Intracranial ganglioglioma

Intracranial ganglioglioma

Children and young patients are usually affected, and no gender predominance is recognised. It accounts for around 2% (from 0.4-3.8%) of all primary intracranial tumors, and up to 10% of primary cerebral tumors in children.

Because of their rarity, large-scale, population-based studies focusing on epidemiology and outcomes are lacking.

Ganglioglioma is a benign slow-growing neoplasm that most frequently occurs at the supratentorial region. Nevertheless, there are occasional reports of ganglioglioma occurring in thebrainstem and spinal cord.

see Cerebellar ganglioglioma.

see Intraventricular ganglioglioma

see Optic pathway ganglioglioma.

see Multifocal intracranial ganglioglioma

Molecular pathogenesis, risk factors for malignant progression, and their frequent association with drug-resistant focal seizures remain poorly understood. This contrasts recent progress in understanding the molecular-genetic basis and targeted treatment options in diffuse gliomas. The Neuropathology Task Force of the International League against Epilepsy examined available literature to identify common obstacles in diagnosis and research of LEAT. Analysis of 10 published tumour series from epilepsy surgery pointed to poor interrater agreement for the histopathology diagnosis. The Task Force tested this hypothesis using a web-based microscopy agreement study. In a series of 30 LEAT, 25 raters from 18 countries agreed in only 40% of cases. Highest discordance in microscopic diagnosis occurred between GG and DNT variants, when oligodendroglial-like cell patterns prevail, or ganglion cells were difficult to discriminate from pre-existing neurons. Suggesting new terminology or major histopathological criteria did not satisfactorily increase the yield of histopathology agreement in 4 consecutive trials. To this end, the Task Force applied the WHO 2016 strategy of integrating phenotype analysis with molecular-genetic data obtained from panel sequencing and 450k methylation arrays. This strategy was helpful to distinguish DNT from GG variants in all cases. The Task Force recommends, therefore, to further develop diagnostic panels for the integration of phenotype-genotype analysis in order to reliably classify the spectrum of LEAT, carefully characterize clinically meaningful entities and make better use of published literature 1).

The most common presentation is with temporal lobe epilepsy, presumably due to the temporal lobes being a favoured location.

Imaging findings mirror the various patterns of growth which these tumours may demonstrate and thus their appearance is very variable. Partially cystic mass with an enhancing mural nodule is seen in ~45% of cases. They may also simply present as a solid mass expanding the overlying gyrus. An infiltrating mass is uncommon and may reflect higher grade.

Findings are of a mass which is often non-specific. General features include:

iso- or hypodense

frequently calcified ~35%

bony remodelling or thinning can indicate the slow growing nature of the tumour

enhancement is seen in approximately 50% of cases (involving the solid non-calcified component)

Reported MR signal characteristics include:

T1 Solid component isointense to hypointense.

T1 C+ (Gd) solid component variable contrast enhancement

T2 hyperintense solid component variable signal in the cystic component depending on the amount of proteinaceous material or the presence of blood products peritumoural FLAIR/T2 oedema is distinctly uncommon

T2* (GE/SWI) calcified areas (common) will show blooming signal loss

Main differential diagnosis is that of other cortical tumours, with helpful distinguishing features including:

Dysembryoplastic neuroepithelial tumors (DNET)

contrast enhancement uncommon ‘bubbly appearance’ common

Pleomorphic xanthoastrocytoma (PXA)

contrast enhancement prominent dural tail sign is often seen

Oligodendroglioma

calcifications common

Desmoplastic infantile astrocytoma and ganglioglioma

young children dural involvement prominent large often multiple lesions

If in the spinal cord consider:

