5-Aminolevulinic Acid False Positives in Cerebral Neuro-Oncology: Not All That Is Fluorescent Is Tumor. A Case-Based Update and Literature Review

Background: One of the most valuable innovations in high-grade glioma surgery is 5-aminolevulinic acid (5-ALA). Fluorescence is a specific and sensitive indicator of metabolically active tumor tissue. In the published literature, the main focus has been placed on false-negative cases, with only a few articles addressing false positivity. The aim of the article was to highlight settings in which 5-ALA fluorescence does not necessarily mean tumor and to point out conditions in which intraoperative 5-ALA fluorescence has to be critically interpreted. Methods: Using PubMed, a review of pertinent literature was done to specifically investigate all conditions, including non-neoplastic and other metabolically active lesions, that can mimic high-grade gliomas and cause a misleading intraoperative diagnosis. In addition, an institutional case characterized by strong 5-ALA fluorescence in radionecrosis is presented. Results: Literature results were grouped in 2 main categories according to the field of application: oncologic setting (9 articles and 1 institutional case) and nononcologic settings (5 articles). Conclusions: As reported, 5-ALA-induced fluorescence is not limited to glioma but is also evident in nonglioma and non-neoplastic conditions. Critical interpretation of intraoperative fluorescence is therefore mandatory in recurrences and in atypical cases that might hinder alternative diagnoses.