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Nature Communications Nov 2023Pediatric high-grade gliomas of the subclass MYCN (HGG-MYCN) are highly aggressive tumors frequently carrying MYCN amplifications, TP53 mutations, or both alterations....
Pediatric high-grade gliomas of the subclass MYCN (HGG-MYCN) are highly aggressive tumors frequently carrying MYCN amplifications, TP53 mutations, or both alterations. Due to their rarity, such tumors have only recently been identified as a distinct entity, and biological as well as clinical characteristics have not been addressed specifically. To gain insights into tumorigenesis and molecular profiles of these tumors, and to ultimately suggest alternative treatment options, we generated a genetically engineered mouse model by breeding hGFAP-cre::Trp53::lsl-MYCN mice. All mice developed aggressive forebrain tumors early in their lifetime that mimic human HGG-MYCN regarding histology, DNA methylation, and gene expression. Single-cell RNA sequencing revealed a high intratumoral heterogeneity with neuronal and oligodendroglial lineage signatures. High-throughput drug screening using both mouse and human tumor cells finally indicated high efficacy of Doxorubicin, Irinotecan, and Etoposide as possible therapy options that children with HGG-MYCN might benefit from.
Topics: Humans; Child; Mice; Animals; N-Myc Proto-Oncogene Protein; Neuroblastoma; Disease Models, Animal; Glioma; Mutation; Gene Amplification
PubMed: 38001143
DOI: 10.1038/s41467-023-43564-w -
Neurosurgical Review Jan 2024The extent of resection and neurological outcome are important prognostic markers for overall survival in glioma patients. Confocal laser endomicroscopy is a tool to...
OBJECTIVE
The extent of resection and neurological outcome are important prognostic markers for overall survival in glioma patients. Confocal laser endomicroscopy is a tool to examine tissue without the need for fixation or staining. This study aims to analyze gliomas in confocal laser endomicroscopy and identify reliable diagnostic criteria for glial matter and glial tumors.
MATERIAL AND METHODS
One-hundred-and-five glioma specimens were analyzed using a 670-nm confocal laser endomicroscope and then processed into hematoxylin-eosin-stained frozen sections. All confocal images and frozen sections were evaluated for the following criteria: presence of tumor, cellularity, nuclear pleomorphism, changes of the extracellular glial matrix, microvascular proliferation, necrosis, and mitotic activity. Recurring characteristics were identified. Accuracy, sensitivity, specificity, and positive and negative predictive values were assessed for each feature.
RESULTS
All 125 specimens could be processed and successfully analyzed via confocal laser endomicroscopy. We found diagnostic criteria to identify white and grey matter and analyze cellularity, nuclear pleomorphism, changes in the glial matrix, vascularization, and necrosis in glial tumors. An accuracy of > 90.0 % was reached for grey matter, cellularity, and necrosis, > 80.0 % for white matter and nuclear pleomorphism, and > 70.0 % for microvascular proliferation and changes of the glial matrix. Mitotic activity could not be identified. Astroglial tumors showed significantly less nuclear pleomorphism in confocal laser endomicroscopy than oligodendroglial tumors (p < 0.001). Visualization of necrosis aids in the differentiation of low grade gliomas and high grade gliomas (p < 0.002).
CONCLUSION
Autofluorescence-based confocal laser endomicroscopy proved not only useful in differentiation between tumor and brain tissue but also revealed useful clues to further characterize tissue without processing in a lab. Possible applications include the improvement of extent of resection and the safe harvest of representative tissue for histopathological and molecular genetic diagnostics.
Topics: Humans; Neoplasm Recurrence, Local; Endoscopy; Glioma; Cerebral Cortex; Necrosis
PubMed: 38265724
DOI: 10.1007/s10143-024-02286-3 -
Brain Pathology (Zurich, Switzerland) Jan 2024The tumor showed extensive microcalcifications and cells with oval, nuclei and a clear perinuclear halo (A), positive immunostaining for OLIG-2 (B), GFAP (C), and CD34...
The tumor showed extensive microcalcifications and cells with oval, nuclei and a clear perinuclear halo (A), positive immunostaining for OLIG-2 (B), GFAP (C), and CD34 (D), and intermingled Neu-N-positive neurons (E). FISH revealed multiple signals for the centromere of chromosome 7 (gains) (green probe) and the EGFR locus (red probe) (F, left), and a single signal for the centromere of chromosome 10 (loss) (F, right).
