Abstract
Myxoid glioneuronal tumor is a newly included entity in the 2021 World Health Organization classification of central nervous system tumors, based on both pathological and molecular evidence, characterized by platelet-derived growth factor receptor alpha mutations. A 23-year-old female presented with intermittent visual field abnormalities and dizziness. Magnetic resonance imaging revealed a 2-cm mass occupying both foramens of Monro, leading to non-communicating hydrocephalus. Endoscopic surgery via the transcortical approach achieved gross total resection of the tumor. Postoperatively, she developed cognitive dysfunction involving recent memory disturbance and progressive ventricular dilation, necessitating a ventriculoperitoneal shunt, which led to significant cognitive recovery. Histopathological analysis confirmed myxoid glioneuronal tumor with a platelet-derived growth factor receptor alpha p.K385L mutation. A review of 23 cases, including ours, indicates that surgical resection is the preferred treatment and is generally associated with a favorable prognosis. However, recurrence and meningeal dissemination have been reported in some cases, emphasizing the need for long-term follow-up. Myxoid glioneuronal tumor is frequently located close to critical structures like the fornix, so careful surgical planning is essential to balance maximal resection with functional preservation. Endoscopic techniques offer advantages for deep-seated lesions by minimizing cortical damage while allowing adequate tumor resection. Further studies are needed to establish the optimal treatment strategies and clarify the long-term prognosis of myxoid glioneuronal tumor.
Introduction
Myxoid glioneuronal tumor (MGNT) is a rare neoplasm that was recently included in the 2021 World Health Organization (WHO) classification of central nervous system tumors. MGNT is characterized by oligodendrocyte-like cells, a mucinous matrix, and platelet-derived growth factor receptor alpha (PDGFRA) mutations. MGNT most commonly arises in the septum pellucidum and ventricular walls, often resulting in hydrocephalus due to obstruction of cerebrospinal fluid (CSF) pathways.1) Some cases previously diagnosed as different tumor types have been retrospectively reclassified as MGNT, but data about long-term outcomes remain limited.2)
The present case of MGNT was located around the foramen of Monro and was surgically treated via an endoscopic transcortical approach. The postoperative course, including transient cognitive dysfunction and hydrocephalus, and a literature review, are discussed.
Case Report
Case
Female, 23 years old, postgraduate student in a pharmaceutical college.
Chief complaint
Intermittent visual field abnormalities.
Past medical history and family history
No significant findings.
Present medical history
Approximately one month prior to her first visit to our hospital, she had noticed intermittent blurring of her visual field, lightheadedness, and dizziness when walking. She visited a local ophthalmologist, but no abnormalities were found.
On admission
Clear consciousness, no obvious visual acuity or visual field abnormalities on ophthalmic examination, and no other obvious neurological findings. Hasegawa's Dementia Scale score was 30, Mini-Mental State Examination 30 points.
Radiographical findings
Magnetic resonance imaging (MRI) showed a mass lesion of approximately 2 cm in diameter appearing hypointense on T1-weighted imaging (T1WI) (Fig. 1A), hyperintense on T2-weighted imaging (T2WI) (Fig. 1B), and isointense on fluid-attenuated inversion recovery (FLAIR) imaging (Fig. 1C), with facilitated diffusion on diffusion-weighted imaging. Gadolinium-enhanced MRI showed no contrast enhancement (Fig. 1D). The mass occupied both foramina of Monro, and the bilateral lateral ventricles were dilated (Evans index 0.42).
Preoperative diagnosis and plan
The preoperative differential diagnosis included subependymoma, central neurocytoma, colloid cyst, and low-grade glioma. The diagnosis was non-communicating hydrocephalus due to a mass lesion causing obstruction of CSF flow through the foramen of Monro, despite the absence of evidence of increased intracranial pressure. Endoscopic resection of the mass lesion was planned to resolve the hydrocephalus and obtain the pathological diagnosis.
