Clinical experience with a rare brainstem tumor: ganglioglioma. Illustrative case

Abstract

BACKGROUND

The authors present a case of bulbar ganglioglioma. Previously, there have only been 4 cases reported in the literature of surgery on a tumor originating in the medulla.

OBSERVATIONS

A psychiatric patient presented with symptoms of intracranial hypertension. An MRI study showed a tumor near the fourth ventricle. Surgical intervention was performed, and complete resection and radiological cure were achieved.

LESSONS

Tumors of the fourth ventricle, especially fibroelastic gangliogliomas, represent a complex surgical challenge due to their eloquent location and adhesions. Complete resection requires the use of microscopy and an ultrasonic aspirator. Treatment should be individualized, prioritizing maximum and safe resection, with close follow-up, while radiotherapy remains controversial and of limited indication.

https://thejns.org/doi/10.3171/CASE25776

Although gangliogliomas represent a challenging rare group among CNS tumors, they are even more challenging when located in the brainstem due to the anatomical and functional complexity of this region. The low incidence of these tumors in the medulla, particularly in adults, clearly limits the possibility of standardizing therapeutic approaches and requires that management be individualized through a careful risk-benefit assessment on a case-by-case basis.

Given the depth and functional importance of the brainstem, complete resection is often not feasible, which compromises disease control and may negatively influence prognosis. The scarcity of robust data in the literature, coupled with the rarity of cases, as evidenced,¹ makes it difficult to formulate well-established therapeutic guidelines. In this context, the detailed description of clinical cases becomes crucial for improving knowledge about the behavior of gangliogliomas in this location, contributing to the development of more effective and evidence-based diagnostic and therapeutic strategies.

Illustrative Case

A 28-year-old White single businesswoman, born and raised in Ijuí, Rio Grande do Sul State, was referred to the High Complexity Oncology Care Center (CACON) at the Ijuí Clinical Hospital. She was under psychiatric treatment for a psychotic disorder with auditory hallucinations since 2022 and had been diagnosed with schizophrenia. She complained of a severe headache unresponsive to standard analgesics for 2 months; the condition progressed with nighttime awakenings due to the headache now being associated with vomiting. On neurological examination, she was lucid, oriented, and conscious and demonstrated gait ataxia, preserved muscle strength, and diffusely increased tendon reflexes. Confrontation testing revealed bilateral concentric visual field restriction and bilateral papilledema.

Previous examinations included a cranial CT study, which showed a solid-cystic tumor of the fourth ventricle extending through the right foramen of Luschka, associated with obstructive hydrocephalus, and a cranial MRI study (Fig. 1A and B). That latter showed a solid-cystic expansive lesion with heterogeneous contrast enhancement, inside the fourth ventricle, extending to the right foramen of Luschka and caudally to the upper spinal canal, with compression and displacement of the medulla and pons ventrally. The 47 × 43 × 38–mm tumor was associated with obstructive hydrocephalus and showed signs of intracranial hypertension.

FIG. 1.

A: Preoperative axial contrast-enhanced cranial MR image showing evidence of a solid-cystic expansive lesion with heterogeneous contrast enhancement, inside the fourth ventricle, extending to the right foramen of Luschka and caudally to the upper spinal canal, with compression and displacement of the medulla and pons ventrally. B: Preoperative sagittal T2-weighted propeller MR image of the skull showing signs of obstructive hydrocephalus.

Operative Procedure

The patient was evaluated by a neurosurgeon who initially suspected an ependymoma or medulloblastoma. After preoperative evaluation, the patient was referred for surgery.

We opted for a semisitting position, with a midline suboccipital craniotomy, using the telovelar approach. Intraoperative external ventricular drainage was also performed to enhance postoperative safety. During the procedure, the lesion did not present the features typically found in the fourth ventricle. Instead, we found a different tumor with fibroelastic consistency that was difficult to detach from the posterior inferior cerebellar arteries and extensively adhered to the floor of the fourth ventricle, confirming the actual exophytic origin of the bulb. It was necessary to use an ultrasonic aspirator to successfully resect the entire neoplasm while preserving the critical structures of the topography.

During the postoperative period, she developed several pulmonary infection complications and cranial nerve motor deficits, which prolonged her stay in the intensive care unit. Postoperative neurological examination revealed spastic tetraparesis, bilateral facial paralysis (7th cranial nerve), bilateral horizontal gaze palsy (6th cranial nerve), oropharyngeal hypoesthesia (9th cranial nerve), inhibited cough reflex (10th cranial nerve), and tongue hypotonia (12th cranial nerve).

After anatomopathological and immunohistochemical evaluation, the diagnosis of a WHO grade 1 ganglioglioma was confirmed. After a long hospital stay, the patient was discharged with subtotal recovery of neurological deficits and continues intensive physical and speech therapy rehabilitation and follow-up in the neurosurgery department of CACON at the Ijuí Clinical Hospital.

