5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement.
BACKGROUND
Because of intratumoral heterogeneity, diffusely infiltrating gliomas that lack significant contrast enhancement on magnetic resonance imaging are prone to tissue sampling error. Subsequent histologic undergrading may delay adjuvant treatments. 5-Aminolevulinic acid (5-ALA) leads to accumulation of fluorescent porphyrins in malignant glioma tissue, and is currently used for resection of malignant gliomas. The aim of this study was to clarify whether 5-ALA might serve as marker for visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement for precise intraoperative tissue sampling.


METHODS
5-ALA was administered in 17 patients with diffusely infiltrating gliomas with nonsignificant contrast enhancement. During glioma resection, positive fluorescence was noted by a modified neurosurgical microscope. Intraoperative topographic correlation of focal 5-ALA fluorescence with maximum (11)C-methionine positron emission tomography uptake (PET(max)) was performed. Multiple tissue samples were taken from areas of positive and/or negative 5-ALA fluorescence. Histopathological diagnosis was established according to World Health Organization (WHO) 2007 criteria. Cell proliferation was assessed for multiregional samples by MIB-1 labeling index (LI).


RESULTS
Focal 5-ALA fluorescence was observed in 8 of 9 patients with WHO grade III diffusely infiltrating gliomas. All 8 of 8 WHO grade II diffusely infiltrating gliomas were 5-ALA negative. Focal 5-ALA fluorescence correlated topographically with PET(max) in all patients. MIB-1 LI was significantly higher in 5-ALA-positive than in nonfluorescent areas within a given tumor.


CONCLUSIONS
The data indicate that 5-ALA is a promising marker for intraoperative visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement. Unaffected by intraoperative brain shift, 5-ALA may increase the precision of tissue sampling during tumor resection for histopathological grading, and therefore optimize allocation of patients to adjuvant treatments.
Widhalm
Georg
G
Department of Neurosurgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Wolfsberger
Stefan
S
Minchev
Georgi
G
Woehrer
Adelheid
A
Krssak
Martin
M
Czech
Thomas
T
Prayer
Daniela
D
Asenbaum
Susanne
S
Hainfellner
Johannes A
JA
Knosp
Engelbert
E
D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007432:Intraoperative Period; D008297:Male; D008875:Middle Aged; D017319:Photosensitizing Agents; D049268:Positron-Emission Tomography / Q000379:methods*
D014408:Biomarkers, Tumor; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid