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Andrea Bianco, Mattia Del Maestro, Andrea Fanti, Chiara Airoldi, Thomas Fleetwood, Emanuela Crobeddu, and Christian Cossandi


In patients with contraindication to open resection, histological diagnosis is obtained through a stereotactic biopsy (SB). Missed diagnoses and sampling errors are important limitations of SB; therefore, various ways have been proposed to increase the diagnostic yield (DY). Intraoperative histopathology can obtain a DY exceeding 98% but with several drawbacks, namely prolonged operative times and logistic concerns. The objective of this study was to evaluate whether intraoperative validation of samples with fluorescein sodium can obtain a high DY with the same ease of use as standard SB.


One hundred three consecutive cases of frameless neuronavigated SB performed at the authors’ center from May 2013 to June 2021 were included. Two groups were compared: 46 patients underwent standard nonassisted SB (nSB), and 57 patients underwent fluorescein sodium–assisted SB (fSB). Data were collected retrospectively before 2017 and prospectively thereafter. DY, operative time, and rate of complications were compared between the two groups. The surgical technique for fSB was standardized, and a novel classification system for intraoperative fluorescence findings was developed.


Statistically significant differences between the two groups were identified. The DY of the fSB group (100%, 95% CI 93.73%–100%) was significantly greater than that of the nSB group (89.13%, 95% CI 80.14%–98.13%) (p = 0.0157). No statistically significant differences were observed in terms of mean operative time (p = 0.7104), intraoperative complications (p = 0.999), or postoperative complications (p = 0.5083).


Compared with standard nSB, fSB showed a significantly higher DY and similar surgical time and rate of complications. The ease of use, wide diagnostic spectrum, and low cost make fluorescein sodium preferable to other fluorophores. The present study strengthens the limited data in the literature indicating routine use of fSB. The proposed workflow suggests that fSB should be the standard of care for contrast-enhanced cases. Intraoperative histopathology should be limited to nonenhancing cases, and nSB should be avoided. Future prospective multicenter studies will be useful for further validation of our findings.