Natural history and neuro-oncological approach in spinal gangliogliomas: a systematic review.

To describe the natural history of spinal gangliogliomas (GG) in order to determine the most appropriate neuro-oncological management. A Medline search for relevant publications up to July 2023 using the key phrase "ganglioglioma spinal" and "ganglioglioma posterior fossa" led to the retrieval of 178 studies. This corpus provided the basis for the present review. As an initial selection step, the following inclusion criteria were adopted: (i) series and case reports on spinal GG; (ii) clinical outcomes were reported specifically for GG; (iii) GG was the only pathological diagnosis for the evaluation of the tumor; (iv) papers written only in English was evaluated; and (v) papers describing each case in the series were included. The World Health Organization (WHO) 2021 grading criteria for gangliogliomas were applied. A total of 107 tumors were evaluated (63 from male patients and 44 from female patients; 1.43 male/1.0 female ratio, mean age 18.34 ± 15.84 years). The most common site was the cervical spine, accounting for 43 cases (40.18%); GTR was performed in 35 cases (32.71%) and STR in 71 cases (66.35%), while this information was not reported in 1 case (0.94%). 8 deaths were reported (7.47%) involving 2 males (25%) and 6 females (75%) aged 4-78 years (mean 34.27 ± 18.22) years. GGs located on the spine displayed the same gender ratio as these tumors in general. The most frequent symptom was pain and motor impairment, while the most prevalent location was the cervical spinal cord. GTR of the tumor posed a challenge for neurosurgeons, due to the difficulty of resecting the lesion without damaging the spinal eloquent area, explaining the lower rate of cure for this tumor type.

Metameric pruritus as the sole manifestation of an intramedullary tumor in a toddler.

An 18-month-old child presented with persistent pruritus and excoriation involving the right T9 and T10 dermatomes. She did not exhibit any other dermatological or neurological anomalies. Based on magnetic resonance imaging investigation of the spine, T8 ganglioglioma was diagnosed and surgically removed resulting in resolution of the pruritus within a few days. This observation underlines the importance of neuroimaging in patients presenting with metameric pruritus without specific skin lesions, especially in young children.

Vestibular seizures and spontaneous downbeat nystagmus of ganglioglioma origin: a case report.

BACKGROUND: Low-grade gangliogliomas (GGs) are typically epileptogenic intracranial neoplasms. Yet, the presentation of simplex vertiginous experience and spontaneous downbeat nystagmus (DBN) has not been reported to date. CASE PRESENTATION: We present the case of a 26-year-old male with focal onset impaired awareness seizures, characterized by vertigo due to right temporal lobe epilepsy caused by ganglioglioma. As rare presentations, a spontaneous, consistent DBN in the absence of vertiginous experience was noticed. MRI suggested lesion in the right temporal pole. Twenty-four-hour continuous electroencephalogram (EEG) monitoring recorded periodic sharp and slow waves, originating from the right temporal lobe. The patient was completely relieved of the symptoms after surgical removal of the tumor, which was histologically confirmed as Grade I Ganglioglioma. CONCLUSIONS: Asides from the cortical pathogenesis of epileptic vertigo, this case also provides insight into the DBN secondary to tumor of the temporal lobe. Moreover, the 24-h EEG is advantageous to recognize vestibular seizures and localize the ictal onset areas.

EANO - EURACAN - SNO Guidelines on circumscribed astrocytic gliomas, glioneuronal, and neuronal tumors.

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.

Ganglioglioma revealed by spontaneous intracerebral hematoma: A cohort study.

BACKGROUND: Gangliogliomas are rare tumors of the central nervous system. Intracerebral hemorrhage (ICH) is a frequent pathological event, rarely related to intracranial tumor. Here we report a cohort of 14 gangliogliomas, 3 of which were revealed by ICH. We also performed a systematic review of the literature on gangliogliomas revealed by ICH. PATIENTS AND METHODS: We retrospectively collected data for all gangliogliomas operated on in our department between January 2015 and December 2019: clinical history, radiological data and outcome, with a special focus on gangliogliomas revealed by spontaneous ICH. All cases had pathological validation. For the systematic review, relevant studies were identified by systematic search of the scientific literature in PubMed. RESULTS: Fifteen patients underwent surgery for ganglioglioma during the study period. Six cases were revealed by seizures, 3 by headache, 1 by hydrocephaly and 1 by developmental disorder. Three patients (21%) had hemorrhagic presentation. All patients were male, aged 30 to 48 years, diagnosed with atypical ICH without vascular abnormality on cerebral angiogram. Conservative management was first decided. Diagnosis of ganglioglioma was made within 3 months for 2 patients and 9 years later for 1, after surgical removal and histological analysis. All hemorrhagic gangliogliomas were BRAF wild type. The systematic review of the literature identified 8 other cases of ganglioglioma revealed by ICH. CONCLUSION: ICH may be a mode of revelation of ganglioglioma, and ganglioglioma is a possible etiology of atypical ICH in young patients. Long-term imaging follow-up is mandatory in patients with unexplained ICH.

Clinical-pathological study of 28 glial and mixed neuronal-glial tumors diagnosed within the first year of life.

Our purpose was to investigate the incidence of gliomas and neuronal-glial tumors, their outcome, and H3.3K27M, BRAFV600E, and IDH status in children within 1 year of age affected by CNS tumor. We collected 28 consecutive gliomas and mixed tumors. Immunohistochemistry and/or molecular analyses were performed on formalin-fixed/paraffin-embedded specimens. 24 (86%) tumors were supratentorial. 15 (54%) tumors were astrocytomas (5 glioblastomas, 1 anaplastic astrocytoma, 1 pilocytic astrocytoma, 3 pilomixoid astrocytomas, 2 subependymal giant cell astrocytomas, 3 astrocytomas not otherwise specified (NOS)), 4 (14%) were anaplastic ependymomas, and 9 (32%) were mixed tumors (5 gangliogliomas, 2 gangliocytomas, 2 desmoplastic infantile gangliogliomas (DIGs)). Alive patients were: 4 (67%) affected by high-grade astrocytoma (mean follow-up 64 months), 4 (67%) affected by low-grade astrocytoma (mean follow-up 83 months), 2 (67%) affected by astrocytoma NOS (mean follow-up 60 months), 1 (25%) affected by anaplastic ependymoma (follow-up 12 months), and 9 (100%) affected by mixed tumors (mean follow-up 74 months). H3.3K27M and IDH were not-mutated in any tumor (100%). BRAFV600E mutation was documented in 6 (21%) tumors (4 gangliogliomas, 1 gangliocytoma, and 1 astrocytoma NOS resulted as anaplastic pleomorphic xanthoastrocytoma 8 years later). Gliomas and mixed tumors diagnosed within 1 year of age are morphologically heterogeneous. Moreover, analogously to those affecting older children, they are IDH1-2 and H3.3K27M (when located outside midline) not-mutated while BRAFV600E mutation is typical of gangliogliomas/gangliocytomas and pleomorphic xanthoastrocytomas. High-grade astrocytomas have a more favorable prognosis compared with the same lesions occurring later in life while ependymomas have a poorer outcome.

Anaplastic gangliogliomas of the spinal cord: a scoping review of the literature.

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.

Tumor teratoide/rabdoide atípico con diferenciación tipo ganglioglioma: reporte de caso / Atypical teratoid/rhabdoid tumor with ganglioglioma-like differentiation: Case report

Antecedentes El tumor teratoide/rabdoide atípico es una entidad muy rara y agresiva que se presenta principalmente en pacientes pediátricos. Hasta donde sabemos, la presentación inicial de este tipo de tumor con diferenciación tipo ganglioglioma es rara dentro de la literatura. Descripción del caso Presentamos el caso de una paciente de nueve meses de edad con parálisis facial izquierda. Se realizó resonancia magnética, la cual reveló una lesión a nivel del ángulo pontocerebeloso izquierdo. Se realizó resección quirúrgica total macroscópica. Los estudios histopatológico e inmunohistoquímico revelan un tumor teratoide/rabdoide atípico con diferenciación de tipo ganglioglioma. Conclusiones El presente reporte de caso presenta un tumor teratoide/rabdoide atípico con una diferenciación inicial de tipo ganglioglioma. Este trabajo aumenta la base de datos literaria y promueve el estudio de este tipo de histogénesis. Creando bases para incentivar estudios mayores que permitan determinar si deben realizarse modificaciones en los protocolos de manejo existentes, y a la vez determinar si existiría variación en cuanto a pronóstico de la patología (AU)

Background Atypical teratoide/rhabdoid tumor is a very rare and aggressive disease that primarily presents in pediatric patients. To the best of our knowledge, the initial presentation of this type of tumor with ganglioglioma-like differentiation is rare in the literature. Case report We present the case of a 9-month-old patient with left facial paralysis. An MRI revealed a lesion at the left cerebellopontine angle. Complete macroscopic surgical resection was performed. Histopathology and immunohistochemistry testing revealed an atypical teratoid/rhabdoid tumor with ganglioglioma-like differentiation. Conclusions This case report presents an atypical teratoid/rhabdoid tumor with initial gangligioma-like differentiation. This study adds to the data in the literature and promotes the study of this type of histogenesis. It lays a foundation for encouraging further studies to determine whether changes should be made to existing management protocols and, at the same time, determine whether there would be any variation with regard to disease prognosis (AU)

Cyclin D1 expression in ganglioglioma, pleomorphic xanthoastrocytoma and pilocytic astrocytoma.

Ganglioglioma, pleomorphic xanthoastrocytoma (PXA) and pilocytic astrocytoma are rare brain neoplasms with frequent activation of mitogen-activated protein (MAP) kinase pathway. A downstream marker of MAP-kinase pathway activation is cyclin D1. However, the expression of cyclin D1 has not been studied in the differential diagnosis between these brain tumors. The aim of this work is to compare the expression of cyclin D1 in ganglioglioma, PXA, pilocytic astrocytoma. We also compared cyclin D1 expression in giant cell glioblastoma and in IDH wild type glioblastoma. Our work shows that roughly half of gangliogliomas have ganglion cells stained by cyclin D1 while two third of PXA have pleormophic cells stained by cyclin D1 and 15% of giant cell glioblastoma have pleomorphic cells stained by cyclin D1 (p < 0.001). Cyclin D1 never stains normal neurons either in the adjacent cortex of circumscribed tumor, or in entrapped neurons in IDH wild type glioblastomas. The expression of cyclin D1 is correlated to the presence of BRAF V600E mutation in ganglioglioma and PXA (p = 0.002). To conclude, cyclin D1 positivity might be used to confirm the neoplastic nature of ganglion cells. Cyclin D1 is expressed in most cases of BRAF V600E mutated gangliogliomas but also in cases without BRAF mutations suggesting an activation of MAP-kinase pathway through another way. Cyclin D1 immunohistochemistry has currently no or little role in the differential diagnosis of pilocytic astrocytoma. Its role in the differential diagnosis between PXA and giant cell glioblastoma needs to be further investigated on external series.

Papillary glioneuronal tumors: Distinctive cytological characteristics and cyto-histologic correlation.

Intraoperative cytological examination and cyto-histologic correlation of papillary glioneuronal tumors have rarely been described in detail in the literature. A 23-year-old female presented at our institution with seizure-like activity, and a 3.0 cm left temporal lobe hypoattenuating lesion. She was accurately diagnosed with papillary glioneuronal tumor on Intraoperative cytology. The patient subsequently proceeded to stealth-guided awake left temporal craniotomy, confirming the diagnosis. In this article, we present a detailed report of papillary glioneuronal tumor (extremely rare central nervous system neoplasm) describing the cytologic and histologic morphologic features, its differential diagnosis with review of the literature.

Pituitary stalk gangliogliomas: Case report and literature review.

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.

Pediatric low-grade glioma in the era of molecular diagnostics.

