Tumor Infiltration in Enhancing and Non-Enhancing Parts of Glioblastoma: A Correlation with Histopathology

Abstract

PurposeTo correlate histopathologic findings from biopsy specimens with their corresponding location within enhancing areas, non-enhancing areas and necrotic areas on contrast enhanced T1-weighted MRI scans (cT1).Materials and MethodsIn 37 patients with newly diagnosed glioblastoma who underwent stereotactic biopsy, we obtained a correlation of 561 1mm3 biopsy specimens with their corresponding position on the intraoperative cT1 image at 1.5 Tesla. Biopsy points were categorized as enhancing (CE), non-enhancing (NE) or necrotic (NEC) on cT1 and tissue samples were categorized as “viable tumor cells”, “blood” or “necrotic tissue (with or without cellular component)”. Cell counting was done semi-automatically.ResultsNE had the highest content of tissue categorized as viable tumor cells (89% vs. 60% in CE and 30% NEC, respectively). Besides, the average cell density for NE (3764 ± 2893 cells/mm2) was comparable to CE (3506 ± 3116 cells/mm2), while NEC had a lower cell density with 2713 ± 3239 cells/mm2. If necrotic parts and bleeds were excluded, cell density in biopsies categorized as “viable tumor tissue” decreased from the center of the tumor (NEC, 5804 ± 3480 cells/mm2) to CE (4495 ± 3209 cells/mm2) and NE (4130 ± 2817 cells/mm2).DiscussionThe appearance of a glioblastoma on a cT1 image (circular enhancement, central necrosis, peritumoral edema) does not correspond to its diffuse histopathological composition. Cell density is elevated in both CE and NE parts. Hence, our study suggests that NE contains considerable amounts of infiltrative tumor with a high cellularity which might be considered in resection planning.

Quantitative histopathologic assessment of perfusion MRI as a marker of glioblastoma cell infiltration in and beyond the peritumoral edema region

“…The high specificity of T 2 in comparison with TCD maps reveals that most abnormal T 2 regions correspond to regions of tumor infiltration. This relationship between high T 2 signal and invasion is in agreement with clinical findings, both with histological data showing high infiltration in the high T 2 signal region surrounding cT 1 enhancement and patient survival analysis showing a negative correlation with abnormal T 2 volume …”

“…T 2 imaging commonly reveals extensive regions of abnormality surrounding the cT 1 enhancing lesion. While these regions are associated with edema, several biopsy studies have demonstrated the presence of infiltrating tumor cells within them, with the extent of the hyperintensity region being inversely correlated with survival . Evaluating progression of T 2 to cT 1 abnormalities suggests that high T 2 signal regions could represent an earlier stage of tumor development.…”

Analysis of human gliomas by swab touch spray-mass spectrometry: applications to intraoperative assessment of surgical margins and presence of oncometabolites

“…Neuronavigation with preoperative MRI images is typically used to judge extent of resection but several studies have highlighted the limitations and the subjectivity of such a practice as tumor infiltration can extend beyond MRI contrast-enhanced areas, and the enhancement itself poorly correlates to tissue histopathology. 3, 4 In our parallel work using DESI-MS, we were able to detect variable and even large amounts of residual tumor via NAA measurements at the resection margins, even when they appeared clear and non-enhanced by postoperative MRI, 23 remarking the utility of such a measurement.…”

Intraoperative assessment of tumor margins during glioma resection by desorption electrospray ionization-mass spectrometry

“…Remarkably, and unfortunately, postoperative MRI provided no evidence of residual tumor in any of the cases except 1 and 2. Limitations in estimating extent of resection by MRI exist and are largely due to lack of correlation between MRI contrast enhancement and histological composition of the tissue, difficulties in calculating tumor volume, and the occurrence of nonenhancing tumors (4). Also, the volume of the resection cavity does not provide a true indication of the residual microscopic tumor burden (3).…”