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Ucar EA, Ozgen U, Kiris T. Dorsally exophytic brain stem ganglioglioma extending to the foramen of Luschka: a case report. J Med Case Rep 2025; 19:87. [PMID: 40025555 PMCID: PMC11872322 DOI: 10.1186/s13256-025-05128-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 02/06/2025] [Indexed: 03/04/2025] Open
Abstract
BACKGROUND Gangliogliomas are rare tumors primarily arising from the central nervous system, mostly in the temporal lobes, with brain stem involvement being particularly infrequent. To the best of our knowledge, this is the first reported instance of a brainstem ganglioglioma exhibiting an extension to foramen of Luschka. CASE PRESENTATION We present a unique case of ganglioglioma of the brainstem. 23-year-old Turkish patient presented with flashing lights in the peripheral visual fields. Imaging studies revealed a distinct mass lesion adjacent to the brainstem, demonstrating an unusual exophytic growth pattern that extended towards the foramen of Luschka. Surgical intervention was performed to prevent tumor progression and obtain a definitive diagnosis. The surgical approach employed was the telovelar approach, which provides excellent visualization of the posterior fossa. Histopathological examination of the resected specimen confirmed the diagnosis of grade 1 ganglioglioma. Postoperative magnetic resonance imaging scans displayed gross total resection of the tumor. The patient's postoperative course was uneventful, and the initial symptom of flashing lights resolved in the postoperative period. CONCLUSION This case report highlights the uniqueness of a dorsally exophytic brain stem ganglioglioma extending to the foramen of Luschka. Utilization of the telovelar approach and sodium fluorescein in the surgical management of this challenging case underscores its efficacy in managing deep-seated lesions within the posterior fossa. Although presenting infrequently, gangliogliomas should be considered in the differential diagnosis of lesions of the foramen of Luschka because early recognition is important for the management and prognosis.
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Affiliation(s)
- Ege Anil Ucar
- School of Medicine, Koc University Hospital, 34010, Zeytinburnu, Istanbul, Turkey.
| | - Utku Ozgen
- Department of Neurosurgery, American Hospital, Istanbul, Turkey
| | - Talat Kiris
- Department of Neurosurgery, American Hospital, Istanbul, Turkey
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2
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Kurzbuch AR, Cooper B, Kitchen J, McLaren A, Tronnier V, Ellenbogen JR. Pediatric cerebral ganglioglioma epilepsy surgery: enhancing seizure outcomes through optimized resection applying high-field intraoperative magnetic resonance imaging. Childs Nerv Syst 2025; 41:110. [PMID: 39934322 DOI: 10.1007/s00381-025-06766-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Accepted: 02/01/2025] [Indexed: 02/13/2025]
Abstract
PURPOSE Gangliogliomas are rare, slow-growing brain tumors frequently associated with seizures in pediatric patients. This study evaluated the utility of high-field intraoperative magnetic resonance imaging (ioMRI) in the surgical management of ganglioglioma-related drug-resistant epilepsy in children. Specifically, it sought to determine whether ioMRI improves outcomes by optimizing the extent of resection, enhancing seizure control, reducing reoperations, and minimizing complications. METHODS This retrospective single-center study included 14 pediatric patients with cerebral ganglioglioma who underwent epilepsy surgery with ioMRI from 2014 to 2022. The median age was 11.5 years (range 3-16 years). Patient demographics, the rate of continued ioMRI-guided surgery, the extent of resection, histology, complications, reoperations, and seizure outcomes at 1 year postoperatively were assessed. RESULTS Residual tumor was detected using ioMRI in 9 of 14 patients (64.3%), leading to further resection. Complete tumor resection was achieved in 12 patients (100%) as intended, while two patients underwent planned tumor debulking. Temporary neurological deficits were observed in two patients, with no permanent deficits documented. One patient required reoperation, and another was scheduled for one. The median follow-up duration was 43 months (range 12-65 months). Seizure outcomes were classified as Engel I in 9 of 10 (90%) and Engel III in 1 of 10 patients (10%). Four patients were lost to follow-up. CONCLUSION The use of ioMRI in pediatric epilepsy surgery for ganglioglioma facilitated more complete resections, contributing to favorable seizure outcomes and a low complication rate. These findings support ioMRI as a valuable tool in optimizing surgical management for this patient population.
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Affiliation(s)
- Arthur R Kurzbuch
- Department of Neurosurgery, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, L12 2AP, UK.
| | - Ben Cooper
- Department of Neurosurgery, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, L12 2AP, UK
| | - John Kitchen
- Department of Neurosurgery, Royal Manchester Children's Hospital, Oxford Rd, Manchester, M12 9WL, UK
| | - Andrea McLaren
- Department of Neurosurgery, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, L12 2AP, UK
| | - Volker Tronnier
- Department of Neurosurgery, University Medical Center Schleswig-Holstein, Campus Luebeck, Ratzeburger Alle 160, 23562, Luebeck, Germany
| | - Jonathan R Ellenbogen
- Department of Neurosurgery, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, L12 2AP, UK
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3
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Pai V, Laughlin S, Ertl-Wagner B. Imaging of pediatric glioneuronal and neuronal tumors. Childs Nerv Syst 2024; 40:3007-3026. [PMID: 38960918 DOI: 10.1007/s00381-024-06502-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 06/10/2024] [Indexed: 07/05/2024]
Abstract
Glioneuronal tumors (GNTs) are an expanding group of primary CNS neoplasms, commonly affecting children, adolescents and young adults. Most GNTs are relatively indolent, low-grade, WHO grade I lesions. In the pediatric age group, GNTs have their epicenter in the cerebral cortex and present with seizures. Alterations in the mitogen-activated protein kinase (MAPK) pathway, which regulates cell growth, are implicated in tumorigenesis. Imaging not only plays a key role in the characterization and pre-surgical evaluation of GNTs but is also crucial role in follow-up, especially with the increasing use of targeted inhibitors and immunotherapies. In this chapter, we review the clinical and imaging perspectives of common pediatric GNTs.
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Affiliation(s)
- Vivek Pai
- Division of Neuroradiology, Department of Diagnostic and Interventional Radiology, The Hospital for Sick Children, 170 Elizabeth Street, Toronto, ON, M5G 1E8, Canada
- Department of Medical Imaging, University of Toronto, 263 McCaul St, 4Th Floor, Toronto, ON, M5T 1W7, Canada
| | - Suzanne Laughlin
- Division of Neuroradiology, Department of Diagnostic and Interventional Radiology, The Hospital for Sick Children, 170 Elizabeth Street, Toronto, ON, M5G 1E8, Canada
- Department of Medical Imaging, University of Toronto, 263 McCaul St, 4Th Floor, Toronto, ON, M5T 1W7, Canada
| | - Birgit Ertl-Wagner
- Division of Neuroradiology, Department of Diagnostic and Interventional Radiology, The Hospital for Sick Children, 170 Elizabeth Street, Toronto, ON, M5G 1E8, Canada.
- Department of Medical Imaging, University of Toronto, 263 McCaul St, 4Th Floor, Toronto, ON, M5T 1W7, Canada.
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Stone TJ, Merve A, Valerio F, Yasin SA, Jacques TS. Paediatric low-grade glioma: the role of classical pathology in integrated diagnostic practice. Childs Nerv Syst 2024; 40:3189-3207. [PMID: 39294363 PMCID: PMC11511714 DOI: 10.1007/s00381-024-06591-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 08/23/2024] [Indexed: 09/20/2024]
Abstract
Low-grade gliomas are a cause of severe and often life-long disability in children. Pathology plays a key role in their management by establishing the diagnosis, excluding malignant alternatives, predicting outcomes and identifying targetable genetic alterations. Molecular diagnosis has reshaped the terrain of pathology, raising the question of what part traditional histology plays. In this review, we consider the classification and pathological diagnosis of low-grade gliomas and glioneuronal tumours in children by traditional histopathology enhanced by the opportunities afforded by access to comprehensive genetic and epigenetic characterisation.
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Affiliation(s)
- Thomas J Stone
- Developmental Biology and Cancer Research and Teaching Department, UCL GOS Institute of Child Health, London, UK
- Department of Histopathology, Great Ormond Street Hospital, London, UK
| | - Ashirwad Merve
- Developmental Biology and Cancer Research and Teaching Department, UCL GOS Institute of Child Health, London, UK
- Department of Histopathology, Great Ormond Street Hospital, London, UK
- Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, London, UK
| | - Fernanda Valerio
- Department of Histopathology, Great Ormond Street Hospital, London, UK
- Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, London, UK
| | - Shireena A Yasin
- Developmental Biology and Cancer Research and Teaching Department, UCL GOS Institute of Child Health, London, UK
- Department of Histopathology, Great Ormond Street Hospital, London, UK
| | - Thomas S Jacques
- Developmental Biology and Cancer Research and Teaching Department, UCL GOS Institute of Child Health, London, UK.
- Department of Histopathology, Great Ormond Street Hospital, London, UK.
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5
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Lacruz CR, Álvarez F. Cytopathology of glioneuronal and neuronal tumours with histological correlations. Cytopathology 2024; 35:545-555. [PMID: 37740719 DOI: 10.1111/cyt.13308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/23/2023] [Accepted: 09/01/2023] [Indexed: 09/25/2023]
Abstract
Glioneuronal and neuronal tumours constitute a diverse group of tumours that feature neuronal differentiation. In mixed glioneuronal tumours, a glial component is present in addition to the neuronal component. With a few exceptions (eg diffuse leptomeningeal glioneuronal tumour) they are well-circumscribed and slow-growing tumours, which is why their prognosis is intrinsically favourable after gross total resection. Rendering an intraoperative diagnosis of glioneuronal/neuronal tumour is therefore important-neurosurgeons should remove them to prevent the persistence of clinical symptoms and/or recurrence. In this context, cytopathological examination can be especially useful for assessing cellular details when frozen section artefacts render poor-quality preparations, as is the case for this group of tumours, which are frequently mistaken for infiltrating gliomas (eg diffuse astrocytoma infiltrating grey matter, oligodendroglioma) on frozen section slides. The aim of this article is to review the cytomorphological features of glioneuronal and neuronal tumours according to the 2021 World Health Organization classification of central nervous system tumours, 5th edition. Additionally, since interpretation in intraoperative cytology relies on intuiting tissue patterns from cytology preparations, representative histological figures of all discussed entities have been included. Clues for specific diagnoses and the primary diagnostic problems encountered during intraoperative procedures are also discussed.
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Affiliation(s)
- César R Lacruz
- Department of Pathology, QuironSalud University Hospital, Madrid, Spain
| | - Federico Álvarez
- Department of Pathology, Infanta Leonor University Hospital, Madrid, Spain
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6
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Chen Y, Buchanan P, Brossier NM, Navalkele P. Incidence and survival characteristics of pediatric ganglioglioma from 2004 to 2018, with focus on infratentorial sites. Neurooncol Pract 2024; 11:328-335. [PMID: 38737603 PMCID: PMC11085854 DOI: 10.1093/nop/npae012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2024] Open
Abstract
Background Ganglioglioma (GG) is a slow-growing glioneuronal neoplasm, most frequently seen in the supratentorial location in older children and associated with epilepsy syndromes. GG is rare in the infratentorial location, hence we embarked upon analyzing the National Cancer Institute's (NCI) Survival, Epidemiology, and End Results (SEER) database to better evaluate GG outcomes by location in comparison to the broader pediatric low-grade glioma (pLGG) population. Methods Pediatric patients diagnosed with GG and pLGG from 2004 to 2018 were included in the study. Their demographic, clinical, and survival characteristics were analyzed using SEER*Stat. Results This study describes the largest cohort of pediatric GG, including 852 cases from year 2004 to 2018, with focus on infratentorial sites. Patients with brainstem GG or those with subtotally resected disease were identified as having higher risk of death. Conclusions Our analysis highlights brainstem GG as a high-risk, poor-prognostic subgroup and elaborates on the incidence and survival characteristic of this lesser-known subgroup.
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Affiliation(s)
- Yongzhen Chen
- Saint Louis University School of Medicine, 1402 S Grand Blvd, Saint Louis, Missouri, USA
| | - Paula Buchanan
- Department of Health and Clinical Outcomes Research, Saint Louis University School of Medicine, Saint Louis, Missouri, USA
| | - Nicole M Brossier
- Department of Pediatrics, Washington University School of Medicine, Saint Louis, Missouri, USA
| | - Pournima Navalkele
- Division of Oncology, Children’s Hospital Orange County, Orange, California, USA
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7
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Gupta A, Lechpammer M, Brossier NM. Germline BRCA2 pathogenic variants in pediatric ganglioglioma: Case report and review of the literature. Childs Nerv Syst 2024; 40:1609-1612. [PMID: 38168858 DOI: 10.1007/s00381-023-06267-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 12/21/2023] [Indexed: 01/05/2024]
Abstract
BACKGROUND BRCA1 and BRCA2 are tumor suppressor genes associated with increased risk of breast and ovarian cancer in adulthood. Patients with germline pathogenic variants in these genes have also been reported to develop brain tumors, although it is unclear whether these syndromes are associated with significant increased risk of brain tumor formation. RESULTS Here, we report a case of a child with germline BRCA2 pathogenic variant presenting with a symptomatic ganglioglioma. To our knowledge, this is the first such patient to be reported. We discuss prior cases of brain tumors in BRCA1/2 patients and evidence for a potential role for BRCA1/2 pathogenic variants in brain tumor formation. CONCLUSION BRCA2 germline variants may increase the risk of developing some types of pediatric brain tumors, but further study is needed to determine its effect on low-grade glioma formation.
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Affiliation(s)
- Anya Gupta
- Departments of Pediatrics, Washington University School of Medicine, Box 8208, 660 South Euclid Avenue, St. Louis, MO, 63110, USA
| | | | - Nicole M Brossier
- Departments of Pediatrics, Washington University School of Medicine, Box 8208, 660 South Euclid Avenue, St. Louis, MO, 63110, USA.
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8
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Pratt D, Penas-Prado M, Gilbert MR. Clinical impact of molecular profiling in rare brain tumors. Curr Opin Neurol 2023; 36:579-586. [PMID: 37973025 DOI: 10.1097/wco.0000000000001211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2023]
Abstract
PURPOSE OF REVIEW The purpose of this review is to describe the commonly used molecular diagnostics and illustrate the prognostic importance to the more accurate diagnosis that also may uncover therapeutic targets. RECENT FINDINGS The most recent WHO Classification of Central Nervous System Tumours (2021) lists over 100 distinct tumor types. While traditional histology continues to be an important component, molecular testing is increasingly being incorporated as requisite diagnostic criteria. Specific molecular findings such as co-deletion of the short arm of chromosome 1 (1p) and long arm of chromosome 19 (19q) now define IDH-mutant gliomas as oligodendroglioma. In recent years, DNA methylation profiling has emerged as a dynamic tool with high diagnostic accuracy. The integration of specific genetic (mutations, fusions) and epigenetic (CpG methylation) alterations has led to diagnostic refinement and the discovery of rare brain tumor types with distinct clinical outcomes. Molecular profiling is anticipated to play an increasing role in routine surgical neuropathology, although costs, access, and logistical concerns remain challenging. SUMMARY This review summarizes the current state of molecular testing in neuro-oncology highlighting commonly used and developing technologies, while also providing examples of new tumor types/subtypes that have emerged as a result of improved diagnostic precision.
