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World Neurosurgery Jun 2024To clarify the relationships between C-methionine (MET) positron emission tomography (PET) metrics and the histology, genetics, and prognosis of adult-type diffuse...
Association Between Pretreatment C-Methionine Positron Emission Tomography Metrics, Histology, and Prognosis in 125 Newly Diagnosed Patients with Adult-Type Diffuse Glioma Based on the World Health Organization 2021Classification.
OBJECTIVE
To clarify the relationships between C-methionine (MET) positron emission tomography (PET) metrics and the histology, genetics, and prognosis of adult-type diffuse glioma (ADG) based on the World Health Organization (WHO) 2021 classification.
METHODS
A total of 125 newly diagnosed patients with ADG were enrolled. We compared the maximum standardized uptake value (SUVmax), tumor-to-normal background ratio (TNR), metabolic tumor volume (MTV), and total lesion methionine uptake (TLMU) to the histology and genetics of the patients with ADG. We also evaluated the prognoses of the 93 surgically treated patients.
RESULTS
The patients with isocitrate dehydrogenase wild ADG showed significantly higher MET-PET metrics (P < 0.05 for all parameters), significantly shorter overall survival and progression-free survival (P < 0.0001 for both) than those of the patients with isocitrate dehydrogenase mutant (IDHm) ADG. In the IDHm ADG group, the SUVmax, MTV, and TLMU values were significantly higher in patients with IDHm grade (G) 4 astrocytoma than patients with IDHm G2/3 astrocytoma (P < 0.05 for all), but not than patients with G2-3 oligodendroglioma. The progression-free survival was significantly shorter in the patients with G4 astrocytoma versus the patients with G2/3 astrocytoma and G3 oligodendroglioma (P < 0.05 for both). The SUVmax and TNR values were significantly higher in recurrent patients than nonrecurrent patients (P < 0.01 for both), but no significant differences were found in MTV or TLMU values.
CONCLUSIONS
MET-PET metrics well reflect the histological subtype, WHO grade and prognosis of ADG based on the 2021 WHO classification, with the exception of oligodendroglial tumors. Volumetric parameters were not significantly associated with recurrence, unlike the SUVmax and TNR.
Topics: Humans; Methionine; Male; Female; Middle Aged; Adult; Brain Neoplasms; Glioma; World Health Organization; Prognosis; Positron-Emission Tomography; Aged; Isocitrate Dehydrogenase; Young Adult; Carbon Radioisotopes; Retrospective Studies; Tumor Burden
PubMed: 38583563
DOI: 10.1016/j.wneu.2024.03.164 -
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 -
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 -
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 -
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 -
Pathology, Research and Practice Dec 2023Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described entity. The clinicopathological features and prognosis of the molecular...
Clinical significance of molecular subgroups of polymorphous low-grade neuroepithelial tumor of the young (PLNTY): A small single institutional case series and integrated analysis.
INTRODUCTION
Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described entity. The clinicopathological features and prognosis of the molecular subgroups of these rare tumors is poorly understood. In this study, we presented a small case series of three new cases and integrated the data with published cases in the literature to characterize the similarities and differences of molecular subgroups of PLNTY.
METHODS
We searched our institutional archive for PLNTY cases and searched PubMed and Web of Science for relevant data. Demographic, clinical, radiologic, histopathological, molecular, and follow-up data of our four cases with published cases were integrated for final analyses.
RESULTS
We identified three institutional cases of PLNTY. The median age of our patients was 17 years (range: 13-42). All patients had a prior history of chronic seizures and all had tumors affecting the temporal lobes. Histopathologically, all cases showed oligodendroglial-like morphology with intratumoral calcifications and at least partially infiltrative growth patterns. Tumor cells were immunoreactive with CD34 and GFAP. Genetically, all cases harbored BRAF V600E mutations. Integrated analyses, including a total of 67 cases, demonstrated that PLNTYs with FGFR2 mutation were significantly younger (median age 11.0 years) than those with BRAF V600E or FGFR3 fusions (median age 41.0 and 16.0 years, respectively). All BRAF V600E-positive PLNTYs were free of tumor recurrence, while four of PLNTYs in other molecular subgroups developed tumor recurrence by imaging.
CONCLUSION
Our study suggests that PLNTYs have distinct clinicopathological features and are driven by genetic alterations in the MAPK pathway. The molecular subgroups of PLNTYs share similar findings, but also demonstrate distinct patient demographics.
