UNASSIGNED: Bilateral, biventricular lesions present a challenging scenario in neurosurgery, often requiring complex surgical techniques for management. Gangliogliomas (GG), while typically indolent, can manifest as anaplastic variants (AGG), necessitating comprehensive treatment strategies. This case study explores a unique surgical approach for a patient with bilateral, intra-extraventricular lesions infiltrating the corpus callosum, highlighting the complexities of managing such cases.
UNASSIGNED: A 63-year-old female presented with a progressive intraventricular lesion infiltrating the left frontal lobe, diagnosed initially as a ganglioglioma. Following resection and histological examination, the lesion was confirmed as a WHO Grade 1 ganglioglioma. Subsequently, a contralateral lesion emerged, necessitating a novel surgical approach to achieve maximal safe resection while minimising neurological deficits. The technique involved extending the surgical corridor contralaterally along the tumour route, guided by neuronavigation and fluorescence imaging.
UNASSIGNED: The surgical approach enabled maximal safe resection of the lesion, with postoperative imaging confirming complete resection in most sites except for a known infiltration in the right posterior lateral ventricle. Histological examination revealed AGG, prompting subsequent adjuvant radiotherapy due to its aggressive nature.
UNASSIGNED: The management of bilateral, biventricular lesions such as AGG requires innovative surgical approaches tailored to individual patient characteristics. The case highlights the efficacy of a transtumoral approach in achieving maximal safe resection while minimising neurological sequelae. Moreover, it underscores the importance of comprehensive treatment strategies, including adjuvant therapies, in addressing aggressive histological variants of gangliogliomas.

Ganglioglioma (GG) is a WHO-grade 1 glioneuronal neoplasm. It is well differentiated with a slow-growing pattern and is composed of a combination of neoplastic ganglion and glial cells. Anaplastic ganglioglioma (AGG) is an extremely rare malignant variant of ganglioglioma, which is not included in the new WHO classification; however, the term is used to talk about gangliogliomas with data of malignancy. AGGs usually occur in children and young adults and are associated with high recurrence and mortality. The authors describe the case of a 62-year-old woman with AGG. She presented with cacosmia, vertigo, nausea, and focal-onset seizures with secondary generalization. Magnetic resonance imaging (MRI) revealed an intra-axial lesion in the left temporal lobe. She underwent microsurgical resection guided by electrocorticography (ECoG), and a diagnosis of AGG based on microscopic morphology and immunohistochemical analysis was obtained. She was discharged a few days after surgery with subtotal resection of the lesion, no additional neurological deficit, and adequate seizure control. AGG is a very rare and poorly studied entity. It is currently a controversial term used to refer to gangliogliomas with signs of malignancy. It occurs mainly in children and young adults with temporal lobe epilepsy. Total resection is the best prognostic factor, given the unknown efficacy of radiotherapy and chemotherapy. In our case, the patient was an adult woman with a subtotal resection followed by concomitant radiotherapy and chemotherapy, obtaining a mean survival similar to that reported in the literature, so it can be thought that there is a benefit obtained with chemotherapy and radiotherapy despite having performed a subtotal resection of the lesion. Further studies are needed to establish clear diagnostic criteria for AGG, and a multicenter database of AGGs is necessary for a better understanding of the pathology and to offer the best treatment and prognosis.

Neuropil-like islands (NIs) are a histologic hallmark of glioneuronal tumors with neuropil-like islands (GTNIs), but GTNIs are presently not considered a homogeneous entity. The essence of GTNI is likely its glial component, and NIs are now considered aberrant neuronal differentiation or metaplasia. The case we report herein is a 41-year-old woman who was synchronously affected by two brain tumors: one was a glioblastoma (glioblastoma multiforme, GBM), of isocitrate dehydrogenase (IDH)-wild type, with NIs in the left parietal lobe, and the other was histologically a composite gangliocytoma (GC)/anaplastic ganglioglioma (GG) with NIs in the right medial temporal lobe. While both tumors were genetically wild type for IDH, histone H3, and v-raf murine sarcoma viral oncogene homolog B1 (BRAF), the former tumor, but not the latter, was mutated for telomerase reverse transcriptase promoter gene (TERT). A recent systematic study using DNA methylation profiling and next-generation sequencing showed that anaplastic GG separate into other WHO tumor types, including IDH-wild-type GBM. It suggested a diagnostic scheme where an anaplastic GG is likely an IDH-wild-type GBM if it is a BRAF wild type, IDH wild type, and TERT promoter mutant tumor. The likely scenario in this patient is that the GBM results from the progression of GC/anaplastic GG due to the superimposed TERT promoter mutation and the propagation of newly generated GBM cells in the contralateral hemisphere. A systematic analysis using DNA methylation profiling and next-generation sequencing was not available in this study, but the common presence of NIs histologically noted in the two tumors could support this scenario. Although a sufficient volume of molecular and genetic testing is sine qua non for the accurate understanding of brain tumors, the importance of histologic observation cannot be overemphasized.

OBJECTIVE: 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.

