Intraoperative diagnosis of myxoid glioneuronal tumor guiding safe limited resection: a case report

Abstract

Myxoid glioneuronal tumor (MGT) is a newly delineated CNS WHO grade 1 neoplasm genetically characterized by PDGFRA p.K385L/I mutation. We describe a 14-year-old boy presenting with gelastic seizures caused by an intraventricular MGT. Intraoperative frozen section allowed minimal resection, preserving surrounding eloquent structures. Histology showed oligodendrocyte-like cells within myxoid stroma and scattered floating neurons, while molecular analysis revealed the canonical PDGFRA p.K385L mutation. At 13-month follow-up, the residual tumor remained stable without any further neurological dysfunction. This case highlights the importance of intraoperative diagnosis for surgical safety in MGT.

Introduction

Myxoid glioneuronal tumor (MGT) is a newly recognized entity in the 2021 WHO Classification of the Central Nervous System (CNS). MGT typically arises in the septum pellucidum, septal nuclei, subcallosal area, corpus callosum, and lateral ventricles [1, 2]. MGT is genetically defined by a dinucleotide mutation at codon 385 of the platelet-derived growth factor receptor alpha (PDGFRA), resulting in the substitution of lysine with either leucine or isoleucine (p.K385L/I). Although MGT is classified as a CNS WHO grade 1 rare benign tumor, some cases have shown recurrence requiring chemoradiotherapy [2]. Surgical complications, such as fornix injury leading to memory deficits, have also been reported [3]. Thus, accumulation of further cases is essential to better understand its clinicopathological characteristics and establish treatment strategies for MGT. Here, we report a case in which intraoperative frozen section enabled a rapid and accurate diagnosis of MGT, which allowed us to limit the extent of resection and avoid injury to surrounding eloquent structures. This case underscores the clinical importance of intraoperative diagnosis in guiding safe surgical management of MGT.

Case presentation

A 14-year-old Japanese boy presented with sudden-onset paroxysmal laughing 1 week prior to admission. On arrival at our hospital, the patient exhibited disorientation, headache, vomiting, and jerking bursts of laughter, consistent with gelastic seizures. Brain magnetic resonance (MR) imaging revealed a solid and cystic mass from the third ventricle into both lateral ventricles. The lesion appeared hypointense on T1-weighted and hyperintense on T2/FLAIR sequences, without gadolinium enhancement. The mass obstructed the foramen of Monro, resulting in hydrocephalus (Fig. 1a–d, g). Initial differential diagnoses included central neurocytoma, subependymoma, glioma, and hypothalamic hamartoma (HH). To relieve intracranial hypertension, an external ventricular drain (EVD) was placed immediately after admission, resulting in improvement of headache and vomiting. Gelastic seizures were suppressed with lacosamide (200 mg/day). Following stabilization, tumor resection and histopathological diagnosis were planned.

Fig. 1.

Integrated radiological findings and treatment courses of MGT. Preoperative T1-weighted (a) and T2-weighted (b) images demonstrate a solid tumor with cystic components occupying the third ventricle. Contrast-enhanced T1-weighted (c) image shows poor Gd enhancement. FLAIR images of preoperative (d, g), postoperative day 11 (e, h) and 13 months after the surgery (f, i) are shown. The route of cerebrospinal fluid flow is patent throughout the postoperative courses (arrow: the foramen of Monro; arrowhead: the fenestration of the septum pellucidum) and no recurrence of tumor and hydrocephalus is observed

A right frontal craniotomy was performed. After dural opening, the right lateral ventricle was approached via the interhemispheric fissure with a 2-cm callosotomy. Prior to tumor resection, a septostomy was immediately performed to establish communication between the left and right ventricles. The tumor appeared white, gelatinous, and partially suckable. Intraoperative frozen section with hematoxylin and eosin (HE) staining demonstrated clusters of oligodendrocyte-like round cells within a myxoid matrix, with scattered large neuron-like cells and few proliferative elements (Fig. 2a). These findings suggested a low-grade glioneuronal tumor, most consistent with MGT. Based on its benign nature, only a minimal resection was performed to restore cerebrospinal fluid communication between the right lateral and third ventricles, thereby avoiding injury to the fornix and hypothalamus. No manipulation was performed around the left foramen of Monro.