Low grade gliomas are the most frequent brain tumors in children and encompass a spectrum of histologic entities which are currently assigned World Health Organisation grades I and II. They differ substantially from their adult counterparts in both their underlying genetic alterations and in the infrequency with which they transform to higher grade tumors. Nonetheless, children with low grade glioma are a therapeutic challenge due to the heterogeneity in their clinical behavior - in particular, those with incomplete surgical resection often suffer repeat progressions with resultant morbidity and, in some cases, mortality. The identification of up-regulation of the RAS-mitogen-activated protein kinase (RAS/MAPK) pathway as a near universal feature of these tumors has led to the development of targeted therapeutics aimed at improving responses while mitigating patient morbidity. Here, we review how molecular information can help to further define the entities which fall under the umbrella of pediatric-type low-grade glioma. In doing so we discuss the specific molecular drivers of pediatric low grade glioma and how to effectively test for them, review the newest therapeutic agents and their utility in treating this disease, and propose a risk-based stratification system that considers both clinical and molecular parameters to aid clinicians in making treatment decisions.

Ganglioglioma in a Survivor of Infantile Glioblastoma.

Congenital tumors account for 2% to 4% of all pediatric central nervous system tumors. Glioblastoma multiforme (GBM) represents a small subset of these tumors. Despite harboring histologic features similar to older patients, infants with GBM exhibit improved survival and respond more favorably to surgery and chemotherapy. To highlight this tumor's unique behavior, we report the case of a survivor of infantile GBM who developed a recurrent tumor in the surgical bed 6 months after diagnosis. The tumor was ultimately resected and was a ganglioglioma. This case shows both a favorable clinical outcome to an infantile GBM and this tumor's natural history.

Composite pleomorphic xanthoastrocytoma-ganglioglioma; assessing and addressing the dilemma of differential expression of neuronal markers: Case report with diagnostic perspective.

We report the case of a 5-year-old male child presenting with seizures for 4 months. Magnetic resonance imaging (MRI) revealed a cortical-based solid cystic lesion in the right parietal lobe. Histopathological examination showed a tumour comprised of spindled glial fibrillary acid protein (GFAP) positive neoplastic cells interspersed with bizarre pleomorphic cells showing nuclear pseudoinclusions and intermingled dysplastic ganglion cells variably immunopositive for synaptophysin, chromogranin, Neu-N and immunonegative for neuron filament protein (NFP). This report highlights the occurrence of the rare composite pleomorphic xanthoastrocytoma-ganglioglioma and the vagaries of immunohistochemical analysis in highlighting neuronal differentiation in such a case setting. In addition, to the best of our knowledge this is the youngest patient till date to present with this entity.

Intramedullary Spinal Cord Ganglioglioma Presenting as Hyperhidrosis: A Rare Case Report and Literature Review.

BACKGROUND: Hyperhidrosis is caused by sympathetic dysfunction of the central or peripheral nervous system. However, intramedullary spinal cord tumors presenting with hyperhidrosis as an initial symptom have been rarely reported in the literature. CASE DESCRIPTION: This case involves an 18-year-old man who presented with abnormal enhanced sweating and flushing on the bilateral side of his face and neck that had persisted for 6 years. Magnetic resonance (MR) images revealed that at the C7-T2 levels of the spinal cord, a large intramedullary tumor was involved in the cervicothoracic region. The patient underwent gross total resection of the tumor via the fluorescein-guided technique and intraoperative neurophysiologic monitoring. The histopathologic diagnosis revealed ganglioglioma. The symptoms gradually improved after surgery, and the patient presented with virtually complete remission at the end of an 18-month follow-up. CONCLUSIONS: Few cases of intramedullary spinal cord tumors presenting as hyperhidrosis in clinical manifestation have been reported in the literature. Sympathetic irritation by the tumor, particularly in the location around the gray matter of the lateral spinal cord, may account for the hyperhidrosis as the initial symptom in this patient. Therefore, if a patient has autonomic dysfunction, the spine cord should be additionally examined using MR imaging.