Two novel tumours with NTRK2 fusion in the methylation class of extraventricular neurocytomas, including one intraventricular.

We report here about two novel tumours classified as extraventricular neurocytomas (EVN) using DNA-methylation profiling, associated with NTRK2 fusions instead of the usual FGFR1 alterations so far attributed to this tumoural entity. We present the second detailed case of an intraventricular presentation in the MC EVN. Our findings broaden the spectrum of MC EVN and have implications in terms of diagnosis, therapy and terminology.

[Genetic diffuse cystic lung disease in adults].

Multiple cystic lung diseases comprise a wide range of various diseases, some of them of genetic origin. Lymphangioleiomyomatosis (LAM) is a disease occurring almost exclusively in women, sporadically or in association with tuberous sclerosis complex (TSC). Patients with LAM present with lymphatic complications, renal angiomyolipomas and cystic lung disease responsible for spontaneous pneumothoraces and progressive respiratory insufficiency.

Whole F8 gene sequencing combined with splicing functional analyses led to a substantial increase of the molecular diagnosis yield for non-severe haemophilia A.

Introduction: Conventional genetic investigation fails to identify the F8 causal variant in 2.5%-10% of haemophilia A (HA) patients with non-severe phenotypes. In these cases, F8 deep intronic variants could be causal.

C-reactive protein: An easy marker for early differentiation between leptospirosis and dengue fever in endemic area.

In tropical regions, leptospirosis and dengue fever (DF) are infectious diseases of epidemiological importance and have overlapping symptomatic features. The objective of this study was to identify the factors associated to diagnosing leptospirosis that differentiate it to DF at the initial hospital evaluation. A multicenter retrospective study was conducted comparing confirmed leptospirosis to DF cases.

French recommendations for the diagnosis and management of lymphangioleiomyomatosis.

Background: The present article is an English-language version of the French National Diagnostic and Care Protocol, a pragmatic tool to optimize and harmonize the diagnosis, care pathway, management and follow-up of lymphangioleiomyomatosis in France.

Methods: Practical recommendations were developed in accordance with the method for developing a National Diagnosis and Care Protocol for rare diseases of the Haute Autorité de Santé and following international guidelines and literature on lymphangioleiomyomatosis. It was developed by a multidisciplinary group, with the help of patient representatives and of RespiFIL, the rare disease network on respiratory diseases.

Clinical Relevance of BRCA1 Promoter Methylation Testing in Patients with Ovarian Cancer.

Purpose: Homologous recombination deficiency (HRD) is closely related to PARP inhibitor (PARPi) benefit in ovarian cancer. The capacity of BRCA1 promoter methylation to predict prognosis and HRD status remains unclear. We aimed to correlate BRCA1 promoter methylation levels in patients with high-grade ovarian cancer to HRD status and clinical behavior to assess its clinical relevance.

Whole F9 gene sequencing identified deep intronic variations in genetically unresolved hemophilia B patients.

Background: The disease-causative variant remains unidentified in approximately 0.5% to 2% of hemophilia B patients using conventional genetic investigations, and F9 deep intronic variations could be responsible for these phenotypes.

Objectives: This study aimed to characterize deep intronic variants in hemophilia B patients for whom genetic investigations failed.

Clinico-pathological and epigenetic heterogeneity of diffuse gliomas with FGFR3::TACC3 fusion.

Background: Gliomas with FGFR3::TACC3 fusion mainly occur in adults, display pathological features of glioblastomas (GB) and are usually classified as glioblastoma, IDH-wildtype. However, cases demonstrating pathological features of low-grade glioma (LGG) lead to difficulties in classification and clinical management. We report a series of 8 GB and 14 LGG with FGFR3:TACC3 fusion in order to better characterize them.

Sjögren syndrome and RFC1-CANVAS sensory ganglionopathy: co-occurrence or misdiagnosis?

Background And Aims: RFC1-CANVAS and primary Sjögren syndrome (pSS) are among the most frequent causes of sensory ganglionopathy (SG) and can present simultaneously in a given patient, sharing confounding signs and symptoms. We describe the clinical characteristics of patients with SG due to CANVAS who were suspected of having or had received a previous diagnosis of pSS.

Methods: Patients with SG and a genetically confirmed RFC1-CANVAS followed in our centre were ascertained and their personal history of pSS was collected.

Balloon pulmonary angioplasty versus riociguat for the treatment of inoperable chronic thromboembolic pulmonary hypertension (RACE): a multicentre, phase 3, open-label, randomised controlled trial and ancillary follow-up study.

Background: Riociguat and balloon pulmonary angioplasty (BPA) are treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, randomised controlled trials comparing these treatments are lacking. We aimed to evaluate the efficacy and safety of BPA versus riociguat in patients with inoperable CTEPH.