Topics: Humans; Adolescent; Young Adult; Adult; Child; Brain Neoplasms; Neoplasm Recurrence, Local; Proto-Oncogene Proteins B-raf; Clinical Relevance; Neoplasms, Neuroepithelial; Mutation
PubMed: 37984047
DOI: 10.1016/j.prp.2023.154922 -
Nature Reviews. Neuroscience Dec 2023Experience sculpts brain structure and function. Activity-dependent modulation of the myelinated infrastructure of the nervous system has emerged as a dimension of... (Review)
Review
Experience sculpts brain structure and function. Activity-dependent modulation of the myelinated infrastructure of the nervous system has emerged as a dimension of adaptive change during childhood development and in adulthood. Myelination is a richly dynamic process, with neuronal activity regulating oligodendrocyte precursor cell proliferation, oligodendrogenesis and myelin structural changes in some axonal subtypes and in some regions of the nervous system. This myelin plasticity and consequent changes to conduction velocity and circuit dynamics can powerfully influence neurological functions, including learning and memory. Conversely, disruption of the mechanisms mediating adaptive myelination can contribute to cognitive impairment. The robust effects of neuronal activity on normal oligodendroglial precursor cells, a putative cellular origin for many forms of glioma, indicates that dysregulated or 'hijacked' mechanisms of myelin plasticity could similarly promote growth in this devastating group of brain cancers. Indeed, neuronal activity promotes the pathogenesis of many forms of glioma in preclinical models through activity-regulated paracrine factors and direct neuron-to-glioma synapses. This synaptic integration of glioma into neural circuits is central to tumour growth and invasion. Thus, not only do neuron-oligodendroglial interactions modulate neural circuit structure and function in the healthy brain, but neuron-glioma interactions also have important roles in the pathogenesis of glial malignancies.
Topics: Humans; Neurons; Oligodendroglia; Myelin Sheath; Neuroglia; Glioma
PubMed: 37857838
DOI: 10.1038/s41583-023-00744-3 -
Child's Nervous System : ChNS :... Feb 2024Polymorphous low grade neuroepithelial tumor of the young (PLNTY) is a newly described epileptogenic tumor first reported by Jason. T. Huse et al. in 2016. Only a very...
INTRODUCTION
Polymorphous low grade neuroepithelial tumor of the young (PLNTY) is a newly described epileptogenic tumor first reported by Jason. T. Huse et al. in 2016. Only a very few cases have been reported so far and has been recently incorporated in the World Health Organization (WHO) Central Nervous System Classification of tumours, 5th edition, 2021. Here we report a rare case of PLNTY which closely resembles DNET (Dysembryoplastic neuroepithelial tumor) with plenty of interesting findings which would otherwise go unnoticed resulting in a nonspecific or misclassified diagnosis.
CASE REPORT
A 12 year old boy presented to the Neurosurgery OPD with seizures for the past five years and was given multiple antiepileptics for the same. Magnetic resonance imaging (MRI) showed a well-defined lobulated cortical mass with T1 hypo intensity and T2 hyperintensity in the left temporal lobe measuring 2.1 × 2 × 1.3 cm suggesting a DNET. Left temporal craniotomy and excision of the lesion was done. Frozen section showed features of a low grade glial neoplasm. Routine sections demonstrated polymorphous findings including oligodendroglia like features, neuronal nuclear pleomorphism, spindled astroglial elements, perivascular rosettes, calcification, and vascular mineralization. By immunohistochemistry (IHC), the tumor cells were diffusely positive for GFAP and CD34.Ki67 labelling index was low. A final diagnosis of PLNTY was made based on the above findings. The child has been epilepsy free since the past one-month post-surgery and is on follow up.
DISCUSSION/CONCLUSION
PLNTY is a newly discovered distinct pediatric low grade glial neoplasm which was earlier grouped into nonspecific forms of DNET. It is characterized morphologically and molecularly by the presence of oligodendroglial component, CD34 expression, BRAFV600E mutation and alterations in the MAP kinase pathway. They are known to behave in a low-grade fashion amenable to control by excision with occasional cases of recurrence reported. It is important to recognize and report similar tumors to determine the long-term risk of recurrence and create a more complete understanding on their radiology and molecular genetics.
Topics: Male; Humans; Child; Neoplasms, Neuroepithelial; Brain Neoplasms; Glioma; Epilepsy; Seizures
PubMed: 37796295
DOI: 10.1007/s00381-023-06162-1 -
Cancer Genetics Nov 2023Either deletion or co-deletion of chromosomal arms 1p or 19q is a characteristic and early genetic event in oligodendroglial tumors that is associated with a better...
Evaluation of chromosome 1p/19q deletion by Fluorescence in Situ Hybridization (FISH) as prognostic factors in malignant glioma patients on treatment with alkylating chemotherapy.
BACKGROUND
Either deletion or co-deletion of chromosomal arms 1p or 19q is a characteristic and early genetic event in oligodendroglial tumors that is associated with a better prognosis and enhanced response to therapy. Information of 1p/19q status is now regarded as the standard of care when managing oligodendroglial tumors for therapeutic options in anticipation of the increased survival and progression-free survival times associated with it. Keeping this in view, we first time attempted to establish the FISH based detection of 1p/19q deletion in glioma tissue samples to evaluate its role and involvement in the disease.
METHOD
Overall 39 glioma cases of different histologies were evaluated by fluorescence in situ hybridization (FISH) technique using specific FISH probes with Olympus BX43 fluorescent microscope to detect chromosomes 1p and 19q or co-deletions therein.
