Dysembryoplastic Neuroepithelial Tumor Research Articles

PATH-45. TREATMENT OF FGFR1 – ALTERED WHO GRADE 1 GLIONEURONAL TUMORS WITH FGFR INHIBITOR ERDAFITINIB

Abstract INTRODUCTION Low-grade mitogen-activated protein kinase (MAPK) pathway-altered glioneuronal tumors carry distinct molecular alterations, which may represent therapeutic opportunities to avoid or delay toxic treatments like radiation. Erdafitinib is a pan-FGFR tyrosine kinase inhibitor, regulatorily approved in recurrent urothelial carcinoma, and is under clinical investigation for recurrent FGFR-altered gliomas (NCT05859334). METHODS We report two patients with FGFR1-altered rosette-forming glioneuronal tumors (RGNT) treated with erdafitinib. RESULTS Patient 1 is a 32-year-old woman who presented with obstructive hydrocephalus and a non-enhancing pineal tumor. She underwent a subtotal resection, with histopathology initially consistent with a low grade dysembryoplastic neuroepithelial tumor. She was under observant management for 7 years, and developed worsening symptoms with slow non-enhancing growth, although stable per RANO low grade criteria. The initial tissue was sent for next-generation sequencing (NGS) and DNA methylation profiling, revealing an FGFR1 pathogenic variant with DNA methylation profiling matching with RGNT. Patient began Erdafitinib 8 mg daily, and had stable disease per RANO at 6 months. She developed CTCAE grade 1 toxicities of subretinal fluid, fatigue, dry skin, and paronychia. Patient 2 is a 34-year-old man diagnosed 1 year prior with a tectal tumor, who underwent biopsy due to non-measurable/ non-enhancing progression. Histopathology was consistent with RGNT. NGS revealed FGFR1 mutation, PIK3CA mutation, and NF1 pathogenic variant, described in the literature as characteristic of RGNT. There was insufficient tissue for DNA methylation profiling. Patient started erdafitinib 8 mg daily and remains clinically stable for 1 month. He developed asymptomatic hyperphosphatemia (CTCAE grade 1). Both patients have tolerated treatment without interruptions or dose reductions. CONCLUSION Erdafitinib is a well-tolerated and potentially efficacious treatment of FGFR1- altered RGNT, and may avoid the need for radiation. Diagnosis of MAPK- altered low-grade glioneuronal tumors, specifically RGNT, is increasingly reliant on molecular data, and can significantly impact treatment options.

Atypical Presentation of Dysembryoplastic Neuroepithelial Tumor

Dysembryoplastic neuroepithelial tumor (DNET) is a benign glioneuronal neoplasm, usually found in children and adolescents, in the vast majority of cases associated with drug-resistant epilepsy. Typically, epileptic seizures are the main, and in most cases, their only clinical manifestation. Although DNET is a benign, biologically stable tumor with few reports of malignancy, it is one of the most common reasons for epileptic surgery. The epileptogenic potential of this tumor is so high that DNET s, along with ganglioglioma, have received the informal term “epileptomas” and are by far the leaders in the group of low-grade tumors associated with long-term epilepsy-associated tumors (LEAT). It is believed that this epileptogenicity is due to localization in the neocortex and frequent association with focal cortical dysplasias (FCD). In the world literature, there are only a few mentions of DNET s not associated with epilepsy. The article presents the experience of complex, interdisciplinary diagnosis of DNET in a child without epilepsy who complained of frequent headaches. During a comprehensive MRI examination, a cortical-subcortical pathological substrate was discovered in the left temporal lobe with radiological signs of DNET. During video-EEG monitoring of night sleep, no epileptiform signs were recorded. There was no history of epileptic seizures or other paroxysms. A control MRI revealed a slight increase in the size of the pathological substrate, which was the reason for surgical treatment. Pathological examination revealed microscopic features of DNET. This case of absence of epilepsy in a child with cortical DNET in the temporal lobe cortex suggests that the spectrum of its clinical manifestations and biological behavior is not fully understood and requires further comprehensive study.

Extra-temporal pediatric low-grade gliomas and epilepsy.

