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Reliability of fluorescein-assisted stereotactic brain biopsies in predicting conclusive tissue diagnosis

  • Original Article - Tumor - Other
  • Published:
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Abstract

Background

The purpose of this study was to assess the reliability of fluorescein sodium in predicting conclusive tissue diagnosis in stereotactic brain biopsies and to characterize features of contrast-enhancing and non-enhancing MRI lesions associated with fluorescence.

Methods

A total of 19 patients were studied, 14 of which had contrast-enhancing and 5 of which had non-enhancing lesions on preoperative T1 post-gadolinium MRI scan. All patients received 3 mg/kg fluorescein sodium during anesthesia induction. Biopsy specimens were photographed under the operating microscope, using the Yellow560 module, prior to histopathological analysis. Two observers blinded to the MRI scans and histopathological results categorized the photographs retrospectively as “fluorescent” or “not fluorescent.” Inter-rater agreement was assessed using Cohen’s kappa coefficient. Sensitivity, specificity, and positive predictive value of fluorescence reliability were calculated for MRI contrast-enhancing lesions and confirmed location-concordance of tumor pathology based on rater’s fluorescence status assessment. Results were correlated finally with final results on permanent sections.

Results

Strength of inter-rater fluorescence status agreement was found to be “substantial” (kappa = 0.771). Sensitivity, specificity, and positive predictive value for “fluorescent” and “not fluorescent” specimen in comparison with MRI contrast-enhancing lesions were 97%, 40%, and 82%, respectively. Sensitivity, specificity, and positive predictive value for confirmed tumor pathology were 100%, 63%, and 91%, respectively. Permanent pathology revealed high-grade glioma n = 5, low-grade glioma n = 3, lymphoma n = 5, pineal tumor n = 2, hamartoma n = 1, and nonspecific hypercellularity n = 3.

Conclusions

Fluorescein-assisted stereotactic brain biopsies demonstrated a high likelihood to manifest fluorescence in contrast-enhancing MRI lesions, while adequately predicting conclusive tumor pathology.

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Author contribution statement

Edin Nevzati and D. Ryan Ormond designed the study. Edin Nevzati, Grégoire P. Chatain, Jessa Hoffman, B.K. Kleinschmidt-DeMasters, Kevin O. Lillehei, and D. Ryan Ormond acquired data. Analysis and interpretation of data was performed by Edin Nevzati, Grégoire P. Chatain, Jessa Hoffman, B.K. Kleinschmidt-DeMasters, Kevin O. Lillehei, and D. Ryan Ormond. Statistical analysis was performed by Edin Nevzati and Grégoire P. Chatain. Edin Nevzati took the lead in writing the manuscript with critical feedback from all authors. Kevin O. Lillehei and D. Ryan Ormond supervised the project, and Edin Nevzati was in charge of the overall direction and planning. All authors approved the final version to be published and agree to be accountable for all aspects of the work.

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Authors and Affiliations

  1. Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO, USA

    Edin Nevzati, Grégoire P. Chatain, Jessa Hoffman, Kevin O. Lillehei & D. Ryan Ormond

  2. Department of Pathology, University of Colorado School of Medicine, Aurora, CO, USA

    Bette K. Kleinschmidt-DeMasters

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  1. Edin Nevzati
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Correspondence to Edin Nevzati.

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All authors meet the following authorship criteria: substantial contribution to the concept and design or analysis and interpretation of data, drafting or critical revision of the manuscript and final approval of the submitted version of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was performed in accordance with the declaration of Helsinki [28] and was approved by the Colorado multiple institutional review board (COMIRB) (protocol 19–1028, APP001–1). An institutional review board (IRB) member reviewed and approved the request for a full waiver of Health Insurance Portability and Accountability Act (HIPAA) Authorization. All criteria for a waiver of HIPAA Authorization were met.

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Comments

Using flourescens as a confirmation for probably conclusive pathology can be useful. In most cases, this should however not be necessary if proper surgical approach and planning of stereotactic biopsy route is used, especially in contrast enhancing lesion where tumor is suspected. In highly experienced center, this adjunct is not needed - especially if framebase technology or robotic arm with higher precision is used.

Here the author also use fluorescein in non-enhancing low grade pathology - this is where I see the potential. The 5-ALA is only reliably fluorescing in high-grade glioma. In low-grade, not frequently. In other pathologies where non-neoplastic lesion are biopsied, the diagnostic yield is even more difficult. And if fluorescein could heighten the diagnostic yield in these cases, it would be of value.

Jane Skjoth-Rasmussen

Copenhagen, Denmark

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This article is part of the Topical Collection on Tumor – Other

Portions of this work have been presented:

• 32nd Neurosurgery in the Rockies Meeting, Beaver Creek, Colorado, USA (February 27, 2019)

• 87th Annual Scientific Meeting American Association of Neurological Surgeons (AANS), San Diego, California, USA (April 17, 2019)

Electronic supplementary material

Supplementary Figure 1

Summary of harvested biopsy specimens photographed under the yellow560 module. The observers rating as “fluorescing” marked with a (+), or “non-fluorescing” marked with a (-), are labeled under each biopsy specimen. (PNG 4974 kb)

High Resolution Image (TIFF 1521 kb)

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Nevzati, E., Chatain, G.P., Hoffman, J. et al. Reliability of fluorescein-assisted stereotactic brain biopsies in predicting conclusive tissue diagnosis. Acta Neurochir 162, 1941–1947 (2020). https://doi.org/10.1007/s00701-020-04318-5

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  • DOI: https://doi.org/10.1007/s00701-020-04318-5

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