Diagnostic discrepancies in malignant astrocytoma due to limited small pathological tumor sample can be overcome by IDH1 testing

Abstract

Background The accurate grading of malignant astrocytomas has significant prognostic and therapeutic implications. Traditional histopathological grading can be challenging due to regional tumor heterogeneity, especially in scenarios where small amounts of tissue are available for pathologic review. Here, we hypothesized that a critical tumor resection volume is needed for correct grading of astrocytomas by histopathology. For insufficient tissue sampling, IDH1 molecular testing can act as a complementary marker to improve diagnostic accuracy. Methods Volumetric analyses were obtained using preoperative and postoperative MRI images. Histological specimens were gathered from 403 patients with malignant astrocytoma who underwent craniotomy. IDH1 status was assessed by immunohistochemistry and sequencing. Results Patients with >20 cubic centimeters (cc) of the total tumor volume resected on MRI have higher rate of GBM diagnosis compared to <20cc (OR 2.57, 95% CI 1.6-4.06, P<0.0001). The rate of IDH1 status remained constant regardless of the tumor volume resected (OR 0.81, 95% CI 0.48-1.36, P<0.43). The rate of GBM diagnosis is 2-fold greater for individual surgical specimen >10cc than those of lower volume (OR 2.48, 95% CI 1.88-3.28, P<0.0001). Overall survival for AA patients with >20cc tumor resection on MRI is significantly better than those with <20cc tumor resected (P<0.05). No volume-dependent differences were observed in patients with GBM (P<0.4), IDH1 wild type (P<0.1) or IDH1 mutation (P<0.88). Conclusions IDH1 status should be considered when total resection volume is <20cc based on MRI analysis and for surgical specimen < 10cc to complement histopathologic diagnosis of malignant astrocytomas. In these specimens, under-diagnosis of GBM may occur when analysis is restricted to histopathology alone.

Age‐specific genome‐wide association study in glioblastoma identifies increased proportion of ‘lower grade glioma’‐like features associated with younger age

“…Changing classification criteria over time as well as gradual adoption of molecular markers could have resulted in a small number of some earlier cases that may not have been classified as GBM if diagnosed during a later period. The incorporation of molecular markers into classification criteria significantly improves diagnostic accuracy and consistency . These markers should be incorporated into glioma GWAS in order to better understand the ways that germline markers confer risk, and for which tumor types they increase susceptibility.…”

Cancer Stem-Like Cells in Glioblastoma

“…Because of the heterogeneity of the cells found in GBM, interobserver variability is not infrequent (6,7), and this makes proper identification a difficult task. A tumor that has been initially identified as a GBM could turn out to be of a different type on subsequent analysis (7). These discrepancies justify the need for tools that will allow the unambiguous identification of GBM.…”

Molecular features assisting in diagnosis, surgery, and treatment decision making in low-grade gliomas

“…For example, in a prospective analysis comparing 246 patients with GBM and 157 with anaplastic astrocytomas, Kim et al 21 found that histopathological diagnosis of GBM was highly dependent on the volume of resection. Smaller resections that were < 20 ml resulted in a much lower rate of diagnosis of GBM than was seen with larger resections > 20 ml.…”

“…In contrast, IDH1 mutation status did not correlate with the size of resection. 21 This indicates a greater likelihood of underdiagnosis of GBM with smaller resections, and molecular genotyping for IDH1 mutation could be used to increase the diagnostic accuracy.…”