Low-grade gliomas, especially glioneuronal tumors, are a common cause of epilepsy in children. Seizures associated with low-grade pediatric tumors are medically refractory and present a significant burden to patients. Often, morbidity and patients´ quality of life are determined rather by the control of seizures than the oncological process itself and the resolution of epilepsy represents an important part in the treatment of LGGs. The pathogenesis of tumor-related seizures in focal LGG tumors is multifactorial, and mechanisms differ probably among patients and tumor types. Pediatric low-grade tumors associated with epilepsy include a series of neoplasms that have a pure astrocytic or glioneuronal lineage. They are usually benign tumors with a neocortical localization typically in the temporal lobes, but also in other supratentorial locations. Gangliogliomas and dysembryoplastic neuroepithelial tumors (DNET) are the most common entities together with astrocytic gliomas (pilocytic astrocytomas and pleomorphic xanthoastrocytoma) and angiocentric gliomas, and dual pathology is found in up to 40% of glioneuronal tumors. The treatment of low-grade gliomas and associated epilepsy is based mainly on resection and the extent of surgery is the main predictor of postoperative seizure control in patients with a LGG. Long-term epilepsy-associated tumors (LEATs) tend to be well-circumscribed, and therefore, the chances for a complete resection and epilepsy control with a safe approach are very high. New treatments have emerged as alternatives to open microsurgical approaches, including laser thermal ablation or the use of BRAF inhibitors. Future advances in identifying seizure-related biomarkers and molecular tumor pathways will facilitate targeted treatment strategies that will have a deep impact both in oncologic and epilepsy outcomes.

Cortically-based Brain Tumors in Children: A Decision-tree Approach in the Radiology Reading Room.

Cortically-based brain tumors in children constitute a unique set of tumors with variably aggressive biological behavior. As radiologists play an integral role on the multidisciplinary medical team, a clinically useful and easy-to-follow flowchart for the differential diagnoses of these complex brain tumors is essential.This proposed algorithm tree provides the latest insights into the typical imaging characteristics and epidemiologic data that differentiate the tumor entities, taking into perspective the 2021 World Health Organization's classification and highlighting classic as well as newly identified pathologic subtypes using current molecular understanding.ABBREVIATIONS: Astroblastoma=AB) Angiocentric glioma (AG) Atypical teratoid rhabdoid tumor (ATRT) Central Nervous System tumor (CNS) CNS neuroblastoma FOXR2-activated (NB-FOXR2) Desmoplastic infantile glioma/astrocytoma (DIG/DIA) Diffuse hemispheric glioma, H3 G34-mutant (DHG) Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) Dysembryoplastic neuroepithelial tumor (DNET) Embryonal Tumors with Multilayered Rosettes (ETMR) Ependymoma (EP) Focal cortical dysplasia (FCD) Ganglioglioma/gangliocytoma (GG) Infant-type hemispheric glioma (IHG) Intracranial pressure (ICP) Long-term epilepsy-associated tumors (LEATs) Pediatric diffuse low-grade gliomas (pLGG) MR spectroscopy (MRS) Multinodular and vacuolating neuronal tumor (MVNT) Overall survival (OS) Pediatric diffuse high-grade gliomas (pHGG).

MR-guided laser interstitial thermal therapy in the treatment of brain tumors and epilepsy.

MR-guided Laser Interstitial Thermal Therapy (MRgLITT) is a minimally invasive neurosurgical technique increasingly used for the treatment of drug-resistant epilepsy and brain tumors. Utilizing near-infrared light energy delivery guided by real-time MRI thermometry, MRgLITT enables precise ablation of targeted brain tissues, resulting in limited corridor-related morbidity and expedited postoperative recovery. Since receiving CE marking in 2018, the adoption of MRgLITT has expanded to more than 40 neurosurgical centers across Europe. In epilepsy treatment, MRgLITT can be applied to various types of focal lesional epilepsy, including mesial temporal lobe epilepsy, hypothalamic hamartoma, focal cortical dysplasias, periventricular heterotopias, cavernous malformations, dysembryoplastic neuroepithelial tumors (DNET), low-grade gliomas, tuberous sclerosis, and in disconnective surgeries. In neuro-oncology, MRgLITT is used for treating newly diagnosed and recurrent primary brain tumors, brain metastases, and radiation necrosis. This comprehensive review presents an overview of the current evidence and technical considerations for the use of MRgLITT in treating various pathologies associated with drug-resistant epilepsy and brain tumors.

