Paediatric low-grade glioma: the role of classical pathology in integrated diagnostic practice.

Low-grade gliomas are a cause of severe and often life-long disability in children. Pathology plays a key role in their management by establishing the diagnosis, excluding malignant alternatives, predicting outcomes and identifying targetable genetic alterations. Molecular diagnosis has reshaped the terrain of pathology, raising the question of what part traditional histology plays.

Decision making for health-related research outcomes that alter diagnosis: A model from paediatric brain tumours.

Aims: The question of how to handle clinically actionable outcomes from retrospective research studies is poorly explored. In neuropathology, this problem is exacerbated by ongoing refinement in tumour classification. We sought to establish a disclosure threshold for potential revised diagnoses as determined by the neuro-oncology speciality.

Pediatric nasal chondromesenchymal hamartomas: a case series.

Purpose: Nasal chondromesenchymal hamartomas (NCMH) are rare, predominantly benign tumors of the sinonasal tract. The distinction from higher grade malignancy may be challenging based on imaging features alone. To increase the awareness of this entity among radiologists, we present a multi-institutional case series of pediatric NCMH patients showing the varied imaging presentation.

Primary orbital rhabdoid tumour masquerading as atypical persistent foetal vasculature.

We present a case of primary rhabdoid tumour of the orbit. Presenting features at birth included congenital ptosis, conjunctival injection, hyphaema and microphthalmia. The unique presentation caused a late diagnosis following the development of rapid proptosis 6 months later.

A Novel Variant in Causing Muscle Weakness and Concomitant Hypercontractile Phenotype.

A novel variant of unknown significance c.8A > G (p.Glu3Gly) in was detected in two unrelated families.

Germline homozygous missense DEPDC5 variants cause severe refractory early-onset epilepsy, macrocephaly and bilateral polymicrogyria.

DEPDC5 (DEP Domain-Containing Protein 5) encodes an inhibitory component of the mammalian target of rapamycin (mTOR) pathway and is commonly implicated in sporadic and familial focal epilepsies, both non-lesional and in association with focal cortical dysplasia. Germline pathogenic variants are typically heterozygous and inactivating. We describe a novel phenotype caused by germline biallelic missense variants in DEPDC5.

Congenital orbital teratoma: A case report with foetal presentation.

Congenital orbital teratomas are rare entities with few case reports detailing their prenatal and perinatal imaging features. We present the case of a congenital orbital teratoma initially detected as cystic lesion on prenatal ultrasound, with foetal and postnatal imaging showing evolution of characteristic MRI appearances. Knowledge of these appearances and the ability to diagnose these rare entities in foetal life can aid management and operative planning in the immediate postnatal period.

Muscle biopsy in myositis: What the rheumatologist needs to know.

The appropriate analysis of skeletal muscle tissues is a key element in many diagnostic procedures and can deliver valuable information about the organ that is affected. Although arguably the frequency of muscle biopsy may be declining in certain domains where genetic analysis is now the first line of diagnostic evaluation, it still has an important role in assessment of patients with neuromuscular disorders such as congenital myopathies, muscular dystrophies, metabolic and inflammatory diseases. Here, we have comprehensively discussed the aspects of a modern and fruitful approach to muscle biopsy histopathological studies in rheumatological disorders.

Bi-allelic loss-of-function OBSCN variants predispose individuals to severe recurrent rhabdomyolysis.

Rhabdomyolysis is the acute breakdown of skeletal myofibres in response to an initiating factor, most commonly toxins and over exertion. A variety of genetic disorders predispose to rhabdomyolysis through different pathogenic mechanisms, particularly in patients with recurrent episodes. However, most cases remain without a genetic diagnosis.

Andersen-Tawil syndrome: deep phenotyping reveals significant cardiac and neuromuscular morbidity.

Andersen-Tawil syndrome is a neurological channelopathy caused by mutations in the KCNJ2 gene that encodes the ubiquitously expressed Kir2.1 potassium channel. The syndrome is characterized by episodic weakness, cardiac arrythmias and dysmorphic features.