Ganglioglioma (GG) is a rare kind of intracranial tumor with low potential malignancy (WHO grade I), which could occur in any part of the brain. However, a patient with anaplastic ganglioglioma (WHO grade III) in the medulla oblongata is a more peculiar and rare clinical case. In our report, we presented a case of a 45-year-old man with anaplastic ganglioglioma (WHO grade III) in the medulla oblongata, who was perplexed with dysphagia, choking and left-sided numbness for two and a half years. The head magnetic resonance imaging (MRI) showed a 2.7 cm × 2.6 cm lesion in the medulla oblongata with slightly low signal on T1 weighted image (T1WI) and heterogeneous high signal without calcifications on T2 weighted image (T2WI). The Physical Examination manifested that the patient showed a chronic appearance, along with the damage of oculomotor nerve, glossopharyngeal and vagus nerves and spinal thalamus lateral tract and rope body. Subsequently, the patient underwent surgical and common radiotherapy treatment, which might delay the tumor recurrence and contribute to a better overall survival. Unexpectedly, tentative chemotherapy was carried out when the tumor showed the recurrence trend and anaplastic feature. Our presentation of this case would emphasize the rarity and significance of the diagnosis, differentiation and treatment of such tumors, demanding more clinical cases for exploration.

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.

Gangliogliomas are central nervous system tumors located in the temporal lobe of young patients, frequently associated with epilepsy. In this paper, we propose a grading system based solely on histopathological criteria. We reevaluated all cases of ganglioglioma, atypical ganglioglioma, and anaplastic ganglioglioma diagnosed between 2011 and 2020 in the Pathology Department of the Emergency Clinical Hospital Bagdasar-Arseni, based on the type of glial mitoses, the number of neuronal and glial mitoses, presence of necrosis, microvascular proliferation, eosinophilic granular bodies, hypercellularity, presence and disposition of inflammatory infiltrate and atypical pleomorphism. Based on the proposed grading system, a score of 0-4 corresponded to a benign ganglioglioma, 5-9 to an atypical ganglioglioma, and 10-18 to an anaplastic ganglioglioma. The survival rates were 90% for benign ganglioglioma, 71.43% for atypical ganglioglioma, and 62.54% for anaplastic ganglioglioma. One case of benign ganglioglioma underwent a malignant transformation into anaplastic ganglioglioma, and recurrences were noticed in 28.57% of atypical ganglioglioma cases and 30.7% of all anaplastic gangliogliomas. The presence of rare glial mitoses and hypercellularity was correlated with mortality in cases of atypical ganglioglioma. We believe this histopathological scoring system could be used as a three-tier system to identify atypical ganglioglioma cases that are bound to have an aggressive course of evolution and require close follow-up. The other option would be to convert it to a two-tier grading system that can separate low-grade gangliogliomas from high-grade ones. The latter category can encompass both atypical and anaplastic ganglioglioma due to the high mortality of both entities.

Anaplastic ganglioglioma (AGG) is a rare and aggressive counterpart of the more benign and frequently encountered glioma. Herein, we present a 21-year-old female who presented with episodes of total amnesia and complex partial seizures, which led to the diagnosis of AGG localized to the medial temporal lobe. She subsequently underwent surgical cytoreduction of the tumor three times with adjuvant chemoradiotherapy. The extent of resection throughout the surgeries was hindered by the extension of the tumor to critical neurovascular structures; during the last surgery, invasion into the pons was noted, which posed a significant clinical challenge.

Here, we report on a 28-year old male patient presenting with neck and shoulder pain, dysesthesia of all four limbs and hypesthesia of both hands, without motor deficits. Magnetic resonance imaging showed an intradural, intramedullary mass of the cervical spinal cord of 6.4 cm length and 1.7 cm diameter. The patient underwent surgical resection. Histological and immunohistochemical evaluation showed pleomorphic glial tumor cells, mitoses, calcifications, and atypical ganglioid cells compatible with the morphology of anaplastic ganglioglioma (WHO Grade III). Extensive molecular workup revealed H3F3A K27M, TERT C228T and PDGFRα Y849C mutations indicating poor prognosis. The H3F3A K27M mutation assigned the tumor to the molecular group of diffuse midline glioma (WHO Grade IV). Epigenome-wide methylation profiling confirmed the methylation class of diffuse midline glioma. Thus, this is a very rare case of malignant glioma with H3 K27M genotype phenotypically mimicking anaplastic ganglioglioma. This case emphasizes the importance of comprehensive morphological and molecular workup including methylome profiling for advanced patient care.

Low-grade gliomas (LGGs) are the commonest benign central nervous system (CNS) tumors seen in children. Unlike LGGs in adults, pediatric LGGs rarely undergo malignant transformation. The incidence of malignant transformation of LGGs in the pediatric population has been reported to be up to 10%. Of these, a few patients have demonstrated this phenomenon even without adjuvant radiation therapy. We report two such unusual cases. A 7-year-old girl presented with a left temporal lesion that was operated upon and was reported as pilocytic astrocytoma (WHO grade I). She presented with a malignant transformation of the tumour 8 years later. The second case was a 10-year-old boy, who had a left frontoparietal ganglioglioma (WHO grade I) that demonstrated malignant transformation to an anaplastic ganglioglioma (WHO grade III) 10 months after the initial surgery. Multiple studies have thrown light on the molecular genetics behind malignant transformation of LGGs in children. These genetic changes can perhaps serve as targets for potential future therapeutic interventions. It is important that patients with LGGs at risk of malignant transformation must be identified early so that a more aggressive treatment strategy can be adopted.