Is the anatomical distribution of low-grade gliomas linked to regions of gliogenesis?

Abstract

Introduction According to the stem cell theory, two neurogenic niches in the adult human brain may harbor cells that initiate the formation of gliomas: The larger subventricular zone (SVZ) and the subgranular zone (SGZ) in the hippocampus. We wanted to explore whether defining molecular markers in low-grade gliomas (LGG; WHO grade II) are related to distance to the neurogenic niches. Methods Patients treated at two Norwegian university hospitals with population-based referral were included. Eligible patients had histopathological verified supratentorial low-grade glioma. IDH mutational status and 1p19q co-deletion status was retrospectively assessed. 159 patients were included, and semi-automatic tumor segmentation was done from pretreatment T2-weighted (T2W) or Fluid-Attenuated Inversion Recovery (FLAIR) images. 3D maps showing the anatomical distribution of the tumors were then created for each of the three molecular subtypes (IDH mutated/1p19q co-deleted, IDH mutated and IDH wild-type). Both distance from tumor center and tumor border to the neurogenic niches were recorded. Results In this population-based cohort of previously untreated low-grade gliomas, we found that low-grade gliomas are more often found closer to the SVZ than the SGZ, but IDH wild-type tumors are more often found near SGZ. Conclusion Our study suggests that the stem cell origin of IDH wild-type and IDH mutated low-grade gliomas may be different.

The Prognostic Value of MRI Subventricular Zone Involvement and Tumor Genetics in Lower Grade Gliomas

“…The first major finding of our study was that SVZ involvement is common in LGGs, but in contrast to what has been previously reported in GBMs, it was overall not a stronger predictor of poor outcomes in our LGG cohort. Similarly, the distance between the tumor border and the SVZ was not found to be prognostic, which aligns with a previous paper that found no difference in the distance to the SVZ between IDH‐mutated and IDH‐wild‐type LGGs 25 . Only occipital SVZ involvement was prognostic for tumor progression and survival.…”

“…Similarly, the distance between the tumor border and the SVZ was not found to be prognostic, which aligns with a previous paper that found no difference in the distance to the SVZ between IDH-mutated and IDH-wild-type LGGs. 25 Only occipital SVZ involvement was prognostic for tumor progression and survival. Seventy percent of the tumors in our cohort demonstrated SVZ involvement, a proportion similar to prior studies that included grade II 7 and grade III gliomas.…”

The link between gliomas infiltration and white matter architecture investigated with electron microscopy and diffusion tensor imaging

“…The initial tumor location and the architecture of the peritumoral tissue are therefore very important for the comprehension and prediction of the possible infiltration patterns. Different preferential locations among DLGG subtypes have also been described with possible link to gliogenesis or cell migration during the developmental stages ( Latini et al, 2020a , Skjulsvik et al, 2020 ). A common preferential location for DLGG within the so called “minimal common brain” has been suggested ( Ius et al, 2011 , Parisot et al, 2016 , Sarubbo et al, 2015 ) with consequent infiltration of crucial white matter bundles ( Duffau and Capelle, 2004 , Latini et al, 2020a , Latini et al, 2019 , Mandonnet et al, 2006 ).…”

“…These studies suggest that the preferential location of these tumors reflect a higher infiltration of specific white matter bundles at the moment of radiological diagnosis. Among these bundles specific regions in the fronto-temporo-insular areas were more often detected as infiltrated compared with other, more posterior regions ( Latini et al, 2020a , Skjulsvik et al, 2020 ). The reason for this tendency is still unknown.…”

Preoperative Patient-Reported Outcomes in Suspected Low-Grade Glioma: Markers of Disease Severity and Correlations with Molecular Subtypes

“…Little is known about preoperative health conditions and fatigue in patients with suspected dLGG classified by the 2016 WHO classification, and whether the patient-reported symptom burden reflects the underlying biology. As dLGG with and without IDH mut have different distributions in the brain [ 18 ], and clinical behavior symptoms may also be different between different subtypes [ 19 ], PRO may be associated with the molecular subtype of dLGG. In such cases, particular symptoms may act as warning signals and help identify patients at risk for a more rapidly progressing tumor despite radiological appearance of a probable dLGG.…”