IMG-14. DIAGNOSTIC UTILITY OF THE T2-FLAIR MISMATCH SIGN FOR DNETS AND ITS ASSOCIATION WITH FGFR1 ALTERATIONS

Abstract BACKGROUND The T2-FLAIR mismatch sign, hyperintense T2-weighted signals with corresponding hypointensity on FLAIR sequence, has emerged as a potential diagnostic tool for identifying specific brain tumor subtypes. We tested the diagnostic utility of the sign in dysembryoplastic neuroepithelial tumors (DNETs) with and without FGFR1 alterations. METHODS We evaluated the T2-FLAIR mismatch sign in a cohort of 43 patients with definitive or probable DNET. Low-grade glioma patients with definite non-DNET diagnoses were chosen as control (n=43). Receiver operative curve analysis was performed, and the corresponding odds ratios were calculated. RESULTS Of the 43 DNET cases, 35 were definite, and 8 were probable DNETs. FGFR1 alterations were confirmed in 9 definitive DNETs. The area under the curve (AUC) for diagnosing DNET with the T2-FLAIR mismatch sign was 0.884 (DeLong CI: 0.2, 0.95) (Accuracy: 0.88, 95% CI: 0.80, 0.94; Sensitivity: 0.84; Specificity: 0.95); for definite DNET it was 0.891 (DeLong CI: 0.82, 0.96) (Accuracy: 0.90, 95% CI: 0.81, 0.95; Sensitivity: 0.87; Specificity: 0.94); for probable DNET it was 0.852 (DeLong CI: 0.69, 1;) (Accuracy 0.92, 95% CI: 0.81, 0.98; Sensitivity: 0.84; Specificity: 0.75), and for DNET with FGFR1 alterations was 0.977 (DeLong CI: 0.95, 1) (Accuracy 0.96, 95% CI: 0.87, 1; Sensitivity: 1; Specificity: 0.81). The odds of having DNET (definite +probable) if the T2-FLAIR mismatch sign was positive was 81.96 (CI: 16.25, 852.48, P<0.001), and DNET with FGFR1 is 315.4 (CI: 312.3, 318.5, P<0.001). CONCLUSION The T2-FLAIR mismatch sign is a reliable radiological biomarker for DNET and strongly predicts FGFR1 alterations in these tumors.

Low-grade glioma of the temporal lobe and tumor-related epilepsy in children.

Low-grade glioma is the most common brain tumor among children and adolescents. When these tumors arise in the temporal lobe, patients frequently present with seizures that are poorly controlled with antiepileptic drugs. Here we summarize the clinical features, pathophysiology, preoperative evaluation, surgical treatment, and outcomes of pediatric patients with low-grade gliomas in the temporal lobe. We reviewed the literature on pediatric low-grade gliomas in the temporal lobe, focusing on cohort studies and systematic reviews that described surgical treatment strategies and reported both oncologic and epilepsy outcomes. The differential diagnoses of pediatric low-grade gliomas in the temporal lobe include ganglioglioma, dysembryoplastic neuroepithelial tumor, desmoplastic infantile ganglioglioma, papillary glioneuronal tumor, pilocytic astrocytoma, pleomorphic xanthoastrocytoma, angiocentric glioma, and polymorphous low-grade neuroepithelial tumor of the young. There is no consensus on the optimal surgical approach for these tumors: lesionectomy alone, or extended lesionectomy with anterior temporal lobectomy, with or without removal of mesial temporal structures. Gross total resection and shorter preoperative duration of epilepsy are strongly associated with favorable seizure outcomes, defined as Engel Class I or Class II, approaching 90% in most series. The risk of surgical complications ranges from 4 to 17%, outweighing the lifetime risks of medically refractory epilepsy. Pediatric patients with temporal low-grade glioma and tumor-related epilepsy are best managed by a multidisciplinary epilepsy surgery team. Early and appropriate surgery leads to prolonged survival and a greater likelihood of seizure freedom, improving their overall quality of life.