This case is noteworthy because of the intraoperative complexity associated with the resection of a bulbar ganglioglioma, which, even when exophytic, presents challenges in preserving structures because of its hardened consistency, which does not allow for easy removal. It is a rare lesion with a prolonged and laborious postoperative period but with a surgical cure as the outcome.

Informed Consent

In this case, emergency surgery was performed on the patient.

Discussion

Observations

As a rare neuroepithelial tumor, ganglioglioma accounts for about 1%–2% of all CNS tumors. However, when we study its occurrence in the brainstem, we are dealing with something even rarer and little discussed in the literature. A systematic review identified only 142 cases over 5 decades.² Most cases of gangliogliomas occur in children, adolescents, and young adults, with peak incidence between the ages of 10 and 30 years.³

Based on surveys and studies conducted, only 1 case was reported and published in 2025.⁴ The case involved a 23-year-old man with a tumor located in the foramen of Luschka, who presented with photopsia. A biopsy and total resection were performed, with normal clinical evolution, and control of the lesion was maintained for up to 15 months. This reinforces the extreme rarity of infratentorial neoplasms, in line with previous reports of isolated cases in adults.

Brainstem location, especially in structures such as the medulla, poses significant clinical challenges due to the high density of cranial nerve nuclei and motor and sensory pathways involved. The most common symptoms include diplopia, dysarthria, dysmetria, paresis, ataxia, and, in some cases, signs of raised intracranial pressure secondary to CSF obstruction.

Some authors have reported that, up to the year of publication, “a review of the literature revealed only 13 other reported cases.”⁵ Another study found that, up to 2001, only 31 cases of brainstem ganglioglioma and 3 new cases of brainstem ganglion cell tumor had been reported.⁶

Therefore, based on a review of all available reports, by 2025 there were 4 well-documented cases in the literature that explicitly identified the origin of the brain tumor in the medulla, including clear anatomical or histological evidence confirming the medullary location. These include an original report of a bulb case in an adult,⁷ a pediatric case report that reviewed previous cases with explicit bulbar origin,⁸ a case report of an anaplastic WHO grade III tumor originating in the medulla,⁹ and a report of an exophytic tumor of the medulla oblongata.⁴

The lack of a consolidated number of cases reinforces the extreme rarity of this tumor location and highlights the importance of new documentation and studies of isolated case reports to expand scientific knowledge and contribute to better diagnostic practices.

The present case illustrates the difficulty in making an initial diagnosis, since there was a possibility of ependymoma or medulloblastoma, both of which are more common tumors in this location and age group. In other words, in line with the literature, it has been proven that a proper diagnosis must, in most cases, be made by histopathological and immunohistochemical examination, given the radiological similarity with other lesions.

Immediately after tumor resection, the sample was sent for histological and immunohistochemical evaluation, which revealed morphological findings and an immunophenotype compatible with ganglioglioma. The collected material was analyzed using microscopy (Fig. 2A and B).

FIG. 2.

A and B: Atypical ganglion cell with binucleation, cytomegaly, and peripheral accumulation of Nissl substance. Eosinophilic granular bodies are also observed. H&E, original magnification ×40.

Histologically, ganglioglioma is characterized by the presence of a biphasic proliferation composed of neoplastic glial cells and dysplastic or neoplastic neuronal cells. Neuronal cells have aberrant morphology, including dysmorphic nuclei, occasional binucleation, and voluminous cytoplasm with evident Nissl bodies (Fig. 2A). The glial component is usually astrocytic, exhibiting varying degrees of nuclear atypia and, in some cases, areas with oligodendroglial features. The tumor stroma may show microvascular changes, focal deposition of hyaline material, and perivascular lymphocytic infiltrate (Fig. 3A and B). Eosinophilic cytoplasmic inclusions and Rosenthal fibers may be observed (Fig. 3B), especially in long-standing tumors.

FIG. 3.

A: Presence of eosinophilic granular bodies (arrow). H&E, original magnification ×40. B: Prominent and tortuous vascularization. Masson’s trichrome, original magnification ×10.

The immunohistochemical profile demonstrates dysplastic ganglion cells expressing neuronal markers such as MAP2, neurofilament, and synaptophysin. The neoplastic glial component shows positivity for glial fibrillary acidic protein (GFAP) (Fig. 4A and B) and Olig2. CD34 expression is frequently observed, either diffuse or in an arboriform pattern, both within the tumor and in the adjacent cortex. The Ki-67 proliferative index is typically low, generally < 5%. A BRAF V600E mutation can be detected using a specific antibody and is commonly positive in dysplastic ganglion cells.

FIG. 4.

A and B: Based on the evaluation performed, the immunohistochemical reaction of GFAP was confirmed, demonstrating biphenotypic cell proliferation with neurofibrillary components and atypical neuroglial elements. The neuronal component presents dysmorphic ganglion cells (arrow) with cytomegaly, binucleation, and aggregate formation. Original magnification ×50.

