Abstract
BACKGROUND: In patients affected by central nervous system tumors not amenable to surgical resection, stereotactic needle biopsy today represents the only available diagnostic approach. Achieving a high diagnostic yield is essential for timely therapeutic decision-making. This study investigates the impact of intraoperative fluorophores (sodium fluorescein and 5-aminolevulinic acid) use on the diagnostic accuracy of stereotactic brain biopsies. METHODS: We retrospectively analyzed 516 stereotactic brain biopsies performed between 2015 and 2024. Data collected included fluorophore use, technique employed, histopathological and molecular results, and procedural outcomes. Diagnostic yield was defined as the proportion of conclusive diagnoses, in accordance with updated WHO classification criteria, while an extended definition, referred to as diagnostic success, included incomplete diagnoses; conversely, diagnostic failure was defined as inconclusive diagnosis. Statistical analyses included Chi-square testing and logistic regression. RESULTS: Fluorophores were used in 314 procedures (60.9%), while 202 (39.1%) were done without (control group). The diagnostic yield was 76.1% with fluorophores versus 68.8% without. When including incomplete diagnoses (diagnostic success) the accuracy rose up to 93.3% in the fluorophore group versus 78.2% in the control group. Fluorophore use was associated with a 69.3% relative reduction in diagnostic failure (p < .001). Logistic regression confirmed that fluorophores significantly increased the odds of diagnostic success (OR = 3.89, p < .001), without significant histology-based selection bias. CONCLUSION: Intraoperative fluorophores application significantly enhances diagnostic yield in stereotactic brain biopsies, independently of tumor histology. These results support a wider implementation of fluorescence-guided biopsy techniques to improve diagnostic accuracy in neuro-oncology. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10072-026-09032-1.