Operative findings
A bicoronal skin incision was made, and a 45 × 45 mm box craniotomy was performed in the right frontal region under general anesthesia. A ViewSite Brain Access System (Vycor Medical Inc., Boca Raton, FL, USA; 28 mm× 20 mm× 5 cm depth) was inserted into the anterior horn of the right lateral ventricle so that the transcortical approach could be taken through the right frontal lobe. The tumor was embedded in the right foramen of Monro in the anterior half of the third ventricle. The tumor surface was soft, greyish-white, and poorly hemorrhagic, but the border with the fornix was unclear from the anterior to medial areas and could not be safely dissected (Fig. 1E). After cutting the right septal vein, the posterior border of the tumor in the third ventricle was separated via the transchoroidal approach. After cutting through the septum pellucidum, the border between the tumor and the fornix was confirmed but remained too indistinct to be safely dissected (Fig. 1F). Therefore, the tumor was removed together with the adhered septum pellucidum using an ultrasonic aspirator, leaving only a small portion of the white structure thought to form the fornix.
Pathological findings
Proliferation of oligodendrocyte-like cells with small round nuclei and mucopurulent interstitium was observed (Fig. 2A and B). Some cells exhibited neuron-like differentiation (Fig. 2C). No obvious signs of mitosis in the tumor cells, and no microvascular proliferation or necrosis were observed. Immunohistochemically, the tumor cells were positive for oligodendrocyte transcription factor 2 (Fig. 2D), glial fibrillary acidic protein (Fig. 2E), SOX10, and S-100 protein (Fig. 2F). The neuron-like cells were positive for neurofilament and neuronal nuclear antigen (NeuN) (Fig. 2G). The tumor cells were negative for the R132H mutation in isocitrate dehydrogenase 1 (IDH1) (Fig. 2H), p53, epithelial membrane antigen, and CD99 (MIC2), with a Ki-67 labeling index of 6.9%.
Genetic analysis revealed a p.K385L mutation (c.AAG>TTG) in the PDGFRA gene and wild-type IDH1 and IDH2 (Fig. 2I).
Postoperative course
Postoperative MRI confirmed that the tumor had been completely removed. Despite resolution of the obstructed CSF pathway, the ventricle gradually continued to enlarge. She developed cognitive dysfunction, mainly in the form of memory impairment, but whether this was due to secondary hydrocephalus or fornix injury was unclear at that time. A ventriculoperitoneal shunt was performed on the 23rd day after tumor resection, after which her cognitive function remarkably improved. She scored 17 out of 24 on the Rivermead Behavioural Memory Test, indicating mild memory impairment on the 39th day after tumor resection, but this had completely improved 6 months later (Fig. 3). She was able to continue her research as a postgraduate student. No recurrence has been found up to 18 months after surgery.
Discussion
Definition and review of MGNT
MGNT is a new tumor entity first included in the WHO classification in 2021. Molecular studies of various tumors that are morphologically similar to dysembryoplastic neuroepithelial tumors (DNETs) and rosette-forming glioneuronal tumors (RGNTs) occurring in the septum pellucidum and lateral ventricles discovered PDGFRA gene mutations not found in other central nervous system tumors, leading to the proposal of MGNT as a distinct tumor group.1,2)
MGNT is rare, so no comprehensive summary has been published regarding the long-term prognosis of cases diagnosed after inclusion in the 2021 WHO classification. However, some cases previously diagnosed as DNET or RGNT have been retrospectively reclassified as MGNT based on molecular studies.2) Recent studies have clarified the distinct histopathological and molecular profiles that differentiate MGNT from other glioneuronal neoplasms such as DNET and RGNT.1,3-10) Histologically, MGNT is characterized by a diffuse growth pattern with uniform oligodendrocyte-like cells embedded in a prominent myxoid matrix, lacking the multinodular architecture typical of DNET1,4) and the biphasic glial-neuronal organization seen in RGNT.5) From a molecular perspective, MGNT shows a highly recurrent PDGFRA p.K385L/I mutation, which is not found in DNET or RGNT.4,6) In contrast, DNET is frequently associated with fibroblast growth factor receptor 1 (FGFR1) alterations, including internal tandem duplications or point mutations,7,8) while RGNT typically harbors co-occurring FGFR1 and PIK3CA mutations.9,10) These findings support MGNT as a distinct molecularly defined entity within the spectrum of glioneuronal tumors. A PubMed search for "myxoid glioneuronal tumor" identified 8 descriptions of 23 cases diagnosed as MGNT through molecular studies.1,2,11-16) Table 1 summarizes a total of 24 cases, including the present case. The median age at diagnosis was 19 years, with many patients in early adulthood, and no significant sex difference (9 males, 15 females). The most common tumor location was intraventricular (13 cases, 54%), involving the septum pellucidum (9 cases, 38%), followed by the white matter of the lateral ventricle (6 cases, 25%), the corpus callosum (3 cases, 13%), and the parenchyma of the midbrain and temporal lobe.