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Affiliation(s)
| | - Marta Penas-Prado
- Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Mark R Gilbert
- Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
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9
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Erkan B, Demir S, Akpinar E, Akkurt TS, Tanriverdi O, Gunaldi O. A rare tumor in the sellar region: ganglioglioma, a case report and a general overview. Childs Nerv Syst 2023; 39:3621-3626. [PMID: 37432397 DOI: 10.1007/s00381-023-06073-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 07/05/2023] [Indexed: 07/12/2023]
Abstract
BACKGROUND Gangliogliomas are rare mixed neuronal-glial tumors of the central nervous system, accounting for less than 2% of intracranial tumors. CASE DESCRIPTION This report presents a rare case of ganglioglioma in the sellar region of a 3-year-old and 5-month-old pediatric patient. The patient underwent surgical intervention initially through a transnasal transsphenoidal approach and subsequently through a transcranial pterional craniotomy approach. Subsequently, radiotherapy and chemotherapy were administered for residual tumor tissue. The purpose of this report is to highlight the presence of ganglioglioma as a distinct diagnosis in sellar region tumors, discuss the surgical, radiotherapy, and/or chemotherapy treatment options for sellar region gangliogliomas based on the literature, and contribute the patient's follow-up and treatment outcomes to the existing literature. CONCLUSION Complete tumor resection may not be feasible in sellar region gangliogliomas, especially in pediatric cases, due to endocrinological and vision-related complications. In cases where complete resection is not possible, radiotherapy and/or chemotherapy may be considered. However, the optimal treatment approach has not yet been established, and further research is needed.
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Affiliation(s)
- Buruc Erkan
- Department of Neurosurgery, Health Science University, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey.
| | - Suat Demir
- Department of Neurosurgery, Health Science University, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
| | - Ebubekir Akpinar
- Department of Neurosurgery, Health Science University, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
| | - Tuce Soylemez Akkurt
- Department of Pathology, Health Science University, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
| | - Osman Tanriverdi
- Department of Neurosurgery, Health Science University, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
| | - Omur Gunaldi
- Department of Neurosurgery, Health Science University, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
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10
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Mesny E, Lesueur P. Radiotherapy for rare primary brain tumors. Cancer Radiother 2023; 27:599-607. [PMID: 37481341 DOI: 10.1016/j.canrad.2023.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 06/08/2023] [Indexed: 07/24/2023]
Abstract
Rare central nervous system tumors are defined by an incidence rate of less than 6 cases per 100 000 individuals a year. It comprises a large panel of entities including medulloblastoma, glioneuronal tumors, solitary fibrous tumors, rare pituitary tumors, ependymal or embryonal tumors. The management of these tumors is not clearly defined and radiotherapy indications should be discussed at a multidisciplinary board. Image-guided and intensity-modulated radiation therapy should be proposed and MRI has a fundamental place in the treatment preparation. To avoid the occurrence of side effects, proton therapy is playing an increasingly role for the treatment of these tumors.
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Affiliation(s)
- E Mesny
- Radiation Oncology Department, centre hospitalier Lyon Sud, Pierre-Bénite, France.
| | - P Lesueur
- Centre de radiothérapie Guillaume-le-Conquérant, 76600 Le Havre, France; Département de radiothérapie, centre François-Baclesse, 14000 Caen, France; Équipe CERVOxy, ISTCT UMR6030-CNRS, CEA, université de Caen-Normandie, 14000 Caen, France
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11
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Wu PB, Filley AC, Miller ML, Bruce JN. Benign Glioma. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1405:31-71. [PMID: 37452934 DOI: 10.1007/978-3-031-23705-8_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/18/2023]
Abstract
Benign glioma broadly refers to a heterogeneous group of slow-growing glial tumors with low proliferative rates and a more indolent clinical course. These tumors may also be described as "low-grade" glioma (LGG) and are classified as WHO grade I or II lesions according to the Classification of Tumors of the Central Nervous System (CNS) (Louis et al. in Acta Neuropathol 114:97-109, 2007). Advances in molecular genetics have improved understanding of glioma tumorigenesis, leading to the identification of common mutation profiles with significant treatment and prognostic implications. The most recent WHO 2016 classification system has introduced several notable changes in the way that gliomas are diagnosed, with a new emphasis on molecular features as key factors in differentiation (Wesseling and Capper in Neuropathol Appl Neurobiol 44:139-150, 2018). Benign gliomas have a predilection for younger patients and are among the most frequently diagnosed tumors in children and young adults (Ostrom et al. in Neuro Oncol 22:iv1-iv96, 2020). These tumors can be separated into two clinically distinct subgroups. The first group is of focal, well-circumscribed lesions that notably are not associated with an increased risk of malignant transformation. Primarily diagnosed in pediatric patients, these WHO grade I tumors may be cured with surgical resection alone (Sturm et al. in J Clin Oncol 35:2370-2377, 2017). Recurrence rates are low, and the prognosis for these patients is excellent (Ostrom et al. in Neuro Oncol 22:iv1-iv96, 2020). Diffuse gliomas are WHO grade II lesions with a more infiltrative pattern of growth and high propensity for recurrence. These tumors are primarily diagnosed in young adult patients, and classically present with seizures (Pallud et al. Brain 137:449-462, 2014). The term "benign" is a misnomer in many cases, as the natural history of these tumors is with malignant transformation and recurrence as grade III or grade IV tumors (Jooma et al. in J Neurosurg 14:356-363, 2019). For all LGG, surgery with maximal safe resection is the treatment of choice for both primary and recurrent tumors. The goal of surgery should be for gross total resection (GTR), as complete tumor removal is associated with higher rates of tumor control and seizure freedom. Chemotherapy and radiation therapy (RT), while not typically a component of first-line treatment in most cases, may be employed as adjunctive therapy in high-risk or recurrent tumors and in some select cases. The prognosis of benign gliomas varies widely; non-infiltrative tumor subtypes generally have an excellent prognosis, while diffusely infiltrative tumors, although slow-growing, are eventually fatal (Sturm et al. in J Clin Oncol 35:2370-2377, 2017). This chapter reviews the shared and unique individual features of the benign glioma including diffuse glioma, pilocytic astrocytoma and pilomyxoid astrocytoma (PMA), subependymal giant cell astrocytoma (SEGA), pleomorphic xanthoastrocytoma (PXA), subependymoma (SE), angiocentric glioma (AG), and chordoid glioma (CG). Also discussed is ganglioglioma (GG), a mixed neuronal-glial tumor that represents a notable diagnosis in the differential for other LGG (Wesseling and Capper 2018). Ependymomas of the brain and spinal cord, including major histologic subtypes, are discussed in other chapters.
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Affiliation(s)
- Peter B Wu
- Department of Neurosurgery, David Geffen School of Medicine at UCLA, UCLA, Los Angeles, USA
| | - Anna C Filley
- Department of Neurosurgery, Columbia University Medical Center, New York, USA
| | - Michael L Miller
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, USA
| | - Jeffrey N Bruce
- Department of Neurosurgery, Columbia University Medical Center, New York, USA.
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12
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Cronin C, McLaughlin R, Lane L, Brett FM, Jansen M, Bermingham N, Wyse G, Grogan L, Morris PG, O’Reilly S. Case report: BRAF-inhibitor therapy in BRAF-mutated primary CNS tumours including one case of BRAF-mutated Rosai-Dorfman disease. Front Med (Lausanne) 2022; 9:1070828. [PMID: 36619621 PMCID: PMC9813211 DOI: 10.3389/fmed.2022.1070828] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 11/29/2022] [Indexed: 12/24/2022] Open
Abstract
BRAF V600E oncogene mutations have been reported in multiple central nervous system (CNS) tumor types, and emerging evidence supports the use of targeted therapy in BRAF-mutated gliomas. BRAF oncogene mutations have been recently identified in Rosai-Dorfman disease (RDD)-a rare non-Langerhans cell histiocytosis. This series describes three patients from two neurosurgical centers in Ireland with BRAF V600E-mutated CNS tumors. The study participants include a 19-year-old male patient with ganglioglioma with anaplastic features, a 21-year-old male patient with CNS involvement of RDD, and a 28-year-old female patient with ganglioglioma with anaplastic features. Two patients received radiation with concurrent temozolomide before BRAF-targeted therapy. This case series describes clinical and radiological responses to BRAF-targeted therapy in BRAF V600E-mutated gliomas across multiple tumor grades and is only the second published report of response to targeted therapy in BRAF-mutated RDD. The durability of disease control with BRAF-targeted therapy was generally superior to that achieved with chemoradiation; one patient has experienced ongoing disease control for 5 years. The reported case of treatment response in BRAF-mutated RDD supports the strategy of genotyping and utilization of targeted therapy in this rare disease. The optimal sequencing of BRAF-targeted therapy in BRAF-mutated gliomas/glioneuronal tumors remains unclear, and further prospective studies are required to guide the use of genome-matched therapy in this patient population.
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Affiliation(s)
| | - Ronan McLaughlin
- Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland
| | - Louise Lane
- Department of Neuropathology, Beaumont Hospital, Dublin, Ireland
| | | | - Michael Jansen
- Department of Neuropathology, Cork University Hospital, Cork, Ireland
| | - Niamh Bermingham
- Department of Neuropathology, Cork University Hospital, Cork, Ireland
| | - Gerald Wyse
- Department of Radiology, Cork University Hospital, Cork, Ireland
| | - Liam Grogan
- Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland
| | | | - Seamus O’Reilly
- Department of Medical Oncology, Cork University Hospital, Cork, Ireland
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13
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Li S, Xiong Y, Hu G, Lv S, Song P, Guo H, Wu L. Suprasellar Ganglioglioma Arising from the Third Ventricle Floor: A Case Report and Review of the Literature. Tomography 2022; 8:2844-2853. [PMID: 36548530 PMCID: PMC9788206 DOI: 10.3390/tomography8060238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 11/10/2022] [Accepted: 11/11/2022] [Indexed: 11/30/2022] Open
Abstract
Gangliogliomas are uncommon intracranial tumors that include neoplastic and abnormal ganglion cells, and show positive immunohistochemical staining for GFAP and syn. This type of lesion occurs more frequently in the temporal lobe than in other areas; they are extremely rare in the suprasellar region. To the best of our knowledge, including our case, 19 cases of GGs have been found in the suprasellar region. Among them, five tumors invaded the optic nerve, nine tumors invaded the optic chiasm, one tumor invaded the optic tract, and two tumors invaded the entire optic chiasmal hypothalamic pathway. In the present study, we describe the first case of suprasellar GGs arising from the third ventricle floor that was removed through the endoscopic endonasal approach. In addition, we summarize the clinical characteristics of GGs, such as age of onset, gender distribution, MRI signs, main clinical symptoms, and treatment methods for GG cases.
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Rudà R, Capper D, Waldman AD, Pallud J, Minniti G, Kaley TJ, Bouffet E, Tabatabai G, Aronica E, Jakola AS, Pfister SM, Schiff D, Lassman AB, Solomon DA, Soffietti R, Weller M, Preusser M, Idbaih A, Wen PY, van den Bent MJ. EANO - EURACAN - SNO Guidelines on circumscribed astrocytic gliomas, glioneuronal, and neuronal tumors. Neuro Oncol 2022; 24:2015-2034. [PMID: 35908833 PMCID: PMC9713532 DOI: 10.1093/neuonc/noac188] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
In the new WHO 2021 Classification of CNS Tumors the chapter "Circumscribed astrocytic gliomas, glioneuronal and neuronal tumors" encompasses several different rare tumor entities, which occur more frequently in children, adolescents, and young adults. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is low particularly for adult patients, and draw recommendations accordingly. Tumor diagnosis, based on WHO 2021, is primarily performed using conventional histological techniques; however, a molecular workup is important for differential diagnosis, in particular, DNA methylation profiling for the definitive classification of histologically unresolved cases. Molecular factors are increasing of prognostic and predictive importance. MRI finding are non-specific, but for some tumors are characteristic and suggestive. Gross total resection, when feasible, is the most important treatment in terms of prolonging survival and achieving long-term seizure control. Conformal radiotherapy should be considered in grade 3 and incompletely resected grade 2 tumors. In recurrent tumors reoperation and radiotherapy, including stereotactic radiotherapy, can be useful. Targeted therapies may be used in selected patients: BRAF and MEK inhibitors in pilocytic astrocytomas, pleomorphic xanthoastrocytomas, and gangliogliomas when BRAF altered, and mTOR inhibitor everolimus in subependymal giant cells astrocytomas. Sequencing to identify molecular targets is advocated for diagnostic clarification and to direct potential targeted therapies.
