Abstract
BackgroundIntraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria.MethodsWe prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status.ResultsA total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%.ConclusionsOur study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift.
Highlights
Decisions concerning postoperative adjuvant therapy of diffusely infiltrating gliomas (DIG) are based on the histopathological World Health Organisation (WHO) criteria: While in high-grade gliomas (WHO grade III and IV) immediate postsurgical radio- or radiochemotherapy is essential [1,2,3], in the majority of low-grade gliomas (WHO grade II) maximum safe tumor resection is currently regarded as first and only treatment until malignant progression develops [4,5,6,7]
5-aminolevulinic acid (5-ALA) was administered in 59 DIG patients with non-significant CE on magnetic resonance imaging (MRI)
Focal PpIX fluorescence was observed in 27 (46%) of the 59 gliomas, no visible PpIX fluorescence was detected in any intratumoral area of the remaining 32 cases (54%)
Summary
Decisions concerning postoperative adjuvant therapy of diffusely infiltrating gliomas (DIG) are based on the histopathological World Health Organisation (WHO) criteria: While in high-grade gliomas (WHO grade III and IV) immediate postsurgical radio- or radiochemotherapy is essential [1,2,3], in the majority of low-grade gliomas (WHO grade II) maximum safe tumor resection is currently regarded as first and only treatment until malignant progression develops [4,5,6,7] This malignant progression generally originates within a circumscribed intratumoral area, the so called ‘‘anaplastic focus’’ [8,9]. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria
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