Comprehensive analysis of F8 large deletions: Characterization of full breakpoint junctions and description of a possible DNA breakage hotspot in intron 6.

Background: Large F8 deletions represent 3-5% of the variations found in severe hemophilia A patients, but only a few deletion breakpoints have been characterized precisely.

Objectives: Resolving at the nucleotide level 24 F8 large deletions to provide new data on the mechanisms involved in these rearrangements.

Methods: Breakpoint junctions of 24 F8 large deletions were characterized using a combination of long-range polymerase chain reaction, whole F8 NGS sequencing, and Sanger sequencing.

Clinical and pathological impact of an optimal assessment of brain invasion for grade 2 meningioma diagnosis: lessons from a series of 291 cases.

Brain invasion has not been recognized as a standalone criterion for atypical meningioma by the WHO classification until 2016. Since the 2007 edition suggested that meningiomas harboring brain invasion could be classified as grade 2, brain invasion study was progressively strengthened in our center, based on a strong collaboration between neurosurgeons and neuropathologists regarding sample orientation and examination. Practice changes were considered homogeneous enough in 2011.

Rosette-forming glioneuronal tumours are midline, FGFR1-mutated tumours.

Aim: Rosette-forming glioneuronal tumour (RGNT) is a rare central nervous system (CNS) World Health Organization (WHO) grade 1 brain neoplasm. According to the WHO 2021, essential diagnostic criteria are a 'biphasic histomorphology with neurocytic and a glial component, and uniform neurocytes forming rosettes and/or perivascular pseudorosettes associated with synaptophysin expression' and/or DNA methylation profile of RGNT whereas 'FGFR1 mutation with co-occurring PIK3CA and/or NF1 mutation' are desirable criteria.

Material And Methods: We report a series of 46 cases fulfilling the essential pathological diagnostic criteria for RGNT.

How to assess eye movements clinically.

Eye movements serve vision in orienting gaze toward an object of interest in order to place its image simultaneously on both foveas and in stabilizing gaze relative to the environment in order to maintain fixation on the object of interest, even in the case of body displacement. Disorders of eye movements can interfere with ocular alignment and/or monocular motility, and result in diplopia, which is the most common symptom. Eye movement disorders can also interfere with binocular motility without ocular misalignment and result in gaze palsy.

One Health compartmental analysis of ESBL-producing Escherichia coli on Reunion Island reveals partitioning between humans and livestock.

Background: Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-Ec) is a major cause of infections worldwide. An understanding of the reservoirs and modes of transmission of these pathogens is essential, to tackle their increasing frequency.

Objectives: We investigated the contributions of various compartments (humans, animals, environment), to human colonization or infection with ESBL-Ec over a 3 year period, on an island.

Discovery of a genetic module essential for assigning left-right asymmetry in humans and ancestral vertebrates.

The vertebrate left-right axis is specified during embryogenesis by a transient organ: the left-right organizer (LRO). Species including fish, amphibians, rodents and humans deploy motile cilia in the LRO to break bilateral symmetry, while reptiles, birds, even-toed mammals and cetaceans are believed to have LROs without motile cilia. We searched for genes whose loss during vertebrate evolution follows this pattern and identified five genes encoding extracellular proteins, including a putative protease with hitherto unknown functions that we named ciliated left-right organizer metallopeptide (CIROP).

Low-grade epilepsy-associated neuroepithelial tumours with a prominent oligodendroglioma-like component: The diagnostic challenges.

Aims: We searched for recurrent pathological features and molecular alterations in a retrospective series of 72 low-grade epilepsy-associated neuroepithelial tumours (LEATs) with a prominent oligodendroglioma-like component, in order to classify them according to the 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumours.

Methods: Centralised pathological examination was performed as well as targeted molecular analysis of v-Raf murine sarcoma viral oncogene homologue B (BRAF) and fibroblast growth factor receptor 1 (FGFR1) by multiplexed digital polymerase chain reaction (mdPCR). DNA methylation profiling was performed in cases with sufficient DNA.

Characteristics and management of hydrocephalus in adult patients with cerebellar glioblastoma: lessons from a French nationwide series of 118 cases.

The characteristics of hydrocephalus associated with cerebellar glioblastoma (cGB) remain poorly known. The objectives were to describe the occurence of hydrocephalus in a French nationwide series of adult patients with cGB, to identify the characteristics associated with hydrocephalus and to analyze the outcomes associated with the different surgical strategies, in order to propose practical guidelines. Consecutive cases of adult cGB patients prospectively recorded into the French Brain Tumor Database between 2003 and 2017 were screened.