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Affiliation(s)
- Roberta Rudà
- Corresponding Author: Roberta Rudà, Department of Neurology, Castelfranco Veneto/Treviso Hospital and Division of Neuro-Oncology, Department of Neuroscience, University of Turin, Turin, Italy ()
| | - David Capper
- Department of Neuropathology, Charité Universitätsmedizin Berlin, Berlin and German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Adam D Waldman
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh and Department of Brain Science, Imperial College London, United Kingdom
| | - Johan Pallud
- Department of Neurosurgery, GHU-Paris Psychiatrie et Neurosciences, Hôpital Sainte Anne, Paris, France
| | - Giuseppe Minniti
- Radiation Oncology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy and IRCCS Neuromed (IS), Italy
| | - Thomas J Kaley
- Department of Neurology, Brain Tumor Service, Memorial Sloan Kettering Cancer Center, New York, US
| | - Eric Bouffet
- Division of Paediatric Oncology, The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Ghazaleh Tabatabai
- Department of Neurology & Neurooncology, University of Tübingen, German Cancer Consortium (DKTK), DKFZ partner site Tübingen, Germany
| | - Eleonora Aronica
- Department of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Amsterdam and Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, the Netherlands
| | - Asgeir S Jakola
- Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden. Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, Sahlgrenska Academy, Gothenburg, Sweden
| | - Stefan M Pfister
- Hopp Children´s Cancer Center Heidelberg (KiTZ), Division of Pediatric Neuro-oncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), and Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany
| | - David Schiff
- Department of Neurology, Division of Neuro-Oncology, University of Virginia, Charlottesville, US
| | - Andrew B Lassman
- Division of Neuro-Oncology, Department of Neurology and the Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons and New York-Presbyterian Hospital, New York, NY, US
| | - David A Solomon
- Department of Pathology, University of California, San Francisco, CA, US
| | - Riccardo Soffietti
- Division of Neuro-Oncology, Department of Neuroscience, University and City of Health and Science Hospital, Turin, Italy
| | - Michael Weller
- Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland
| | - Matthias Preusser
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - Ahmed Idbaih
- Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris, France
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15
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Hartanto RA, Dwianingsih EK, Panggabean AS, Wicaksono AS, Dananjoyo K, Asmedi A, Malueka RG. Seizure in Indonesian Glioma Patients: Associated Risk Factors and Impact on Survival. Asian Pac J Cancer Prev 2021; 22:691-697. [PMID: 33773530 PMCID: PMC8286685 DOI: 10.31557/apjcp.2021.22.3.691] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Indexed: 12/26/2022] Open
Abstract
Objective: Seizure is commonly found in patients with glioma. This study aimed to find risk factors for seizures in Indonesian patients with glioma. We also sought to determine the association between seizure and survival in this patient population. Methods: Patients with glioma were enrolled from the Dr. Sardjito General Hospital and other hospitals in Yogyakarta Province, Indonesia. Detailed demographic and clinical data were collected from medical records. DNA extraction and polymerase chain reaction (PCR) were performed to detect IDH1 mutation. Tumor tissue samples were stained by hematoxylin-eosin and classified according to the 2016 World Health Organization (WHO) classification of central nervous system (CNS) tumors. Expression of Ki-67 was detected by immunohistochemistry staining. Survival data were also collected. Results: In total, 107 patients were included in the analysis. Age, gender, history of smoking, tumor side, tumor grade, Ki-67 expression, and IDH1 mutation were not associated with seizure. Tumors involving the frontal lobe (p=0.037) and oligodendroglioma histology (p=0.031) were associated with the development of seizures in this study. However, multivariate analysis showed that only oligodendrogial histology was associated with seizure [p=0.032, odds ratio (OR) = 4.77, 95% confidence interval (CI) = 1.146-19.822]. Patients with seizures have significantly longer median overall survival than patients without seizures (69.3±25.01 vs. 10.6±6.14 months, respectively, p=0.04). Conclusion: This study showed that seizure in patients with glioma in Indonesia is associated with frontal lobe location and oligodendroglioma histology. Patients with seizures also have significantly longer overall survival.
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Affiliation(s)
- Rahmat Andi Hartanto
- Division of Neurosurgery, Department of Surgery, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Dr. Sardjito General Hospital, Yogyakarta, Indonesia
| | - Ery Kus Dwianingsih
- Department of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Dr. Sardjito General Hospital, Yogyakarta, Indonesia
| | - Andre Stefanus Panggabean
- Neurology Department, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Dr Sardjito General Hospital, Yogyakarta, Indonesia
| | - Adiguno Suryo Wicaksono
- Division of Neurosurgery, Department of Surgery, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Dr. Sardjito General Hospital, Yogyakarta, Indonesia
| | - Kusumo Dananjoyo
- Neurology Department, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Dr Sardjito General Hospital, Yogyakarta, Indonesia
| | - Ahmad Asmedi
- Neurology Department, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Dr Sardjito General Hospital, Yogyakarta, Indonesia
| | - Rusdy Ghazali Malueka
- Neurology Department, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Dr Sardjito General Hospital, Yogyakarta, Indonesia
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16
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Omofoye OA, Lechpammer M, Steele TO, Harsh GR. Pituitary stalk gangliogliomas: Case report and literature review. Clin Neurol Neurosurg 2020; 201:106405. [PMID: 33340839 DOI: 10.1016/j.clineuro.2020.106405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 10/27/2020] [Accepted: 11/28/2020] [Indexed: 11/17/2022]
Abstract
INTRODUCTION Gangliogliomas rarely occur in the sella or suprasellar region and are almost never seen in the pituitary stalk. Seven cases of gangliogliomas occurring in this region have been reported; only one case involved a tumor within the pituitary stalk. Of the six tumors external to the pituitary stalk, two occurred in the neurohypophysis, one was in the adenohypophysis, the location of one was unspecified, and two extensively invaded the optic chiasm, hypothalamus and brainstem. This is only the second reported case of a pituitary stalk ganglioglioma, and it is unique in its use of an extended endoscopic endonasal approach for biopsy. CASE REPORT A 51-year old woman presented with an eleven-month history of polydipsia and polyuria leading to the diagnosis of diabetes insipidus. Magnetic Resonance Imaging of the brain revealed contrast-enhanced thickening and anterior bowing of the hypophyseal stalk. An extended endoscopic endonasal approach permitted midline removal of the tuberculum sella, opening of underlying dura, and exposure of the pituitary stalk. A firm, white, 4 mm diameter mass, integral to the right side of the enlarged pituitary stalk was seen and biopsied. Histopathological analysis was consistent with WHO grade 1 ganglioglioma. The patient tolerated the procedure well and required no endocrinologic treatment other than desmopressin. CONCLUSION Pituitary stalk gangliogliomas are extremely rare. The diagnosis should be considered in patients with pituitary stalk enlargement. Endoscopic endonasal approach is a safe surgical approach to establish a tissue diagnosis which is essential for pathologic certainty given the wide differential diagnosis of stalk lesions.
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Affiliation(s)
- Oluwaseun A Omofoye
- Department of Neurological Surgery, University of California Davis Health, 4860 Y Street Suite 3740, Sacramento, CA 95817, USA.
| | - Mirna Lechpammer
- Department of Pathology and Laboratory Medicine, University of California Davis Health, 4400 V Street, Sacramento, CA 95817, USA.
| | - Toby O Steele
- Department of Otolaryngology - Head and Neck Surgery, University of California Davis Health, 2521 Stockton Boulevard, Sacramento, CA 95817, USA.
| | - Griffith R Harsh
- Department of Neurological Surgery, University of California Davis Health, 4860 Y Street Suite 3740, Sacramento, CA 95817, USA.
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Lin X, Huang R, Zhang P, Sun J, Dong G, Huang Y, Tian X. Low-grade gangliogliomas in adults: A population-based study. Cancer Med 2020; 10:416-423. [PMID: 33107220 PMCID: PMC7826489 DOI: 10.1002/cam4.3577] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 10/01/2020] [Accepted: 10/12/2020] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Low-grade gangliogliomas (GGs) are rare tumors of the central nervous system in adults. This study aims to define their characteristics, prognostic factors, and the impact of different treatment patterns on survival. METHODS The Surveillance, Epidemiology, and End Results (SEER) database was used to investigate the potential clinicopathological factors of low-grade GGs in adult patients (age ≥18 years). Kaplan-Meier method and Cox regression model were utilized to evaluate the associations between variables and overall survival (OS). RESULTS A total of 703 adult patients diagnosed with low-grade GGs were identified between 2004 and 2016, with a median follow-up period of 60.0 months. The median age at diagnosis was 32.0 years, with 50.1% of patients being male, 84.2% white people, and 40.2% of married status. The predominant tumor site was located in temporal lobe (38.8%). The median OS time for the whole cohort was not reached. The 5- and 10-year OS rates for patients underwent gross total resection (GTR) were 92.5% and 87.2%, respectively. Univariate and multivariate analysis showed age, gender, tumor site, and treatment pattern were significant factors for OS. The employment of adjuvant radiotherapy (RT) and/or chemotherapy would significantly shorten OS time. CONCLUSIONS This is the largest retrospective study of adult low-grade GGs up to date. Younger age, female gender, temporal lobe location, and GTR indicated better survival. Adjuvant RT and/or chemotherapy should not be considered after whatever surgery in adult patients with low-grade GGs, unless the malignant transformation has been confirmed.
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Affiliation(s)
- Xiaoning Lin
- Department of Neurosurgery, Zhongshan Hospital Xiamen University, Xiamen, China
| | - Rong Huang
- Department of Child Health, Women and Children's Hospital, Xiamen University, Xiamen, China
| | - Pengfei Zhang
- Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Jin Sun
- Department of Neurosurgery, Zhongshan Hospital Xiamen University, Xiamen, China
| | - Guijiang Dong
- Department of Neurosurgery, Zhongshan Hospital Xiamen University, Xiamen, China
| | - Yanlin Huang
- Department of Neurosurgery, Zhongshan Hospital Xiamen University, Xiamen, China
| | - Xinhua Tian
- Department of Neurosurgery, Zhongshan Hospital Xiamen University, Xiamen, China
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Shi Y, Zhang B, Zhu J, Huang W, Han B, Wang Q, Qi C, Wang M, Liu F. miR-106b-5p Inhibits IRF1/IFN-β Signaling to Promote M2 Macrophage Polarization of Glioblastoma. Onco Targets Ther 2020; 13:7479-7492. [PMID: 32801770 PMCID: PMC7398755 DOI: 10.2147/ott.s238975] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Accepted: 07/06/2020] [Indexed: 01/01/2023] Open
Abstract
Purpose The microRNA (miRNA) profile changes in the tumor-associated macrophages. However, the role of miR-106b-5p in the glioblastoma-associated macrophages is poorly understood. Materials and Methods In our study, miR-106b-5p and M2 macrophage markers were detected by qRT-PCR and Western blotting in THP1 cells, with the conditioned medium from U251 cells or M2 macrophages in response to IL-4 stimulation and M1 macrophages stimulated by LPS and IFN-γ. IFN regulatory factor (IRF1) was identified as a target of miR-106b-5p in the glioma infiltrating macrophages by luciferase reporter assay. The molecular mechanisms involved in the miR-106b-5p-mediated regulation of M2 polarization were clarified by shRNA knockdown assay. Results Our results showed miR-106b-5p expression was upregulated in glioma-infiltrating macrophages. miR-106b-5p regulated M2 polarization of glioma infiltrating macrophages and enhanced the growth of glioma-infiltrating macrophages. IRF1 was identified as a target of miR-106b-5p. Furthermore, miR-106b-5p inhibited IRF1 expression by targeting IRF1/IFN-β pathway to promote M2 polarization of macrophages. Conclusion miR-106b-5p may inhibit IRF1/IFN-β signaling to promote M2 macrophage polarization of glioblastoma, and it may become a novel target for the treatment of glioblastoma.
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Affiliation(s)
- Yu Shi
- Department of Neurology, Xuzhou Hospital Affiliated to Jiangsu University, Xuzhou, Jiangsu, People's Republic of China
| | - Bin Zhang
- Department of Neurosurgery, Jintan People's Hospital, Changzhou, Jiangsu, People's Republic of China
| | - Jian Zhu
- Department of Neurosurgery, Yancheng No.1 People's Hospital, Yancheng, Jiangsu, People's Republic of China
| | - Wu Huang
- Department of Neurosurgery, Nanjing Medical University Affiliated Changzhou NO.2 People's Hospital, Changzhou, Jiangsu, People's Republic of China
| | - Bin Han
- Department of Neurosurgery, Nanjing Medical University Affiliated Changzhou NO.2 People's Hospital, Changzhou, Jiangsu, People's Republic of China
| | - Qilong Wang
- Department of Neurosurgery, Nanjing Medical University Affiliated Changzhou NO.2 People's Hospital, Changzhou, Jiangsu, People's Republic of China
| | - Chunjian Qi
- Department of Central Lab, Nanjing Medical University Affiliated Changzhou NO.2 People's Hospital, Changzhou, Jiangsu, People's Republic of China
| | - Minghai Wang
- Department of Neurosurgery, Nanjing Medical University Affiliated Changzhou NO.2 People's Hospital, Changzhou, Jiangsu, People's Republic of China
| | - Fang Liu
- Department of Neurosurgery, Nanjing Medical University Affiliated Changzhou NO.2 People's Hospital, Changzhou, Jiangsu, People's Republic of China
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Bartek J, Dhawan S, Thurin E, Alattar A, Gulati S, Rydenhag B, Henriksson R, Chen CC, Jakola AS. Short-term outcome following surgery for rare brain tumor entities in adults: a Swedish nation-wide registry-based study and comparison with SEER database. J Neurooncol 2020; 148:281-290. [PMID: 32424575 PMCID: PMC7316679 DOI: 10.1007/s11060-020-03490-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Accepted: 04/08/2020] [Indexed: 01/03/2023]
Abstract
Objective To investigate outcomes after surgery for rare brain tumors using the Swedish Brain Tumor Registry (SBTR). Methods This is a nationwide study of patient in the SBTR, validated in the Surveillance, Epidemiology, and End Results (SEER) registries. We included all adults diagnosed 2009–2015 with a rare brain tumor entity (n = 216), defined as ependymoma (EP, n = 64), subependymoma (SUBEP, n = 21), ganglioglioma (GGL, n = 54), pilocytic astrocytoma (PA, n = 56) and primitive neuroectodermal tumor (PNET, n = 21). We analyzed symptomatology, tumor characteristics and outcomes. Results Mean age was 38.3 ± 17.2 years in GGL, 36.2 ± 16.9 in PA, 37.0 ± 19.1 in PNET, 51.7 ± 16.3 in EP and 49.8 ± 14.3 in SUBEP. The most common symptom was focal deficit (39.6–71.4%), and this symptom was most common in GGL patients with 64.2% of GGL presenting with seizures. Most patients had no or little restriction in activity before surgery (Performance Status 0–1), although up to 15.0% of PNET patients had a performance status of 4. Gross total resection was achieved in most (> 50%) tumor categories. Incidence of new deficits was 11.1–34.4%. In terms of postoperative complications, 0–4.8% had a hematoma of any kind, 1.9–15.6% an infection, 0–7.8% a venous thromboembolism and 3.7–10.9% experienced a complication requiring reoperation. There were 3 deaths within 30-days of surgery, and a 1-year mortality of 0–14.3%. Conclusion We have provided benchmarks for the current symptomatology, tumor characteristics and outcomes after surgery for rare brain tumors as collected by the SBTR and validated our results in an independent registry. These results may aid in clinical decision making and advising patients.
