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Background/purpose:
Anaplastic ganglioglioma (AGG) is a rare tumor with both glial and neuronal component accounting for less than 1% of all CNS tumors with limited information about the optimum treatment and outcome of these tumors.
Method and materials:
We did a thorough search of the PubMed with the following MesH terms: "Ganglioglioma; Anapl...
Citations
... Adjuvant radiation or chemotherapy is often recommended, though this is controversial because of the scant evidence for its efficacy. [14,23] Due to the rarity of spinal AGGs in particular, there are no specific guidelines for their treatment. Use of surgery and adjuvant therapy was advocated by Vlachos et al. (2/22 achieved progression-free survival; both received combination surgery and adjuvant therapy), although they noted that this should be taken anecdotally. ...
... Use of surgery and adjuvant therapy was advocated by Vlachos et al. (2/22 achieved progression-free survival; both received combination surgery and adjuvant therapy), although they noted that this should be taken anecdotally. [26] e survival benefit of GTR compared with subtotal resection in treating AGGs has been reported by Mallick et al. and Selvanathan et al. [14,23] Both studies, however, failed to conclude whether adjuvant therapy improved outcome, most likely due to small sample size. As molecular characteristics of AGGs become further delineated, they may help guide therapy based on the underlying molecular profiles. ...
Background:
Gangliogliomas (GGs) are rare tumors of the central nervous system composed of neoplastic neural and glial cells and are typically low-grade. Intramedullary spinal anaplastic GGs (AGG) are rare, poorly understood, and often aggressive tumors that can result in widespread progression along the craniospinal axis. Due to the rarity of these tumors, data are lacking to guide clinical and pathologic diagnosis and standard of care treatment. Here, we present a case of pediatric spinal AGG to provide information on our institutional approach to work-up and to highlight unique molecular pathology.
Case description:
A 13-year-old female presented with signs of spinal cord compression including right sided hyperreflexia, weakness, and enuresis. Magnetic resonance imaging (MRI) revealed a C3-C5 cystic and solid mass which was treated surgically with osteoplastic laminoplasty and tumor resection. Histopathologic diagnosis was consistent with AGG, and molecular testing identified mutations in H3F3A (K27M), TP53, and NF1. She received adjuvant radiation therapy and her neurological symptoms improved. However, at 6-month follow-up, she developed new symptoms. MRI revealed metastatic recurrence of tumor with leptomeningeal and intracranial spread.
Conclusion:
Primary spinal AGGs are rare tumors, but a growing body of literature shows some trends that may improve diagnosis and management. These tumors generally present in adolescence and early adulthood with motor/sensory impairment and other spinal cord symptoms. They are most commonly treated by surgical resection but frequently recur due to their aggressive nature. Further reports of these primary spinal AGGs along with characterization of their molecular profile will be important in developing more effective treatments.
... The optimal treatment would be complete surgical resection followed by radiotherapy [77]. A Stupp protocol can be proposed as a first-line of treatment after surgery [78] adjuvant radiotherapy with chemotherapy in case of STR [77]. ...
... The optimal treatment would be complete surgical resection followed by radiotherapy [77]. A Stupp protocol can be proposed as a first-line of treatment after surgery [78] adjuvant radiotherapy with chemotherapy in case of STR [77]. In case of relapse, targeted molecular therapies including BRAF inhibitor alone or combined with MEK inhibitor, can be proposed [78][79][80] (combination of both can overcome BRAFi resistance) [81]. ...
Simple Summary
Glioneuronal and neuronal tumours are rare and mostly found in young adults and children, representing less than 5% of primary central nervous system (CNS) tumours. Accurate diagnosis is often difficult, requiring a significant body of evidence (clinical, radiological, pathology and molecular). The aim of this paper is to describe the main entities reported in the 2021 World Health Organization (WHO) classification, including, on the one hand, their histomolecular and imaging features and, on the other hand, their therapeutic management. Gross total resection is the cornerstone of the treatment of these tumours when achievable. MAPK pathway abnormalities could represent an interesting target for novel drugs.
