10150-GGE-16 INTRAOPERATIVE INTEGRATED DIAGNOSTIC SYSTEM FOR MALIGNANT CENTRAL NERVOUS SYSTEM TUMORS

Abstract

Abstract INTRODUCTION As the most of adult malignant brain tumors are gliomas and primary central nervous system lymphomas (PCNSL)., differentiating between PCNSL and glioma during surgery is crucial for determining the treatment strategy. Also, the WHO CNS5 criteria indicates common genetic alterations according to tumor types. Thus, intraoperatively identifying these genomic abnormalities could aid diagnosis, which may contribute in more personalized therapeutic approaches. Here, we report an intraoperative integrated diagnostic system (i-ID system) that combines frozen section (FS) diagnosis with quantitative PCR (qPCR) based genotyping. MATERIAL & METHODS Rapid histopathological diagnosis by FS was performed for all cases. For cases requiring differentiation from PCNSL, rapid immunohistochemical staining (R-IHC) for CD20 and GFAP was performed. qPCR genotyping was used for the rapid evaluation of IDH1R132H, IDH2R172K, TERTC228T, C250T, BRAFV600E, H3F3AK27M, MYD88L265P, and CDKN2A copy number alteration. The diagnostic accuracy for adult diffuse glioma and PCNSL using i-ID system was examined. RESULTS i-ID system was required 100 min to obtain complete information. After retrospectively analyzing of 151 cases for setting diagnostic algorithm, 101 cases were prospectively assessed for diagnostic potential. The matched ratios for IDH1/2, TERT, BRAF, H3F3A, and CDKN2A evaluations using qPCR were 100%, 98.8%, 100%, 100%, and 93.9%, respectively. In cases of glioblastoma, astrocytoma, and oligodendroglioma, the sensitivity of FS was low, with values of 0.18, 0.17, and 0.00, respectively. On the other hand by combining genotyping, the sensitivity improved up to 0.94, 1.00, and 0.88, respectively. The sensitivity for PCNSL improved from 0.47 (genotyping alone) to 0.95 with combination of R-IHC. Overall, i-ID based intraoperative diagnosis was matched to the permanent diagnosis in 80/82 (97.6%) patients with glioma and 18/19 (94.7%) PCNSL patients, respectively. CONCLUSIONS The i-ID system provides rapid and reliable integrated diagnosis of adult malignant CNS tumors.