Long-term seizure outcome after epilepsy surgery of neuroglial tumors

PurposeNeuroglial tumors are frequently associated with pharmacorefractory epilepsies. However, comprehensive knowledge about long-term outcomes after epilepsy surgery and the main prognostic factors for outcome is still limited. We sought to evaluate long-term outcomes and potential influencing factors in a large cohort of patients who underwent surgery for neuroglial tumors in a single-center setting.MethodsThe study analyzed the outcomes of 107 patients who underwent epilepsy surgery for neuroglial tumors between 2001 and 2020 at the Department of Epileptology, University Hospital Bonn, in Germany. The outcomes were evaluated using Engel classification. Differences in outcome related to potential prognostic factors were examined using the Chi2-test, Fisher’s exact test and sign test. Additionally, stepwise logistic regression analysis was employed to identify independent prognostic factors.ResultsComplete seizure freedom (Engel Class IA) was achieved in 75% of the operated patients at 12 months, and 56% at the last follow-up visit (70.4 ± 6.2 months, median: 40 months). Completeness of resection was a crucial factor for both 12-month follow-up outcomes and the longest available outcomes, whereas lobar tumor localization, histology (ganglioglioma vs. dysembryoplastic neuroepithelial tumor), history of bilateral tonic–clonic seizures prior to surgery, invasive diagnostics, side of surgery (dominant vs. non-dominant hemisphere), age at epilepsy onset, age at surgery, and epilepsy duration did not consistently impact postsurgical outcomes. Among temporal lobe surgeries, patients who underwent lesionectomy and lesionectomy, including hippocampal resection, demonstrated similar outcomes.ConclusionNeuroglial tumors present as excellent surgical substrates in treating structural epilepsy. To achieve an optimal postsurgical outcome, a complete lesion resection should be pursued whenever possible.

Lateral Transorbital Endoscope-Assisted Resection of Anterior Temporal Lobe Neoplasm: 2-Dimensional Operative Video.

Transorbital neuroendoscopic surgery (TONES) is a minimally invasive approach, providing excellent access to extradural pathology of the sphenoid wing, orbital apex, Meckel's cave, and lateral cavernous sinus.1-10 Few cases of intradural pathology, such as gliomas or epileptic foci of the temporal lobe, have been described, apart from cadaveric anatomic studies.11-13 In this video, we present the case of a 63-year-old man with first time seizure. MRI demonstrated a fluid-attenuated inversion recovery hyperintense, noncontrast enhancing medial temporal lobe lesion consistent with low grade glioma. While frontotemporal craniotomy is the standard approach for this lesion, the TONES approach detailed in the video (the patient consented to the procedure and to the publication of his image) provided excellent access to the lesion, which minimized unnecessary trauma or removal of the lateral temporal lobe during the approach.4,14,15 The dura was closed primarily, overlayed with abdominal fat and fibrin glue, and a lumbar drain was left in place for 24 hours. The TONES approach avoided not only temporal lobe violation but also temporalis muscle disruption and any sort of external bone manipulation, which expedited the patient's recovery.16 The patient's eyelid incision was barely visible as early as postoperative day 7 with minimal ecchymosis. Postoperative MRI demonstrated a gross total resection. Pathology was consistent with a central nervous system World Health Organization grade 1 dysembryoplastic neuroepithelial tumor, a low-grade lesion with low risk of recurrence.17,18.

Enrichment of oligodendrocyte precursor phenotypes in subsets of low-grade glioneuronal tumours.

