Fluorescein-guided removal of peripheral nerve sheath tumors: a preliminary analysis of 20 cases

View More View Less
  • 1 Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta;
  • 2 Neurological Unit 1, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; and
  • 3 Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

OBJECTIVE

Benign peripheral nerve sheath tumors (PNSTs) include mainly schwannomas—the most common tumors arising from peripheral nerves—and neurofibromas. Due to their origin, distinguishing between functional intact nerve and the fibers from whence the PNST arose may not always be easy to perform. The introduction of intraoperative tools to better visualize these tumors could be helpful in achieving a gross-total resection. In this study, the authors present a series of patients harboring PNST in which the surgery was performed under fluorescein guidance.

METHODS

Between September 2018 and February 2019, 20 consecutive patients with a total of 25 suspected PNSTs underwent fluorescein-guided surgery performed under microscopic view with a dedicated filter integrated into the surgical microscope (YELLOW 560) and with intraoperative monitoring. All patients presented with a different degree of contrast enhancement at preoperative MRI. Fluorescein was intravenously injected after intubation at a dose of 1 mg/kg. Preoperative clinical and radiological data, intraoperative fluorescein characteristics, and postoperative neurological and radiological outcomes were collected and analyzed.

RESULTS

Six patients were affected by neurofibromatosis or schwannomatosis. There were 14 schwannomas, 8 neurofibromas, 1 myxoma, 1 reactive follicular hyperplasia, and 1 giant cell tumor of tendon sheath. No patient experienced worsening of neurological status after surgery. No side effects related to fluorescein injection were found in this series. Fluorescein allowed an optimal intraoperative distinction between tumor and surrounding nerves in 13 of 14 schwannomas and in all neurofibromas. In 6 neurofibromas and in 1 schwannoma, the final YELLOW 560 visualization showed the presence of small tumor remnants that were not visible under white-light illumination and that could be removed, obtaining a gross-total resection.

CONCLUSIONS

Fluorescein was demonstrated to be a feasible, safe, and helpful intraoperative adjunct to better identify and distinguish PNSTs from intact functional nerves, with a possible impact on tumor resection, particularly in diffuse neurofibromas.

ABBREVIATIONS AIFA = Italian Drug Agency; 5-ALA = 5-aminolevulinic acid; BBB = blood-brain barrier; BNB = blood-nerve barrier; ICG = indocyanine green; PNS = peripheral nervous system; PNST = peripheral nerve sheath tumor; SF = sodium fluorescein.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

Correspondence Ignazio G. Vetrano: Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. ignazio.vetrano@istituto-besta.it.

INCLUDE WHEN CITING Published online December 6, 2019; DOI: 10.3171/2019.9.JNS19970.

Disclosures Dr. Acerbi received honoraria from the Carl Zeiss Meditec Company for lectures at international meetings.

  • 1

    Abram SE, Yi J, Fuchs A, Hogan QH: Permeability of injured and intact peripheral nerves and dorsal root ganglia. Anesthesiology 105:146153, 2006

    • Search Google Scholar
    • Export Citation
  • 2

    Acerbi F, Broggi M, Broggi G, Ferroli P: What is the best timing for fluorescein injection during surgical removal of high-grade gliomas? Acta Neurochir (Wien) 157:13771378, 2015

    • Search Google Scholar
    • Export Citation
  • 3

    Acerbi F, Broggi M, Schebesch KM, Höhne J, Cavallo C, De Laurentis C, : Fluorescein-guided surgery for resection of high-grade gliomas: a multicentric prospective phase II study (FLUOGLIO). Clin Cancer Res 24:5261, 2018

    • Search Google Scholar
    • Export Citation
  • 4

    Acerbi F, Cavallo C, Schebesch KM, Akçakaya MO, de Laurentis C, Hamamcioglu MK, : Fluorescein-guided resection of intramedullary spinal cord tumors: results from a preliminary, multicentric, retrospective study. World Neurosurg 108:603609, 2017

    • Search Google Scholar
    • Export Citation
  • 5

    Acerbi F, Vetrano IG, Sattin T, de Laurentis C, Bosio L, Rossini Z, : The role of indocyanine green videoangiography with FLOW 800 analysis for the surgical management of central nervous system tumors: an update. Neurosurg Focus 44(6):E6, 2018

    • Search Google Scholar
    • Export Citation
  • 6

    Cavallo C, De Laurentis C, Vetrano IG, Falco J, Broggi M, Schiariti M, : The utilization of fluorescein in brain tumor surgery: a systematic review. J Neurosurg Sci 62:690703, 2018

    • Search Google Scholar
    • Export Citation
  • 7

    Cho SS, Salinas R, Lee JYK: Indocyanine-green for fluorescence-guided surgery of brain tumors: evidence, techniques, and practical experience. Front Surg 6:11, 2019

