5-Aminolevulinic acid-induced protoporphyrin IX fluorescence as immediate intraoperative indicator to improve the safety of malignant or high-grade brain tumor diagnosis in frameless stereotactic biopsies

Abstract

Background: Frameless stereotactic biopsies are replacing frame-based stereotaxy as a diagnostic approach to brain lesions. In order to avoid a sampling bias or negative histology, multiple specimens are often taken. This in turn increases the risk of hemorrhagic complications.

Objective: We present the use of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX fluorescence in frameless stereotaxy to improve the procedure duration and yield, and thereby reduce the risk of complications.

Methods: Patients with suspected high-grade brain tumors are given 5-ALA 4 h prior to stereotactic biopsy. The biopsy needle is guided to the target using frameless stereotaxy based either on preoperative images or combined with intraoperative MRI sequences. The specimen is illuminated with blue light to look for fluorescence. In case of a positive fluorescence within the tissue sample, no frozen sections are obtained, and no further specimens are taken.

Results: The samples of 13 patients revealed a positive fluorescence and were histologically confirmed as malignant or high-grade brain neoplasms. four cases were fluorescence-negative, requiring frozen section confirmation and/or multiple samples. In theses cases histology was either nonspecific gliotic changes or low-grade tumors. There were no complications related to the additional use of 5-ALA.

Conclusion: 5-ALA fluorescence in stereotactic biopsies can increase the safety and accuracy of these procedures by reducing sampling errors and eliminating the need for multiple samples and/or frozen section verification, creating a more accurate, faster and safer procedure for cases of suspected malignant or high-grade brain tumors situated in deep or eloquent areas.

Fig. 1

The opening of the biopsy needle (10 mm) is larger than the target lesion (5 mm), and the needle itself has a 2-mm fore-run (Fig. 1, top). Only the distal part of the actual specimen was expected to hold pathological tissue, which was confirmed by visible 5-ALA-induced protoporphyrin IX (PpIX) fluorescence only within the tumor tissue (Fig. 1, bottom)

Fig. 2

Immunohistochemistry revealed a malignant lymphoma (B-cell lymphoma), and showed the border between the target lesion and the surrounding brain (CD 20)