Current histological classification of low-grade glioneuronal tumours does not adequately represent their underlying biology. The neural lineage(s) and differentiation stage(s) involved and the cell state(s) affected by the recurrent genomic alterations are unclear. Here, we describe dysregulated oligodendrocyte lineage developmental programmes in three low-grade glioneuronal tumour subtypes. Ten dysembryoplastic neuroepithelial tumours, four myxoid glioneuronal tumours and five rosette-forming glioneuronal tumours were collected. Besides a comprehensive characterization of clinical features, known diagnostic markers and genomic alterations, we used comprehensive immunohistochemical stainings to characterize activation of rat sarcoma/mitogen-activated protein kinase pathway, involvement of neuronal component, resemblance to glial lineages and differentiation blockage along the stages of oligodendrocyte lineage. The findings were further complemented by gene set enrichment analysis with transcriptome data of dysembryoplastic neuroepithelial tumours from the literature. Dysembryoplastic neuroepithelial tumours, myxoid glioneuronal tumours and rosette-forming glioneuronal tumours occur at different ages, with symptoms closely related to tumour location. Dysembryoplastic neuroepithelial tumours and myxoid glioneuronal tumours contain oligodendrocyte-like cells and neuronal component. Rosette-forming glioneuronal tumours contained regions of rosette-forming neurocytic and astrocytic features. Scattered neurons, identified by neuronal nuclei antigen and microtubule-associated protein-2 staining, were consistently observed in all dysembryoplastic neuroepithelial tumours and myxoid glioneuronal tumours examined, but only in one rosette-forming glioneuronal tumour. Pervasive neurofilament-positive axons were observed only in dysembryoplastic neuroepithelial tumour and myxoid glioneuronal tumour samples. Alterations in B-Raf proto-oncogene, serine/threonine kinase, fibroblast growth factor receptor 1, fibroblast growth factor receptor 3 and platelet-derived growth factor receptor alpha occurred in a mutually exclusive manner, coinciding with strong staining of phospho-p44/42 mitogen-activated protein kinase and low apoptotic signal. All dysembryoplastic neuroepithelial tumours, myxoid glioneuronal tumours and the neurocytic regions of rosette-forming glioneuronal tumours showed strong expression of neuron-glia antigen 2, platelet-derived growth factor receptor alpha (markers of oligodendrocyte precursor cells) and neurite outgrowth inhibitor-A (a marker of developing oligodendrocytes), but lacked the expression of oligodendrocyte markers ectonucleotide pyrophosphatase/phosphodiesterase family member 6 and myelin basic protein. Notably, transcriptomes of dysembryoplastic neuroepithelial tumours were enriched in oligodendrocyte precursor cell signature, but not in signatures of neural stem cells, myelinating oligodendrocytes and astrocytes. Dysembryoplastic neuroepithelial tumour, myxoid glioneuronal tumour and rosette-forming glioneuronal tumour resemble oligodendrocyte precursor cells, and their enrichment of oligodendrocyte precursor cell phenotypes is closely associated with the recurrent mutations in rat sarcoma/mitogen-activated protein kinase pathway.

Appearance of intracranial cottonoids on intraoperative magnetic resonance imaging.

To our knowledge, this is a unique report of intraoperative magnetic resonance imaging (iMRI) of an intracranial cottonoid. The current literature describes images of cottonoids as a post-operative finding in the setting of an unintentionally retained foreign body; however, the iMRI images we present are important as the use of iMRI in the resection of complex tumors and epilepsy foci increases. This series of images was obtained during a craniotomy for tumor resection of a patient with dysembryoplastic neuroepithelial tumor. To determine both the degree of tumor resection and the amount of residual tumor, cottonoids were left in our patient's resection cavity and underwent iMRI. The ability to distinguish cottonoids in these images is important for intraoperative localization of resection margins and to prevent the retention of cottonoids.

When the Stomach Pain Is Literally “In Your Head”

Abdominal epilepsy (AE) is an extremely rare condition, classified as temporal lobe epilepsy, and is usually a diagnosis of exclusion. Temporal lobe epilepsy often has no clear cause, although it may be associated with diseases such as temporal lobe sclerosis, dysembryoplastic neuroepithelial tumours, and other benign tumours, as well as arterio-venous malformations, gliomas, defects in neuronal migration, or lesions of the cortex caused by encephalitis. AE is more common in children but has been reported in adults. AEs are characterised by recurrent and unexplained gastrointestinal symptoms such as seizure pain, nausea, bloating and diarrhoea, which improve with antiepileptic treatment. Given the vague nature of these symptoms, patients are at high risk of misdiagnosis. An electroencephalogram and neuroimaging of the brain are needed to confirm the diagnosis.
 We present the clinical case of a 67-year-old female patient who was investigated at the Gastroenterology Department for a sharp pain in the left side of the abdomen, frequent abdominal distension and gurgles, diarrhoeal episodes, weight loss, paroxysmal hallucinations, and headaches. After a thorough gastroenterological examination, consultations with a psychiatrist and a neurologist, an MRI and an EEG were performed and the patient was diagnosed with focal temporal lobe epilepsy.

"Hemispheric pilocytic astrocytoma" revisited: A comprehensive clinicopathological and molecular series emphasizing their overlap with other glioneuronal tumors.