    • Search Google Scholar
    • Export Citation
  • 8

    da Silva CE, da Silva VD, da Silva JLB: Skull base meningiomas and cranial nerves contrast using sodium fluorescein: a new application of an old tool. J Neurol Surg B Skull Base 75:255260, 2014

    • Search Google Scholar
    • Export Citation
  • 9

    Danis RP, Wolverton S, Steffens T: Phototoxicity from systemic sodium fluorescein. Retina 20:370373, 2000

  • 10

    Date R, Muramatsu K, Ihara K, Taguchi T: Advantages of intra-capsular micro-enucleation of schwannoma arising from extremities. Acta Neurochir (Wien) 154:173178, 2012

    • Search Google Scholar
    • Export Citation
  • 11

    Gibbs-Strauss SL, Nasr KA, Fish KM, Khullar O, Ashitate Y, Siclovan TM, : Nerve-highlighting fluorescent contrast agents for image-guided surgery. Mol Imaging 10:91101, 2011

    • Search Google Scholar
    • Export Citation
  • 12

    Göker B, Kırış T: Sodium fluorescein-guided brain tumor surgery under the YELLOW-560-nm surgical microscope filter in pediatric age group: feasibility and preliminary results. Childs Nerv Syst 35:429435, 2019

    • Search Google Scholar
    • Export Citation
  • 13

    Guha D, Davidson B, Nadi M, Alotaibi NM, Fehlings MG, Gentili F, : Management of peripheral nerve sheath tumors: 17 years of experience at Toronto Western Hospital. J Neurosurg 128:12261234, 2018

    • Search Google Scholar
    • Export Citation
  • 14

    Haubner F, Gassner HG, Brawanski A, Schebesch KM: Fluorescein sodium-guided surgery of parotid gland tumors as a technical advance. BMC Ear Nose Throat Disord 17:6, 2017

    • Search Google Scholar
    • Export Citation
  • 15

    Hirbe AC, Gutmann DH: Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol 13:834843, 2014

  • 16

    Hussain T, Mastrodimos MB, Raju SC, Glasgow HL, Whitney M, Friedman B, : Fluorescently labeled peptide increases identification of degenerated facial nerve branches during surgery and improves functional outcome. PLoS One 10:e0119600, 2015

    • Search Google Scholar
    • Export Citation
  • 17

    Kim DH, Murovic JA, Tiel RL, Moes G, Kline DG: A series of 397 peripheral neural sheath tumors: 30-year experience at Louisiana State University Health Sciences Center. J Neurosurg 102:246255, 2005

    • Search Google Scholar
    • Export Citation
  • 18

    Kornblau IS, El-Annan JF: Adverse reactions to fluorescein angiography: a comprehensive review of the literature. Surv Ophthalmol 64:679693, 2019

    • Search Google Scholar
    • Export Citation
  • 19

    Kretschmer T, Antoniadis G, Heinen C, Börm W, Scheller C, Richter HP, : Nerve sheath tumor surgery: case-guided discussion of ambiguous findings, appropriateness of removal, repeated surgery, and nerve repairs. Neurosurg Focus 22(6):E19, 2007

    • Search Google Scholar
    • Export Citation
  • 20

    Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, : The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131:803820, 2016

    • Search Google Scholar
    • Export Citation
  • 21

    Mahjoub A, Morales-Restrepo A, Fourman MS, Mandell JB, Feiqi L, Hankins ML, : Tumor resection guided by intraoperative indocyanine green dye fluorescence angiography results in negative surgical margins and decreased local recurrence in an orthotopic mouse model of osteosarcoma. Ann Surg Oncol 26:894898, 2019

    • Search Google Scholar
    • Export Citation
  • 22

    Malmgren LT, Olsson Y: Differences between the peripheral and the central nervous system in permeability to sodium fluorescein. J Comp Neurol 191:103107, 1980

    • Search Google Scholar
    • Export Citation
  • 23

    Millesi M, Kiesel B, Woehrer A, Hainfellner JA, Novak K, Martínez-Moreno M, : Analysis of 5-aminolevulinic acid-induced fluorescence in 55 different spinal tumors. Neurosurg Focus 36(2):E11, 2014

    • Search Google Scholar
    • Export Citation
  • 24

    Montano N, D’Alessandris QG, D’Ercole M, Lauretti L, Pallini R, Di Bonaventura R, : Tumors of the peripheral nervous system: analysis of prognostic factors in a series with long-term follow-up and review of the literature. J Neurosurg 125:363371, 2016

    • Search Google Scholar
    • Export Citation
  • 25

    Moore GE: Fluorescein as an agent in the differentiation of normal and malignant tissues. Science 106:130131, 1947

  • 26

    Ouyang X, Dong C, Ubogu EE: In situ molecular characterization of endoneurial microvessels that form the blood-nerve barrier in normal human adult peripheral nerves. J Peripher Nerv Syst 24:195206, 2019

