Fluorescence Guided Resection and Photodynamic Therapy in Meningiomas


  • Martin Hefti Centre of neurological surgery Hirslanden, Switzerland
  • Gord von Campe Dept. of Neurosurgery University Hospital Graz




Meningioma, photodynamic therapy, 5-aminolevulinic acid, fluorescence, resection, intraoperative imaging, ferrochelatase, tumour heterogeneity, dural tail, bone invasion.


 Meningiomas represent 30% of all intracranial neoplasms. They are predominantly slow growing, extra axial brain tumours arising from arachnoidal cells and usually have an excellent prognosis if completely removed. However, radical tumour removal near vital functional structures and areas of infiltration is not always possible and histologically "benign" meningiomas may exhibit aggressive behaviour like infiltration and early recurrence. Biological markers to make areas of infiltration visible by fluorescence might therefore have a significant impact on patient survival and quality of life. 5-Aminolevulinic acid (5-ALA) is a precursor in the cellular heme biosynthesis. The application of exogenous 5-ALA leads to an intracellular accumulation of protoporphyrin IX (PpIX), causing PpIX saturated cells to become fluorescent and photosensitive under light of an appropriate wavelength. 5-ALA induced PpIX fluorescence has the ability to define infiltration zones into dural structures and bone and mark residual meningioma tissue. It has the potential to facilitate meningioma resection and to individualize the extent of dural resection for each patient. Specific intracellular accumulation of PpIX can be used for photodynamic therapy (PDT). Induction of selective apoptosis, reduction of tumour vessel density and no risk of secondary carcinogenesis make PDT an ideal treatment option for meningiomas. Due to the variable potential for PpIX accumulation within different meningioma subtypes, further research is required to ensure sufficiently intense fluorescence to enable PDT in these cases.


Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO Classification of Tumours of the Central Nervous System Acta Neuropathol 2007; 114(2): 97-109.

Simpson D. The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatr 1957; 20(1): 22-39. http://dx.doi.org/10.1136/jnnp.20.1.22

Kallio M, Sankila R, Hakulinen T, Jäskelinen J. Factors affecting operative and excess long-term mortality in 935 patients with intracranial meningioma. Neurosurgery 1992; 31(1): 2-12. http://dx.doi.org/10.1227/00006123-199207000-00002

Hashemi M, Schick U, Hassler W, Hefti M. Tentorial meningiomas with special aspect to the tentorial fold: management, surgical technique, and outcome. Acta Neurochirurgica 2010; 152(5): 827-34. http://dx.doi.org/10.1007/s00701-009-0591-z

Philippon J, Cornu P. The recurrence of meningiomas. In Meningiomas (Edited by O. Al-Mefty), Raven Press, New York 1991; pp. 87-106.

Pfisterer WK, Coons SW, Aboul-Enein F, Hendricks WP, Scheck AC, Preul MC. Implicating chromosomal aberrations with meningioma growth and recurrence: results from FISH and MIB-I analysis of grades I and II meningioma tissue. J Neuro-Oncol 2007; 87(1): 43-50. http://dx.doi.org/10.1007/s11060-007-9498-9

Kajimoto Y, Kuroiwa T. Miyatake S, et al. Use of 5-aminolevulinic acid in fluorescence-guided resection of meningioma with high risk of recurrence. Case report. J Neurosurg 2007; 10: 1070-74. http://dx.doi.org/10.3171/jns.2007.106.6.1070

Morofuji Y, Matsuo T, Hayashi Y, Suyama K, Nagata I. Usefulness of intraoperative photodynamic diagnosis using 5-aminolevulinic acid for meningiomas with cranial invasion: Technical case report. Neurosurgery 2008; 62(3 Suppl 1): 102-104. http://dx.doi.org/10.1227/01.neu.0000317378.22820.46

Kawahara Y, Niiro M, Yokoyama S, Kuratsu J. Dural congestion accompanying meningioma invasion into vessels: the dural tail sign. Neuroradiology 2001; 43(6): 462-5. http://dx.doi.org/10.1007/s002340000524

Pieper DR, Al-Mefty O, Hanada Y, Buechner D. Hyperostosis associated with meningioma of the cranial base: secondary changes or tumor invasion. Neurosurgery 1999; 44(4): 742-6; discussion 746-7. http://dx.doi.org/10.1097/00006123-199904000-00028

Gabeau-Lacet D, Aghi M, Betensky RA, Barker FG, Loeffler JS, Louis DN. Bone involvement predicts poor outcome in atypical meningioma. J Neurosurg 2009; 111(3): 464-71. http://dx.doi.org/10.3171/2009.2.JNS08877

Hefti M, Holenstein F, Albert I, Looser H, Luginbühl V. Susceptibility to 5-Aminolevulinic Acid Based Photodynamic Therapy in WHO I Meningioma Cells Corresponds to Ferrochelatase Activity Photochemistry and Photobiology 2011; 87(1): 235-41. http://dx.doi.org/10.1007/s00701-011-0950-4

Bekelis K, Valdés PA, Erkmen K, et al. Quantitative and qualitative 5 aminolevulinic acid-induced protoporphyrin IX fluorescence in skull base meningiomas. Neurosurg Focus 2011; 30(5): E8.