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Affiliation(s)
- Jiri Bartek
- Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
- Department of Clinical Neuroscience and Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
- Department of Neurosurgery, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
| | - Sanjay Dhawan
- Department of Neurosurgery, University of Minnesota, Minneapolis, MN, USA
| | - Erik Thurin
- Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden
| | - Ali Alattar
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Sasha Gulati
- Department of Neurosurgery, St. Olav University Hospital, Trondheim, Norway
| | - Bertil Rydenhag
- Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden
| | - Roger Henriksson
- Department of Radiation Sciences, University of Umeå, S-901 85, Umeå, Sweden
| | - Clark C Chen
- Department of Neurosurgery, University of Minnesota, Minneapolis, MN, USA
| | - Asgeir Store Jakola
- Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden
- Department of Neurosurgery, St. Olav University Hospital, Trondheim, Norway
- Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden
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Abstract
Tumors of the central nervous system comprise nearly a quarter of all childhood cancers and are the most frequent solid tumor in the pediatric population. The most common location is in the posterior fossa, but tumors can occur anywhere intracranially. The spectrum of lesions encountered varies, from being completely benign and requiring surveillance alone to being highly malignant and requiring aggressive treatment in the form of surgery and adjuvant therapy. The extent of resection plays a crucial role in the oncological outcome of many of these tumors. A variety of surgical approaches are available for the spectrum of lesions encountered. This review focuses on summarizing the location, types, and neurosurgical management strategies for pediatric brain intracranial brain tumors. Here, we discuss neurosurgical approaches for a variety of brain tumors and regions, including the management of tumors of the posterior fossa, brainstem, pineal region, intraventricular region, sellar and suprasellar regions, optic pathway and hypothalamus, and supratentorial hemispheres.
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Affiliation(s)
- Adikarige H D Silva
- Department of Neurosurgery, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, England, WC1N 3JH, UK
| | - Kristian Aquilina
- Department of Neurosurgery, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, England, WC1N 3JH, UK.
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21
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Yau WH, Ameratunga M. Combination of BRAF and MEK inhibition in BRAF V600E mutant low-grade ganglioglioma. J Clin Pharm Ther 2020; 45:1172-1174. [PMID: 31985841 DOI: 10.1111/jcpt.13112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Accepted: 01/05/2020] [Indexed: 12/25/2022]
Abstract
WHAT IS KNOWN AND OBJECTIVE Post-surgical management of low grade gangliogliomas is controversial with paucity of data for the use of chemotherapy. BRAF mutations are present in a number of glioma subtypes and offer an opportunity for treatment with targeted therapy. CASE SUMMARY A 32-year-old man with an unresectable, BRAF V600E mutant, WHO grade 1 ganglioglioma is commenced on combination BRAF and MEK inhibition (vemurafenib and cobimetinib). Partial radiological and clinical response was noted after 13 weeks of treatment. Treatment complication with grade 2 skin and liver toxicity was resolved with dose interruption and reduction. WHAT IS NEW AND CONCLUSION Combination BRAF and MEK inhibition present a safe and feasible treatment strategy in unresectable BRAF V600E mutant low grade ganglioglioma.
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Affiliation(s)
- Wing Hing Yau
- Department of Medical Oncology, Alfred Health, Melbourne, Victoria, Australia
| | - Malaka Ameratunga
- Department of Medical Oncology, Alfred Health, Melbourne, Victoria, Australia.,Monash University, Melbourne, Victoria, Australia
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22
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Oushy S, Perry A, Graffeo CS, Raghunathan A, Carlstrom LP, Daniels DJ. Pediatric ganglioglioma of the brainstem and cervicomedullary junction: a retrospective cohort study. J Neurosurg Pediatr 2020; 25:30-36. [PMID: 31585412 DOI: 10.3171/2019.7.peds1961] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Accepted: 07/29/2019] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Ganglioglioma is a low-grade central nervous system neoplasm with a pediatric predominance, accounting for 10% of all brain tumors in children. Gangliogliomas of the cervicomedullary junction (GGCMJs) and brainstem (GGBSs) present a host of management challenges, including a significant risk of surgical morbidity. At present, understanding of the prognostic factors-including BRAF V600E status-is incomplete. Here, the authors report a single-institution GGCMJ and GGBS experience and review the pertinent literature. METHODS A prospectively maintained neurosurgical database at a large tertiary care academic referral center was retrospectively queried for cases of GGCMJ pathologically confirmed in the period from 1995 to 2015; appropriate cases were defined by diagnosis codes and keywords. Secondary supplemental chart review was conducted to confirm or capture relevant data. The primary study outcome was treatment failure as defined by evidence of radiographic recurrence or progression and/or clinical or functional decline. A review of the literature was conducted as well. RESULTS Five neurosurgically managed GGBS patients were identified, and the neoplasms in 4 were classified as GGCMJ. All 5 patients were younger than 18 years old (median 15 years, range 4-16 years) and 3 (60%) were female. One patient underwent gross-total resection, 2 underwent aggressive subtotal resection (STR), and 2 underwent stereotactic biopsy only. All patients who had undergone STR or biopsy required repeat resection for tumor control or progression. Progressive disease was treated with radiotherapy in 2 patients, chemotherapy in 2, and chemoradiotherapy alone in 1. Immunostaining for BRAF V600E was positive in 3 patients (60%). All 5 patients experienced at least one major complication, including wound infection, foot drop, hemiparesis, quadriparesis, cranial neuropathy, C2-3 subluxation, syringomyelia, hydrocephalus, aspiration, and coma. Overall mortality was 20%, with 1 death observed over 11 years of follow-up. CONCLUSIONS GGBS and GGCMJ are rare, benign posterior fossa tumors that carry significant perioperative morbidity. Contemporary management strategies are heterogeneous and include combinations of resection, radiotherapy, and chemotherapy. The BRAF V600E mutation is frequently observed in GGBS and GGCMJ and appears to have both prognostic and therapeutic significance with targeted biological agents.
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She DJ, Lu YP, Xiong J, Cao DR, Geng DY, Yin B. Comparison of conventional, diffusion, and perfusion MRI between infratentorial ganglioglioma and pilocytic astrocytoma. Acta Radiol 2019; 60:1687-1694. [PMID: 31032625 DOI: 10.1177/0284185119845088] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- De-jun She
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai, PR China
| | - Yi-ping Lu
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai, PR China
| | - Ji Xiong
- Institute of Functional and Molecular Medical Imaging, Fudan University, Shanghai, PR China
| | - Dai-rong Cao
- Department of Pathology, Huashan Hospital, Fudan University, Shanghai, PR China
| | - Dao-ying Geng
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai, PR China
- Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, PR China
| | - Bo Yin
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai, PR China
- Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, PR China
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Phi JH, Kim SK. Clinical Pearls and Advances in Molecular Researches of Epilepsy-Associated Tumors. J Korean Neurosurg Soc 2019; 62:313-320. [PMID: 31085957 PMCID: PMC6514318 DOI: 10.3340/jkns.2019.0033] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 03/07/2019] [Accepted: 03/17/2019] [Indexed: 11/30/2022] Open
Abstract
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 lowgrade 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 epilepsyassociated 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.
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Affiliation(s)
- Ji Hoon Phi
- Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul, Korea
| | - Seung-Ki Kim
- Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul, Korea
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25
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Garnier L, Ducray F, Verlut C, Mihai MI, Cattin F, Petit A, Curtit E. Prolonged Response Induced by Single Agent Vemurafenib in a BRAF V600E Spinal Ganglioglioma: A Case Report and Review of the Literature. Front Oncol 2019; 9:177. [PMID: 30984614 PMCID: PMC6448025 DOI: 10.3389/fonc.2019.00177] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 03/04/2019] [Indexed: 12/11/2022] Open
Abstract
Spinal ganglioglioma is a rare low-grade, slow-growing tumor of the central nervous system affecting mostly children and young adults. After surgery, some patients show tumor recurrence and/or malignant transformation. Gangliogliomas harbor molecular deficiencies such as mutations in the B-rapidly accelerated fibrosarcoma (BRAF) gene, resulting in activation of a downstream signaling pathway and cancer development. Vemurafenib is a BRAF inhibitor used to treat patients with BRAF V600E-mutated cancer. Although a few studies have reported the clinical responses in gangliogliomas, the sequence and duration of treatment have not been established. We describe a case of an adult with a progressive BRAF V600E mutant spinal cord ganglioglioma 9 years after surgery who was treated with vemurafenib. This treatment resulted in a partial response within 2 months, which was sustained for more than a year. The patient then decided to stop treatment because of side effects. Despite this decision, the tumor showed no sign of progression 21 months after treatment discontinuation. This is the first reported case of a response to vemurafenib in an adult with progressive spinal cord BRAF V600E-mutated ganglioglioma which was sustained after treatment discontinuation.
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Affiliation(s)
- Louis Garnier
- Department of Medical Oncology, University Hospital of Besançon, Besançon, France
| | - François Ducray
- Department of Neuro-Oncology, Hospices Civils de Lyon, Lyon, France
| | - Clotilde Verlut
- Department of Neurology, University Hospital of Besançon, Besançon, France
| | | | - Françoise Cattin
- Department of Radiology, University Hospital of Besançon, Besançon, France
| | - Antoine Petit
- Department of Neurosurgery, University Hospital of Besançon, Besançon, France
| | - Elsa Curtit
- Department of Medical Oncology, University Hospital of Besançon, Besançon, France
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Chatrath A, Mastorakos P, Mehta GU, Wildeman M, Moosa S, Jane JA. Ganglioglioma Arising from the Septum Pellucidum: Case Report and Review of the Literature. Pediatr Neurosurg 2019; 54:36-45. [PMID: 30620941 DOI: 10.1159/000495043] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 10/27/2018] [Indexed: 11/19/2022]
Abstract
BACKGROUND Gangliogliomas are low-grade neoplasms that typically affect patients under the age of 30 and present with epilepsy and symptoms of mass effect. Here, we report a case of an intraventricular ganglioglioma involving the septum pellucidum in a pediatric patient with history of optic glioma. Only one other pediatric intraventricular ganglioglioma arising from the septum pellucidum has been reported previously. CASE REPORT The patient initially presented at 9 months of age with a pilocytic astrocytoma centered on the optic chiasm, treated with chemotherapy and radiation at 3 years of age. Routine follow-up imaging at 13 years of age revealed the development of a mass in the septum pellucidum, which was subtotally resected endoscopically because of its proximity to the fornices. Pathology confirmed a ganglioglioma positive for the BRAF V600E mutation. The tumor residual progressed and was treated with stereotactic radiosurgery. The patient was asymptomatic at her 6-month follow-up visit and the size of the nodule remained stable. LITERATURE REVIEW Our review of the 25 previously reported intraventricular gangliogliomas found that their pre-surgical diagnoses were often incorrect, reflecting the difficulty of making the diagnosis with signs, symptoms, and imaging alone. Patients can be reassured that the prognosis is generally favorable following uncomplicated neurosurgical resection.
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Affiliation(s)
- Ajay Chatrath
- Department of Neurological Surgery, University of Virginia Health Science Center, University of Virginia, Charlottesville, Virginia, USA
| | - Panagiotis Mastorakos
- Department of Neurological Surgery, University of Virginia Health Science Center, University of Virginia, Charlottesville, Virginia, USA.,Department of Neurological Surgery, NIH/NINDS, Bethesda, Maryland, USA
| | - Gautam U Mehta
- Department of Neurological Surgery, University of Virginia Health Science Center, University of Virginia, Charlottesville, Virginia, USA.,Department of Neurological Surgery, NIH/NINDS, Bethesda, Maryland, USA.,Department of Neurosurgery, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
| | - Miriam Wildeman
- Department of Pathology, University of Virginia Health Science Center, University of Virginia, Charlottesville, Virginia, USA
| | - Shayan Moosa
- Department of Neurological Surgery, University of Virginia Health Science Center, University of Virginia, Charlottesville, Virginia, USA
| | - John A Jane
- Department of Neurological Surgery, University of Virginia Health Science Center, University of Virginia, Charlottesville, Virginia, USA,
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Hong Y, Fang Y, Wu Q, Zhang J, Wang Y. Ganglioglioma of the adenohypophysis mimicking pituitary adenoma: A case report and review of the literature. Medicine (Baltimore) 2018; 97:e11583. [PMID: 30045287 PMCID: PMC6078729 DOI: 10.1097/md.0000000000011583] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
INTRODUCTION Ganglioglioma is a generally benign tumor, mostly occurring in patients <30 years old. Temporal lobe is most frequently involved. Up to now, only 3 cases were reported of ganglioglioma in the pituitary gland, all being confined to the neurohypophysis. Here, we are the first to report an adenohypophysis ganglioglioma. CASE PRESENTATION A 43-year-old woman presented with chronic headache was referred to our hospital. Magnetic resonance imaging (MRI) indicated pituitary adenoma. Endoscopic transnasal transsphenoidal surgery was performed. The tumor was rich in blood supply, with tough texture, therefore only subtotal resection was conducted. Pathology analysis revealed an adenohypophysial tumor composed of dysplastic ganglion cells and neoplastic glial cells collided with nonspecific hyperplasia of pituitary cells. Immunohistochemistry revealed positive staining of synaptophysin, glial-fibrillary acidic protein, and CD34. The results were consistent with the diagnosis of ganglioglioma. After the surgery the patient recovered well except developing cerebrospinal fluid rhinorrhea, which was controlled by lumbar drainage. MRI 6 months later did not show any sign of progression. CONCLUSION According to the findings of our case, concerns should be raised considering ganglioglioma as a differential diagnosis of mass located in the sellar region. Furthermore, an ideal management strategy for pituitary ganglioglioma is not known; therefore, more cases and long-term follow-up are needed to enrich our knowledge of the diagnosis, treatment, and prognosis of this rare intracranial lesion.
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Affiliation(s)
- Yuan Hong
- Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine
| | - Yuanjian Fang
- Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine
| | - Qun Wu
- Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine
| | - Jianmin Zhang
- Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine
- Brain Research Institute
- Collaborative Innovation Center for Brain Science, Zhejiang University, Hangzhou, Zhejiang, P.R. China
| | - Yongjie Wang
- Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine
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28
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Brain tumor related-epilepsy. Neurol Neurochir Pol 2018; 52:436-447. [PMID: 30122210 DOI: 10.1016/j.pjnns.2018.06.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Revised: 06/19/2018] [Accepted: 06/20/2018] [Indexed: 11/21/2022]
Abstract
INTRODUCTION Gliomas are commonly associated with the development of epilepsy; in some cases the two conditions share common pathogenic mechanisms and may influence each other. Brain tumor related-epilepsy (BTRE) complicates the clinical management of gliomas and can substantially affect daily life. STATE OF THE ART The incidence of seizures is high in patients with slow growing tumors located in the frontotemporal regions. However, recent studies suggest that epileptogenesis may be more associated with tumor molecular genetic markers than tumor grade or location. Although the exact mechanism of epileptogenesis in glioma is incompletely understood, glutamate-induced excitotoxicity and disruption of intracellular communication have garnered the most attention. CLINICAL MANAGEMENT Management of BTRE requires a multidisciplinary approach involving the use of antiepileptic drugs (AEDs), surgery aided by electrocorticography, and adjuvant chemoradiation. FUTURE DIRECTIONS Insight into the mechanisms of glioma growth and epileptogenesis is essential to identify new treatment targets and to develop effective treatment for both conditions. Selecting AEDs tailored to act against known tumor molecular markers involved in the epileptogenesis could enhance treatment value and help inform individualized medicine in BRTE.