Although gangliogliomas generally follow an indolent course, their location in the brainstem significantly complicates the patient’s prognosis. In such cases, even though the morbidity associated with surgery is higher and the feasibility of complete resection is often limited, with a negative impact on local disease control,¹¹ the decision is often made to proceed with total resection. In our case, although the conditions for performing surgery were challenging, it was possible to proceed with a median suboccipital approach via the telovelar route. In fact, the intraoperative description of a fibroelastic exophytic tumor arising from the medulla, without the usual pattern of ependymomas, suggests that the anatomical aspect could justify the high postoperative morbidity. This was observed in our patient, who developed spastic tetraparesis and multiple cranial nerve palsies. These findings underscore the considerable complexity of surgical manipulation within the brainstem.

In partially resected or unresectable lesions, especially in the brainstem, conformal or intensity-modulated radiotherapy (RT) may be considered, particularly in cases of tumor progression or radiological growth during follow-up.12 Chemotherapy, on the other hand, has no established role in the treatment of these tumors, except in exceptional situations or in cases of malignant transformation.

In this regard, it is understood that the role of RT is highly controversial, and it is unclear whether postoperative RT influences the prognosis of patients with ganglioglioma. Furthermore, because of the potential for radiation-related morbidity in survivors, many physicians hesitate to administer RT, suggesting uncertainties and concerns about the feasibility of the procedure, which is particularly worrying in patients who are often younger than 30 years of age.13

It is worth emphasizing that, in cases of subtotal resection, there are contraindications for RT, such as patients who previously underwent RT not experiencing regression, which indicates a poor response to treatment. Another factor that needs to be considered is that complications related to RT, such as radionecrosis and the risk of malignant transformation, may become future problems.14

The case also underscores the importance of ongoing multidisciplinary monitoring and treatment, including intensive motor and speech therapy rehabilitation, in addition to outpatient neurosurgical monitoring and imaging control.15 The partial recovery of deficits reinforces the fundamental role of early and prolonged rehabilitation, especially after involvement of the bulbar cranial nerves and central motor pathways.

Given the importance of closely monitoring neuro-oncology patients, we referred our patient to specialized rehabilitation services with intensive physical and speech therapy, which resulted in partial recovery of deficits, improvement in assisted walking, and partial functional recovery of the cranial nerves. Four months after surgery, the patient underwent a follow-up examination and no tumor progression was seen (Fig. 5).

FIG. 5.

A: Axial contrast-enhanced cranial MR image showing that there is no impregnating lesion (radiological cure). B: Sagittal T2-weighted propeller cranial MR image showing that there is no residual compression of the brainstem and the absence of hydrocephalus.

She is currently undergoing neurosurgical monitoring and physical and speech therapy rehabilitation and remains in good condition with positive prospects for full recovery.

Lessons

Tumors that originate in or extend to the fourth ventricle, whether intraventricular or exophytic, represent a complex surgical challenge due to their eloquent location. In addition to the usual anatomical limitations, fibroelastic and adherent gangliogliomas require careful surgical management to preserve neurological function. The use of ultrasonic aspirators and microscopy techniques is essential to achieve safe and effective resection, which can minimize morbidity.

When dealing with a lesion in the region of the fourth ventricle with radiological features suggestive of an ependymoma or medulloblastoma, the classic recommendation is total resection. In cases involving eloquent structures of the brainstem, though, subtotal resection may be justified to avoid neurological deficits.

However, when resecting a lesion with uncertain behavior, we can consider three options for dealing with residual tumor: follow-up, reoperation, and RT. We can pursue follow-up if we expect that the lesion will not grow; however, if it does grow, resecting it will be challenging, as it is more difficult to separate the planes during reoperation and the lesion may become more adherent to adjacent structures. In gangliogliomas, the benefit of RT in cases of postoperative subtotal resection is uncertain, with limited evidence of efficacy. However, RT may have a limited role in situations of documented tumor progression, usually after further resection. Potential adverse effects, particularly radionecrosis and malignant transformation, which are especially relevant in patients younger than 30 years of age, should be considered. Management should be individualized, prioritizing maximum and safe resection.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: de Almeida, FY Castro, LY Castro. Acquisition of data: de Almeida, FY Castro. Analysis and interpretation of data: LY Castro. Drafting the article: de Almeida, FY Castro. Critically revising the article: de Almeida, FY Castro, LY Castro. Reviewed submitted version of manuscript: de Almeida, FY Castro. Approved the final version of the manuscript on behalf of all authors: de Almeida. Study supervision: FY Castro, LY Castro. Supportive analyses (pathological analysis, imaging study, and immunohistochemistry): Ferri.

Correspondence

Rafael de Almeida: Regional University of Northwestern Rio Grande do Sul, Rio Grande do Sul, Brazil. rafael.da@sou.unijui.edu.br.