• Giuseppe La Rocca, Giovanni Sabatino, Grazia Menna, Roberto Altieri, Tamara Ius, Enrico Marchese, Alessandro Olivi, Valeria Barresi, and Giuseppe Maria Della Pepa.
• Institute of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University, Rome, Italy; Department of Neurosurgery, Mater Olbia Hospital, Olbia, Italy.
• World Neurosurg. 2020 May 1; 137: 187-193.

BackgroundOne 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.MethodsUsing 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.ResultsLiterature 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).ConclusionsAs 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.Copyright © 2020 Elsevier Inc. All rights reserved.

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