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Zaky W, Patil SS, Park M, Liu D, Wang WL, Wani KM, Calle S, Ketonen L, Khatua S. Ganglioglioma in children and young adults: single institution experience and review of the literature. J Neurooncol 2018; 139:739-747. [PMID: 29882043 DOI: 10.1007/s11060-018-2921-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 06/01/2018] [Indexed: 11/26/2022]
Abstract
BACKGROUND Ganglioglioma (GG) is a rare mixed glial-neuronal neoplasm accounting for 0.5-5% of all pediatric central nervous system (CNS) tumors. Rarity of this tumor has precluded defining robust treatment guidelines. This retrospective study evaluates the prognostic factors and outcomes of this rare neoplasm. PATIENTS AND METHODS Retrospective analysis of 55 patients with GG was conducted to describe clinical findings, and outcomes. Kaplan-Meier survival and Cox-regression analyses were performed to assess the overall survival (OS) and progression-free survival (PFS). RESULTS The mean age at diagnosis was 11.8 years (range 1-21 years) with a median follow-up period of 9.5 years. 53 patients (92.7%) had low grade GG and 2 patients had anaplastic GG. 25 patients had tumor progression, whose median PFS was 12 years. Six patients with low grade GG progressed to a higher grade, with median survival of 9.1 month after transformation. The 5 and 10 year PFS were 65 and 57%, respectively. The 5 and 10 year OS was 96 and 86% respectively. 8 of the 19 (42%) samples tested demonstrated positivity for the BRAF V600E mutation. Multivariate Cox regression analyses showed location and extent of resection were significant factors for PFS and presence of metastatsis attained significance for OS. CONCLUSION This is the one of the largest retrospective study of pediatric GG. Identifying clinical variables, which could stratify these tumors into low- and high-risk groups might help to profile a risk-based therapeutic strategy. Collaborative multiinstitutional prospective studies are warranted to delineate treatment consensus and investigate prognostic factors.
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Affiliation(s)
- Wafik Zaky
- Department of Pediatric Patient Care, UT MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 87, Houston, TX, 77030, USA
| | - Shekhar S Patil
- Department of Internal Medicine, McGovern Medical School, UT Health Science Center, 7440 Cambridge Street, Houston, TX, 77054, USA
| | - Minjeong Park
- Department of Biostatistics, UT MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Diane Liu
- Department of Biostatistics, UT MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Wei-Lien Wang
- Department of Pathology, UT MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
- Department of Translational Molecular Pathology, UT MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Khalida M Wani
- Department of Translational Molecular Pathology, UT MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Susana Calle
- Department of Diagnostic Radiology, UT MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Leena Ketonen
- Department of Diagnostic Radiology, UT MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Soumen Khatua
- Department of Pediatric Patient Care, UT MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 87, Houston, TX, 77030, USA.
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Lundar T, Due-Tønnessen BJ, Fric R, Egge A, Krossnes B, Due-Tønnessen P, Stensvold E, Brandal P. Neurosurgical treatment of gangliogliomas in children and adolescents: long-term follow-up of a single-institution series of 32 patients. Acta Neurochir (Wien) 2018; 160:1207-1214. [PMID: 29680921 PMCID: PMC5948304 DOI: 10.1007/s00701-018-3550-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Accepted: 04/11/2018] [Indexed: 11/28/2022]
Abstract
Object The object of this study was to delineate long-term results of the surgical treatment of pediatric tumors classified as ganglioglioma or gangliocytoma. Methods A cohort of consecutive patients 19 years or younger who had undergone primary resection of CNS tumors during the years 1980–2016 at a single institution were reviewed in this retrospective study of surgical morbidity, mortality, and academic achievement and/or work participation. Gross motor function and activities of daily living were scored using the Barthel Index (BI). Results Patient records for 32 consecutive children and adolescents who had undergone resection for a ganglioglioma were included in this study. Of the 32 patients, 13 were in the first decade at the first surgery, whereas 19 were in the second decade. The male/female ratio was 1.0 (16/16). No patient was lost to follow-up. The tumor was localized to the supratentorial compartment in 26 patients, to the posterior fossa in 5 patients, and to the spinal cord in 1 patient. Only two of the tumors were classified as anaplastic. Of the 30 low-grade tumors, 2 were classified as gangliocytomas, 6 were desmoplastic infantile gangliogliomas, and 22 were ordinary gangliogliomas. The aim of primary surgery was gross-total resection (GTR) and was achieved in 23 patients (71.9%). Altogether, 43 tumor resections were performed. Eight patients underwent a second resection from 1 to 10 years after primary surgery and three of these also had a third resection from 2 to 24 years after initial surgery. The reason for further resection was clinical (seizure control failure/recurrence of epilepsy or progressive neurological deficit) and/or residual tumor progression/recurrence. There was no operative mortality in this series and all 32 patients are alive with follow-up periods from 0.5 to 36 years (median 14 years). Observed 14-year survival is thus 100%. One out of two children with primary anaplastic tumor received local radiotherapy (proton) postoperatively. The other 31 patients did not have any kind of non-surgical adjuvant therapy. Twenty-one out of 26 children with supratentorial tumor had epilepsy as one of their presenting symptoms. Nineteen of these became seizure-free after initial surgery (18 of them after GTR), but 3 patients experienced recurrence of seizures within some years. Functional outcome in terms of ADL, schooling, and work participation was gratifying in most patients. Five patients have persistent hydrocephalus (HC), treated with ventriculoperitoneal (VP) shunts. Conclusion Low-grade gangliogliomas (GGs) can be surgically treated with good long-term results including seizure and tumor control as well as school and working participation.
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Affiliation(s)
- Tryggve Lundar
- Department of Neurosurgery, Oslo University Hospital, Postboks 4054, Nydalen, 0407, Oslo, Norway.
- Faculty of Medicine, University of Oslo, Oslo, Norway.
| | | | - Radek Fric
- Department of Neurosurgery, Oslo University Hospital, Postboks 4054, Nydalen, 0407, Oslo, Norway
| | - Arild Egge
- Department of Neurosurgery, Oslo University Hospital, Postboks 4054, Nydalen, 0407, Oslo, Norway
| | - Bård Krossnes
- Department of Pathology, Oslo University Hospital, Oslo, Norway
| | | | - Einar Stensvold
- Department of Pediatrics, Oslo University Hospital, Oslo, Norway
| | - Petter Brandal
- Department of Oncology, Oslo University Hospital, Oslo, Norway
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31
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Terrier LM, Bauchet L, Rigau V, Amelot A, Zouaoui S, Filipiak I, Caille A, Almairac F, Aubriot-Lorton MH, Bergemer-Fouquet AM, Bord E, Cornu P, Czorny A, Dam Hieu P, Debono B, Delisle MB, Emery E, Farah W, Gauchotte G, Godfraind C, Guyotat J, Irthum B, Janot K, Le Reste PJ, Liguoro D, Loiseau H, Lot G, Lubrano V, Mandonnet E, Menei P, Metellus P, Milin S, Muckenstrum B, Roche PH, Rousseau A, Uro-Coste E, Vital A, Voirin J, Wager M, Zanello M, François P, Velut S, Varlet P, Figarella-Branger D, Pallud J, Zemmoura I. Natural course and prognosis of anaplastic gangliogliomas: a multicenter retrospective study of 43 cases from the French Brain Tumor Database. Neuro Oncol 2018; 19:678-688. [PMID: 28453747 DOI: 10.1093/neuonc/now186] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Accepted: 07/21/2016] [Indexed: 12/11/2022] Open
Abstract
Background Anaplastic gangliogliomas (GGGs) are rare tumors whose natural history is poorly documented. We aimed to define their clinical and imaging features and to identify prognostic factors. Methods Consecutive cases of anaplastic GGGs in adults prospectively entered into the French Brain Tumor Database between March 2004 and April 2014 were screened. After diagnosis was confirmed by pathological review, clinical, imaging, therapeutic, and outcome data were collected retrospectively. Results Forty-three patients with anaplastic GGG (median age, 49.4 y) from 18 centers were included. Presenting symptoms were neurological deficit (37.2%), epileptic seizure (37.2%), or increased intracranial pressure (25.6%). Typical imaging findings were unifocal location (94.7%), contrast enhancement (88.1%), central necrosis (43.2%), and mass effect (47.6%). Therapeutic strategy included surgical resection (95.3%), adjuvant radiochemotherapy (48.8%), or radiotherapy alone (27.9%). Median progression-free survival (PFS) and overall survival (OS) were 8.0 and 24.7 months, respectively. Three- and 5-year tumor recurrence rates were 69% and 100%, respectively. The 5-year survival rate was 24.9%. Considering unadjusted significant prognostic factors, tumor midline crossing and frontal location were associated with shorter OS. Temporal and parietal locations were associated with longer and shorter PFS, respectively. None of these factors remained statistically significant in multivariate analysis. Conclusions We report a large series providing clinical, imaging, therapeutic, and prognostic features of adult patients treated for an intracerebral anaplastic GGG. Our results show that pathological diagnosis is difficult, that survivals are only slightly better than for glioblastomas, and that complete surgical resection followed with adjuvant chemoradiotherapy offers longer survival.
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Affiliation(s)
- Louis-Marie Terrier
- CHRU de Tours, Service de Neurochirurgie, Tours, France.,Université François-Rabelais de Tours, Inserm, Imagerie et Cerveau UMR U930, Tours, France
| | - Luc Bauchet
- Department of Neurosurgery and INSERM U1051, Hôpital Saint Eloi - Gui de Chauliac, Montpellier, France.,French Brain Tumor DataBase, ICM, Montpellier, France
| | - Valérie Rigau
- French Brain Tumor DataBase, ICM, Montpellier, France.,Department of Neuropathology and INSERM U1051, Hôpital Saint Eloi - Gui de Chauliac, Montpellier, France
| | - Aymeric Amelot
- Department of Neurosurgery, Hôpital La Pitié Salpétrière, APHP, Paris, France
| | - Sonia Zouaoui
- Department of Neurosurgery and INSERM U1051, Hôpital Saint Eloi - Gui de Chauliac, Montpellier, France.,French Brain Tumor DataBase, ICM, Montpellier, France
| | - Isabelle Filipiak
- Plateforme CIRE, UMR-PRC, 37380 Nouzilly, Centre INRA Val de Loire, France
| | - Agnès Caille
- Université François-Rabelais de Tours, Tours, France.,Inserm, CIC 1415, CHRU de Tours, Tours, France.,Service de Neurochirurgie, CHU Jean-Minjoz, 3 boulevard Alexander-Fleming, Besançon cedex, France
| | - Fabien Almairac
- Department of Neurosurgery, Hôpital Pasteur, University Hospital Center, 06000, Nice, France
| | - Marie-Hélène Aubriot-Lorton
- Department of Pathology, Hôpital François Mitterand, CHU de Dijon, 14 rue Paul Gaffarel, 21000 Dijon, France
| | | | - Eric Bord
- Department of Neurosurgery and Neurotraumatology, Nantes University Hospital, Nantes, France
| | - Philippe Cornu
- Department of Neurosurgery, Hôpital La Pitié Salpétrière, APHP, Paris, France
| | - Alain Czorny
- Service de Neurochirurgie, CHU Jean-Minjoz, 3 boulevard Alexander-Fleming, Besançon cedex, France
| | - Phong Dam Hieu
- Department of Neurosurgery, CHU de la Cavale Blanche, Brest, France
| | - Bertrand Debono
- Department of Neurosurgery, Cèdres Hospital, Toulouse, France
| | - Marie-Bernadette Delisle
- Laboratoire Universitaire d'Anatomie Patholgique, Neuropathologie humaine et expérimentale, CHU Rangueil, Toulouse, France
| | - Evelyne Emery
- Department of Neurosurgery, University Hospital of Caen, Caen, France
| | - Walid Farah
- Service de Neurochirurgie, Hôpital François Mitterand, CHU de Dijon, 14 rue Paul Gaffarel, 21000 Dijon, France
| | - Guillaume Gauchotte
- Department of Pathology, CHU Nancy and INSERM U954, Faculty of Medicine, Université de Lorraine, France
| | | | - Jacques Guyotat
- Department of Neurosurgery, Neurological Hospital, Lyon, France
| | - Bernard Irthum
- Service de neurochirurgie, hôpital Gabriel-Montpied, CHU de Clermont-Ferrand, 58, rue Montalembert, 63003 Clermont-Ferrand, France
| | - Kevin Janot
- Service de Neuroradiologie, CHRU de Tours, Tours, France
| | - Pierre-Jean Le Reste
- Department of Neurosurgery, University Hospital Pontchaillou, 2, Rue Henri Le Guilloux, 35000, Rennes, France
| | - Dominique Liguoro
- Service de neurochirurgie A, place Amélie-Raba-Léon, 33076 Bordeaux cedex, France
| | - Hugues Loiseau
- Université de Bordeaux - Service de Neurochirurgie B, hôpital Pellegrin Tripode, Bordeaux, France
| | - Guillaume Lot
- Department of Neurosurgery, Fondation Ophtalmologique Rothschild, Paris, France
| | - Vincent Lubrano
- Service de neurochirurgie, hôpital de Rangueil, CHU de Toulouse, 1, avenue du Professeur-Jean-Poulhès, TSA, Toulouse, France
| | | | - Philippe Menei
- Département de neurochirurgie, CHU d'Angers, 4, rue Larrey, 49940 Angers cedex 9, France
| | - Philippe Metellus
- Département de neurochirurgie, Aix-Marseille université, CHU Timone, Assistance publique-Hôpitaux de Marseille, 264, rue Saint-Pierre, 13385 Marseille cedex 05, France
| | - Serge Milin
- Department of Pathology, CHU de Poitiers, Hôpital la Milétrie, Poitiers, France
| | | | - Pierre-Hugues Roche
- Service de Neurochirurgie, Hôpital Nord, APHM, University Hospital of Marseille Aix-Marseille Univ, Marseille, France
| | - Audrey Rousseau
- Département de Pathologie Cellulaire et Tissulaire, Centre Hospitalo-universitaire d'Angers, 4 rue Larrey, Angers Cedex, France
| | - Emmanuelle Uro-Coste
- CHU Toulouse, Hôpital de Rangueil, Service d'Anatomie et Cytologie Pathologique, Toulouse, France
| | - Anne Vital
- Bordeaux Institute of Neuroscience, CNRS UMR 5227, F-33076, Bordeaux, France
| | - Jimmy Voirin
- Department of Neurosurgery, Strasbourg-Colmar Hospital, France
| | - Michel Wager
- Department of Neurosurgery, Imaging Laboratory, University Hospital Poitiers, 2 Rue de La Miletrie, Poitiers Cedex, France
| | - Marc Zanello
- Paris Descartes University, Sorbonne Paris Cité, Paris, France.,Department of Neurosurgery, Sainte-Anne Hospital, Paris, France
| | | | - Stéphane Velut
- CHRU de Tours, Service de Neurochirurgie, Tours, France.,Université François-Rabelais de Tours, Inserm, Imagerie et Cerveau UMR U930, Tours, France
| | - Pascale Varlet
- Paris Descartes University, Sorbonne Paris Cité, Paris, France.,Department of Neuropathology, Sainte-Anne Hospital, Paris, France
| | | | - Johan Pallud
- Paris Descartes University, Sorbonne Paris Cité, Paris, France.,Department of Neurosurgery, Sainte-Anne Hospital, Paris, France
| | - Ilyess Zemmoura
- CHRU de Tours, Service de Neurochirurgie, Tours, France.,Université François-Rabelais de Tours, Inserm, Imagerie et Cerveau UMR U930, Tours, France
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Lesional Temporal Lobe Epilepsy: Beware the Deceitful "Panic Attack". World Neurosurg 2017; 111:197-200. [PMID: 29288854 DOI: 10.1016/j.wneu.2017.12.124] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2017] [Revised: 12/18/2017] [Accepted: 12/19/2017] [Indexed: 11/24/2022]
Abstract
BACKGROUND Ganglioglioma is a rare, benign, intraaxial glioneuronal tumor but a relatively common cause of pharmacoresistant temporal lobe epilepsy (TLE). Given its often nonspecific neuropsychiatric manifestations and frequently negative electroencephalographic workup, TLE can be easily misdiagnosed as a psychiatric disorder, particularly panic attacks. CASE DESCRIPTION We present a case of a 17-year-old boy who was found to have lesional TLE secondary to a left temporal ganglioglioma, 5 years after having been misdiagnosed with panic disorder and having undergone ineffective and unnecessary psychotherapy. He was successfully cured by surgery. Although a few similar cases of TLE masquerading as a panic disorder have been previously reported in the literature, this is the youngest and only pediatric patient described to date. CONCLUSION This report underscores the challenges in making an accurate clinical diagnosis of TLE and the importance of timely brain imaging whenever an atypical or medically refractory panic disorder is encountered.