Pilocytic astrocytomas (PA) typically exhibit distinct clinical, radiological, histopathological, and genetic features. DNA-methylation profiling distinguishes PA according to their location (infratentorial, midline, hemispheric, or spinal). In the hemispheric location, distinguishing PA from glioneuronal tumors remains a common diagnostic challenge for neuropathologists. Furthermore, the current version of the DKFZ classifier seems to have difficulty separating them from gangliogliomas. In this study, after central radiological review, we identified a histopathologically defined set of PA (histPA, n = 11) and a cohort of DNA-methylation defined PA (mcPA, n = 11). Nine out of the 11 histPA matched the methylation class of hemispheric PA, whereas 2 cases were classified at the end of the study as dysembryoplastic neuroepithelial tumors. Similarly, the mcPA cohort contained tumors mainly classified as PA (7/11), but 4 cases were classified as glioneuronal. The analysis of the 16 tumors with an integrated diagnosis of PA revealed that they affect mainly children with a wide spectrum of radiological, histopathological (i.e. a predominantly diffuse growth pattern), and genetic characteristics (large range of mitogen-activated protein kinase alterations). Based on these results, we consider hemispheric PA to be different from their counterparts in other locations and to overlap with other glioneuronal tumors, reinforcing the necessity of interpreting all data to obtain an accurate diagnosis.

A Pediatric Case Report: Dysembryoplastic Neuroepithelial Tumor or Ganglioglioma?

Dysembryoplastic neuroepithelial tumor (DNET) is a benign glioneuronal neoplasm that most frequently affects children and young adults. It can cause chronic seizures that are medically refractory. This tumor's cortical architecture and absence of a bulk effect or perilesional edema on radiographs are its defining features. The most typical manifestation of seizures is focal seizures with impaired awareness. Three DNET histologic subtypes have been identified. For either complicated or simple DNET types, histological detection of a distinct, particular glioneuronal component in brain tumor samples from individuals with medically refractory, chronic epilepsy serves as a diagnostic characteristic. We present one case of a child diagnosed with DNETs, who arrived at the hospital following seizures. The clinical, radiographic, histological, immunohistochemical, and molecular genetic characteristics of all three forms of DNETs as well as the differences between DNETs and gangliogliomas will be the main topics of this review.

Bright diffusion sign: A sensitive and specific radiologic biomarker for multinodular and vacuolating neuronal tumor

Background and purposeAccurate differentiation between multinodular and vacuolating neuronal tumor (MVNT) and dysembryoplastic neuroepithelial tumor (DNET) is important for treatment decision-making. We aimed to develop an accurate radiologic diagnostic model for differentiating MVNT from DNET using T2WI and diffusion-weighted imaging (DWI). Materials and methodsA total of 56 patients (mean age, 47.48±17.78 years; 31 women) diagnosed with MVNT (n = 37) or DNET (n = 19) who underwent brain MRI, including T2WI and DWI, were included. Two board-certified neuroradiologists performed qualitative (bubble appearance, cortical involvement, bright diffusion sign, and bright apparent diffusion coefficient [ADC] sign) and quantitative (nDWI and nADC) assessments. A diagnostic tree model was developed with significant and reliable imaging findings using an exhaustive chi-squared Automatic Interaction Detector (CHAID) algorithm. ResultsIn visual assessment, the imaging features that showed high diagnostic accuracy and interobserver reliability were the bright diffusion sign and absence of cortical involvement (bright diffusion sign: accuracy, 94.64 %; sensitivity, 91.89 %; specificity, 100.00 %; interobserver agreement, 1.00; absence of cortical involvement: accuracy, 92.86 %; sensitivity, 89.19 %; specificity, 100.00 %; interobserver agreement, 1.00). In quantitative analysis, nDWI was significantly higher in MVNT than in DENT (1.52 ± 0.34 vs. 0.91 ± 0.27, p < 0.001), but the interobserver agreement was fair (intraclass correlation coefficient = 0.321). The overall diagnostic accuracy of the tree model with visual assessment parameters was 98.21 % (55/56). ConclusionThe bright diffusion sign and absence of cortical involvement are accurate and reliable imaging findings for differentiating MVNT from DNET. By using simple, intuitive, and reliable imaging findings, such as the bright diffusion sign, MVNT can be accurately differentiated from DNET.