Abstract
Rare glial, neuronal and glioneuronal tumours in adults form a heterogeneous group of rare, primary central nervous system tumours. These tumours, with a glial and/or neuronal component, are challenging in terms of diagnosis and therapeutic management. The novel classification of primary brain tumours published by the WHO in 2021 has significantly improved the diagnostic criteria of these entities. Indeed, diagnostic criteria are nowadays multimodal, including histological, immunohistochemical and molecular (i.e., genetic and methylomic). These integrated parameters have allowed the specification of already known tumours but also the identification of novel tumours for a better diagnosis.
... states that anaplasia has been observed in the glial component including conspicuous mitotic activity, high Ki67 proliferation index, necrosis and microvascular proliferation [7]. Based on the data available, patients with aGG fare worse than patients with GG CNS WHO Grade 1. Recurrence was observed in 50% of the aGG patients, and median overall survival ranged from 25 to 44 months [2,5,6,[8][9][10][11][12]. ...
Aims:
Anaplastic ganglioglioma is a rare tumour, and diagnosis has been based on histological criteria. The 5th edition of the World Health Organization Classification of Tumours of the Central Nervous System (CNS WHO) does not list anaplastic ganglioglioma as a distinct diagnosis due to lack of molecular data in previous publications. We retrospectively compiled a cohort of 54 histologically diagnosed anaplastic gangliogliomas to explore whether the molecular profiles of these tumours represent a separate type or resolve into other entities.
Methods:
Samples were subjected to histological review, desoxyribonucleic acid (DNA) methylation profiling and next-generation sequencing. Morphological and molecular data were summarised to an integrated diagnosis.
Results:
The majority of tumours designated as anaplastic gangliogliomas resolved into other CNS WHO diagnoses, most commonly pleomorphic xanthoastrocytoma (16/54), glioblastoma, isocitrate dehydrogenase protein (IDH) wild type and diffuse paediatric-type high-grade glioma, H3 wild type and IDH wild type (11 and 2/54), followed by low-grade glial or glioneuronal tumours including pilocytic astrocytoma, dysembryoplastic neuroepithelial tumour and diffuse leptomeningeal glioneuronal tumour (5/54), IDH mutant astrocytoma (4/54) and others (6/54). A subset of tumours (10/54) was not assignable to a CNS WHO diagnosis, and common molecular profiles pointing to a separate entity were not evident.
Conclusions:
In summary, we show that tumours histologically diagnosed as anaplastic ganglioglioma comprise a wide spectrum of CNS WHO tumour types with different prognostic and therapeutic implications. We therefore suggest assigning this designation with caution and recommend comprehensive molecular workup.
... Treatment for this condition is the same during pregnancy than in general population, and consists in surgical resection aiming to improve symptoms, survival and the obtention of a histopathologic diagnosis. Maternal-fetal outcomes are not worsened by surgical treatment [10] and there are greater survival rates when complete tumor resection is achieved [11]. ...
... Anaplastic ganglioglioma has an aggressive behavior. As such, better control of disease has been reported when local radiation and adjuvant chemotherapy are used in addition to surgery [11]. Chemotherapy during the first trimester of pregnancy has been associated with spontaneous miscarriage, CNS malformations and hematopoietic disturbances. ...
Objectives
The true incidence of anaplastic ganglioglioma during pregnancy is extremely rare, very few cases have been reported in the literature.
Case presentation
This is a report of a case of anaplastic ganglioglioma diagnosed in pregnancy. The patient is a 23-year-old primigravida who presented at 19 weeks of gestation headache and a convulsive episode. Her workup revealed a rare cerebral tumor that progressed to a neurological decline and died during the postpartum period.
Conclusions
Anaplastic ganglioglioma is an aggressive counterpart of Glial tumors; in pregnancy they are rare and symptoms are nonspecific. The outcome for the mother in this case fatal and a protocol for these cases has not yet been reported.
... In terms of adjuvant RTR, a trend is reported towards better survival of patients who received RTR [31]. Mallick and colleagues emphasize the importance of GTR for better PFS and OS but, like Selvanathan and colleagues, to conclude whether adjuvant CTR and RTR could enhance the outcome [21], probably because of the small numbers involved. ...