Fig. 2.

Histopathological findings of MGT. Intraoperative rapid HE images are shown (a). OLC is indicated by an arrowhead and the floating neuron is indicated by an arrow. Permanent HE staining (b). OLC is indicated by an arrowhead and the floating neuron is indicated by an arrow. Alcian blue staining (c). Results of immunohistochemistry for Olig2 (d), GFAP (e), and NeuN (f) are displayed. Snapshot from the IGV visualizing the result of next-generation sequencing identifying PDGFRA p.K385L mutation in the tumor (g). The upper panel shows the tumor specimen, and the lower panel shows the matched blood sample. Tumor specimen showing a dinucleotide substitution at c.1153_1154 (delinsTT), corresponding to the hotspot mutation p.K385L. In contrast, the blood sample displays a wild-type sequence at the same position, confirming the somatic origin of the mutation. Reference transcript: NM_006206

Permanent HE staining confirmed the intraoperative diagnosis, revealing diffuse oligodendrocyte-like cells (OLCs) within a myxoid stroma, scattered “floating neurons,” and absence of microvascular proliferation or necrosis (Fig. 2b). Alcian blue staining highlighted the myxoid stroma (Fig. 2c). Immunohistochemistry showed Olig2 positivity in 90% of tumor cells (Fig. 2d). GFAP-positive cells indicated glial differentiation (Fig. 2e), while scattered NeuN-positive large cells were observed (Fig. 2f). Those components were negative for EMA and p53. The Ki-67 labeling index was 3%. A next-generation sequencing platform as visualized in the Integrative Genomics Viewer (IGV) revealed a dinucleotide substitution in PDGFRA at codon 385 (p.K385L) with an allele frequency of 47.9% (Fig. 2g). The final diagnosis was MGT, PDGFRA p.K385L-mutant, CNS WHO grade 1.

Postoperative MR imaging confirmed restoration of cerebrospinal fluid flow between the lateral and the third ventricle. Although the bulk of the tumor remained, no progression was observed over 13 months of follow-up (Fig. 1d–i). The patient returned to school within 1 month after the surgery, with no cognitive deficits.

Discussion

MGT was originally described by Baisden et al. and other groups as dysembryoplastic neuroepithelial tumors (DNTs) of the septum pellucidum. These atypical DNTs lacked BRAF and FGFR1 mutations that genetically characterize DNT [1, 4, 5, 6]. MGT was formally defined in the 2021 WHO Classification as a CNS WHO grade 1 neoplasm [1, 7]. Histologically, MGT is characterized by OLCs and floating neurons within abundant myxoid stroma. OLCs are typically positive for Olig2 and GFAP, while floating neurons express NeuN and neurofilament. The Ki-67 labeling index is generally low (< 1%–3%). MGT is genetically characterized by a hotspot mutation in PDGFRA codon 385 (p.K385L/I) [2, 8]. The main histological differentials include DNT and rosette-forming glioneuronal tumor; genetic testing for PDGFRA mutation is useful for definitive diagnosis [8].

Seizures and headaches are the most common clinical presentations of MGT [9]. To our knowledge, this is the first reported case of MGT presenting with gelastic seizures. This seizure type is classically associated with HH, which is intrinsically epileptogenic due to abnormal networks of small GABAergic interneuron-like and large glutamatergic projection-like neurons [10]. Given that MGT also contains neuronal and glial components, MGT may similarly form aberrant neuronal circuits that underlie gelastic seizures. Further subtyping of neuronal populations in MGT could help clarify its epileptogenic potential.

