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Table of Contents    
Year : 2015  |  Volume : 63  |  Issue : 6  |  Page : 960-963

Intraoperative fluorescence reveals diffuse subpial spread in glioblastoma

1 Department of Neurosurgery, Division of Surgical Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
2 Department of Surgical Pathology, Tata Memorial Centre, Mumbai, Maharashtra, India

Date of Web Publication20-Nov-2015

Correspondence Address:
Aliasgar Moiyadi
Department of Neurosurgery, Division of Surgical Oncology, Tata Memorial Centre, Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.170106

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How to cite this article:
Moiyadi A, Sridhar E. Intraoperative fluorescence reveals diffuse subpial spread in glioblastoma. Neurol India 2015;63:960-3

How to cite this URL:
Moiyadi A, Sridhar E. Intraoperative fluorescence reveals diffuse subpial spread in glioblastoma. Neurol India [serial online] 2015 [cited 2022 Aug 16];63:960-3. Available from: https://www.neurologyindia.com/text.asp?2015/63/6/960/170106


The aim of surgery in malignant gliomas is maximal safe removal of the enhancing tumor mass. The extent of resection (EOR) is an important prognostic marker. However, malignant gliomas are notoriously infiltrating. Various pathways facilitating the spread of malignant gliomas have been described, including subpial spread and spread along the white matter tracts, blood vessels, and ependymal lining.[1] This extension is almost impossible to demonstrate surgically and is only discovered during the subsequent pathological examination. We describe a case of glioblastoma where the use of 5-aminolevulinic acid (ALA)-induced tumor fluorescence demonstrated subpial spread intraoperatively and helped in deciding the limits of surgical resection. A 60-year-old woman presented to us with a short history of headache and left-sided hemiplegia. She had been detected with a right posterior frontal mass, for which a craniotomy and biopsy had been performed elsewhere. The biopsy did not yield a positive diagnosis. When she presented to us, the MRI revealed a heterogeneously enhancing centrally necrotic mass with surrounding edema [Figure 1]. Suspecting a glioblastoma and with the intention of radically resecting the mass, a reoperation was planned using 5-aminolevulinic acid (ALA; Gliolan; Medac GmbH, Germany) for fluorescence guidance. At surgery, the tumor was strongly fluorescing, with a large central necrotic nonfluorescing component. The fluorescence at the deeper periphery of the tumor was fainter, and the tumor was resected till the nonfluorescing edge all around. Superiorly on the surface, there appeared persistent strong fluorescence extending diffusely across the entire visualized cortical surface. The walls of the cavity (subcortical white matter) adjoining the cortical fluorescence were, however, nonfluorescing [Figure 2]. On careful inspection, it was evident that the fluorescence was restricted only to the cortical surface (subpial space). Representative samples were taken for histological confirmation. As the subpial spread was diffuse, it was decided not to resect the fluorescing areas on the surface. The biopsy sent from the subpial zone revealed the presence of a high-grade glial tumor adjacent to the underlying normal cortical tissue, confirming its subpial tumor spread [Figure 3]. Fluorescence- guided resection (FGR) has been shown clinically to improve extent of resection (EOR) and thereby survival.[2] Strong fluorescence is a reliable intraoperative marker for solid tumor tissue.[3] Leaving behind fluorescing tissue has been shown to adversely impact survival, even though on radiological imaging, a complete resection may have been achieved.[4] It is also important to respect brain eloquence. The introduction of ALA-FGR has provided neurosurgeons with the opportunity to visualize tumor extensions hitherto invisible even with magnification under white light. Fluorescence in the periventricular zone has also been reported in GBMs.[5],[6] In our case, however, strong fluorescence was seen in the subpial space. In this context, our report highlights two important points. First, we demonstrated the phenomenon of subpial spread "live" during surgery using fluorescence (which has not been reported so far). This is seldom appreciated during surgery and only comes to light at the eventual pathology (if at all). Though previous surgery could have contributed to this, it also reinforces the (sadly demoralizing) reality about the diffuse nature of malignant gliomas. Second, this report also serves to remind surgeons to exercise caution and NOT to chase all the visible fluorescence. In our case, the fluorescence was strong (and similar to the rest of the solid tumor mass). However, it was distinctly restricted to the subpial space on the cortical surface, with no fluorescence in the subcortical zone whatsoever. This led us to conclude that the use of ALA-FGR helps to improve intraoperative visualization and demonstrates tumor extent reliably. It should be used judiciously, interpreting with caution, the findings of tumor extension into eloquent areas as well as unresectable tumor infiltration, as seen in our case.
Figure 1: Preoperative MR imaging (upper row, T2; middle, T1; lower, post-gadolinium T1 images) showing the heterogeneously enhancing tumor mass. Note the small enhancing focus anterior to the main tumor (lower row, center image)

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Figure 2: Intraoperative photograph showing the tumor resection cavity; left, white light appearance, and right, appearance under BLUE 400 filter. Diffuse strong red fluorescence is seen on surface (white arrow) around the resection cavity (white arrowhead). The cavity walls themselves are nonfluorescing

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Figure 3: Representative photomicrographs (hematoxylin.eosin: a, ×40; b, c, ×100; d, e, ×200; and f, ×400) of the subpial fluorescent tissue showing cellular tumor with the adjoining cortical brain parenchyma (as represented by the black line with arrow heads in a, b, c, and d). The tumor as shown in (f) is cellular with nuclear anaplasia representing its high-grade histomorphology

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  References Top

Cuddapah VA, Robel S, Watkins S, Sontheimer H. A neurocentric perspective on glioma invasion. Nat Rev Neurosci 2014;15:455-65.  Back to cited text no. 1
Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ; ALA-Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: A randomised controlled multicentre phase III trial. Lancet Oncol 2006;7:392-401.  Back to cited text no. 2
Stummer W, Tonn JC, Goetz C, Ullrich W, Stepp H, Bink A, et al. 5-Aminolevulinic acid-derived tumor fluorescence: The diagnostic accuracy of visible fluorescence qualities as corroborated by spectrometry and histology and postoperative imaging. Neurosurgery 2014;74:310-20.  Back to cited text no. 3
Aldave G, Tejada S, Pay E, Marigil M, Bejarano B, Idoate MA, et al. Prognostic value of residual fluorescent tissue in glioblastoma patients after gross total resection in 5-aminolevulinic acid-guided surgery. Neurosurgery 2013;72:915-21.  Back to cited text no. 4
Cage TA, Pekmezci M, Prados M, Berger MS. Subependymal spread of recurrent glioblastoma detected with the intraoperative use of 5-aminolevulinic acid: Case report. J Neurosurg 2013;118:1220-3.  Back to cited text no. 5
Tejada-Solis S, Aldave-Orzaiz G, Pay-Valverde E, Marigil-Sanchez M, Idoate-Gastearena MA, Diez-Valle R. Prognostic value of ventricular wall fluorescence during 5-aminolevulinic-guided surgery for glioblastoma. Acta Neurochir (Wien) 2012;154:1997-2002.  Back to cited text no. 6


  [Figure 1], [Figure 2], [Figure 3]

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