Gangliogliomas (GGs) are rare, usually low-grade tumors that account for 1–2% of all central nervous system (CNS) neoplasms. Spinal GGs are exceedingly rare (1% of all spinal tumors) and the presentation of anaplastic features in them is even rarer. According to the last World Health Organization (WHO) classification of CNS neoplasms, anaplastic GG (AGG) is classified as a malignant neoplasm (grade III). We performed a scoping review of the literature to elucidate the epidemiology, clinical features, histopathology, treatment, and outcome of primary spinal AGGs, which, to the best of our knowledge, is the first such review. Relevant studies were identified by a search of the MEDLINE and SCOPUS databases, using the following combination of search strings: (anaplastic ganglioglioma or malignant ganglioglioma or high grade ganglioglioma) AND (spine or spinal or spinal cord). We included studies related to primary or recurrent AGGs and malignant transformation of low-grade GGs. The search produced 15 eligible studies, plus two studies from the references, all of which were case reports of patients with spinal AGGs (17 studies with 22 patients). The mean age of the patients was 21.4 years and the sex ratio was 1:1, with male predominance. Motor impairment was the most common presentation, followed by sensory impairment, gait problems, urinary disturbances, and back pain. The thoracic spine was the most frequently involved area (14/22) followed by the cervical (6/22) and lumbar (5/22) spine. In terms of histology, the anaplastic features were usually predominant in the glial element, resembling high-grade astrocytomas, while the neuronal element was composed of the so-called dysplastic ganglion (neuronal) synaptophysin-positive cells, without mitotic figures. Complete surgical resection of the tumor without neurological compromise, plus adjuvant chemotherapy and radiotherapy, was the treatment protocol implemented in the two patients with the best outcome. Primary spinal AGG is an exceedingly rare entity, with only 22 cases being retrieved after an extensive literature search. They appear to affect children and young adults and tend to manifest aggressive behavior. Most studies report that only the glial component of AGGs presents high-grade malignant features, with low mitotic activity in the neuronal component. We therefore suggest that, pending novel targeted therapy, AGGs should be treated as high-grade gliomas, with an aggressive treatment protocol consisting of maximal safe resection and adjuvant chemotherapy and radiotherapy.
... Currently, the most successful treatment option in GG is neurosurgical resection with almost no tumor recurrence (2,8) or seizure relapse during a postsurgical follow-up period of 5 years (9). Histopathologically, most GG are considered as World Health Organization (WHO) grade I. Some GG with anaplastic features are considered WHO grade III (4,10,11). Anaplastic changes in the glial component and a high ki-67 proliferation index may indicate aggressive behavior and a less favorable prognosis (12,13). At present, no criteria for a GG WHO grade II were established (1,4). ...
The BRAF p.V600E mutation is the most common genetic alteration in ganglioglioma (GG). Herein, we collected a consecutive series of 30 GG specimens from Xuanwu Hospital in order to corroborate the genetic landscape and genotype–phenotype correlation of this enigmatic and often difficult‐to‐classify epilepsy‐associated brain tumor entity. All specimens with histopathologically confirmed lesions were submitted to targeted next‐generation sequencing using a panel of 131 genes. Genetic alterations in three cases with histologically distinct tumor components, that is, GG plus pleomorphic xanthoastrocytoma (PXA), dysembryoplastic neuroepithelial tumor (DNT), or an oligodendroglioma (ODG)‐like tumor component, were separately studied. A mean post‐surgical follow‐up time‐period of 23 months was available in 24 patients. Seventy seven percent of GG in our series can be explained by genetic alterations, with BRAF p.V600E mutations being most prevalent (n = 20). Three additional cases showed KRAS p.Q22R and KRAS p.G13R, IRS2 copy number gain (CNG) and a KIAA1549‐BRAF fusion. When genetically studying different histopathology patterns from the same tumor we identified composite features with BRAF p.V600E plus CDKN2A/B homozygous deletion in a GG with PXA features, IRS2 CNG in a GG with DNT features, and a BRAF p.V600E plus CNG of chromosome 7 in a GG with ODG‐like features. Follow‐up revealed no malignant tumor progression but nine patients had seizure recurrence. Eight of these nine GG were immunoreactive for CD34, six patients were male, five were BRAF wildtype, and atypical histopathology features were encountered in four patients, that is, ki‐67 proliferation index above 5% or with PXA component. Our results strongly point to activation of the MAP kinase pathway in the vast majority of GG and their molecular‐genetic differentiation from the cohort of low‐grade pediatric type diffuse glioma remains, however, to be further clarified. In addition, histopathologically distinct tumor components accumulated different genetic alterations suggesting collision or composite glio‐neuronal GG variants. Our results strongly point to activation of the MAP kinase pathway in the vast majority of ganglioglioma (GG). Composite genetic alterations were found in cases with histologically distinct tumor components firstly, i.e. GG plus pleomorphic xanthoastrocytoma (PXA), dysembryoplastic neuroepithelial tumor, or an oligodendroglioma‐like tumor. Seizure recurrence is inclined to ganglioglioma with atypical histopathology features (i.e. GG containing a ki‐67 proliferation index above 5% or GG with PXA component).