Although MGT is histologically benign, it often arises adjacent to eloquent structures, particularly in the third ventricle. Surgery for third ventricular lesions carries specific risks because of the proximity of the fornix, anterior thalamic nuclei, thalamocortical fibers, deep venous structures, and pericallosal arterial branches. The fornix, a C-shaped tract of the Papez circuit from the hippocampus critical for episodic memory, is particularly vulnerable [3]. Fornix injury can cause profound amnesia, and previous reports have described long-standing memory dysfunction following subtotal intraventricular resection of MGT [3]. Venous infarction, arterial injury, and postoperative cerebrospinal fluid disturbance are additional risks associated with manipulation of the third ventricle, even when endoscopic techniques are used, and may result in further neurological morbidity [11]. Therefore, even when a tumor is soft and partially suckable, the extent of resection should be determined not only by its texture but also its attachment, invasiveness, vascularity, and relationship to critical neurovascular structures. In our case, intraoperative frozen section enabled early recognition of MGT, which allowed us to restrict resection and prevent neurological deficits. At 13-month follow-up, the residual tumor has remained stable without recurrence, supporting the feasibility of limited resection when intraoperative diagnosis is available. Recent diagnostic advances using nanopore sequencing have enabled the intraoperative evaluation of molecular features, including DNA methylation profiles and selected tumor-defining genetic alterations [12, 13 ]. This novel approach may support surgical decision-making when the extent of resection must be balanced against neurological risk. Although intraoperative sequencing was not performed in the present case, such approaches may further strengthen intraoperative diagnosis for rare tumors such as MGT.

The extent of tumor resection varies across reported cases. In a series by Lucas et al., three of eight patients experienced recurrence after gross-total or subtotal resection and required additional therapy, while others underwent biopsy followed by irradiation or chemotherapy; all patients were alive with stable disease [2]. These findings indicate that MGT generally follows a benign course. However, MGT can progress to exhibit leptomeningeal or intraventricular dissemination [14]. The disseminating MGT showed MSX1 transcriptomic elevation and the activation of the MAPK, PI3K/AKT/mTOR, MYC, and RAS pathways as well as multiple metabolic pathways including translation, oxidative phosphorylation, and cell cycle pathways [14]. Therefore, assessing metabolic pathways using epigenetic and transcriptional profiling may help characterize the biological diversity among MGT cases.

Conclusion

This case highlights the importance of intraoperative diagnosis of MGT for minimal resection to avoid neurological complications. The extent of tumor resection should be determined not only by tumor malignancy, but also by its texture, vascularity, attachment, and relationship to eloquent structures. While our patient remains recurrence-free 13 months after the surgery, longer follow-up is required to clarify the prognostic significance of MGT.

Abbreviations

CNS

Central nervous system

Delins

Deletion-insertion

DNT

Dysembryoplastic neuroepithelial tumor

EVD

External ventricular drain

FLAIR

Fluid-attenuated inversion recovery

HE

Hematoxylin and eosin

HH

Hypothalamic hamartoma

IGV

Integrated Genome Viewer

MGT

Myxoid glioneuronal tumor

MR

Magnetic resonance

OLC

Oligodendrocyte-like cell

PDGFRA

Platelet-derived growth factor receptor alpha

WHO

World Health Organization

Author contributions

All authors contributed to the treatment of this patient. Material preparation and data collection were performed by K. Morita, Y. Nakashima, A. Nishiyama, and H. Fujisawa. Histopathological data were prepared by N. Kurose and A. Kawashima. The first draft of the manuscript was written by K. Morita. All authors read and approved the final manuscript.

Funding

Open Access funding provided by Kanazawa University. This research received funding from Japan Society for the Promotion of Science; Grant ID 25K23839.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Kanazawa Medical Center and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent to participate

Written informed consent was obtained from the patient.

Consent for publication

The participant has consented to the submission of the case report to the journal.

Conflict of interest

The authors declare no competing interests.