Brain tumors are the second most common type of structural brain lesion that causes chronic epilepsy. Patients with low-grade brain tumors often experience chronic drug-resistant epilepsy starting in childhood, which led to the concept of long-term epilepsy-associated tumors (LEATs). Dysembryoplastic neuroepithelial tumor and ganglioglioma are representative LEATs and are characterized by young age of onset, frequent temporal lobe location, benign tumor biology, and chronic epilepsy. Although highly relevant in clinical epileptology, the concept of LEATs has been criticized in the neuro-oncology field. Recent genomic and molecular studies have challenged traditional views on LEATs and low-grade gliomas. Molecular studies have revealed that low-grade gliomas can largely be divided into three groups : LEATs, pediatric-type diffuse low-grade glioma (DLGG; astrocytoma and oligodendroglioma), and adult-type DLGG. There is substantial overlap between conventional LEATs and pediatric-type DLGG in regard to clinical features, histology, and molecular characteristics. LEATs and pediatric-type DLGG are characterized by mutations in BRAF, FGFR1, and MYB/MYBL1, which converge on the RAS-RAF-MAPK pathway. Gene (mutation)-centered classification of epilepsy-associated tumors could provide new insight into these heterogeneous and diverse neoplasms and may lead to novel molecular targeted therapies for epilepsy in the near future.
Age of Onset ; Astrocytoma ; Biology ; Brain ; Brain Neoplasms ; Classification ; Epilepsy ; Ganglioglioma ; Glioma ; Humans ; Molecular Targeted Therapy ; Neoplasms, Neuroepithelial ; Seizures ; Temporal Lobe

Astroblastoma is an uncommon glial tumor with predominant manifestation in the young age. Herein, we report a case of 18-year-old astroblastoma female patient who presented with history of two months headache. Magnetic resonance imaging (MRI) of the brain demonstrated well circumscribed, intra-axial abnormal signal intensity lesion (size=5×4 cm²) in the right parieto-occipital region of the brain. The patient underwent complete surgical resection of the gross tumor, as confirmed by an early post-surgical MRI (i.e., within 24 hours of surgery). Histopathological examination revealed neoplastic lesion exhibiting perivascular pseudo-rosettes with centrally hyalinized blood vessel and focal nuclear pleomorphism. Immunohistochemistry staining illustrated reactivity for glial fibrillary acidic protein and integrase interactor 1 (INI-1). These features rendered the diagnosis of astroblastoma. A comprehensive review of the current literature to summarize the clinicopathological and radiological characteristics, prognostic factors and current treatment strategies of astroblastomas is also presented. Our study would expand the pool of this uncommon tumor towards its better understanding and optimal treatment.
Adolescent ; Blood Vessels ; Brain ; Brain Neoplasms ; Craniotomy ; Diagnosis ; Female* ; Glial Fibrillary Acidic Protein ; Headache ; Humans ; Hyalin ; Immunohistochemistry ; Integrases ; Magnetic Resonance Imaging ; Neoplasms, Neuroepithelial*

Ependymoma is the third most common pediatric primary brain tumor. Ependymomas are categorized according to their locations and genetic abnormalities, and these two parameters are important prognostic factors for patient outcome. For supratentorial (ST) ependymomas, RELA fusion-positive ependymomas show a more aggressive behavior than YAP1 fusion-positive ependymomas. Extracranial metastases of intra-axial neuroepithelial tumors are extremely rare. In this paper, we report a case of aggressive anaplastic ependymoma arising in the right frontoparietal lobe, which had genetically 1q25 gain, CDKN2A homozygous deletion, and L1CAM overexpression. The patient was a 10-year-old boy who underwent four times of tumor removal and seven times of gamma knife surgery. Metastatic loci were scalp and temporalis muscle overlying primary operation site, lung, liver, buttock, bone, and mediastinal lymph nodes. He had the malignancy for 10 years and died. This tumor is a representative case of RELA fusion-positive ST ependymoma, showing aggressive behavior.
Brain Neoplasms ; Buttocks ; Child ; Ependymoma* ; Genetics ; Humans ; Liver ; Lung ; Lymph Nodes ; Male ; Neoplasm Metastasis* ; Neoplasms, Neuroepithelial ; Neural Cell Adhesion Molecule L1 ; Scalp ; Supratentorial Neoplasms ; Transcription Factor RelA