Topics: Humans; Brain Neoplasms; Microtubule-Associated Proteins; Glioma; Oligodendroglia; Calcinosis
PubMed: 37409721
DOI: 10.1111/bpa.13187 -
European Journal of Radiology Feb 2024To evaluate the feasibility of a multimodal approach involving dynamic contrast-enhanced (DCE) perfusion imaging and diffusion kurtosis imaging (DKI) in the preoperative...
Improved diagnostic confidence and tumor type prediction in adult-type diffuse glioma by multimodal imaging including DCE perfusion and diffusion kurtosis mapping - A standardized multicenter study.
BACKGROUND AND PURPOSE
To evaluate the feasibility of a multimodal approach involving dynamic contrast-enhanced (DCE) perfusion imaging and diffusion kurtosis imaging (DKI) in the preoperative imaging of brain tumors in a multicenter setting, and to evaluate the effect on diagnostic confidence and accuracy for tumor grade and type prediction.
MATERIALS AND METHODS
One hundred and thirty-three patients with brain tumors were imaged in six hospitals with a standardized multimodal protocol. Standard imaging and six parameter maps derived from DCE and DKI sequences were reviewed off-site by two independent readers. Image quality and diagnostic confidence were evaluated in qualitative analyses. Quantitative analyses were performed to assess diagnostic accuracy and the performance of DKI and DCE parameters for tumor grade differentiation and molecular tumor type determination.
RESULTS
Standardized acquisition of DCE and DKI maps was feasible with excellent image quality. Diagnostic confidence was significantly improved from 85 % to 96 % (p = 0.0005) by additional review of the DCE and DKI maps. The combination of mean kurtosis and CBV was particularly advantageous for differentiating low-grade and high-grade glioma, oligodendroglial vs. astrocytic, and IDH1/2 wild type vs. mutated tumors.
CONCLUSION
A multimodal imaging approach with DCE and DKI improves diagnostic confidence and yields higher diagnostic accuracy for predicting tumor grade and type in adult-type glioma.
Topics: Adult; Humans; Glioma; Brain Neoplasms; Diffusion Tensor Imaging; Perfusion; Multimodal Imaging; Diffusion Magnetic Resonance Imaging
PubMed: 38218066
DOI: 10.1016/j.ejrad.2024.111293 -
Case Reports in Oncology 2024Diffuse leptomeningeal glioneuronal tumor (DLGNT), a new addition to the 2016 World Health Organization (WHO) classification, is a rare childhood neoplasm presenting...
INTRODUCTION
Diffuse leptomeningeal glioneuronal tumor (DLGNT), a new addition to the 2016 World Health Organization (WHO) classification, is a rare childhood neoplasm presenting with disseminated leptomeningeal enhancement and an occasional intraparenchymal mass. Diagnosis is often impeded by infectious/immunological differentials, necessitating a biopsy to confirm the diagnosis. We report an adult male with DLGNT without hydrocephalus, which is rare in patients with cerebellar masses.
CASE PRESENTATION
A 56-year-old man presented with headaches, vertigo, diplopia, impaired hearing, and gait imbalance over 6 months. Magnetic resonance imaging showed a cystic right cerebellar mass with its leptomeningeal dissemination but without hydrocephalus. Cerebrospinal fluid analysis revealed elevated proteins with CD56-positive tumor cells. Cerebellar lesion biopsy verified the diagnosis of DLGNT (WHO Grade 3) with fusion and 1p deletion. Radiotherapy was prematurely aborted due to clinical deterioration. The patient was subsequently discharged to palliative home care and lost to follow-up.
CONCLUSION
We conducted the first review of all 34 adult DLGNT cases, including ours (one of the oldest), hitherto published in the literature. The majority presented with signs and symptoms of increased intracranial pressure. 52.0% of adult DLGNT patients were alive at follow-up. DLGNT should be considered in the differential diagnoses of diffuse leptomeningeal enhancement in imaging. Further studies comparing pediatric and adult subgroups of DLGNT are needed to evaluate histopathological prognosticators and standardize therapy for both subpopulations.
PubMed: 38404404
DOI: 10.1159/000536400