USEFULNESS OF INTRAOPERATIVE PHOTODYNAMIC DIAGNOSIS USING 5‐AMINOLEVULINIC ACID FOR MENINGIOMAS WITH CRANIAL INVASION: TECHNICAL CASE REPORT

OBJECTIVE We present a case of a meningioma in which photodynamic diagnosis (PDD) using 5-aminolevulinic acid was very useful in identifying the cranial involvement. CLINICAL PRESENTATION An 83-year-old woman presented with a bony, hard, immobile bulge in her left forehead. Computed tomographic scans showed a thickening in the left frontal bone with a flat mass underneath. Magnetic resonance imaging scans revealed that enhancing lesions spread to the dura mater and subcutaneous tissue around the thickened frontal bone, reaching the upper margin of the left orbit. INTERVENTION Intraoperative PDD using 5-aminolevulinic acid indicated the optimal extent of the excision by showing clear fluorescence of affected tissues. The tumor was totally resected and diagnosed as an atypical meningioma. Histopathological examination confirmed the consistency of the extent of tumor invasion with affected lesions on PDD. CONCLUSION To the best of our knowledge, this is the first case demonstrating the efficacy of PDD using 5-aminolevulinic acid for a meningioma with cranial invasion. Additional studies are warranted, as shown in cases of malignant gliomas.

P hotodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) has been performed much more frequently in recent years and has become an important intraoperative technique. Because of its convenience and usefulness in the field of neurosurgery, PDD is being performed on patients with malignant gliomas at many institutions (2,4,7,8,9). However, to the best of our knowledge, there have been no studies on PDD using 5-ALA in patients with cranial lesions. Here, we present a case of a meningioma in which PDD using 5-ALA was very useful in identifying cranial involvement.

Clinical Presentation
An 83-year-old woman complained of headache and a bulge on the left side of her forehead. She had no notable medical history, including head trauma, and previous cranial magnetic resonance imaging (MRI) scans did not show any abnormalities. She was referred to our department in June 2006 because the subcutaneous mass (diameter, ∼3 cm) had become painful. It was bony, hard, immobile, and not tender. Cranial computed tomographic (CT) scans showed well demarcated thickening in the left frontal bone and a flat mass exhibiting isodensity immediately underneath. Destruction of both the inner and outer tables of the cranium was confirmed. Contrast-enhanced MRI scans showed even enhancement spreading to the dura mater and subcutaneous tissue around the thickened bone, reaching the upper margin of the left orbit. Diffuse meningeal enhancement was also seen adjacent to the tumor (Fig. 1), suggesting a rapidly progressing meningioma. In order to determine the extent of tumor excision intraoperatively, PDD using 5-ALA was planned and written informed consent was obtained. The protocol of PDD using 5-ALA was approved by the Ethics Committee of Nagasaki University.

Intervention
Three hours before the induction of anesthesia, 20 mg/kg of 5-ALA was administered orally. The patient was kept in a dark room for 48 hours after drug administration to avoid possible skin phototoxicity. After the scalp incision was made, adhesion between the cranial lesion and galea was seen in the area of bone thickening. The cranial lesion, along with the dura mater, was excised as a single mass. Intraoperative PDD showed that the tumor itself was highly fluorescent, but that the dura mater surrounding the tumor was not (Fig. 2). PDD also clearly showed fluorescence from the dipole to the inner table at the stump of the upper orbital margin (Fig. 3), whereas no tumor invasion was observed microscopically. Drilling was performed until the fluorescence disappeared while preserving the outer table. Surgery was completed after confirming the absence of residual fluorescence in the surgical field. The patient was discharged in good health 9 days after surgery. MRI scans performed 9 months after surgery showed no evidence of tumor recurrence (Fig. 4).

Histology
The tumor on the medial surface of the dura mater grew in a turbinated or fascicular manner and obviously involved the cranium. Tumor cells densely existed from the dipole to the outer table of the cranium, and cellular atypia and nuclear fission were seen.

DISCUSSION
First attempted by Moore (6) in 1948, fluorescent dyes have long been used to identify brain tumors. Since then, fluorescent materials and light sources have been developed and improved. At present, PDD using 5-ALA is accepted for its convenience and usefulness, particularly in excising malignant gliomas (2,7,8). In addition, randomized, controlled studies on PDD have documented favorable results in glioma excision and progression-free survival (9). To the best of our knowledge, however, no studies on PDD for meningiomas with cranial invasion have been reported.
In cranial or brain tumors with cranial involvement, the extent of bone resection is determined mostly on the basis of preoperative imaging and intraoperative findings. However, in clinical settings, it is often difficult to determine the boundary between normal bone and tumor tissues. Therefore, we used PDD in order to identify the extent of cranial invasion in the present case. Because intraoperative PDD showed lesional fluorescence in the operative field, additional bone resection was needed, including the superior wall of the left orbit. By confirming the negative fluorescence within the surgical field, the tumor was completely excised. Histopathological examination confirmed that PDD accurately assessed the extent of cranial involvement of the meningioma. Although rapid intraoperative pathological diagnosis of bone lesions without demineralization was not technically feasible, the degree of bone invasion was easily assessed on PDD.
Linear thickening and contrast enhancement of the meninges adjacent to a meningioma have been called the "dural tail signs," "dural thickening," "flare," or "meningeal sign." However, the histological basis of the dural tail with a meningioma is not completely understood. In the present case, preoperative contrast-enhanced MRI scans showed an enhancement of the dura mater adjacent to the meningioma. During the operation, the tumor itself was strongly fluorescent, and the surrounding dura mater was not. Pathological examination confirmed the existence of tumor cells in the fluorescent area, but none were seen in the nonfluorescent dura mater. This suggests that PDD using 5-ALA is quite useful in determining the extent of dura mater involvement in meningioma surgery.
5-ALA has been reported to have several adverse effects, such as skin sensitivity (phototoxicity), nausea, vomiting, and transient liver dysfunction. 5-ALA also produces protoporphyrin IX, which may increase the risk of phototoxic skin reactions within 48 hours of induction. Therefore, after the administration of 5-ALA, we kept the patient in dark surroundings for 48 hours. Thus far, we have used PDD using 5-ALA with a low-dose regimen in 75 cases, but we have never experienced such serious adverse effects.
The reliability of PDD using 5-ALA has not been fully verified. Positive reactions to photosensitive materials in nontumor tissue and 85% sensitivity in even malignant gliomas have been reported (1,3,5,8). Nevertheless, to the best of our knowledge, this is the first case demonstrating the usefulness of PDD using 5-ALA for a meningioma with cranial invasion. PDD using 5-ALA is convenient and inexpensive, and, because most adverse reactions are avoidable, it may be applied in diagnosing brain tumors other than malignant gliomas. for gliomas wherein margins between tumor and brain are less well defined. The benefits of this technique in patients with meningiomas are marginal because the tumor interface with surrounding structures is usually easily discernible. Additional studies, however, may demonstrate its utility in patients with bone invasion such as the one in this case report.

Jeffrey N. Bruce
New York, New York