Humans ; Ganglioglioma/pathology* ; Central Nervous System Neoplasms/pathology* ; Central Nervous System/pathology* ; Brain Neoplasms/pathology* ; World Health Organization

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

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

Ganglion cell tumors (GCT) are divided into two subtypes : gangliocytoma and ganglioglioma. Intramedullary gangliocytomas are extremely rare. A 20-year-old male patient with pain of neck, who also had a previously known neuroendocrine tumor of lung, was operated for mass found in the cervicomedullary junction with a presumptive diagnosis of metastases. Only partial resection could be performed. Pathological diagnosis had been reported as gangliocytoma. Only ten cases of intramedullary gangliocytoma have been reported in the literature. Although association with scoliosis and Von Recklinghausen's disease were previously reported in the literature, no gangliocytoma case concomitant with endocrine tumor of lung have been published. Pathological study is the most important diagnostic method for gangliocytomas. Surgical excision is the primary treatment, but difficulty in total surgical tumor resection is the most important problem.
Diagnosis ; Ganglioglioma ; Ganglion Cysts ; Ganglioneuroma* ; Humans ; Lung* ; Male ; Neck ; Neoplasm Metastasis ; Neuroendocrine Tumors* ; Neurofibromatosis 1 ; Scoliosis ; Young Adult

Intracranial neoplasms usually have definitive symptoms, causing a need for medical intervention, but a few cases result in sudden unexpected death even before diagnosis. In these cases, autopsy or post-mortem imaging may be the only way of identifying the existence of a tumor, so investigators or forensic specialists who participate in the post-mortem inspection should be aware of these possibilities. We report on a case of a 26-year-old woman without any medical history found dead in her home. A 5-cm intraventricular tumor was found during autopsy, which was histologically consistent with anaplastic ganglioglioma a very rare type of neuroglial tumor with the potential for malignant behavior. The tumor showed the characteristic features of anaplastic ganglioglioma, such as increased cellularity, a high Ki-67 proliferative index, and necrosis. There were signs of increased intracranial pressure, including flattened gyri and dilated ventricles, which led to the conclusion that this brain tumor was the cause of death.
Adult ; Autopsy ; Brain Neoplasms ; Cause of Death ; Diagnosis ; Female ; Ganglioglioma* ; Humans ; Intracranial Pressure ; Necrosis ; Neoplasms, Unknown Primary ; Research Personnel ; Specialization

Ganglioglioma is an infrequent tumor of the central nervous system (CNS); mostly supratentorial region. But, they can occur anywhere in the central nervous system such as brainstem, cerebellopontine angle (CPA), thalamus, optic nerve and spinal cord. Although it occurs rarely, ganglioglioma should be included in the differential diagnosis of a posterior fossa mass because early recognition is important for treatment and patient counseling.
Brain Stem* ; Central Nervous System ; Cerebellopontine Angle ; Counseling ; Diagnosis, Differential ; Ganglioglioma* ; Humans ; Optic Nerve ; Spinal Cord ; Thalamus

BACKGROUND: Ganglioglioma is a rare and slowly growing benign tumor. We investigated the outcomes of patients who underwent different combination treatments. METHODS: Between 1998 and 2012, 16 patients, including 11 men and 5 women, with a median age of 12.5 years (range, 2.5-65 years) were treated for intracranial gangliogliomas at our institution. The median follow-up period was 5.7 years (range, 48 days-15.6 years). Fifteen cases were included in the outcome assessment because one patient was lost to follow-up. Complete resection was achieved in 8 (53%) patients. Six (40%) patients underwent incomplete resection with or without adjuvant radiotherapy, and one patient with a brainstem tumor underwent only stereotactic biopsy. RESULTS: Gangliogliomas predominantly affected young (87.5%), male patients and most frequently presented with seizures (64%). Of eight patients who underwent complete resection, seven did not show recurrence, whereas only three of six with incomplete resection showed no recurrence. Four patients with recurrence received salvage treatments (two repeat surgeries and two radiosurgeries). A tumor control rate of 93% (14/15) was achieved at the last follow-up. No recurrence or malignant changes were observed after a median follow-up of 12 and 4.5 years in four patients who received gamma knife (GK) radiosurgery as adjuvant and salvage treatment. CONCLUSION: Complete resection produced the best outcomes and incomplete resection followed by adjuvant or salvage treatments showed favorable outcomes. In patients who are not eligible for complete resection because of tumor location or potential neurologic deficits following surgery, GK radiosurgery should be considered for the treatment of residual or recurrent tumors.
Biopsy ; Brain Stem Neoplasms ; Female ; Follow-Up Studies ; Ganglioglioma* ; Humans ; Lost to Follow-Up ; Male ; Neurologic Manifestations ; Radiosurgery ; Radiotherapy, Adjuvant ; Recurrence ; Seizures

OBJECTIVETo investigate the expression of TSC1, TSC2, p-mTOR, p-4E-BP1, p-p70S6K and p-S6 in refractory epilepsy associated malformation of cortical development (MCD) tissues.

