diffuse glioma in adults.

Prognostic relevance of adding MRI data to WHO 2016 and cIMPACT-NOW updates for diffuse astrocytic tumors in adults. Working toward the extended use of MRI data in integrated glioma diagnosis.

Assess the contribution of preoperative MRI data in improving grading of adult astrocytomas reclassified according to the WHO 2016 and cIMPACT-NOW update 3. Retrospective unicentric cohort study of 679 adult patients treated for newly diagnosed diffuse astrocytic and oligodendroglial tumors (January 2006-December 2016). We first systematically compared radiological (contrast enhancement present [CE+] vs.

Promoter Hypermethylation of Genes Encoding for RASSF/Hippo Pathway Members Reveals Specific Alteration Pattern in Diffuse Gliomas.

Ras association domain family (RASSF)/Hippo pathway alterations are poorly characterized in diffuse gliomas. We assayed promoter methylation of LATS1/2, MST1(STK4)/MST2(STK3), RASSF1, RASSF2, Nore1A/RASSF5, RASSF6, and RASSF10 genes in 133 diffuse gliomas. The RASSF/Hippo pathway was highly silenced in gliomas, particularly RASSF1A (79.

Meningeal Metastasis Relapse With Focal Involvement of Cranial Bone Flap: A Case Resolved by 18F-DOPA PET/MRI.

A 63-year-old woman was referred to our PET/MRI platform to evaluate the possible relapse of a meningeal metastasis, complicating an invasive ductal carcinoma of the left breast. This metastasis was diagnosed on a left hemiparesis and treated by surgery and radiation therapy. One year later, the same symptoms led to another brain MRI examination that found a contrast-enhanced lesion in the operating site.

Cerebrospinal fluid flow increases from newborn to adult stages.

Solute transport through the brain is of major importance for the clearance of toxic molecules and metabolites, and it plays key roles in the pathophysiology of the central nervous system. This solute transport notably depends on the cerebrospinal fluid (CSF) flow, which circulates in the subarachnoid spaces, the ventricles and the perivascular spaces. We hypothesized that the CSF flow may be different in the perinatal period compared to the adult period.

A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas.

Chordoid glioma (ChG) is a characteristic, slow growing, and well-circumscribed diencephalic tumor, whose mutational landscape is unknown. Here we report the analysis of 16 ChG by whole-exome and RNA-sequencing. We found that 15 ChG harbor the same PRKCA mutation.

FMISO-PET-derived brain oxygen tension maps: application to glioblastoma and less aggressive gliomas.

Quantitative imaging modalities for the analysis of hypoxia in brain tumors are lacking. The objective of this study was to generate absolute maps of tissue pO from [F]-FMISO images in glioblastoma and less aggressive glioma patients in order to quantitatively assess tumor hypoxia. An ancillary objective was to compare estimated pO values to other biomarkers: perfusion weighted imaging (PWI) and tumor metabolism obtained from H-MR mono-voxel spectroscopy (MRS).

Clinical validation of the CE-IVD marked Therascreen MGMT kit in a cohort of glioblastoma patients.

Background: Pyrosequencing is recognized as a strong technique to analyze the MGMT status of glioblastoma patients. The most commonly used assay, quantifies the methylation levels of CpGs 74 to 78. A more recent CE-marked In Vitro Diagnostic Medical Device (CE-IVD) assay, Therascreen, analyzes CpGs 76-79.

Deep intronic hotspot variant explaining rhabdoid tumor predisposition syndrome in two patients with atypical teratoid and rhabdoid tumor.

About one third of patients with rhabdoid tumors (RT) harbor a heterozygous germline variant in SMARCB1. Molecular diagnosis therefore keeps a crucial place in the diagnosis of RT, and genetic counseling should be systematically recommended. However, immunohistochemistry has progressively replaced molecular tools to assess the status of SMARCB1 in tumors; the necessity of analyzing SMARCB1 status in the tumor may thus be less considered by neuropathologists and pediatric neuro-oncologists.

Immune Reconstitution Inflammatory Syndrome Unmasking or Worsening AIDS-Related Progressive Multifocal Leukoencephalopathy: A Literature Review.

Incidence of progressive multifocal leukoencephalopathy (PML) in HIV-infected patients has declined in the combined antiretroviral therapy (cART) era although a growing number of acquired immunodeficiency syndrome (AIDS)-related PML-immune reconstitution inflammatory syndromes (PML-IRIS) have been published during the same period. Therapeutic management of PML-IRIS is not consensual and mainly relies on corticosteroids. Our main aim was, in addition to provide a thoughtful analysis of published PML-IRIS cases, to assess the benefit of corticosteroids in the management of PML-IRIS, focusing on confirmed cases.