Hefti M. Comment concerning: Intraoperative 5-aminolevulinic-acid-induced fluorescence in meningiomas, Acta Neurochir DOl 1O.1007/s00701-010-0708-4, Intratumoral heterogeneity and fluorescence intensity in meningioma after 5-ALA pretreatment. Acta Neurochir 2011; 153(4): 959-60.

Hefti M, von Campe G, Signer A, Looser H, Landolt H. 5-aminolevulinic acid induced protoporphyrin IX fluorescence in high-grade glioma surgery: a one-year experience at a single institution Swiss Med Wkly 2008; 138(11-12): 180-85.

Sayaguès JM, Tabernero MD, MaÌllo A, et al. Intratumoral patterns of clonal evolution in meningiomas as defined by multicolor interphase fluorescence in situ hybridization (FISH): is there a relationship between histopathologically benign and atypical/anaplastic lesions? J Mol Diagn 2004; 6(4): 316-25.

Scheck AC, Shapiro JR, Coons SW, Norman SA, Johnson PC. Biological and molecular analysis of a low grade recurrence of a glioblastoma multiforme. Clin Cancer Res 1996; 2: 187-99.

Whitson WJ, Valdes PA, Harris BT, Paulsen KD, Roberts DW. Confocal Microscopy for the Histologic Fluorescence Pattern of a Recurrent Atypical Meningioma. Neurosurgery 2011; 68(6): E1768-73. http://dx.doi.org/10.1227/NEU.0b013e318217163c

Bartolomei M, Bodei L, De Cicco C, et al. Peptide receptor radionuclide therapy with (90)Y-DOTATOC in recurrent meningioma. Eur J Nucl Med Imaging 2009; 25: 1407-16.

Dougherty TJ. Photodynamic therapy. Photochem Photobiol 1993; 58(6): 895-900. http://dx.doi.org/10.1111/j.1751-1097.1993.tb04990.x

Schmidt MH, Meyer GA, Reichert KW, et al. Evaluation of photodynamic therapy near functional brain tissue in patients with recurrent brain tumors. J Neurooncol 2004; 67(1-2): 201-7. http://dx.doi.org/10.1023/B:NEON.0000021804.50002.85

Fisher AM, Murphree AL, Gomer CJ, Clinical and preclinical photodynamic therapy Lasers in surgery 1995; 17(1): 2-31.

Diamond I, Granelli SG, McDonagh AF, Nielsen S, Wilson CB, Jaenicke R. Photodynamic therapy of malignant tumours Lancet 1972; 2(7788): 1175-7. http://dx.doi.org/10.1016/S0140-6736(72)92596-2

Kostron H, Fritsch E, Grunert V. Photodynamic therapy of malignant brain tumours: a phase I/II trial. Br J Neurosurg 1988; 2(2): 241-8. http://dx.doi.org/10.3109/02688698808992675

Stylli SS, Kaye AH. Photodynamic therapy of cerebral glioma - a review. Part II - clinical studies. J Clin Neurosci. 2006; 13(7): 709-17. Review. http://dx.doi.org/10.1016/j.jocn.2005.11.012

Marks PV, Furneaux C, Shivvakumar R. An in vitro study of the effect of photodynamic therapy on human meningiomas. Br J Neurosurg 1992; 6(4): 327-32. http://dx.doi.org/10.3109/02688699209023791

Malham GM, Thomsen RJ, Finlay GJ, Baguley BC. Subcellular distribution and photocytotoxicity of aluminium phthalocyanines and haematoporphyrin derivative in cultured human meningioma cells. Br J Neurosurg 1996; 10(1): 51-7. http://dx.doi.org/10.1080/02688699650040520

Kostron H. photodynamic diagnosis and Therapy and the brain Photodynamic therapy methods and protocols ed. Charles J. Gomer Humana Press Springer 2010.

Lilge L, Wilson BC. Photodynamic therapy of intracranial tissues: A preclinical comparative study of four different photosensitizers. J Clin Laser Med Surg 1998; 16: 81-92.

Kennedy JC, Pottier, RH. Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. J Photochem Photobiol 1992; 14: 275-92.

Tsai JC, Hsiao YY, Teng LJ, Chen CT, Kao MC. Comparative study on the ALA photodynamic effects of human glioma and meningioma cells. Lasers Surg Med 1999; 24(4): 296-305. http://dx.doi.org/10.1002/(SICI)1096-9101(1999)24:4<296::AID-LSM7>3.0.CO;2-F

Madsen SJ, Sun CH, Tromberg BJ, Yeh AT, Sanchez J, Hirschberg H. Effects of combined photodynamic therapy and ionizing radiation on human glioma spheroids. Photochem Photobiol 2002; 76(4): 411-16. http://dx.doi.org/10.1562/0031-8655(2002)076<0411:EOCPTA>2.0.CO;2




How to Cite

Martin Hefti, & Gord von Campe. (2012). Fluorescence Guided Resection and Photodynamic Therapy in Meningiomas. Journal of Analytical Oncology, 1(1), 56–61. https://doi.org/10.6000/1927-7229.2012.01.01.8