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Devaux B, Chassoux F, Landré E, Turak B, Laurent A, Zanello M, Mellerio C, Varlet P. Surgery for dysembryoplastic neuroepithelial tumors and gangliogliomas in eloquent areas. Functional results and seizure control. Neurochirurgie 2017; 63:227-234. [PMID: 28506485 DOI: 10.1016/j.neuchi.2016.10.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Revised: 10/04/2016] [Accepted: 10/09/2016] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Dysembryoplastic neuroepithelial tumors and gangliogliomas are developmental glioneuronal tumors usually revealed by partial epilepsy. High epileptogenicity, childhood epilepsy onset, drug-resistance, temporal location, and seizure freedom after complete resection are common characteristics of both tumors. We report the specificity of surgical management, functional results and seizure outcome in cases of a tumor location in eloquent areas. METHODS Among 150 patients (88 males, 3-55 years) operated on for refractory epilepsy due to a glioneuronal tumor (1990-2015), 30 (20%, dysembryoplastic neuroepithelial tumors=21; gangliogliomas=9) had a tumor located in an eloquent cortex (sensory-motor, insular or language areas). Surgery was performed after a preoperative work-up, including stereo-electroencephalography in 48 patients (26%) and functional MRI in 100 (67%). MRI-guided lesionectomy was mainly performed in extra-temporal location, whereas an additional corticectomy was performed in a temporal location. Tumor microsurgical resections were guided using neuronavigation and cortical/subcortical electrical stimulations. Multiple stereotactic thermocoagulations were performed in two insular tumors. RESULTS New motor/language deficits related to eloquent areas occurred postoperatively in 6/30 patients (20%) without any major permanent disability. Minor sensorimotor (n=2) and moderate language disturbance (n=1) persisted in three of them. Postoperative seizure-free outcome (mean follow-up>5 years) was obtained in 81% of the entire series, but significantly decreased to 60% in eloquent areas. Incomplete tumor resection was the main cause of surgical failure. However, unfavorable seizure outcome was also observed despite complete tumor resection. Malignant transformation occurred in one ganglioglioma. CONCLUSION Epilepsy surgery for benign glioneuronal tumors in eloquent areas provides acceptable results regarding the functional risks. Complete tumor resection is crucial for long-term favorable outcome.
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Affiliation(s)
- B Devaux
- Service de neurochirurgie, hôpital Sainte-Anne, université Paris Descartes, 1, rue Cabanis, 75014 Paris, France.
| | - F Chassoux
- Service de neurochirurgie, hôpital Sainte-Anne, université Paris Descartes, 1, rue Cabanis, 75014 Paris, France
| | - E Landré
- Service de neurochirurgie, hôpital Sainte-Anne, université Paris Descartes, 1, rue Cabanis, 75014 Paris, France
| | - B Turak
- Service de neurochirurgie, hôpital Sainte-Anne, université Paris Descartes, 1, rue Cabanis, 75014 Paris, France
| | - A Laurent
- Service de neurochirurgie, hôpital Sainte-Anne, université Paris Descartes, 1, rue Cabanis, 75014 Paris, France
| | - M Zanello
- Service de neurochirurgie, hôpital Sainte-Anne, université Paris Descartes, 1, rue Cabanis, 75014 Paris, France
| | - C Mellerio
- Service d'imagerie morphologique et fonctionnelle, hôpital Sainte-Anne, université Paris Descartes, 75014 Paris, France
| | - P Varlet
- Service d'anatomie pathologique, hôpital Sainte-Anne, université Paris Descartes, 75014 Paris, France
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Dysplastic Cerebellar Epilepsy: Complete Seizure Control Following Resection of a Ganglioglioma. THE CEREBELLUM 2017. [PMID: 26208704 DOI: 10.1007/s12311-015-0705-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Subcortical epilepsy has been a controversial issue, partially settled by evidence showing seizure generation in hypothalamic hamartomas and also by reports of seizures caused by cerebellar lesions. We report 4-year-old girl with right hemifacial seizures and autonomic phenomena, in whom MRI showed an irregular mass in the right cerebellar peduncle. Despite several unremarkable video-EEG recordings, seizure origin in the lesion was hypothesized. Complete resection was feasible, histopathology showed a ganglioglioma, and she has been seizure free for 3 years. A fine line separates these developmental tumors from focal cortical dysplasia, and the homogeneous presentation of this entity led us to propose the terminology dysplastic cerebellar epilepsy.
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Pagès M, Beccaria K, Boddaert N, Saffroy R, Besnard A, Castel D, Fina F, Barets D, Barret E, Lacroix L, Bielle F, Andreiuolo F, Tauziède-Espariat A, Figarella-Branger D, Puget S, Grill J, Chrétien F, Varlet P. Co-occurrence of histone H3 K27M and BRAF V600E mutations in paediatric midline grade I ganglioglioma. Brain Pathol 2017; 28:103-111. [PMID: 27984673 DOI: 10.1111/bpa.12473] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2016] [Accepted: 12/01/2016] [Indexed: 12/31/2022] Open
Abstract
Ganglioglioma (GG) is a grade I tumor characterized by alterations in the MAPK pathway, including BRAF V600E mutation. Recently, diffuse midline glioma with an H3 K27M mutation was added to the WHO 2016 classification as a new grade IV entity. As co-occurrence of H3 K27M and BRAF V600E mutations has been reported in midline tumors and anaplastic GG, we searched for BRAF V600E and H3 K27M mutations in a series of 54 paediatric midline grade I GG (midline GG) to determine the frequency of double mutations and its relevance for prognosis. Twenty-seven patients (50%) possessed the BRAF V600E mutation. The frequency of the co-occurrence of H3F3A/BRAF mutations at diagnosis was 9.3%. No H3 K27M mutation was detected in the absence of the BRAF V600E mutation. Double-immunostaining revealed that BRAF V600E and H3 K27M mutant proteins were present in both the glial and neuronal components. Immunopositivity for the BRAF V600E mutant protein correlated with BRAF mutation status as detected by massARRAY or digital droplet PCR. The median follow-up of patients with double mutation was 4 years. One patient died of progressive disease 8 years after diagnosis, whereas the four other patients were all alive with stable disease at the last clinical follow-up (at 9 months, 1 year and 7 years) without adjuvant therapy. We demonstrate in this first series of midline GGs that the H3 K27M mutation can occur in association with the BRAF V600E mutation in grade I glioneuronal tumors. Despite the presence of H3 K27M mutations, these cases should not be graded and treated as grade IV tumors because they have a better spontaneous outcome than classic diffuse midline H3 K27M-mutant glioma. These data suggest that H3 K27M cannot be considered a specific hallmark of grade IV diffuse gliomas and highlight the importance of integrated histomolecular diagnosis in paediatric brain tumors.
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Affiliation(s)
- Mélanie Pagès
- Department of Neuropathology, Sainte-Anne Hospital, Paris, France.,Paris V Descartes University, Paris, France.,Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry,", Université Paris Sud, Orsay
| | - Kevin Beccaria
- Department of Paediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France
| | - Nathalie Boddaert
- Department of Paediatric Neuroradiology, Necker Enfants Malades Hospital, Paris, France
| | - Raphaël Saffroy
- Department of Biochemistry, Paul Brousse Hospital, Paris, France
| | - Aurore Besnard
- Department of Neuropathology, Sainte-Anne Hospital, Paris, France
| | - David Castel
- UMR8203 "Vectorologie et Thérapeutiques Anticancéreuses," CNRS, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, 94805, France.,Département de Cancérologie de l'Enfant et de l'Adolescent, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, 94805, France
| | - Frédéric Fina
- Service de transfert d'Oncologie Biologique, LBM APHM Marseille, France
| | - Doriane Barets
- APHM, Hôpital de la Timone, Service d'Anatomie Pathologique et de Neuropathologie, Marseille, France
| | - Emilie Barret
- UMR8203 "Vectorologie et Thérapeutiques Anticancéreuses," CNRS, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, 94805, France.,Département de Cancérologie de l'Enfant et de l'Adolescent, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, 94805, France
| | - Ludovic Lacroix
- Departement de Biologie et Pathologie Médicales, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, 94805, France
| | - Franck Bielle
- Department of Neuropathology, Laboratoire Escourolle, Hôpitaux Universitaires Pitié Salpêtrière Charles Foix, AP-HP, Paris, France
| | | | | | - Dominique Figarella-Branger
- APHM, Hôpital de la Timone, Service d'Anatomie Pathologique et de Neuropathologie, Marseille, France.,Aix-Marseille Université, Inserm, CRO2 UMR_S 911, Marseille, France
| | - Stéphanie Puget
- Department of Paediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France
| | - Jacques Grill
- UMR8203 "Vectorologie et Thérapeutiques Anticancéreuses," CNRS, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, 94805, France.,Département de Cancérologie de l'Enfant et de l'Adolescent, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, 94805, France
| | - Fabrice Chrétien
- Department of Neuropathology, Sainte-Anne Hospital, Paris, France.,Paris V Descartes University, Paris, France.,Infection & Epidemiology Department, Human Histopathology and Animal Models Unit, Institut Pasteur, Paris, France
| | - Pascale Varlet
- Department of Neuropathology, Sainte-Anne Hospital, Paris, France.,Paris V Descartes University, Paris, France.,Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry,", Université Paris Sud, Orsay
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Gaudino S, Martucci M, Russo R, Visconti E, Gangemi E, D'Argento F, Verdolotti T, Lauriola L, Colosimo C. MR imaging of brain pilocytic astrocytoma: beyond the stereotype of benign astrocytoma. Childs Nerv Syst 2017; 33:35-54. [PMID: 27757570 DOI: 10.1007/s00381-016-3262-4] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Accepted: 10/03/2016] [Indexed: 01/21/2023]
Abstract
BACKGROUND Pilocytic astrocytoma (PA) is the most common pediatric brain glioma and is considered the prototype of benign circumscribed astrocytoma. Despite its low malignancy, the CT and MRI features of brain PA may resemble those of much more aggressive brain tumors. Misdiagnosis of PA is particularly easy when it demonstrates MR morphological and non-morphological findings that are inconsistent with its non-aggressive nature and that overlap with the features of more aggressive brain tumors. METHOD Basing on the evidence that the variation in the histological, genetic, and metabolic "fingerprint" for brain PA is dependent on tumor location, and the hypothesis that tumor location is related to the broad spectrum of morphological and non-morphological MR imaging findings, the authors discuss the MR imaging appearance of brain PA using a location-based approach to underline the typical and less typical imaging features and the main differential diagnosis of brain PA. A brief summary of the main pathological and clinical features, the natural history, and the treatment of brain PA is also provided. RESULT A combination of morphological and non-morphological MR imaging features and a site-based approach to differential diagnosis are required for a pre-operative diagnosis. The new "cutting-edge" MR imaging sequences have the potential to impact the ease and confidence of pediatric brain tumor interpretation and offer a more efficient diagnostic work-up. CONCLUSIONS Although the typical imaging features of brain pilocytic astrocytoma make radiological diagnosis relatively easy, an atypical and more aggressive appearance can lead to misdiagnosis. Knowing the broad spectrum of imaging characteristics on conventional and advanced MR imaging is important for accurate pre-operative radiological diagnosis and correctly interpreting changes during follow-up.