Table 1
Summary of 24 Reported Cases of Myxoid Glioneuronal Tumor, Platelet-Derived Growth Factor Receptor Alpha p.K385 L-Mutant, Including the Present Case
| CCNU: 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea; FLAIR: fluid-attenuated inversion recovery; IQR: interquartile range |
| Age, median (IQR), yrs |
19 (9-29) |
| Sex |
|
| male |
9 (38%) |
| female |
15 (63%) |
| Initial symptoms |
|
| headaches |
9 (38%) |
| seizures |
6 (25%) |
| none (incidental) |
4 (17%) |
| cognitive impairment |
3 (13%) |
| visual impairment |
2 (8%) |
| ataxia |
1 |
| Locations |
|
| intraventricular |
13 (54%) |
| involving the septum pellucidum |
9 (38%) |
| periventricular white matter of the lateral ventricle |
6 (25%) |
| corpus callosum |
3 (13%) |
| temporal lobe |
1 |
| midbrain |
1 |
| Magnetic resonance imaging findings |
|
| hypointense on T1-weighted imaging |
22 (100%) |
| hyperintense on T2-weighted imaging |
23 (100%) |
| hyperintense on FLAIR imaging |
18 (95%) |
| facilitation on diffusion-weighted imaging |
14 (100%) |
| contrast enhancement |
1 (4%) |
| Extent of tumor removal |
|
| gross total removal |
15 (63%) |
| subtotal removal |
5 (21%) |
| biopsy |
3 (13%) |
| Ki-67 labeling index |
|
| ≥6% |
1 (6%, ours) |
| 4%-5% |
2 (12%) |
| ≤3% |
14 (82%) |
| Additional treatment |
|
| radiation + chemotherapy |
1 |
| stereotactic laser interstitial thermal therapy |
1 |
| Follow-up time, median (IQR), yrs |
1.2 (0.9-4.0) |
| Recurrence |
3 (13%) |
| Additional treatment for recurrence |
|
| surgical removal |
2 |
| temozolomide, CCNU + radiation |
1 |
| Ventricular disseminations |
4 (17%) |
| at initial diagnoses |
3 (13%) |
| postoperative |
1 |
| Clinical outcomes |
|
| alive without a deficit |
21 (100%) |
| complications |
2 (10%) |
| memory disturbances |
2 (10%) |
| permanent |
1 |
| transient |
1 (ours) |
Most MGNT lesions appear as hypointensity on T1WI and hyperintensity on T2WI, iso-to-hyperintensity on FLAIR imaging, and show facilitated diffusion on diffusion-weighted imaging.1,2,11,12) Since only T1WI and T2WI primarily show cyst-like signal changes, high-resolution FLAIR or heavily T2-weighted sequences such as constructive interference in steady state and fast imaging employing steady-state acquisition, which can better detect internal tissue signals, may be useful for preoperative diagnosis.17) Additionally, the bright rim sign, commonly observed in DNETs, is a characteristic imaging feature.18)
Prognoses
Surgical intervention was performed in all 24 cases with reported treatment details. Gross total resection (GTR) was achieved in 15 cases (63%), subtotal resection in 5 cases (21%), and biopsy in 3 cases (13%). Adjuvant therapy, such as radiotherapy or chemotherapy, was administered postoperatively in the 2 cases with only biopsy.1,13) Tumor recurrence was observed in 3 cases (13%), including 2 cases that had undergone GTR and 1 case with prior subtotal resection. All recurrences occurred within 1-2 years post-surgery. Two of the 3 patients underwent additional surgery, and the other received chemoradiotherapy.1) Meningeal dissemination was reported in 4 cases (17%), which was present at the time of initial diagnosis in 3 cases, and detected upon recurrence in 1 case.1,13) The overall survival rate during follow-up remains high, despite the cases of recurrence and meningeal dissemination, consistent with the characteristics of a WHO grade 1 tumor.
