Pleomorphic xanthoastrocytoma and treatment of epilepsy: a case report

Introduction

Background

Pleomorphic xanthoastrocytoma (PXA) is a rare central nervous system (CNS) tumor that accounts for less than 1% of all brain tumors. It was first named in 1979 and PXA can be grade 2 or 3 according to mitotic count, as reported in World Health Organization (WHO) blue book (1). PXA is more common in children than in young adults and does not have sex differences (2). Clinical manifestations often start with seizures, and the lesions are often located in the superficial parts of the cerebral hemisphere, especially in the temporal lobe (3-5). Head computed tomography (head CT) and magnetic resonance imaging (MRI) examinations can reveal cystic nodular, cystic, and parenchymal lesions. In recent years, the PXA cases reported in the literature have been mostly cystic or cystic nodular (5). Patients with PXA can be cured via surgical treatment, but whether the seizure can be controlled by simply removing the tumor through surgery still needs to be determined.

In this report, we report on a male pediatric patient who was subsequently diagnosed with PXA and epilepsy to gain deeper insight into the coexistence of PXA and epilepsy. We present this article in accordance with the CARE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-24-306/rc).

Case presentation

The patient is a 10-year-old male who visited our epilepsy center in January 2024 because of “recurrent episodic consciousness disorders for 5 months”. The patient presented with loss of consciousness, staring eyes, and overall immobility during seizures, followed by limb stiffness and spasms. Each episode lasted for 2–3 minutes and resolved on its own; it had occurred twice since disease onset. After the onset of the disease, the patient was diagnosed with “epilepsy”. Taking into account of body weight, treatment with 900 mg/d of oxcarbazepine was given, but the treatment had no significant effect.

A general physical examination revealed that the patient’s mental state was good, development was normal, intelligence was normal, and there were no signs of neurological abnormalities.

The patient underwent a comprehensive preoperative evaluation, including long-term video electroencephalogram (VEEG), MRI, positron emission tomography-CT (PET-CT), and neuropsychological testing. MRI scans were performed using a 3T scanner. Three-dimensional (3D) volumetric rapid fields were used to obtain echo T1-weighted images and fluid attenuated inversion recovery (FLAIR) images and any additional required sequences from the reconstruction. Fludeoxyglucose-PET (FDG-PET) was superimposed on 3D brain MRI to identify potential changes in brain metabolism.

The electroencephalogram (EEG) was monitored for a total of 16 hours, but no clinical seizures were detected. Interactive EEG revealed spike waves, slow spike waves, and superposed waves in the right anterior head area (Figure 1).

Figure 1 EEG. (A) EEG before surgery. EEG revealed spike waves, slow spike waves, and superposed waves in the right anterior head area. (B) Postoperative EEG. Slow wave changes in the surgical area. EEG, electroencephalogram.

The head MRI revealed that the solid area of the lesion in the image presented slightly longer T1 and T2 signals, with slightly higher T2 FLAIR and double inversion recovery (DIR) signals, and had empty blood vessels. The majority of the cystic area had long T1 and T2 signals with some mixed fluid components in the cyst. The T2 FLAIR showed large areas of high signal and layered changes. The lesion was pushing adjacent to the amygdala and hippocampus and adjacent to the temporal horn of the lateral ventricle and narrowed adjacent to the annulus (Figure 2A-2F).

Figure 2 Imaging examinations and pathological images of the patient. (A-C) MRI-T1 (axial, sagittal, and coronal), (D-F) MRI-T2 FLAIR (axial, sagittal, and coronal). (G-I) PET-MRI (axial, sagittal, and coronal). (J) Stereoscopic imaging of brain tissue. MRI, magnetic resonance imaging; PET, positron emission tomography; FLAIR, fluid attenuated inversion recovery.

A PET-MRI examination revealed a cystic solid mass shadow in the anterior part of the middle and lower gyri of the right temporal lobe. It also revealed local calcification of the cyst wall and an uneven increase in FDG uptake in the solid area and cyst wall. The lesion was located mainly in the anterior lower part with no FDG uptake in the cystic area. The mass was approximately 56 mm × 48 mm × 38 mm in size, irregular in shape, locally bulging forward and downward, and locally thinning adjacent to the skull. There were no clear signs of bone destruction. The solid cystic components inside the lesion were mixed, and the density was uneven (Figure 2G-2I).

After comprehensive evaluation by the epilepsy center, it was decided that the patient undergo surgery. Before surgery, we used PET-MRI fusion, 3D imaging of the brain tissue (Figure 2J), and diffusion tensor imaging (DTI) (Figure 3) to determine the possible resection range.

Figure 3 Display of the enlarged resection range of the right temporal lobe lesion on DTI. (A) DTI before surgery. (B) DTI after surgery. (C) DTI-sagittal MR image. The fusion image of DTI and sagittal MR images after surgery shows complete resection of the lesion. DTI, diffusion tensor imaging; MR, magnetic resonance.