astrocytoma

ependymoma

The aim of a study was to evaluate whether ganglioglioma (GGL), dysembryoplastic neuroepithelial tumour (DNET) and FCD (focal cortical dysplasia) are distinguishable through diffusion tensor imaging. Additionally, it was investigated whether the diffusion measures differed in the perilesional (pNAWM) and in the contralateral normal appearing white matter (cNAWM). Six GGLs, eight DNETs and seven FCDs were included in this study. Quantitative diffusion measures, that is, axial, radial and mean diffusivity and fractional anisotropy, were determined in the lesion identified on isotropic T2 or FLAIR-weighted images and in pNAWM and cNAWM, respectively. DNET differed from FCD in mean diffusivity, and GGL from FCD in radial diffusivity. Both types of glioneuronal tumours were different from pNAWM in fractional anisotropy and radial diffusivity. For identifying the tumour edges, threshold values for tumour-free tissue were investigated with receiver operating characteristic analyses: tumour could be separated from pNAWM at a threshold ≤ 0.32 (fractional anisotropy) or ≥ 0.56 (radial diffusivity) *10-3 mm2/s (area under the curve 0.995 and 0.990 respectively). While diffusion parameters of FCDs differed from cNAWM (radial diffusivity (*10-3 mm/s2): 0.74 ± 0.19 vs. 0.43 ± 0.05; corrected p-value < 0.001), the pNAWM could not be differentiated from the FCD 2).

Advances in the immunohistochemical detection of neuron-specific and neuronal-associated antigens have resulted in the discovery of neuronal elements in certain primary human brain tumors. The results have been not only to expand what neuropathologists commonly recognize as gangliogliomas, including the tumors now known as glioneurocytic tumor with neuropil rosettes and papillary ganglioneuroma, but also to expand the spectrum of tumor types to now include tumors such as central neurocytoma, dysembryoplastic neuroepithelial tumor, and desmoplastic infantile ganglioglioma.

Gangliogliomas are WHO grade I tumours most frequently found in the temporal lobes (70%) 3) 4) but do occur anywhere in the central nervous system.

In a minority of cases (5%) these tumours show aggressive behaviour and histopathologic features and are then called anaplastic gangliogliomas (WHO grade III) 5) 6)

At this stage, no criteria for WHO II gangliogliomas have been established 7).

Gangliogliomas, as their name suggests, are composed of two cell populations:

ganglion cells (large mature neuronal elements): ganglio- neoplastic glial element: -glioma primarily astrocytic, although oligodendroglial or pilocytic astroctytoma components are also enountered 9 The proportion of each component varies widely, and it is the grade of the glial component that determines biological behaviour.

Dedifferentiation into high-grade tumours does occasionally occur, and it is usually the glial component (into a GBM). Only rarely is it the neuronal component (into a neuroblastoma).

They are closely related to both gangliocytomas (which contain only the mature neural ganglion cellular component) and ganglioneurocytoma (which also have small mature neoplastic neurones).

Neuronal origin is demonstrated by positivity to neuronal markers:

Synaptophysin: positive

Neurofilament protein: positive

MAP2: positive

Chromogranin-A: positive (usually negative in normal neurones)

CD34: positive in 70-80%

The glial component may also show cytoplasmic positivity for GFAP.

Ganglioglioma and pleomorphic xanthoastrocytoma were the histologic types with the strongest association with CD34 positivity with an odds ratio of 9.2 and 10.4, respectively, compared with dysembryoplastic neuroepithelial tumors in Low-Grade Epilepsy-Associated Tumors 8).

BRAFV600 mutations are frequently found in several glioma subtypes, including pleomorphic xanthoastrocytoma (PXA) and ganglioglioma and much less commonly in glioblastoma.

Gross total resection is achieved in the majority of cases.

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 9)

In the surgical treatment of temporal lobe epilepsy with mesial temporal lobe tumor, whether to remove the hippocampus aiming for a better seizure outcome in addition to removing the tumor is a dilemma. Two pediatric cases treated successfully with tumor removal alone are presented.

The first case was an 11-year-old girl with a ganglioglioma in the left uncus, and the second case was a 9-year-old girl with a pleomorphic xanthoastrocytoma in the left parahippocampal gyrus. In both cases, the hippocampus was not invaded, merely compressed by the tumor. Tumor removal was performed under intraoperative electrocorticography (ECoG) monitoring. After tumor removal, abnormal discharges remained at the hippocampus and adjacent temporal cortices, but further surgical interventions were not performed. The seizures disappeared completely in both cases.

When we must decide whether to remove the hippocampus, the side of the lesion, the severity and chronicity of the seizures, and the presence of invasion to the hippocampus are the factors that should be considered. Abnormal discharges on ECoG at the hippocampus or adjacent cortices are one of the factors related to epileptogenicity, but it is simply a result of interictal irritation, and it is not an absolute indication for additional surgical intervention 10).