Differential diagnosis of epileptogenic substrates of unknown etiology using a modification of the routine MRI protocol

To evaluate the diagnostic capabilities of modifying the standard MRI protocol as part of an interdisciplinary presurgical examination of patients with epileptogenic substrates of unknown etiology. The results of dynamic MRI of 8 patients with a referral diagnosis of focal cortical dysplasia (FCD) were analyzed. In 7 patients, epilepsy was the reason for a standard MRI of the brain; in another patient with myasthenia, MRI was performed as part of a comprehensive examination. All patients, in addition to standard MRI, underwent a modification of the real-time scanning protocol to include contrast, tractography (DTI), and perfusion techniques (ASL/DSC). In 1 case, with questionable results, the results of a modification of the standard MRI protocol, high-resolution MRI (HR MRI) and hybrid positron emission CT with 11C-methionine (PET/CT with 11C-MET) were combined. Seven patients underwent epileptic surgery and 1 patient was operated on for a tumor. In 4 out of 8 patients, based on the results of a modification of the standard MRI protocol, radiological signs of a neoplastic process were identified, which suggested a low-grade tumor. One of them needed PET/CT to confirm the assumption. The results of pathomorphological examination correlated with the direct diagnosis for surgical treatment. One of the 4 patients was suspected to have dysembryoplastic neuroepithelial tumor (DNET) based on the results of the protocol modification, which was also confirmed by pathological examination. In another 4 patients in whom it was possible to narrow the differential between FCD type II and DNET based on the results of the modification, FCD IIb was pathomorphologically verified. The proposed modification of the standard MRI protocol can significantly facilitate the differential diagnosis between the neoplastic and dysplastic origin of an epileptogenic substrate of unknown etiology, which in turn affects the patient's management tactics.

Disseminated ependymal dysembryoplastic neuroepithelial tumor: a case report and literature review

We present a rare case of T1- and T2-negative ventricular system tumor. Only FIESTA imaging revealed dissemination with multiple focal lesions of the third ventricle, its bottom and lateral walls, anterior horns of lateral ventricles, cerebellar vermis, cervical and lumbar spinal cord. The patient underwent transcortical endoscopic biopsy of the third ventricle tumor with simultaneous ventriculoperitoneal shunting. DNET was diagnosed, and radiotherapy was subsequently performed. Literature data on this issue were analyzed. To date, disseminated forms of DNET are extremely rare. X-ray features and morphological results allow us to establish the correct diagnosis and determine further treatment strategy.

Long-term epilepsy associated-tumors (LEATs): what is new?

Long-term epilepsy-associated tumors (LEATs) include a series of neoplasms that commonly occur in children, adolescents, or young adults, have an astrocytic or glioneuronal lineage, are histologically benign (WHO grade1) with a neocortical localization predominantly situated in the temporal lobes. Clinically, chronic refractory epilepsy is usually the unique symptom. Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNT) are the most common representative entities besides pilocytic astrocytomas (PA) and angiocentric gliomas (AG). Recent molecular studies have defined new clinicopathological entities, which are recognized by the WHO 2021 classification of brain tumors. Some of them such as diffuse astrocytoma MIB or MYBL1 altered, polymorphous low-grade neuroepithelial tumor of the young (PLNTY), and multilocular and vacuolating neuronal tumor (MVNT) are currently considered LEATs. The relationship between LEATs and epilepsy is still a matter of debate, and there is a general agreement about the beneficial effects of an early neurosurgical intervention on the clinical outcome.

Leat-associated seizures the possible role of EAAT2, pyruvate carboxylase and glutamine synthetase