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Affiliation(s)
- Simona Gaudino
- Institute of Radiology, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli, 1, 00168, Rome, Italy.
| | - Matia Martucci
- Institute of Radiology, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli, 1, 00168, Rome, Italy
| | - Rosellina Russo
- Institute of Radiology, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli, 1, 00168, Rome, Italy
| | - Emiliano Visconti
- Institute of Radiology, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli, 1, 00168, Rome, Italy
| | - Emma Gangemi
- Institute of Radiology, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli, 1, 00168, Rome, Italy
| | - Francesco D'Argento
- Institute of Radiology, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli, 1, 00168, Rome, Italy
| | - Tommaso Verdolotti
- Institute of Radiology, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli, 1, 00168, Rome, Italy
| | - Libero Lauriola
- Institute of Pathological Anatomy, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli, 1, 00168, Rome, Italy
| | - Cesare Colosimo
- Institute of Radiology, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli, 1, 00168, Rome, Italy
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Ertürk Çetin Ö, İşler C, Uzan M, Özkara Ç. Epilepsy-related brain tumors. Seizure 2016; 44:93-97. [PMID: 28041673 DOI: 10.1016/j.seizure.2016.12.012] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Revised: 12/16/2016] [Accepted: 12/16/2016] [Indexed: 02/02/2023] Open
Abstract
Seizures are among the most common presentations of brain tumors. Several tumor types can cause seizures in varying rates; neuroglial tumors and the gliomas are the most common ones. Brain tumors are the second most common cause of focal intractable epilepsy in epilepsy surgery series, with the highest frequency being dysembryoplastic neuroepithelial tumors and gangliogliomas. Seizure management is an important part of the treatment of patients with brain tumors. This review discusses clinical features and management of seizures in patients with brain tumors, including, neuroglial tumors, gliomas, meningioma and metastases; with the help of recent literature data. Tumor-related seizures are focal seizures with or without secondary generalization. Seizures may occur either as initial symptom or during the course of the disease. Brain tumors related epilepsy tends to be resistant to antiepileptic drugs and treatment of tumor is main step also for the seizure treatment. Early surgery and extent of the tumor removal are important factors for achieving seizure freedom particularly in neuroglial tumors and low grade gliomas. During selection of the appropriate antiepileptic drug, the general approach to partial epilepsies can be followed. There are several factors influencing epileptogenesis in brain tumor-related epilepsy which also explains clinical heterogeneity of epilepsy among tumor types. Identification of molecular markers may guide future therapeutic approaches and further studies are needed to prove antitumor effects of different antiepileptic drugs.
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Affiliation(s)
- Özdem Ertürk Çetin
- Istanbul University, Cerrahpasa Faculty of Medicine, Department of Neurology, 34098, Fatih, Istanbul, Turkey
| | - Cihan İşler
- Istanbul University, Cerrahpasa Faculty of Medicine, Department of Neurosurgery, Istanbul, Turkey
| | - Mustafa Uzan
- Istanbul University, Cerrahpasa Faculty of Medicine, Department of Neurosurgery, Istanbul, Turkey
| | - Çiğdem Özkara
- Istanbul University, Cerrahpasa Faculty of Medicine, Department of Neurology, 34098, Fatih, Istanbul, Turkey.
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Mandel JJ, Goethe EA, Patel AJ, Heck K, Hutton GJ. Newly diagnosed ganglioglioma in an adult patient with multiple sclerosis. J Neurol Sci 2016; 369:51-52. [PMID: 27653865 DOI: 10.1016/j.jns.2016.07.024] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Revised: 06/09/2016] [Accepted: 07/11/2016] [Indexed: 10/21/2022]
Affiliation(s)
- Jacob J Mandel
- Baylor College of Medicine, Department of Neurology, 7200 Cambridge 9th Floor, Suite 9A MS: BCM 609, Houston, TX 77030, United States.
| | - Eric A Goethe
- Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, United States
| | - Akash J Patel
- Baylor College of Medicine, Department of Neurosurgery, 7200 Cambridge 9th Floor, Houston, TX 77030, United States
| | - Kent Heck
- Baylor College of Medicine, Department of Pathology, One Baylor Plaza, Houston, TX 77030, United States
| | - George J Hutton
- Baylor College of Medicine, Department of Neurology, 7200 Cambridge 9th Floor, Suite 9A MS: BCM 609, Houston, TX 77030, United States
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Awake surgery for hemispheric low-grade gliomas: oncological, functional and methodological differences between pediatric and adult populations. Childs Nerv Syst 2016; 32:1861-74. [PMID: 27659829 DOI: 10.1007/s00381-016-3069-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2016] [Accepted: 03/14/2016] [Indexed: 10/21/2022]
Abstract
INTRODUCTION Brain mapping through a direct cortical and subcortical electrical stimulation during an awake craniotomy has gained an increasing popularity as a powerful tool to prevent neurological deficit while increasing extent of resection of hemispheric diffuse low-grade gliomas in adults. However, few case reports or very limited series of awake surgery in children are currently available in the literature. METHODS In this paper, we review the oncological and functional differences between pediatric and adult populations, and the methodological specificities that may limit the use of awake mapping in pediatric low-grade glioma surgery. RESULTS This could be explained by the fact that pediatric low-grade gliomas have a different epidemiology and biologic behavior in comparison to adults, with pilocytic astrocytomas (WHO grade I glioma) as the most frequent histotype, and with WHO grade II gliomas less prone to anaplastic transformation than their adult counterparts. In addition, aside from the issue of poor collaboration of younger children under 10 years of age, some anatomical and functional peculiarities of children developing brain (cortical and subcortical myelination, maturation of neural networks and of specialized cortical areas) can influence direct electrical stimulation methodology and sensitivity, limiting its use in children. CONCLUSIONS Therefore, even though awake procedure with cortical and axonal stimulation mapping can be adapted in a specific subgroup of children with a diffuse glioma from the age of 10 years, only few pediatric patients are nonetheless candidates for awake brain surgery.
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Glioneuronal tumors of cerebral hemisphere in children: correlation of surgical resection with seizure outcomes and tumor recurrences. Childs Nerv Syst 2016; 32:1839-48. [PMID: 27659827 DOI: 10.1007/s00381-016-3140-0] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2016] [Accepted: 06/01/2016] [Indexed: 01/05/2023]
Abstract
OBJECT Glioneuronal tumors are common neoplasms among the cerebral hemisphere during childhood. They consist of several histological types, of which gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNTs) are most common and often present with seizures. A great majority of glioneuronal tumors are benign. However, there are conflict reports regarding postoperative tumor recurrence rates and seizure control. The authors analyzed and compared these tumors for their locations and histology and the tumor and seizure control following resection. METHODS The authors conducted a retrospective analysis of patients with pediatric glioneuronal tumors in the cerebral hemisphere. All histology reports and neuroimaging are reviewed. Seizure group and non-seizure group were compared with their tumor types and locations. The extent of tumor resections were divided into gross total resection (GTR) and subtotal resection (STR). Postoperative tumor recurrence-free survival (RFS) and seizure-free survival for patients who had the initial surgery done at our institution were calculated using Kaplan-Meier method. RESULTS There were 90 glioneuronal tumors including 58 GGs, 22 DNTs, 3 papillary glioneuronal tumor, 3 desmoplastic infantile gangliogliomas, 3 anaplastic GGs, and 1 central neurocytoma. Seventy-one patients (seizure group) presented with seizures. The temporal lobe is the most common location, 50 % in this series. GTR was attained in 79 patients and STR in 11. All of the patients with GTR had lesionectomy, and only six of them had extended corticectomy or partial lobectomy. Postoperative seizure outcome showed that 64 (90 %) of seizure group had Engel's class I, but five patients subsequently developed recurrent seizures. Patients with DNTs had a higher seizure recurrence rate. Tumor RFS was 87 % at 5 years and 75.5 % at 10 years. There are no significant difference in tumor recurrences between GGs and DNTs (p = 0.876). Comparison between GRT (67) and STR (9) showed that in spite of the better 5-year tumor RFSs among GRT group (94 %) than STR group (66 %), the 10-year RFSs showed no significant difference between GRT and STR groups (p = 0.719). Recurrent seizures are often related to recurrent tumor. CONCLUSION Lesionectomy alone often provides a high-rate seizure freedom. GGs and DNTs are benign tumor, but recurrences of GGs and DNTs are not uncommon. They may show late recurrences in spite of GTR. These patients need longer follow-up for 10 years. Recurrent seizures are often related to a tumor recurrence.
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Facial spasms, but not hemifacial spasm: a case report and review of literature. Childs Nerv Syst 2016; 32:1735-9. [PMID: 26984806 DOI: 10.1007/s00381-016-3057-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Accepted: 03/06/2016] [Indexed: 10/22/2022]
Abstract
INTRODUCTION Facial spasms represent a complicated array of neurological motor disorders with unique diagnostic and treatment algorithms. Due to the rarity of many of these disorders in the pediatric population, special care must be taken in identifying subtle differences in presentation of these disorders. METHODS We present a case of a 3-year-old boy diagnosed with a brainstem ganglioglioma, Chiari 1 malformation, and a 2-year history of left-sided facial spasms. Stereotyped facial contractions and subtle eye deviation occurred every 10 s, with downward movement rather than upward elevation of the eyebrow. RESULTS MRI revealed absence of a clear compressive vessel of the centrally-myelinized portion of the facial nerve, and EMG of the left facial nerve demonstrated no abnormal motor response or evidence of "lateral spread." Given these findings, a diagnosis of hemifacial seizures was made. Microvascular decompression was not recommended, and botulinum toxin injection was not pursued; however, the patient has remained refractory to antiepileptic drugs, possibly due to biochemical alteration by his ganglioglioma. He may eventually require surgical debulking should his symptoms progress. CONCLUSION Hemifacial spasm is a well-recognized disorder, but similar conditions can, at times, imitate its appearance. While our patient presented with facial spasms, his clinical history, examination, and radiographic and electrophysiological findings were more consistent with hemifacial seizures secondary to a brainstem lesion, rather than hemifacial spasms. It is important to distinguish the two entities, as misdiagnosis and inappropriate diagnostic or therapeutic measures may be taken inadvertently.
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Zanello M, Pagès M, Roux A, Peeters S, Dezamis E, Puget S, Devaux B, Sainte-Rose C, Zerah M, Louvel G, Dumont SN, Meder JF, Grill J, Huberfeld G, Chrétien F, Parraga E, Sauvageon X, Varlet P, Pallud J. Epileptic seizures in anaplastic gangliogliomas. Br J Neurosurg 2016; 31:227-233. [PMID: 27550627 DOI: 10.1080/02688697.2016.1220506] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
AIM Prevalence and predictors of epileptic seizures are unknown in the malignant variant of ganglioglioma. METHODS In a retrospective exploratory dataset of 18 supratentorial anaplastic World Health Organization grade III gangliogliomas, we studied: (i) the prevalence and predictors of epileptic seizures at diagnosis; (ii) the evolution of seizures during tumor evolution; (iii) seizure control rates and predictors of epilepsy control after oncological treatments. RESULTS Epileptic seizures prevalence progresses throughout the natural course of anaplastic gangliogliomas: 44% at imaging discovery, 67% at histopathological diagnosis, 69% following oncological treatment, 86% at tumor progression, and 100% at the end-of-life phase. The medical control of seizures and their refractory status worsened during the tumor's natural course: 25% of uncontrolled seizures at histopathological diagnosis, 40% following oncological treatment, 45.5% at tumor progression, and 45.5% at the end-of-life phase. Predictors of seizures at diagnosis appeared related to the tumor location (i.e. temporal and/or cortical involvement). Prognostic parameters of seizure control after first-line oncological treatment were temporal tumor location, eosinophilic granular bodies, TP53 mutation, and extent of resection. Prognostic parameters of seizure control at tumor progression were a history of epileptic seizures at diagnosis, seizure control after first-line oncological treatment, eosinophilic granular bodies, and TP53 mutation. CONCLUSION Epileptic seizures are frequently observed in anaplastic gangliogliomas and both prevalence and medically refractory status worsen during the tumor's natural course. Both oncological and antiepileptic treatments should be employed to improve the control of epileptic seizures and the quality of life of patients harboring an anaplastic ganglioglioma.
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Affiliation(s)
- Marc Zanello
- a Department of Neurosurgery , Sainte-Anne Hospital , Paris , France.,b Paris Descartes University, Sorbonne Paris Cité , Paris , France
| | - Mélanie Pagès
- b Paris Descartes University, Sorbonne Paris Cité , Paris , France.,c Department of Neuropathology , Sainte-Anne Hospital , Paris , France
| | - Alexandre Roux
- a Department of Neurosurgery , Sainte-Anne Hospital , Paris , France.,b Paris Descartes University, Sorbonne Paris Cité , Paris , France
| | - Sophie Peeters
- a Department of Neurosurgery , Sainte-Anne Hospital , Paris , France.,b Paris Descartes University, Sorbonne Paris Cité , Paris , France
| | - Edouard Dezamis
- a Department of Neurosurgery , Sainte-Anne Hospital , Paris , France.,b Paris Descartes University, Sorbonne Paris Cité , Paris , France
| | - Stéphanie Puget
- b Paris Descartes University, Sorbonne Paris Cité , Paris , France.,d Department of Pediatric Neurosurgery , Necker Enfants Malades Hospital , Paris , France
| | - Bertrand Devaux
- a Department of Neurosurgery , Sainte-Anne Hospital , Paris , France.,b Paris Descartes University, Sorbonne Paris Cité , Paris , France
| | - Christian Sainte-Rose
- b Paris Descartes University, Sorbonne Paris Cité , Paris , France.,d Department of Pediatric Neurosurgery , Necker Enfants Malades Hospital , Paris , France
| | - Michel Zerah
- b Paris Descartes University, Sorbonne Paris Cité , Paris , France.,d Department of Pediatric Neurosurgery , Necker Enfants Malades Hospital , Paris , France
| | - Guillaume Louvel
- e Department of Neurooncology , Gustave Roussy , Villejuif , France
| | - Sarah N Dumont
- e Department of Neurooncology , Gustave Roussy , Villejuif , France
| | - Jean-François Meder
- b Paris Descartes University, Sorbonne Paris Cité , Paris , France.,f Department of Neuroradiology , Sainte-Anne Hospital , Paris , France
| | - Jacques Grill
- g Department of Pediatric Oncology , Gustave Roussy , Villejuif , France
| | - Gilles Huberfeld
- h Clinical Neurophysiology Department & Epileptology Unit , Pitié-Salpêtrière University Hospital, UPMC - APHP , Paris , France
| | - Fabrice Chrétien
- b Paris Descartes University, Sorbonne Paris Cité , Paris , France.,c Department of Neuropathology , Sainte-Anne Hospital , Paris , France
| | - Eduardo Parraga
- a Department of Neurosurgery , Sainte-Anne Hospital , Paris , France.,b Paris Descartes University, Sorbonne Paris Cité , Paris , France
| | - Xavier Sauvageon
- b Paris Descartes University, Sorbonne Paris Cité , Paris , France.,i Department of Neuro-Anaesthesia and Neuro-Intensive Care , Sainte-Anne Hospital , Paris , France
| | - Pascale Varlet
- b Paris Descartes University, Sorbonne Paris Cité , Paris , France.,c Department of Neuropathology , Sainte-Anne Hospital , Paris , France
| | - Johan Pallud
- a Department of Neurosurgery , Sainte-Anne Hospital , Paris , France.,b Paris Descartes University, Sorbonne Paris Cité , Paris , France
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Arko L, Passer JZ, Ahye N, Quach E, Gibani S, Manoochehri S, Fierst TM. Journal Club. Neurosurgery 2016; 79:306-8. [DOI: 10.1227/neu.0000000000001273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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Harreld JH, Hwang SN, Qaddoumi I, Tatevossian RG, Li X, Dalton J, Haupfear K, Li Y, Ellison DW. Relative ADC and Location Differ between Posterior Fossa Pilocytic Astrocytomas with and without Gangliocytic Differentiation. AJNR Am J Neuroradiol 2016; 37:2370-2375. [PMID: 27469209 DOI: 10.3174/ajnr.a4892] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Accepted: 06/13/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND PURPOSE Pilocytic astrocytomas, the most common posterior fossa tumors in children, are characterized by KIAA1549-BRAF fusions and shows excellent 5-year survival rates. Pilocytic astrocytoma with gangliocytic differentiation, a recently defined pilocytic astrocytoma variant that includes glial and neuronal elements similar to a ganglioglioma, may be distinguished from a classic ganglioglioma by molecular, radiologic, and histopathologic features. This study investigated whether imaging could distinguish posterior fossa pilocytic astrocytoma with and without gangliocytic differentiation. MATERIALS AND METHODS Preoperative MRIs (± CTs) of 41 children (age range, 7 months to 15 years; mean age, 7.3 ± 3.7 years; 58.5% male) with pilocytic astrocytoma with gangliocytic differentiation (n = 7) or pilocytic astrocytoma (n = 34) were evaluated; differences in tumor location, morphology, and minimum relative ADC between tumor types were compared (Wilcoxon rank sum test, Fisher exact test). Histopathology and BRAF fusion/mutation status were reviewed. Associations of progression-free survival with diagnosis, imaging features, and BRAF status were examined by Cox proportional hazards models. RESULTS Pilocytic astrocytoma with gangliocytic differentiation appeared similar to pilocytic astrocytoma but had lower minimum relative ADC (mean, 1.01 ± 0.17 compared with 2.01 ± 0.38 for pilocytic astrocytoma; P = .0005) and was more commonly located within midline structures (P = .0034). BRAF status was similar for both groups. Non-total resection (hazard ratio, 52.64; P = .0002), pilocytic astrocytoma with gangliocytic differentiation diagnosis (hazard ratio, 4.66; P = .0104), and midline involvement (hazard ratio, 3.32; P = .0433) were associated with shorter progression-free survival. CONCLUSIONS Minimum relative ADC and tumor location may be useful adjuncts to histopathology in differentiating pilocytic astrocytoma with gangliocytic differentiation from pilocytic astrocytoma. Shorter progression-free survival in pilocytic astrocytoma with gangliocytic differentiation is likely due to a propensity for involvement of midline structures and poor resectability.