The World Health Organization (WHO) classification of central nervous system (CNS) tumors was revised in 2016 with a basis on the integrated diagnosis of molecular genetics. We herein provide the guidelines for using molecular genetic tests in routine pathological practice for an accurate diagnosis and appropriate management. While astrocytomas and IDH-mutant (secondary) glioblastomas are characterized by the mutational status of IDH, TP53, and ATRX, oligodendrogliomas have a 1p/19q codeletion and mutations in IDH, CIC, FUBP1, and the promoter region of telomerase reverse transcriptase (TERTp). IDH-wildtype (primary) glioblastomas typically lack mutations in IDH, but are characterized by copy number variations of EGFR, PTEN, CDKN2A/B, PDGFRA, and NF1 as well as mutations of TERTp. High-grade pediatric gliomas differ from those of adult gliomas, consisting of mutations in H3F3A, ATRX, and DAXX, but not in IDH genes. In contrast, well-circumscribed low-grade neuroepithelial tumors in children, such as pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and ganglioglioma, often have mutations or activating rearrangements in the BRAF, FGFR1, and MYB genes. Other CNS tumors, such as ependymomas, neuronal and glioneuronal tumors, embryonal tumors, meningothelial, and other mesenchymal tumors have important genetic alterations, many of which are diagnostic, prognostic, and predictive markers and therapeutic targets. Therefore, the neuropathological evaluation of brain tumors is increasingly dependent on molecular genetic tests for proper classification, prediction of biological behavior and patient management. Identifying these gene abnormalities requires cost-effective and high-throughput testing, such as next-generation sequencing. Overall, this paper reviews the global guidelines and diagnostic algorithms for molecular genetic testing of brain tumors.
Adult ; Astrocytoma ; Brain Neoplasms* ; Brain* ; Central Nervous System ; Child ; Classification ; Diagnosis ; Ependymoma ; Ganglioglioma ; Genes, myb ; Glioblastoma ; Glioma ; Humans ; Molecular Biology ; Neoplasms, Neuroepithelial ; Neurons ; Oligodendroglioma ; Promoter Regions, Genetic ; Telomerase ; World Health Organization

This reports a case of dysembryoplastic neuroepithelial tumor (DNET) in a 5-year old male presenting with visual hallucination and seizures. Diagnostic workup revealed a homogenous cystic tumor located in the right temporo-parietal area which was considered as a low grade glioma. The patient underwent endoscopic third ventriculostomy with complete tumor excision and biopsy, revealing NET. Findings were confirmed by immunohistochemical staining with glial fibrillary action protein (GFAP), Alcian blue and synaptophysin. DNET is a recently described intracranial tumor under the World Health Organization classification of central nervous system (CNS) tumors. It is a unique entity of neuroglial tumors with excellent prognosis. Its worldwide incidence among all neuroepithelial tumors is 1.2% in patients under 20 years and 0.2% among patients over 20 years. This is the first case of DNET in the country as well as in our institution. Key points on the clinical manifestation, approach to diagnosis, distinctive radiologic and histopathologic characteristics, and management are discussed.
Neoplasms, Neuroepithelial

Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous syndrome that affects ectomesodermal tissues (skin, eyes, adipose tissue, and brain). The neurologic manifestations associated with ECCL are various including seizures. However, ECCL patients very rarely develop brain tumors that originate from the neuroepithelium. This is the first described case of ECCL in combination with dysembryoplastic neuroepithelial tumor (DNET) that presented with intractable seizures. A 7-year-old girl was admitted to our center because of ECCL and associated uncontrolled seizures. She was born with right anophthalmia and lipomatosis in the right temporal area and endured right temporal lipoma excision at 3 years of age. Seizures began when she was 3 years old, but did not respond to multiple antiepileptic drugs. Brain magnetic resonance (MR) imaging performed at 8 and 10 years of age revealed an interval increase of multifocal hyperintense lesions in the basal ganglia, thalamus, cerebellum, periventricular white matter, and, especially, the right temporal area. A nodular mass near the right hippocampus demonstrated the absence of N-acetylaspartate decrease on brain MR spectroscopy and mildly increased methionine uptake on brain positron emission tomography, suggesting low-grade tumor. Twenty-four-hour video electroencephalographic monitoring also indicated seizures originating from the right temporal area. Right temporal lobectomy was performed without complications, and the nodular lesion was pathologically identified as DNET. The patient has been seizure-free for 14 months since surgery. Although ECCL-associated brain tumors are very rare, careful follow-up imaging and surgical resection is recommended for patients with intractable seizures.
Adipose Tissue ; Anophthalmos ; Anticonvulsants ; Basal Ganglia ; Brain ; Brain Neoplasms ; Cerebellum ; Child ; Drug Resistant Epilepsy ; Female ; Follow-Up Studies ; Hippocampus ; Humans ; Lipoma ; Lipomatosis* ; Magnetic Resonance Spectroscopy ; Methionine ; Neoplasms, Neuroepithelial* ; Neurocutaneous Syndromes ; Neurologic Manifestations ; Positron-Emission Tomography ; Seizures* ; Thalamus ; White Matter

Adult ; Biopsy ; Cerebral Ventricle Neoplasms ; diagnosis ; Diagnosis, Differential ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Neoplasms, Neuroepithelial ; diagnosis ; Third Ventricle ; diagnostic imaging

Pilocytic astrocytomas (PAs) are World Heath Organization Grade I tumors and are most common in children. PA calcification is not a common finding and has been reported more frequently in the optic nerve, hypothalamic/thalamus and superficially located cerebral tumors. We present a cerebellar PA in a 3-year-old male patient with cystic components and massive calcification areas. The residual tumor grew rapidly after the first operation, and the patient was operated on again. A histopathological examination revealed polar spongioblastoma-like cells. Massive calcification is not a common feature in PAs and can lead to difficulties in radiological and pathological differential diagnoses.
Astrocytoma* ; Child ; Child, Preschool ; Diagnosis, Differential ; Humans ; Male ; Neoplasm, Residual ; Neoplasms, Neuroepithelial ; Optic Nerve ; Recurrence*

Dysembryoplastic neuroepithelial tumor (DNT) is a benign glioneuronal neoplasm that most commonly occurs in children and young adults and may present with medically intractable, chronic seizures. Radiologically, this tumor is characterized by a cortical topography and lack of mass effect or perilesional edema. Partial complex seizures are the most common presentation. Three histologic subtypes of DNTs have been described. Histologically, the recognition of a unique, specific glioneuronal element in brain tumor samples from patients with medically intractable, chronic epilepsy serves as a diagnostic feature for complex or simple DNT types. However, nonspecific DNT has diagnostic difficulty because its histology is indistinguishable from conventional gliomas and because a specific glioneuronal element and/or multinodularity are absent. This review will focus on the clinical, radiographic, histopathological, and immunohistochemical features as well as the molecular genetics of all three variants of DNTs. The histological and cytological differential diagnoses for this lesion, especially the nonspecific variant, will be discussed.
Brain Neoplasms ; Child ; Diagnosis, Differential ; Edema ; Epilepsy ; Glioma ; Humans ; Microtubule-Associated Proteins ; Molecular Biology ; Neoplasms, Neuroepithelial* ; Seizures ; Young Adult

Adult ; Female ; Humans ; Neoplasms, Neuroepithelial ; diagnosis