Regional variation in histopathologic features of tumor specimens from treatment-naive glioblastoma correlates with anatomic and physiologic MR Imaging

Abstract

Histopathologic evaluation of glioblastoma multiforme (GBM) at initial diagnosis is typically performed on tissue obtained from regions of contrast enhancement (CE) as depicted on gadolinium-enhanced, T1-weighted images. The non-enhancing (NE) portion of the lesion, which contains both reactive edema and infiltrative tumor, is only partially removed due to concerns about damaging functioning brain. The purpose of this study was to evaluate histopathologic and physiologic MRI features of image-guided tissue specimens from CE and NE regions to investigate correlations between imaging and histopathologic parameters. One hundred nineteen tissue specimens (93 CE and 26 NE regions) were acquired from 51 patients with newly diagnosed GBM by utilizing stereotactic image-guided sampling. Variables of anatomic, diffusion-weighted imaging (DWI), and dynamic susceptibility-weighted, contrast-enhanced perfusion imaging (DSC) from each tissue sample location were obtained and compared with histopathologic features such as tumor score, cell density, proliferation, architectural disruption, hypoxia, and microvascular hyperplasia. Tissue samples from CE regions had increased tumor score, cellular density, proliferation, and architectural disruption compared with NE regions. DSC variables such as relative cerebral blood volume, peak height, and recovery factor were significantly higher, and the percentage of signal intensity recovery was significantly lower in the CE compared with the NE regions. DWI variables were correlated with histopathologic features of GBM within NE regions. Image-guided tissue acquisition and assessment of residual tumor from treatment-naive GBM should be guided by DSC in CE regions and by DWI in NE regions.

Fig. 1.

Frequency distribution of histopathologic features of glioblastoma multiforme among contrast-enhancing and non-enhancing regions. Histopathologic features were noted to be heterogeneously distributed within both enhancing and non-enhancing regions. Bar graphs of the entire cohort’s histopathological features demonstrate significantly increased distribution of tumor score, architectural disruption, and complex vascular hyperplasia morphology within contrast-enhancing regions compared with non-enhancing biopsy regions (P < .05). Delicate vascular morphology distribution was increased within non-enhancing biopsy regions compared with contrast-enhancing regions (P = .01). The distributions of overall vascular hyperplasia and simple microvascular hyperplasia morphology were not different between enhancing and non-enhancing regions. Hypoxia and pseudopalisading necrosis were not observed in non-enhancing regions.

Fig. 2.

Distribution of dynamic susceptibility–weighted, contrast-enhanced perfusion imaging (DSC) perfusion, diffusion, and anatomic T1- and T2-weighted magnetic resonance imaging (MRI) characteristics among contrast-enhancing (CE) and non-enhancing (NE) regions. Histograms as a distribution of the entire cohort's MRI values demonstrate significantly elevated relative T1 enhancing value (rT1C), relative fast spin echo T2 hyperintensity value (rFSE), relative cerebral blood volume (rCBV), relative peak height (rPH), and recirculation factor (RF) values within contrast-enhancing regions compared with non-enhancing regions (P < .01). Mean PSR values were significantly lower within contrast-enhancing regions compared with non-enhancing regions (P < .01). Relative apparent diffusion coefficient (rADC), relative fractional anisotropy (rFA), and relative fluid-attenuated inversion recovery T2 hyperintensity value (rFLAIR) were not observed to be differentially distributed between contrast-enhancing and non-enhancing regions.

Fig. 3.

Regional correlation between histopathologic features of GBM and physiologic MRI within contrast-enhancing regions. Site of 2 tumor samples (colored circles: [A] green, [B] yellow) planned on axial T1-weighted MRI (column 1), co-registered CBV maps, average dynamic ΔR2*-time curve within the tissue sample region (columns 2 and 3), and histopathologic features (column 4, microvascular hyperplasia (MVH); column 5, cellular proliferation) demonstrates significant correlation between perfusion MRI, MVH, and cellular proliferation within contrast-enhancing regions. Contrast-enhancing regions with elevated MVH and cellular proliferation (A) demonstrated elevated rCBV and rPH values (column 3) compared with similar-appearing contrast-enhancing regions that demonstrate less aggressive tumor features (B). Abbreviation: PSR, percentage of signal intensity recovery.

Fig. 4.

Regional correlation between histopathologic features of GBM and physiologic MRI within non-enhancing regions. Site of 2 tumor samples (colored circles: [A] violet and [B] blue) planned on axial T1-weighted MRI (column 1), co-registered diffusion-weighted imaging maps (column 2), and histopathologic features (column 3, architectural disruption; column 4, cellular proliferation) demonstrates significant inverse correlation between diffusion-weighted MRI, architectural disruption, and cellular proliferation within non-enhancing regions. Non-enhancing regions with increased architectural disruption and cellular proliferation (B) demonstrated decreased rADC values (column 2) compared with similar-appearing non-enhancing regions that demonstrate less aggressive tumor features (A).