BackgroundDrug-resistant epilepsy is a common condition in patients with brain neoplasms. The pathogenesis of tumor-associated seizures is poorly understood. Among the possible pathogenetic mechanisms, the increase in glutamate concentration has been proposed. Glutamate transporters, glutamine synthetase and pyruvate carboxylase are involved in maintaining the physiological concentration of glutamate in the intersynaptic spaces. In our previous research on angiocentric gliomas, we demonstrated that all tumors lacked the expression of the main glutamate transporter EAAT2, while the expression of glutamine synthetase and pyruvate carboxylase was mostly preserved. MethodsIn the present study, we evaluated the immunohistochemical expression of EAAT2, glutamine synthetase and pyruvate carboxylase in a heterogeneous series of 25 long-term epilepsy-associated tumors (10 dysembryoplastic neuroepithelial tumors, 7 gangliogliomas, 3 subependymal giant cell astrocytomas, 3 rosette forming glioneuronal tumors, 1 diffuse astrocytoma MYB- or MYBL1-altered and 1 angiocentric glioma). In order to evaluate the incidence of variants in the SLC1A2 gene, encoding EAAT2, in a large number of central nervous system tumors we also queried the PedcBioPortal. ResultsEAAT2 protein expression was lost in 9 tumors (36 %: 3 dysembryoplastic neuroepithelial tumors, 1 ganglioglioma, 3 subependymal giant cell astrocytomas, 1 diffuse astrocytoma MYB- or MYBL1-altered and 1 angiocentric glioma). Glutamine synthetase protein expression was completely lost in 2 tumors (8 %; 1 ganglioglioma and 1 diffuse astrocytoma MYB- or MYBL1-altered). All tumors of our series but rosette forming glioneuronal tumors (in which neurocytic cells were negative) were diffusely positive for pyruvate carboxylase. Consultation of the PedcBioPortal revealed that of 2307 pediatric brain tumors of different histotype and grade, 20 (< 1%) had variants in the SLC1A2 gene. Among the SLC1A2-mutated tumors, there were no angiocentric gliomas or other LEATs ConclusionsIn conclusion, unlike angiocentric gliomas where the EAAT2 loss is typical and constant, the current study shows the loss of EAAT2 expression only in a fraction of the LEATs. In these cases, we may hypothesize some possible epileptogenic role of the EAAT2 loss. The retained expression of pyruvate carboxylase may contribute to determining a pathological glutamate excess unopposed by glutamine synthetase that resulted expressed to a variable extent in the majority of the tumors. Furthermore, we can assume that the EAAT2 loss in brain tumors in general and in LEATs in particular is more conceivably epigenetic.

SURG-13. PEDIATRIC PRIMARY CENTRAL NERVOUS SYSTEM NEOPLASMS: RELATIVE UTILITY OF OPEN, MULTI-STAGE CRANIAL SURGERY

Abstract OBJECTIVE Staged surgery for skull base lesions has been utilized to facilitate maximal safe resection and optimize outcomes in pediatric patients. Despite its extensive applications, there is a paucity of information regarding open multi-stage resection of intrinsic, intra-axial neoplasms. We reviewed the literature in order to shed light on relevant considerations including the timing between surgeries, indications for staged approaches, and clinical outcomes following staged resection of pediatric intra-axial neoplasms. METHODS We conducted a literature search using PubMed, Web of Science, and Cochrane databases according to PRISMA recommendations. RESULTS Of 115 results, 7 articles were included for final analysis and consisted of 17 pediatric patients, including 6 (35%) male, 5 (29%) female, and 6 (35%) unspecified sex patients. Age ranged from 18 months to 17 years (mean 9 years). Tumor pathologies consisted of 5 (29%) astrocytomas, 2 (12%) ependymomas, 2 (12%) teratoid rhabdoid tumors, 2 (12%) oligodendromas, 1 (6%) glioma, 1 (6%) dysembryoplastic neuroepithelial tumor, 1 (6%) meningioangiomatosis, 1 (6%) pleomorphic xanthoastrocytoma, 1 (6%) ganglioglioma, and 1 (6%) germ cell tumor. Primary sites of the tumor included 4 (24%) temporal lobe, 3 (18%) thalamic, 3 (18%) thalamopeduncular, 3 (18%) frontal lobe, 2 (12%) posterior fossa, 1 (6%) cerebral hemisphere, and 1 (6%) frontoparietal lobe. Three studies reported complications, which included subtle hemiparesis, hydrocephalus, cranial nerve (CN) VI and VII palsies, truncal ataxia, and cerebellar mutism. Timing between surgeries varied from 5 days to several weeks CONCLUSION Indications for performing multi-stage resections included large tumor volume requiring multiple long stages of debulking, significant tumor vascularity, multicompartmental lesions, and planned staging due to presence of large tumors requiring resection around eloquent speech and motor cortical and white matter tract lesions that enabled use of awake functional mapping after a primary debulking performed in proximity to less eloquent regions.