After general anesthesia, a “U” incision approximately 5 cm × 6 cm in size was made in the right temporal region of the patient. A routine craniotomy revealed the clear structure of the local gyrus in the right temporal lobe, but the cortex of the middle temporal gyrus was slightly swollen and yellowish in color. The depth of anesthesia (sevoflurane inhalation concentration <1 Mac) should be reduced for electrocorticography (ECoG). Epilepsy discharges are located mainly around lesions in the posterior part of the temporal gyrus, with few spike waves emanating from the temporal pole. When the lesion was removed, the local tissue texture was tough, the boundary was unclear, and the blood supply was average. The lesion grew from the cortical surface to the deep part (Figure 4).

Figure 4 Monitoring of ECoG during surgical procedures. (A) The surgical area is shown to be located in the right temporal lobe. (B,C) ECoG, epilepsy discharges are located mainly around the lesion in the posterior part of the temporal gyrus, with a few spike waves emanating from the temporal pole. (D) After surgery, the lesion in the right temporal lobe had been removed. ECoG, electrocorticography.

The excised lesion area was expanded while the tumor was removed according to the preoperative plan. After strict hemostasis, the skull was closed, and surgery was complete. Routine treatments, such as anti-infection measures, elimination of edema, and prevention of bleeding, were given to patients after surgery. Histopathological examination (Figure 5A). Under a microscope, the polymorphic cells were significantly different sizes. The cells were stained, and xanthoma-like changes were observed.

Figure 5 Histopathological examination and postoperative imaging. (A) Pathology (HE ×100). (B) Postoperative magnetic resonance imaging shows complete resection of the lesion. HE, hematoxylin and eosin.

Immunohistochemistry revealed the following: B2 GPAP (t+) S-100 (+), SYN (lesion+), CK− NF (lesion+), CD34, vascular+, P16, CD163 (lesion+), BRAF (+), LCA (lymphocyte+), P53 (occasional+), NeuN (occasional+), IDH132H (−), and Ki67 (+) approximately 40%, slice A2 GFAP (+).

The pathological results showed that the PXA (CNS WHO III grade). On the second day after surgery, oral antiepileptic drugs were administered, and there were no seizures or complications. A postoperative magnetic resonance (MR) image revealed a complete resection of the lesion (Figure 5B). The patient was discharged on the 14^th day post-surgery.

Follow-up and prognosis: the patient was seizure-free and no functional impairments who was followed-up for 6 months after surgery.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the parents of the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

PXA is a rare CNS tumor. Since Kepes first reported and named it, only a few hundred of cases have been reported in the literature, and the vast majority are individual case reports or case analyses (2). When encountering CNS tumors that are difficult to diagnose clinically, the possibility of PXA should be considered.

Compared with those of other gliomas, the imaging features of PXA have the following characteristics (6,7).

• The vast majority of PXAs are located on the surface or superficial parts of the cerebral hemisphere, involving the pia mater and cortex, and have relatively clear boundaries with normal brain tissue. A few tumors have unclear contours and invasive growth patterns.
• The tumor-occupying effect is not significant with no or only mild edema response.
• According to the MRI signal manifestations of the lesion, PXA is classified into cystic, cystic nodular, and parenchymal types. Plain MRI scans often show long T1 and long T2 watery signals (although the protein content in the cyst fluid is relatively high). Tumor nodules or parenchymal types are often slightly longer or have equal signal intensity in T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) sequences. Enhanced scanning shows no enhancement in cystic types, but there may be enhancement in the cyst wall. Tumor nodules or parenchymal types often have significant enhancement, presenting as patchy or uniform enhancement.
• There may be degenerative changes such as bleeding, calcification, necrosis, and deposition of hemosiderin within the tumor.

The MRI findings of this patient are consistent with the imaging characteristics of the vast majority of PXAs mentioned above. The plain MR images of the lesions revealed slight equi signals in the T1WI and T2WI sequences without an occupying effect. There were no obvious boundaries with normal brain tissue.

A PET-CT can be used to evaluate the metabolic status of brain tumors and has significant advantages in grading the malignancy of tumors, defining the tumor scope, reflecting tumor proliferation activity, and heterogeneity (8,9). Tumors with high malignancy and active cell proliferation, such as Grade III–IV gliomas, are generally characterized by high metabolic activity on PET-CT; in contrast, PET-CT results in slightly greater or lower metabolic activity. As shown by the PET-CT findings of this patient, most areas had low metabolic activity, but there was slightly higher metabolic activity at the bottom of the temporal lobe. This change suggests the possibility of malignancy in the lesion, which has been confirmed by postoperative pathology. However, a simple PET examination is not enough to confirm the possible scope of the surgery.

