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Introduction

Glioblastoma (GBM) is the most frequently occurring primary tumor of the central nervous system and represents one of the most lethal malignancies. Surgical resection and postoperative radiotherapy with concomitant and adjuvant temozolomide (TMZ) are employed as a first-line treatment for GBM (1,2), and more recently bevasizumab and/or carmustine wafers have also been used in Japan (3,4). We report here an unusual case of temporal lobe GBM fed from the middle meningeal artery that underwent double implantation of carmustine wafers and triple surgery.

The present study was approved by the Ethics Committee of Nihon University Itabashi Hospital (Tokyo, Japan) and written informed consent was obtained from the patient and his family.

Case report

A 66-year-old male was admitted to the Department of Neurosurgery at Nihon University Itabashi Hosipital (Tokyo, Japan) with epilepsy. He had complained of headache a week before the epilepsy. Laboratory evaluations including tumor markers demonstrated no abnormalities. His consciousness level was clear and neurological examinations revealed no abnormalities except for headache and deja vu. Magnetic resonance imaging (MRI) disclosed a 1.8 cm-diameter right middle fossa mass lesion which was attached to the dura mater, and displayed low-intensity on T1-weighted MRI and high-intensity on T2-weighted MRI; enhancement was evident following contrast medium administration (Fig. 1A). The lesion was diagnosed preoperatively as a meningioma. However, preoperative MRI one month after the first MRI, disclosed rapid mass growth (Fig. 1B). The patient underwent surgical resection and the tumor was completely removed (Fig. 1C). An angiogram showed a stain fed from the right middle meningeal artery without branches of the internal carotid artery (Fig. 1D and E). The intraoperative findings indicated that the tumor was attached to the dura mater and the tumor border was relatively clear. Eight pieces of carmustine wafers were implanted in the tumor resection cavity. Pathological examinations of the tumor specimen demonstrated a high cellularity, mitosis, pseudopalisading, necrosis, and microvascular proliferation (Fig. 2A). Immunohistochemically, the tumor cells exhibited positive expression for glial fibril acid protein (Fig. 2B), whereas they were negative for cytokeratin and epithelial membrane antigen. These pathological findings were consistent with GBM. The tumor cells were negative for IDH1-R132H and EGFR (Fig. 2C). The MIB-1 labeling index was 55% (Fig. 2D). The patient underwent TMZ chemotherapy with 60 gray radiation therapy and was discharged from hospital, with a Karnofsky Performance Status score of 100, at 70 days after the first surgery.

Figure 1. Radiological findings before and after the first operation. (A) Initial MRI (axial gadolinium-enhanced T1-weighted MRI). (B) Pre-first operation MRI (axial gadolinium-enhanced T1-weighted MRI). (C) Post-first operation MRI (axial gadolinium-enhanced T1-weighted MRI). (D and E) Pre-first operation cerebral angiograms. (D) The angiography revealed tumor stain fed by the right meningeal artery. (E) No tumor stain was observed on the cerebral angiogram of the internal carotid artery.

Figure 2. Pathological findings. (A) Photomicrograph demonstrating high cellularity, mitosis, pseudopalisading necrosis and microvascular proliferation (hematoxylin and eosin stain, original magnification ×50). (B-D) Immunohistochemical staining revealing positive expression for glial fibril acid protein,[(B) original magnification ×50], negative expression for IDH1-R132H [(C) original magnification ×50], and an MIB-1 labeling index of 55% [(D) original magnification ×50].

Six months later, after five courses of TMZ maintenance therapy, evidence of tumor recurrence was found around the resection cavity (Fig. 3A). The patient underwent a second operation via the same approach as for the first operation, and the tumor was again completely removed (Fig. 3B). Eight pieces of carmustine wafers were implanted in the cavity. Pathological examinations of the tumor specimen demonstrated the same pattern as for the first tumor specimen. Five days after the second surgery, a third operation was performed because a cyst formed in the surgical cavity (Fig. 3C and D). The cyst was opened to the basal cisterns and the carmustine wafers were removed at the third operation (Fig. 3E). The cyst contents were found to comprise cerebrospinal fluid with slight xanthochromia. The opened cyst reformed within a few days after the third operation, and tumor recurrence was found at 25 days after the third operation (Fig. 3F). Despite another four courses of TMZ maintenance therapy with additional administration of bevasizumab, the tumor became uncontrollable and the patient died at 11 months after the first operation.

Figure 3. Radiological findings before and after the second/third operations. (A) Pre-second operation MRI (axial gadolinium-enhanced T1-weighted MRI). (B) Post-second operation MRI (axial gadolinium-enhanced T1-weighted MRI). (C and D) Pre-third operation CT scans demonstrating a cyst in the resection cavity [(C) axial; (D) coronal]. (E) Post-third operation CT scan (axial). (F) MRI after the last recurrence (axial gadolinium-enhanced T1-weighted MRI).

Discussion

The extent of resection by surgery affects survival time in GBM patients (5,6). A better prognosis might therefor be predicted for right temporal lobe localized GBM, since total removal can be carried out.

The present case was initially diagnosed as meningioma, because the tumor stain was clearly seen from the middle meningeal artery but not from the internal carotid artery. Only a few case reports of such GBMs have been described (7,8). The timing of surgical treatment may easily be delayed if the lesion is misdiagnosed as a meningioma, and may be of concern for the prognosis of GBM patients.

Cyst formation is known to occur as an adverse event of carmustine wafer implantation for malignant gliomas (9), and there have been several reports of space-occupying cysts in the cavity, which required additional surgical treatment (10–13). Yoshida et al reported that adverse events associated with implantation of carmustine wafers tend to occur in the repeated surgery for the malignant gliomas (11). Although there have been few reports on multiple implantation of carmustine wafers, the risk of adverse events, including cyst formation, might be high when double implantation is performed as in the present case. Basic research has not been done about the mechanism of cyst formation induced by carmustine wafers implantation, so that further studies including basic researches are clearly needed to clarify the mechanism.

In conclusion, we have described an atypical and suggestive case of GBM. We need to be aware GBM should not be excluded in preoperative diagnoses made from imaging studies, even if the tumor is fed only by the middle meningeal artery. Moreover, careful attention should be exercised when carmustine wafers have to be implanted in repeated surgery.

References