Repurposing Vandetanib plus Everolimus for the Treatment of -Mutant Diffuse Intrinsic Pontine Glioma.

Somatic mutations in are found in a quarter of children with diffuse intrinsic pontine glioma (DIPG), but there are no ACVR1 inhibitors licensed for the disease. Using an artificial intelligence-based platform to search for approved compounds for -mutant DIPG, the combination of vandetanib and everolimus was identified as a possible therapeutic approach. Vandetanib, an inhibitor of VEGFR/RET/EGFR, was found to target ACVR1 ( = 150 nmol/L) and reduce DIPG cell viability but has limited ability to cross the blood-brain barrier.

Progressive myoclonic epilepsy due to rare mitochondrial ND6 mutation, m.14487T>C.

Introduction: Mitochondrial diseases exhibit wide phenotypic heterogeneity, and can present as progressive myoclonic epilepsy.

Summary: We report a case of adult-onset drug-resistant epilepsy, cortical myoclonus and bilateral optic neuropathies due to m.14487T>C, a rare mitochondrial gene mutation identified on whole-genome sequencing.

Ectopic thoracic meningioma: a diagnostically challenging case.

Whilst meningiomas are common neoplasms of the central nervous system; ectopic meningiomas are very rare. When they do occur, they are typically in the head and neck. Due to their rarity, they propose a diagnostic challenge with interesting pathological findings.

Constitutional mismatch repair deficiency (CMMRD) presenting with high-grade glioma, multiple developmental venous anomalies and malformations of cortical development-a multidisciplinary/multicentre approach and neuroimaging clues to clinching the diagnosis.

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare cancer-predisposition syndrome associated with a high risk of developing a spectrum of malignancies in childhood and adolescence, including brain tumours. In this report, we present the case of an 8-year-old boy with acute headache, vomiting and an episode of unconsciousness in whom brain imaging revealed a high-grade glioma (HGG). The possibility of an underlying diagnosis of CMMRD was suspected radiologically on the basis of additional neuroimaging findings, specifically the presence of multiple supratentorial and infratentorial developmental venous anomalies (DVAs) and malformations of cortical development (MCD), namely, heterotopic grey matter.

Differential Diagnoses of Inclusion Body Myositis.

Inclusion body myositis is a slowly progressive myopathy, characteristically affecting quadriceps and long finger flexors. Atypical presentations do occur, however, and there is overlap with other myopathies, including inflammatory and hereditary etiologies. This article discusses atypical cases and differential diagnoses and considers the role of imaging and histopathology in differentiating inclusion body myositis.

DNA methylation-based profiling for paediatric CNS tumour diagnosis and treatment: a population-based study.

Background: Marked variation exists in the use of genomic data in tumour diagnosis, and optimal integration with conventional diagnostic technology remains uncertain despite several studies reporting improved diagnostic accuracy, selection for targeted treatments, and stratification for trials. Our aim was to assess the added value of molecular profiling in routine clinical practice and the impact on conventional and experimental treatments.

Methods: This population-based study assessed the diagnostic and clinical use of DNA methylation-based profiling in childhood CNS tumours using two large national cohorts in the UK.

Correction to: c-MYC overexpression induces choroid plexus papillomas through a T-cell mediated inflammatory mechanism.

In the original version of this article [1], there was 1 error in the affiliation of the European Institute of Oncology (affiliation 3). In this correction article the updated affiliation is shown for clarification.

Recurrent Langerhans cell histiocytosis at the site of prior craniotomy: case report.

Tumors of the CNS represent the largest group of solid tumors found in the pediatric patient population. Langerhans cell histiocytosis (LCH) is an inflammatory lesion that may present in bone and/or soft tissue, including the CNS. Management depends on the extent of multisystem involvement, which determines resection with or without systemic chemotherapy.