METHODSA total of 43 cases of refractory epilepsy were involved in the study, and all the patients were treated in Xuanwu Hospital during 2005 - 2008, including focal cortical dysplasia type IIa (11 cases) and type IIb (11 cases), tuberous sclerosis complex (10 cases) and ganalioglioma (11 cases), and other 12 cases were used as control. These cases were divided into 7 study groups and immunohistochemical EnVision method was used. To detect the location and intensity of TSC1, TSC2, p-mTOR, p-4E-BP1, p-p70S6K and p-S6 expression in every group. Then the Image-Pro Plus 6.0 image processing and analysis software were used to measure the number, area, integrating absorbance (IA) of positive cells in every samples. The statistical software SPSS 16.0 was used to analyze the data.

RESULTSThe immunolocalization of TSC1 and TSC2 was similar. It could be observed the expression of various levels in the cytoplasm of dysmorphic neurons, balloon cells, giant cells, ganglioglioma cells and normal neurons. TSC1 staining in normal neurons was more notably than others but TSC2 staining in giant cells was weaker than other samples. p-mTOR mainly presented in giant cells, which could also be observed in astrocyte. P-4E-BP1 presented in the cytoplasm and nuclear membrane of balloon cells, giant cells and ganglioglioma cells, the staining of giant cells was stronger than balloon cells, but their staining were weaker than ganglioglioma cells. P-p70S6K mainly expressed in giant cells and less commonly presented in balloon cells. P-S6 typically presented in all abnormal glioneuronal cells and it nearly did not present in the normal neurons of N-CTX group.

CONCLUSIONSPI3K pathway, at least in part, involves in the occurrence of MCD, and may play an important role in the pathogenesis.

Adaptor Proteins, Signal Transducing ; metabolism ; Adolescent ; Adult ; Child ; Epilepsy ; metabolism ; pathology ; Female ; Ganglioglioma ; metabolism ; pathology ; Humans ; Male ; Malformations of Cortical Development ; metabolism ; pathology ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphoproteins ; metabolism ; Ribosomal Protein S6 Kinases ; metabolism ; Ribosomal Protein S6 Kinases, 70-kDa ; metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases ; metabolism ; Tuberous Sclerosis ; metabolism ; pathology ; Tumor Suppressor Proteins ; metabolism ; Young Adult

This study was performed to assess the usefulness of magnetoencephalography (MEG) as a presurgical evaluation modality in Korean pediatric patients with lesional localization-related epilepsy. The medical records and MEG findings of 13 pediatric patients (6 boys and 7 girls) with localization-related epilepsy, who underwent epilepsy surgery at Seoul National University Children's Hospital, were retrospectively reviewed. The hemispheric concordance rate was 100% (13/13 patients). The lobar or regional concordance rate was 77% (10/13 patients). In most cases, the MEG spike sources were clustered in the proximity of the lesion, either at one side of the margin (nine patients) or around the lesion (one patient); clustered spike sources were distant from the lesion in one patient. Among the patients with clustered spike sources near the lesion, further extensions (three patients) and distal scatters (three patients) were also observed. MEG spike sources were well lateralized and localized even in two patients without focal epileptiform discharges in the interictal scalp electroencephalography. Ten patients (77%) achieved Engel class I postsurgical seizure outcome. It is suggested that MEG is a safe and useful presurgical evaluation modality in pediatric patients with lesion localization-related epilepsy.
Adolescent ; Brain/radionuclide imaging ; Brain Diseases/pathology ; Child ; Child, Preschool ; Epilepsies, Partial/pathology/*surgery ; Female ; Ganglioglioma/pathology ; Humans ; Infant ; Magnetic Resonance Imaging ; *Magnetoencephalography ; Male ; Malformations of Cortical Development/pathology ; Neoplasms, Neuroepithelial/pathology ; Positron-Emission Tomography ; Retrospective Studies ; Seizures/diagnosis

OBJECTIVE: The incidence of leptomeningeal dissemination from malignant glioma is rare, so the clinical features of this are not well documented yet. We attempted to determine the clinical features of leptomeningeal dissemination from malignant gliomas. METHODS: We retrospectively analyzed 11 cases of leptomeningeal dissemination of malignant glioma, who were treated at our institution between 2006 and 2009. We investigated the clinical features of these patients by considering the following factors : tumor locations, the events of ventricular opening during surgery and the cerebrospinal fluid (CSF) profiles, including the cytology. RESULTS: The group was composed of 9 males and 2 females. The histological diagnosis of their initial intracranial tumors were 4 primary glioblastoma, 3 anaplastic astrocytoma, 1 anaplastic oligoastrocytoma, 2 ganglioglioma and 1 pleomorphic xanthoastrocyotma with anaplastic features. The mean age of the patients at the time of the initial presentation was 42.8+/-10.3 years. The mean time between surgery and the diagnosis of spinal dissemination was 12.3+/-7.9 (3-28) months. The mean overall survival after dissemination was 2.7+/-1.3 months. All our patients revealed a history of surgical opening of the ventricles. Elevated protein in the CSF was reported for eight patients who had their CSF profiles checked. CONCLUSION: We propose that in the malignant gliomas, the surgical opening of ventricles can cause the spinal leptomeningeal dissemination and the elevated protein content of CSF may be a candidate marker of leptomeningeal dissemination.
Astrocytoma ; Female ; Ganglioglioma ; Glioblastoma ; Glioma ; Humans ; Incidence ; Male ; Retrospective Studies