[18F]-FMISO PET study of hypoxia in gliomas before surgery: correlation with molecular markers of hypoxia and angiogenesis.

Purpose: Hypoxia in gliomas is associated with tumor resistance to radio- and chemotherapy. However, positron emission tomography (PET) imaging of hypoxia remains challenging, and the validation of biological markers is, therefore, of great importance. We investigated the relationship between uptake of the PET hypoxia tracer [18F]-FMISO and other markers of hypoxia and angiogenesis and with patient survival.

Histopathologic diagnosis of brain metastases: current trends in management and future considerations.

Confronted with brain metastases (BM), pathologists aim to rule out a primary central nervous system (CNS) tumor and to identify or verify the primary tumor site to guide the clinician to specific therapies. Apart from morphological features, ancillary immunohistochemical analysis is the most effective tool for characterizing a metastatic neoplasm of unknown origin. A limited array of antibodies is used, taking into account relevant clinical information and the known brain tropism of lung cancer, breast cancer and melanoma.

Prognostic impact of the 2016 WHO classification of diffuse gliomas in the French POLA cohort.

The new WHO classification of diffuse gliomas has been refined and now includes the 1p/19q codeletion, IDH1/2 mutation, and histone H3-K27M mutation. Our objective was to assess the prognostic value of the updated 2016 WHO classification in the French POLA cohort. All cases of high-grade oligodendroglial tumors sent for central pathological review and included into the French nationwide POLA cohort were reclassified according to the updated 4th WHO classification.

Validation of the high-performance of pyrosequencing for clinical MGMT testing on a cohort of glioblastoma patients from a prospective dedicated multicentric trial.

Background: The goal of this prospective multicentric trial was to validate a technique that allowed for MGMT promoter methylation analysis in routine clinical practice.

Methods: The MGMT status of 139 glioblastoma patients, whom had received standard first line treatment, was determined using pyrosequencing (PSQ) and a semi-quantitative Methylation-specific PCR (sqMS-PCR) method, using both frozen and formalin-fixed paraffin-embedded FFPE samples. Eight participating centers locally performed the analysis, including external quality controls.

Supratentorial clear cell ependymomas with branching capillaries demonstrate characteristic clinicopathological features and pathological activation of nuclear factor-kappaB signaling.

Background: Clear cell ependymoma is one of the 4 main histological subtypes of ependymomas defined by the World Health Organization (WHO) classification of tumors of the CNS. DNA methylation profiling can distinguish 4 subgroups of intracranial ependymomas, including supratentorial (ST) ependymomas with Yes-associated protein 1 fusion (YAP1), ST ependymomas with fusion of v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA), posterior fossa ependymomas with balanced genome, and posterior fossa ependymomas with chromosomal instability. In addition, trisomy 19 is a genomic hallmark of ependymomas with rich branching capillaries.

Papillary glioneuronal tumors: histological and molecular characteristics and diagnostic value of SLC44A1-PRKCA fusion.

Introduction: Papillary Glioneuronal Tumor (PGNT) is a grade I tumor which was classified as a separate entity in the World Health Organization Classification of the Central Nervous System 2007 in the group of mixed glioneuronal tumors. This tumor is rare and subclassifying PGNT represents a challenge. Recently, a fusion between SLC44A1 and PRKCA which encodes a protein kinase C involved in MAPK signaling pathway has been described in two studies (five cases).

Long-term results of carmustine wafer implantation for newly diagnosed glioblastomas: a controlled propensity-matched analysis of a French multicenter cohort.

Background: The standard of care for newly diagnosed glioblastoma is maximal safe surgical resection, followed by chemoradiation therapy. We assessed carmustine wafer implantation efficacy and safety when used in combination with standard care.

Methods: Included were adult patients with (n = 354, implantation group) and without (n = 433, standard group) carmustine wafer implantation during first surgical resection followed by chemoradiation standard protocol.

Chordoid gliomas of the third ventricle share TTF-1 expression with organum vasculosum of the lamina terminalis.

Chordoid glioma of the third ventricle (CG3V) is a rare tumor developing in a stereotyped localization. It has been related to the circumventricular organ of the lamina terminalis, in the anterior part of the third ventricle, but its oncogenesis is poorly understood. TTF-1 transcription factor is involved in the development and adult physiology of the ventral forebrain.