In the 17 previously reported cases, the Ki-67 labeling index-a marker of tumor cell proliferative potential-was assessed. Among these, one case demonstrated a rate of 5%, another 4%, and the remaining 15 cases (88%) showed values of 3% or less. Furthermore, in the 3 previously reported cases with recurrence, the Ki-67 labeling index was ≤3% in all instances (1 case at 3%, 2 cases at 3%). In the 3 cases with dissemination, the index was also ≤3% across all cases. In contrast, the present case exhibited a slightly higher value of 6.7%. Although the association between prognosis and the Ki-67 labeling index remains uncertain, this observation warrants close attention during follow-up.
MGNT predominantly affects younger patients and carries a risk of recurrence or dissemination, so maximizing the extent of tumor resection during surgery is currently recommended. However, further accumulation of clinical data and research may enable the development of more effective treatments, including molecular targeted therapies tailored to specific genetic mutations.
Endoscopic transcortical approach to remove MGNT
MGNT often originates from the septum pellucidum, ventricular walls, and corpus callosum. Surgical approaches to these regions carry the risk of higher brain dysfunction, particularly memory impairment due to damage to the fornix.14) Endoscopes are advantageous for deep-seated lesions, as they provide a panoramic view with high-resolution imaging in deep regions. MGNT frequently develops near the foramen of Monro, so lateral ventricle enlargement is present in many cases, including ours. Endoscopic surgery is particularly effective under such anatomical conditions with deep, expanded cavities.19) A recent case report described a similar procedure in which an endoscopic transcortical approach was employed for the resection of an MGNT, yielding favorable outcomes.16)
Access to the anterior horn of the lateral ventricle around the foramen of Monro or the third ventricle can be achieved with either a transcortical or transcallosal approach. These approaches show no significant difference in the rate of tumor resection, but each has a different set of complications. The transcortical approach carries risks such as postoperative seizures due to cortical damage and difficulties in navigation if ventricular enlargement is absent. The transcallosal approach is associated with complications such as venous infarction caused by lateral traction of the bilateral frontal lobes, injury to the pericallosal artery, and mutism due to traction on the cingulate gyrus.20-22)
The transcortical approach carries a higher risk of epilepsy due to frontal cortex damage, but our use of the ViewSite Brain Access System was effective in minimizing cortical injury. As a result, no episode of epilepsy was observed during the 18-month postoperative follow-up.
In the present case, the transcallosal approach, which follows a trajectory tangent to the fornix, was considered less suitable than the transcortical approach. The latter allows for a more widely extended surgical trajectory, enabling diagonal visualization to better distinguish the tumor from critical structures such as the fornix. Intraoperatively, the tumor-fornix boundary was not entirely clear, but we could sufficiently distinguish the tumor margins to achieve GTR. Postoperatively, our patient presented with transient memory disturbance, which was suspected to be caused by right fornix injury. However, hydrocephalus was also thought to be a contributing factor, and after a ventriculoperitoneal shunt placement for hydrocephalus, her cognitive function, including memory, had fully recovered within 6 months. The incidence of hydrocephalus following resection of intraventricular tumors has been reported to be approximately 13%,23) indicating that the risk of hydrocephalus may persist even after relief of the initial obstruction. Regarding the development of hydrocephalus after treatment for colloid cysts, factors such as cyst size and the presence of intraventricular hemorrhage have been identified as contributing factors. It has been hypothesized that prolonged surgical procedures may increase the risk of intraventricular hemorrhage, and that spillage of tumor contents into the ventricular system may also be associated with postoperative hydrocephalus.24) Although the present case represents the only reported instance of postoperative hydrocephalus following resection of a ventricular tumor within this tumor category, the effusion of mucin-rich tumor material into the ventricles may likewise increase the risk of hydrocephalus.
Conclusions
The present case of MGNT with a PDGFRA p.K385L mutation was successfully removed using an endoscopic transcortical approach. Although the patient developed transient postoperative cognitive dysfunction, significant recovery was achieved within 6 months. MGNT is frequently located close to critical structures such as the fornix, so surgical planning must carefully balance achieving GTR with preserving neurological function. Further experience with MGNT cases is essential to establish optimal treatment strategies and clarify the long-term outcomes.
Disclaimer
Author Kojiro Wada is one of the Editorial Board members of the Journal. This author was not involved in the peer-review or decision making process for this paper.
Conflicts of Interest Disclosure
All authors have no conflict of interest.
Consent for Publication
Consent for publication was obtained from the patient and her family.
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