Therefore, PET-MRI fusion can effectively combine structural imaging and metabolic imaging, along with 3D stereoscopic imaging, to predict the possible surgical range. DTI imaging may be utilized to protect white matter fibers as much as possible.

Pathology revealed that the immunohistochemistry results of this patient were GFAP (+), S-100 (+), and Syn (+), strongly suggesting that the tumor originated from astrocytes and multipotent neuroepithelial stem cells. In addition, some studies have shown that the CD34 (+) positivity rate of typical PXA is higher than that of mutant PXA, which also supports the pathological diagnosis of this patient (10,11). However, the Ki-67 index of this patient was 40%, which indicates the possibility of malignant transformation and the need for long-term follow-up.

For patients with PXA and other tumors accompanied by epilepsy, the dialectical relationship between “lesions are not necessarily epileptic foci” and “epileptic foci are not necessarily lesions” has been elucidated in multiple studies, but the pathological and physiological mechanisms involved are not yet clear (12).

At present, most scholars believe several events can lead to epileptic seizures, including tumor space-occupying effects or peritumoral edema, stimulation by inflammatory products containing hemosiderin, gliosis, and changes in the concentration of excitatory amino acids. However, there is still no theory that can fully explain the pathophysiological mechanism of secondary epileptic seizures caused by tumors (13).

From the perspective of nerve fiber connections and brain networks, the occurrence and extent of epilepsy depend on the anatomical and physiological interactions between tumors and surrounding tissues. The disappearance of epileptic seizures after tumor resection may also be due to interference with the fibrous network between the tumor and surrounding tissues (14,15).

Through observation and reflection on the reoperations of epilepsy patients, several studies have divided the relevant brain regions for secondary epilepsy caused by tumors: the smallest range is the lesion area, which is the brain region where the tumor is located; the outer circle is the epileptic zone, also known as the epileptic focus; and the outer circle is the easily irritated area, which can be delineated by EEG or ECoG monitoring. Therefore, removing only the lesion area cannot effectively control epileptic seizures (16).

PXA often presents with epilepsy as the initial symptom. This may be related to the prone area of the tumor, growth characteristics, and tumor components. For epileptic seizures caused by tumors, “total tumor resection” is required to effectively control epileptic seizures. Only removing the tumor without completely removing the accompanying cortical dysplasia is the main reason for epileptic seizures after surgery (17). In addition, in our actual operation process, for some tumors with unclear boundaries, to achieve “total resection”, unless real-time and multiple pathological examinations or expanded resections are performed, “total resection” under the microscope may only be a concept. According to the WHO classification of CNS tumors (1), PXA is indicated a good prognosis for the vast majority of patients. The literature reports that the 5-year survival rate of PXA is 81%, the 10-year survival rate is 72%, and the survival period of a few patients can be as long as 25 years. However, there is also a possibility of postoperative recurrence, metastasis, deterioration (18). Some studies have also shown that the prognosis of patients is closely related to the degree of tumor resection (6,19). For patients with unclear tumor boundaries and invasive growth, intraoperative navigation and MRI can help improve the total resection rate of tumors (20). For patients with secondary seizures caused by PXA, simply removing the tumor may not necessarily eliminate seizures. It is best to perform simultaneous resection of tumors and epileptic foci or expanded resection of tumors under ECoG monitoring to improve survival rates and eliminate epileptic seizures (21).

Epilepsy is usually a brain network disease (22); therefore, its electrical conduction range is usually larger than that of the original lesion area (23). MRI of Benli patients has a relatively limited lesion range, but PET imaging has a lower metabolic range than MRI does. Therefore, after PET-MRI fusion, combined with intraoperative ECoG monitoring, expanded resection can be performed to avoid uncontrolled epilepsy because the resection range is too small. The patient had no seizures 6 months after surgery.

Therefore, a simple preoperative evaluation during neurosurgery is clearly not sufficient. For epilepsy, a multidisciplinary collaboration model is crucial for surgical treatment (including departments such as neurology and imaging departments). For this patient, we adopted this preoperative evaluation model.

Conclusions

In summary, for this patient with PXA accompanied by epilepsy, the following three conclusions can be drawn. Firstly, surgical resection can be the first line of treatment. Secondly, a comprehensive multidisciplinary preoperative evaluation should be conducted rather than solely relying on neurosurgery to determine surgical treatment. Additionally, imaging and intraoperative ECoG are crucial for the success of surgery. Finally, appropriate enlargement and resection can effectively eliminate epileptic seizures.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-24-306/rc

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-24-306/prf

Funding: The work was supported by the National Natural Science Foundation of Tianjin City (No. 23JCYBJC01430) and the Tianjin Key Medical Discipline (Specialty) Construction Project (No. TJYXZDXK-040A).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-24-306/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the parents of the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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