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Affiliation(s)
- J H Harreld
- From the Departments of Diagnostic Imaging (J.H.H., S.N.H.)
| | - S N Hwang
- From the Departments of Diagnostic Imaging (J.H.H., S.N.H.)
| | | | | | - X Li
- Biostatistics (X.L., Y.L.), St. Jude Children's Research Hospital, Memphis, Tennessee
| | - J Dalton
- Pathology (R.G.T., J.D., K.H., D.W.E.)
| | | | - Y Li
- Biostatistics (X.L., Y.L.), St. Jude Children's Research Hospital, Memphis, Tennessee
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Hooten KG, Oliveria SF, Sadrameli SS, Gandhi S, Yachnis AT, Lewis SB. Bilateral internal auditory canal gangliogliomas mimicking neurofibromatosis Type II. Surg Neurol Int 2016; 7:39. [PMID: 27127704 PMCID: PMC4838925 DOI: 10.4103/2152-7806.180300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2014] [Accepted: 02/16/2016] [Indexed: 11/20/2022] Open
Abstract
Background: Gangliogliomas are rare low grade, typically well-differentiated, tumors that are composed of mature ganglion cells and neoplastic glial cells. These tumors can appear at virtually any location along the neuroaxis but classically occur in the temporal lobe of young patients. In a small number of cases, gangliogliomas have presented as masses in the brainstem or involving cranial nerves. With the exception of vestibular schwannomas, bilateral tumors in the region of the internal auditory canal (IAC) or cerebellopontine angle (CPA) are exceedingly rare. Case Description: We report a case of a 58-year-old male who presented with hearing loss, tinnitus, and vertigo. Initial magnetic resonance imaging revealed bilateral nonenhancing IAC/CPA tumors. Based on this finding, a presumptive diagnosis of neurofibromatosis Type II was made, which was initially managed conservatively with close observation. He returned for follow-up with worsening vertigo and tinnitus, thus prompting the decision to proceed with surgical resection of the symptomatic mass. Intriguingly, pathological study demonstrated a WHO Grade I ganglioglioma. Description: We report a case of a 58-year-old male who presented with hearing loss, tinnitus, and vertigo. Initial magnetic resonance imaging revealed bilateral nonenhancing IAC/CPA tumors. Based on this finding, a presumptive diagnosis of neurofibromatosis Type II was made, which was initially managed conservatively with close observation. He returned for follow-up with worsening vertigo and tinnitus, thus prompting the decision to proceed with surgical resection of the symptomatic mass. Intriguingly, pathological study demonstrated a WHO Grade I ganglioglioma. Conclusion: This is the first reported case of bilateral IAC/CPA gangliogliomas. When evaluating bilateral IAC/CPA lesions with unusual imaging characteristics, ganglioglioma should be included in the differential diagnosis.
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Affiliation(s)
- Kristopher G Hooten
- Department of Neurological Surgery, University of Florida, Gainesville, Florida, USA
| | - Seth F Oliveria
- Department of Neurological Surgery, University of Florida, Gainesville, Florida, USA
| | - Saeed S Sadrameli
- Department of Neurological Surgery, University of Florida, Gainesville, Florida, USA
| | - Shashank Gandhi
- Department of Neurosurgery, North Shore Long Island Jewish, Manhasset, NY, USA
| | - Anthony T Yachnis
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida, USA
| | - Stephen B Lewis
- Department of Neurological Surgery, University of Florida, Gainesville, Florida, USA
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Varshneya K, Sarmiento JM, Nuño M, Lagman C, Mukherjee D, Nuño K, Babu H, Patil CG. A national perspective of adult gangliogliomas. J Clin Neurosci 2016; 30:65-70. [PMID: 27083133 DOI: 10.1016/j.jocn.2015.12.028] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Accepted: 12/27/2015] [Indexed: 11/30/2022]
Abstract
Gangliogliomas (GG) are rare tumors of the nervous system. Patient characteristics and clinical outcomes of low and high-grade GG have been difficult to elucidate in the adult population. This study aims to further elaborate on GG treatment and overall survival utilizing a larger cohort than previously published. The USA National Cancer Database was utilized to evaluate adult (age 18years and older) patients diagnosed with GG between 2004 and 2006. Descriptive statistics and Kaplan-Meier overall survival estimates were provided. A total of 198 adult GG patients were diagnosed between 2004 and 2006. Of these, 181 (91.4%) were low-grade and 17 (8.6%) high-grade GG. Overall, the median age was 36years; approximately 50% of patients were female, and 86.5% Caucasian. Most patients (59%) had near/gross total resection. Radiation and chemotherapy were prescribed in 18 (9.1%) and 11 (5.7%) patients, respectively. Radiation (64.7% versus 3.9%, p<.0001) and chemotherapy (47.1% versus 1.7%, p<.0001) were more frequently given to patients with high-grade tumors than low-grade. The median overall survival of high-grade GG was 44.4months (95% confidence interval [CI]: 10.5-92.5) while the corresponding estimate for low-grade tumors was not reached. Older age (hazard ratio [HR] 1.72, 95% CI: 1.26-2.34) and high tumor grade (HR 3.91, 95% CI: 1.43-10.8) were found to be associated with poor survival. Adult GG have a temporal lobe predilection and overall gross total resection rate of 59%. Older patients with high-grade tumors had an increased hazard of mortality. High-grade GG were significantly more likely to be treated with radiation therapy and chemotherapy.
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Affiliation(s)
- Kunal Varshneya
- Center for Neurosurgical Outcomes Research, Maxine Dunitz Neurosurgical Institute, Department of Neurosurgery, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, 127 S. San Vicente Boulevard, Suite A6600, Los Angeles, CA 90048, USA
| | - J Manuel Sarmiento
- Center for Neurosurgical Outcomes Research, Maxine Dunitz Neurosurgical Institute, Department of Neurosurgery, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, 127 S. San Vicente Boulevard, Suite A6600, Los Angeles, CA 90048, USA
| | - Miriam Nuño
- Center for Neurosurgical Outcomes Research, Maxine Dunitz Neurosurgical Institute, Department of Neurosurgery, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, 127 S. San Vicente Boulevard, Suite A6600, Los Angeles, CA 90048, USA
| | - Carlito Lagman
- Center for Neurosurgical Outcomes Research, Maxine Dunitz Neurosurgical Institute, Department of Neurosurgery, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, 127 S. San Vicente Boulevard, Suite A6600, Los Angeles, CA 90048, USA
| | - Debraj Mukherjee
- Center for Neurosurgical Outcomes Research, Maxine Dunitz Neurosurgical Institute, Department of Neurosurgery, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, 127 S. San Vicente Boulevard, Suite A6600, Los Angeles, CA 90048, USA
| | - Karla Nuño
- Center for Neurosurgical Outcomes Research, Maxine Dunitz Neurosurgical Institute, Department of Neurosurgery, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, 127 S. San Vicente Boulevard, Suite A6600, Los Angeles, CA 90048, USA
| | - Harish Babu
- Center for Neurosurgical Outcomes Research, Maxine Dunitz Neurosurgical Institute, Department of Neurosurgery, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, 127 S. San Vicente Boulevard, Suite A6600, Los Angeles, CA 90048, USA
| | - Chirag G Patil
- Center for Neurosurgical Outcomes Research, Maxine Dunitz Neurosurgical Institute, Department of Neurosurgery, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, 127 S. San Vicente Boulevard, Suite A6600, Los Angeles, CA 90048, USA.
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Abstract
This chapter describes the epidemiology, pathology, molecular characteristics, clinical and neuroimaging features, treatment, outcome, and prognostic factors of the rare glial tumors. This category includes subependymal giant cell astrocytoma, pleomorphic xanthoastrocytoma, astroblastoma, chordoid glioma of the third ventricle, angiocentric glioma, ganglioglioma, desmoplastic infantile astrocytoma and ganglioma, dysembryoplastic neuroepithelial tumor, papillary glioneuronal tumor, and rosette-forming glioneuronal tumor of the fourth ventricle. Many of these tumors, in particular glioneuronal tumors, prevail in children and young adults, are characterized by pharmacoresistant seizures, and have an indolent course, and long survival following surgical resection. Radiotherapy and chemotherapy are reserved for recurrent and/or aggressive forms. New molecular alterations are increasingly recognized.
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Affiliation(s)
- Riccardo Soffietti
- Department of Neuro-Oncology, University and City of Health and Science Hospital, Turin, Italy.
| | - Roberta Rudà
- Department of Neuro-Oncology, University and City of Health and Science Hospital, Turin, Italy
| | - David Reardon
- Center for Neuro-Oncology, Harvard Medical School and Dana-Farber Cancer Institute, Boston, USA
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Patibandla MR, Ridder T, Dorris K, Torok MR, Liu AK, Handler MH, Stence NV, Fenton LZ, Hankinson TC. Atypical pediatric ganglioglioma is common and associated with a less favorable clinical course. J Neurosurg Pediatr 2016; 17:41-8. [PMID: 26431248 DOI: 10.3171/2015.6.peds15215] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECT Ganglioglioma (GG) is commonly recognized as a low-grade tumor located in the temporal lobe, often presenting with seizures. Most are amenable to complete resection and are associated with excellent oncological outcome. The authors encountered several GGs in various locations, which seem to have a less favorable clinical course than GGs in the temporal lobe. METHODS The authors performed a single-center retrospective review of all children with a histological diagnosis of GG who were treated at Children's Hospital Colorado between 1997 and 2013. Each tumor was categorized by 2 pediatric neuroradiologists as typical or atypical based on preoperative MRI appearance. Typical lesions were cortically based, within a single cerebral lobe, well-circumscribed, and solid or mixed solid/cystic. The treatment and clinical course of each patient was analyzed. RESULTS Thirty-seven children were identified, with a median age at presentation of 8.2 years and median follow-up of 38.0 months. Eighteen tumors (48.6%) were typical and 19 (51.4%) were atypical. All typical lesions presented with seizures, whereas no atypical lesions did so. Sixteen (88.9%) typical lesions were located in the temporal lobe. In the atypical group, tumor location was variable, including 11 (57.9%) in the brainstem. Death during follow-up was statistically more common in the atypical group (31.6% vs 0%, p = 0.02). Gross-total resection (GTR) was achieved for 15 of 16 typical tumors (93.8%), compared with 3 atypical tumors (15.8%, p < 0.0001). Presentation with seizure or non-brainstem location were each associated with survival (p = 0.02 and 0.004, respectively). The presence of mutation in BRAF exon 15 did not differ between the 2 groups. CONCLUSIONS Pediatric GG with typical imaging features is associated with excellent rates of GTR and overall survival. Atypical GG is commonly encountered, less amenable to GTR, and associated with a worse outcome. This may relate to anatomical or biological characteristics and merits further investigation.
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Affiliation(s)
| | | | | | - Michelle R Torok
- Adult and Child Center for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | | | | | - Nicholas V Stence
- Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus; and
| | - Laura Z Fenton
- Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus; and
| | - Todd C Hankinson
- Pediatric Neurosurgery;,Adult and Child Center for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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Abstract
PURPOSE Pediatric infratentorial gangliogliomas are exceedingly rare tumors; thus, the factors affecting their outcome are poorly understood and their optimal management has still to be defined. METHODS We reviewed the literature on pediatric gangliogliomas with a focus on those located in the posterior fossa to study treatment and outcome data. We added to this review some of our clinical cases. RESULTS We found 100 and 80 cases of brainstem and cerebellar pediatric ganglioglioma, respectively, in our literature review. The surgical management varied from biopsy to gross total resection, and adjuvant treatment was given after incomplete resection or at time of progression. A gross total resection should be attempted to remove the contrast enhancing part of the tumor, which may be possible in most of the cerebellar gangliogliomas and some of the brainstem lesions. The cervicomedullary ganglioglioma seems to be the most infiltrative and least amenable to complete resection. Chemotherapy has a limited role and BRAF mutation was reported in 38 to 54 % of cases. The use of radiotherapy exposes the patient to a risk of malignant transformation and should be reserved for unresectable tumors which progress. CONCLUSION Pediatric posterior fossa gangliogliomas are rare and challenging tumors due to their frequent infiltrative component involving the brainstem. To date, adjuvant therapy has a limited role that may evolve with time thanks to the use of targeted therapies against BRAF mutation. The surgical resection of well-defined contrast enhancing parts should be attempted even in staged surgeries and balanced with the risks of neurological deterioration.
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