    • Search Google Scholar
    • Export Citation
  • 27

    Pedro MT, Eissler A, Schmidberger J, Kratzer W, Wirtz CR, Antoniadis G, : Sodium fluorescein-guided surgery in peripheral nerve sheath tumors: first experience in 10 cases of schwannoma. World Neurosurg 124:e724e732, 2019

    • Search Google Scholar
    • Export Citation
  • 28

    Perez ER, Bracho O, Ein L, Szczupak M, Monje PV, Fernandez-Valle C, : Fluorescent detection of Merlin-deficient Schwann cells and primary human vestibular schwannoma cells using sodium fluorescein. Otol Neurotol 39:10531059, 2018

    • Search Google Scholar
    • Export Citation
  • 29

    Richner M, Ferreira N, Dudele A, Jensen TS, Vaegter CB, Gonçalves NP: functional and structural changes of the blood-nerve-barrier in diabetic neuropathy. Front Neurosci 12:1038, 2019

    • Search Google Scholar
    • Export Citation
  • 30

    Rodriguez FJ, Folpe AL, Giannini C, Perry A: Pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems. Acta Neuropathol 123:295319, 2012

    • Search Google Scholar
    • Export Citation
  • 31

    Russell SM: Preserve the nerve: microsurgical resection of peripheral nerve sheath tumors. Neurosurgery 61 (3 Suppl):113118, 2007

  • 32

    Schebesch KM, Proescholdt M, Höhne J, Hohenberger C, Hansen E, Riemenschneider MJ, : Sodium fluorescein-guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery—a feasibility study. Acta Neurochir (Wien) 155:693699, 2013

    • Search Google Scholar
    • Export Citation
  • 33

    Stone JJ, Boland JM, Spinner RJ: Analysis of peripheral nerve schwannoma pseudocapsule. World Neurosurg 119:e986e990, 2018

  • 34

    Stone JJ, Graffeo CS, de Ruiter GCW, Rock MG, Spinner RJ: Intraoperative intravenous fluorescein as an adjunct during surgery for peroneal intraneural ganglion cysts. Acta Neurochir (Wien) 160:651654, 2018

    • Search Google Scholar
    • Export Citation
  • 35

    Stone JJ, Spinner RJ: Go for the gold: a “plane” and simple technique for resecting benign peripheral nerve sheath tumors. Oper Neurosurg (Hagerstown) [epub ahead of print], 2019

    • Search Google Scholar
    • Export Citation
  • 36

    Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ: Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7:392401, 2006

    • Search Google Scholar
    • Export Citation
  • 37

    Sugitachi A, Otsuka K, Endo F, Toshimoto K, Takahara T, Akiyama Y, : Intraoperative fluorescence-imaging of nerves—a contribution to navigation surgery. Imaging Med 9:143148, 2017

    • Search Google Scholar
    • Export Citation
  • 38

    Tiel R, Kline D: Peripheral nerve tumors: surgical principles, approaches, and techniques. Neurosurg Clin N Am 15:167175, vi, 2004

  • 39

    Vetrano IG, Bagatti D, Cordella R, Tramacere I, Nazzi V: Intraoperative compound muscle action potentials (CMAPs) amplitude changes after decompression and neurolysis of peripheral nerves in upper limbs neuropathies: electrophysiologial considerations and relation with clinical outcome. J Neurosurg Sci [epub ahead of print], 2018

    • Search Google Scholar
    • Export Citation
  • 40

    Vetrano IG, Lucarella F, Dalolio M, Di Cristofori A, Nataloni IF, Tiberio F, : The importance of predicting factors in the surgical outcome of peripheral nerve sheath tumors. J Neurol Surg A Cent Eur Neurosurg 75:104109, 2014

    • Search Google Scholar
    • Export Citation
  • 41

    Vetrano IG, Saletti V, Nazzi V: Fluorescein-guided resection of plexiform neurofibromas: how I do it. Acta Neurochir (Wien) 161:21412145, 2019

    • Search Google Scholar
    • Export Citation
  • 42

    Wainwright JV, Endo T, Cooper JB, Tominaga T, Schmidt MH: The role of 5-aminolevulinic acid in spinal tumor surgery: a review. J Neurooncol 141:575584, 2019

    • Search Google Scholar
    • Export Citation
  • 43

    Whitney MA, Crisp JL, Nguyen LT, Friedman B, Gross LA, Steinbach P, : Fluorescent peptides highlight peripheral nerves during surgery in mice. Nat Biotechnol 29:352356, 2011

    • Search Google Scholar
    • Export Citation
  • 44

    Young ED, Ingram D, Metcalf-Doetsch W, Khan D, Al Sannaa G, Le Loarer F, : Clinicopathological variables of sporadic schwannomas of peripheral nerve in 291 patients and expression of biologically relevant markers. J Neurosurg 129:805814, 2018

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 48 47 47
Full Text Views 26 26 26
PDF Downloads 23 23 23
EPUB Downloads 0 0 0