RESULTS
Of the 39 glioma samples, overall 27 (69.2%) were found to have deletion either in 1p, 19q or both. Deletions were observed in 23.0%, 7.6% and 38.4% in 1p, 19q and 1p/19q co-deletions respectively. Overall oligidendrioglioma presented with 53.8% (21 of 39) deletions, astrocytoma group showed 12.8% and GBM accounted for 2.5% deletions. Overall survival and disease free survival was seen significantly better in oligidendrioglioma and astrocytoma with deleted tumors as compared to non-deleted ones (p<0.05).
CONCLUSION
Allelic losses on 1p and 19q, either discretely or shared, were more frequent in classic oligodendrogliomas than in either astrocytoma or Glioblastoma with better survival and response to therapy.
Topics: Humans; Prognosis; In Situ Hybridization, Fluorescence; Brain Neoplasms; Chromosome Deletion; Glioma; Oligodendroglioma; Astrocytoma; Chromosome Aberrations; Chromosomes; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19
PubMed: 37625215
DOI: 10.1016/j.cancergen.2023.08.005 -
Journal of Cancer Research and... 2023Gliomas are the most common primary intracranial tumors. The current World Health Organization (WHO) classification of central nervous system tumors recommends...
INTRODUCTION
Gliomas are the most common primary intracranial tumors. The current World Health Organization (WHO) classification of central nervous system tumors recommends integrated histo-molecular diagnosis of gliomas. However, molecular testing is not available in even most of the advanced centers of our country, and histopathology aided with immunohistochemistry (IHC) is still widely used for diagnosis. Immunohistochemical markers such as iso-citrate dehydrogenase1 (IDH1) and Alpha Thalassemia/Mental Retardation Syndrome X-linked (ATRX) can be reliably used for the correct diagnosis, prognosis, and treatment of gliomas.
AIM
We aimed to develop a diagnostic algorithm by integrating morphology, IDH1, and ATRX status of gliomas seen in our institute for 1 year.
SETTINGS AND DESIGN
Analytical cross-sectional study.
MATERIALS AND METHODS
This study included 60 histopathologically confirmed cases of astrocytic (n = 51) and oligodendroglial tumors (n = 9). Clinical, radiological, and histopathological features were noted and tumor grades assigned according to the WHO recommendations. IDH1 and ATRX mutation status was evaluated using IHC. The tumors were divided into three molecular groups on the basis of their IDH1 and ATRX mutation status: (1) Group 1: IDH1 negative and ATRX positive, (2) Group 2: IDH1 positive and ATRX positive, (3) Group 3: IDH1 positive and ATRX negative.
RESULTS
The mean age of presentation was 45.0 ± 15.8 years with a male-to-female ratio of 2:1. Seizures, headache, and hemiparesis were the most common modes of presentation. The tumor subtypes studied were glioblastoma (n = 32), anaplastic astrocytoma (n = 7), diffuse astrocytoma (n = 6), oligodendroglioma (n = 6), pilocytic astrocytoma (n = 6), and anaplastic oligodendroglioma (n = 3). IDH1 mutation was present in 26 cases including anaplastic astrocytoma (n = 7), diffuse astrocytoma (n = 6), oligodendroglioma (n = 5), secondary glioblastoma (n = 5), and anaplastic oligodendroglioma (n = 3). ATRX mutation, i. e., loss of ATRX was observed in 17 cases including diffuse astrocytoma (n = 5), anaplastic astocytoma (n = 5), anaplastic oligodendroglioma (n = 3), oligodendroglioma (n = 3), and secondary glioblastoma (n = 1). All six cases of pilocytic astrocytoma were negative for IDH1 and ATRX mutation. There were 34 patients in Group 1 (IDH1- and ATRX +), nine cases in Group 2 (IDH1 + and ATRX +), and 17 patients in Group 3 (IDH1 + and ATRX-).
CONCLUSION
Diagnosis of gliomas should be based on a detailed clinicoradiological and histopathological assessment, followed by genotypic characterization. Evaluation for IDH1and ATRX status has both diagnostic and prognostic value as it helps in differentiating gliomas from reactive gliosis, primary glioblastoma from secondary glioblastoma, and pilocytic astrocytoma (WHO grade I) from diffuse astrocytoma (WHO grade II). Tumors with IDH1 mutations have a better outcome than those with wild-type IDH. IHC can serve as a useful surrogate to conventional molecular tests in resource-constrained settings. By devising an algorithm based on morphological and IHC features, we were able to stratify gliomas into three prognostic subgroups.
Topics: Humans; Male; Female; Adult; Middle Aged; Oligodendroglioma; Glioblastoma; Cross-Sectional Studies; X-linked Nuclear Protein; Glioma; Astrocytoma; Brain Neoplasms; Mutation; Prognosis; Citrates; Citric Acid; Isocitrate Dehydrogenase; Algorithms
PubMed: 37470575
DOI: 10.4103/jcrt.jcrt_102_21