Gangliogliomas and ganglioneuromas are slow growing benign tumors.

In the largest retrospective study of adult low-grade GGs till 2020. 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 11)

Local resection is the treatment of choice and determines prognosis. In the brain, where a reasonable resection margin can be achieved, the prognosis is good, with recurrence-free survival reported to be 97% at 7.5-year follow-up 12).

In contrast, in the spinal cord where complete resection is often not possible without devastating deficits, local recurrence is very common.

Although the majority of patients have an excellent prognosis, infants and patients with brainstem tumors have worse survival rates.

Intracranial ganglioglioma case series.

Ganglioglioma case reports.


1)

Blümcke I, Coras R, Wefers AK, Capper D, Aronica E, Becker A, Honavar M, Stone TJ, Jacques TS, Miyata H, Mühlebner A, Pimentel J, Söylemezoğlu F, Thom M. Challenges in the histopathological classification of ganglioglioma and DNT: microscopic agreement studies and a preliminary genotype-phenotype analysis. Neuropathol Appl Neurobiol. 2018 Oct 16. doi: 10.1111/nan.12522. [Epub ahead of print] Review. PubMed PMID: 30326153.
2)

Rau A, Kellner E, Foit NA, Lützen N, Heiland DH, Schulze-Bonhage A, Reisert M, Kiselev VG, Prinz M, Urbach H, Mader I. Discrimination of epileptogenic lesions and perilesional white matter using diffusion tensor magnetic resonance imaging. Neuroradiol J. 2018 Nov 21:1971400918813991. doi: 10.1177/1971400918813991. [Epub ahead of print] PubMed PMID: 30461353.
3)

Rumboldt Z, Castillo M, Huang B et-al. Brain Imaging with MRI and CT. Cambridge University Press. (2012) ISBN:1139576399.
4) , 6) , 7) , 12)

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK “WHO Classification of Tumours of the Central Nervous System. 4th Edition Revised” ISBN: 9789283244929
5)

Song JY, Kim JH, Cho YH et-al. Treatment and outcomes for gangliogliomas: a single-center review of 16 patients. Brain Tumor Res Treat. 2014;2 (2): 49-55. doi:10.14791/btrt.2014.2.2.49
8)

Giulioni M, Marucci G, Cossu M, Tassi L, Bramerio M, Barba C, Buccoliero AM, Vornetti G, Zenesini C, Consales A, De Palma L, Villani F, Di Gennaro G, Vatti G, Zamponi N, Colicchio G, Marras CE. CD34 Expression in Low-Grade Epilepsy-Associated Tumors: Relationships with Clinicopathologic Features. World Neurosurg. 2018 Oct 9. pii: S1878-8750(18)32267-8. doi: 10.1016/j.wneu.2018.09.212. [Epub ahead of print] PubMed PMID: 30308344.
9) , 11)

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 Oct 27. doi: 10.1002/cam4.3577. Epub ahead of print. PMID: 33107220.
10)

Uda T, Kunihiro N, Nakajo K, Kuki I, Fukuoka M, Ohata K. Seizure freedom from temporal lobe epilepsy with mesial temporal lobe tumor by tumor removal alone without hippocampectomy despite remaining abnormal discharges on intraoperative electrocorticography: Report of two pediatric cases and reconsideration of the surgical strategy. Surg Neurol Int. 2018 Sep 10;9:181. doi: 10.4103/sni.sni_61_18. eCollection 2018. PubMed PMID: 30283714; PubMed Central PMCID: PMC6157038.

Intraventricular ganglioglioma

see also Third ventricle ganglioglioma.

Involvement of the ventricular system is rare.

Clinical features

The symptoms are intracranial hypertension or seizure. The degree of hydrocephalus is closely related to the site of tumor’s basement 1).

Outcome

The prognosis is good after total resection. The patients with GTR should be followed-up 2).

Diagnosis

The review of 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 3).

http://aws.labome.com/figure/te-651-2.png

(A) Coronal T1-weighted image and (B) Axial T2-weighted image showing a solid-cystic intraventricular lesion in the trigone of the right lateral ventricle. The solid component was isointense, and heterogeneous contrast enhancement was observed. Additionally, (C) Axial T1-weighted image showing lobulated isointense lesion in the optic chiasm.

