Frequent Diagnostic Under-Grading in Isocitrate Dehydrogenase Wild-Type Gliomas due to Small Pathological Tissue Samples

BACKGROUND: In contrast to isocitrate dehydrogenase (IDH) mutation analysis, which is homogenous within a given tumor, diagnostic errors in histological analysis following the 2016 World Health Organization (WHO) classification could be due to small samples because of histological heterogeneity. OBJECTIVE: To assess whether the sample size sent to histopathology influences the tumor grading in IDH wild-type gliomas. METHODS: Histologically diagnosed WHO grade, sample volume, and preoperative tumor volume data of 111 patients aged who received resection of IDHwt gliomas between January 2007 and December 2015 at our hospital were evaluated. The differences between absolute and relative pathological sample sizes stratified by WHO grade were conducted using One-Way-Permutation-Test. RESULTS: With a mean sample size of 10.9 cc, 83.8% of patients were histologically diagnosed as WHO grade IV, while 16.2% of patients with a mean sample size of 2.62 cc were diagnosed as WHO grade II/III. One-Way-Permutation-Test showed a significant difference between absolute tissue samples stratified by WHO grade (P=.0374). The distribution of preoperative tumor volumes with WHO grade IV vs WHO grade II/III showed no significant difference (P=.8587). Of all tumors with a sample size >10 cc 100% were pathologically diagnosed as WHO grade IV and those with sample size >5 cc 93.5% were diagnosed as WHO grade IV. CONCLUSION: Small sample sizes are associated with a higher risk of under-estimating malignancy in histological grading in IDHwt gliomas. This study suggests a standard minimum sample size (>5cc) in every resection. Modalities of adjuvant treatment for IDHwt, WHO grade II/III gliomas need to reflect a prognosis that is only marginally better than of a glioblastoma.