... 2,3,8,11,16 Even with anaplastic GGs, GTR is also regarded as a predictor with improved outcomes. 24,[27][28][29] ...
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.
... Gross total resection is considered the standard of care for anaplastic gangliogliomas [64,74,75]. However, even after a complete surgical resection tumor recurrence can occur; thus, many centers recommend adjuvant radiotherapy or chemo-radiotherapy to improve tumor control and survival [64,74,75]. ...
... Gross total resection is considered the standard of care for anaplastic gangliogliomas [64,74,75]. However, even after a complete surgical resection tumor recurrence can occur; thus, many centers recommend adjuvant radiotherapy or chemo-radiotherapy to improve tumor control and survival [64,74,75]. Even after adjuvant treatment survival is poor. ...
... Mallick et al. [75] performed a search of PubMed to find all the publications related to anaplastic ganglioglioma to establish the optimum treatment of this tumor type. A total of 40 publications with overall 69 patients were found eligible. ...
Glioneuronal tumors are very rare CNS neoplasms that demonstrate neuronal differentiation, composed of mixed glial and neuronal cells. The majority of these lesions are low grade and their correct classification is crucial in order to avoid misidentification as ‘ordinary’ gliomas and prevent inappropriate aggressive treatment; nevertheless, precise diagnosis is a challenge due to phenotypic overlap across different histologic subtype. Surgery is the standard of therapeutic approach; literature concerning the benefit of adjuvant treatments is inconclusive and a globally accepted treatment of recurrence does not exist. Targetable mutations in the genes BRAF and FGFR1/2 are recurrently found in these tumors and could take a promising role in future treatment management.
Brain tumors account for the majority of cancer-related deaths in adolescents and young adults (AYAs), defined as individuals aged 15 to 39. AYAs constitute a distinct population in which both pediatric- and adult-type central nervous system (CNS) tumors can be observed. Clinical manifestations vary depending on tumor location and often include headaches, seizures, focal neurological deficits, and signs of increased intracranial pressure. With the publication of the updated World Health Organization CNS tumor classification in 2021, diagnoses have been redefined to emphasize key molecular alterations. Gliomas represent the majority of malignant brain tumors in this age group. Glioneuronal and neuronal tumors are associated with longstanding refractory epilepsy. The classification of ependymomas and medulloblastomas has been refined, enabling better identification of low-risk tumors that could benefit from treatment de-escalation strategies. Owing to their midline location, germ cell tumors often present with oculomotor and visual alterations as well as endocrinopathies. The management of CNS tumors in AYA is often extrapolated from pediatric and adult guidelines, and generally consists of a combination of surgical resection, radiation therapy, and systemic therapy. Ongoing research is investigating multiple agents targeting molecular alterations, including isocitrate dehydrogenase inhibitors, SHH pathway inhibitors, and BRAF inhibitors. AYA patients with CNS tumors should be managed by multidisciplinary teams and counselled regarding fertility preservation, psychosocial comorbidities, and risks of long-term comorbidities. There is a need for further efforts to design clinical trials targeting CNS tumors in the AYA population.
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.