Case series

A total of 7 cases with intraventricular ganglioglioma diagnosed by the surgical pathology examination from June 2004 to April 2011 in our center were retrospectively analyzed. The clinical data were collected from the clinical medical records, and the tumor site, size and basement of tumor were analyzed. Follow up was performed to obtain the clinical outcomes.

The 7 cases included 5 males and 2 females, with disease onset at 23.6 ± 14.9 years old. Epilepsy as the initial symptom was observed in 1 case. Reduced hearing, dizziness and weakness of both lower limbs were found in 1 case. Intracranial hypertension were detected in 5 cases, including 1 case complicating by decreased visual acuity. Tumors were located in the lateral ventricle in 5 cases, while 2 cases in the third ventricle. Hydrocephalus was observed in 5 cases, including 2 cases with severe hydrocephalus, and both underwent ventriculoperitoneal shunting. Total resection of tumors was performed in 5 cases, and 2 cases underwent gross total resection. The mean duration of follow-up was 28.7 months (8-90 months). Intracranial hypertension in all cases disappeared. Even radiotherapy post-surgery, one case with GTR relapsed 1 year later. However, the other 6 cases didn’t relapse.

Ganglioglioma in ventricular system is extremely rare, mainly with the symptoms of intracranial hypertension or seizure. The degree of hydrocephalus is closely related to the site of tumor’s basement. The prognosis is good after total resection. The patients with GTR should be followed-up 4).

Case reports

Chatrath et al., from the University of Virginia School of MedicineBethesdaMD Anderson Cancer Center Houston, 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.

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 V600Emutation. 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.

The 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 5).


Samdani et al., from the Shriners Hospital for Children, described an illustrative case of an intraventricular ganglioglioma with a prominent cystic component and enhancing mural nodule, which represents the classic radiographic appearance of gangliogliomas described in other locations. A superior parietal lobule approach offered excellent surgical access for tumor removal and the patient has remained free of neurological deficits following surgery. Regardless of location within the central nervous system, ganglioglioma should be on the differential diagnosis for any cystic mass with a mural nodule, particularly in the setting of epilepsy 6).


A patient with a ganglioglioma is presented in the previously unreported location of the anterior third ventricle at the foramen of Monro, mimicking a colloid cyst. We review all other reported cases of intraventricular ganglioglioma (n=6) to characterize this entity. Intraventricular gangliogliomas typically affect younger patients with female predominance (male:female, 2:5; median age 25 years). Symptoms occur secondary to obstruction of physiological cerebrospinal fluid circulation. Complete surgical resection with re-establishment of cerebrospinal fluid drainage is the goal of treatment 7).

References

1) , 2) , 4)

Deling L, Nan J, Yongji T, Shuqing Y, Zhixian G, Jisheng W, Liwei Z. Intraventricular ganglioglioma prognosis and hydrocephalus: the largest case series and systematic literature review. Acta Neurochir (Wien). 2013 Jul;155(7):1253-60. doi: 10.1007/s00701-013-1728-7. Epub 2013 May 3. PubMed PMID: 23640526.
3) , 5)

Chatrath A, Mastorakos P, Mehta GU, Wildeman M, Moosa S, Jane JA Jr. Ganglioglioma Arising from the Septum Pellucidum: Case Report and Review of the Literature. Pediatr Neurosurg. 2019 Jan 8:1-10. doi: 10.1159/000495043. [Epub ahead of print] PubMed PMID: 30620941.
6)

Samdani AF, Torre-Healy A, Khalessi A, McGirt M, Jallo GI, Carson B. Intraventricular ganglioglioma: a short illustrated review. Acta Neurochir (Wien). 2009 Jun;151(6):635-40. doi: 10.1007/s00701-009-0246-0. Epub 2009 Mar 17. Review. PubMed PMID: 19290468.
7)

Hauck EF, Vu L, Campbell GA, Nauta HJ. Intraventricular ganglioglioma. J Clin Neurosci. 2008 Nov;15(11):1291-3. doi: 10.1016/j.jocn.2007.09.013. Epub 2008 Oct 1. Review. PubMed PMID: 18829326.
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