Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors.

Area of Science:

• Neuro-oncology
• Molecular Pathology
• Diagnostic Technology

Background:

• The 2021 World Health Organization (WHO) classification for central nervous system (CNS) tumors integrates histopathology and molecular data.
• Accurate and rapid differentiation between gliomas and primary CNS lymphomas (PCNSL) is crucial for timely therapeutic intervention.
• Molecular profiling, including single-nucleotide variants (SNV) like IDH1/2, is essential for diffuse glioma classification.

Purpose of the Study:

• To develop and validate an intraoperative integrated diagnostic (i-ID) system for classifying adult malignant CNS tumors.
• To enhance the diagnostic accuracy of frozen-section (FS) diagnosis by incorporating quantitative polymerase chain reaction (qPCR)-based genotyping.
• To provide a reliable diagnostic tool that aligns with the latest WHO classification guidelines.

Main Methods:

• Utilized FS evaluation with rapid immunohistochemistry (IHC) for GFAP and CD20.
• Performed qPCR-based genotyping for IDH1/2, TERT SNV, CDKN2A copy-number alterations, and selected H3F3A and BRAF SNVs.
• Compared i-ID results with permanent integrated diagnosis (p-ID) for reliability assessment.

Main Results:

• Prospective analysis of 101 cases demonstrated high concordance between i-ID and permanent genomic analysis (up to 100% for most markers).
• The i-ID system achieved high diagnostic accuracy, matching p-ID in 97.6% of glioma cases and 94.7% of PCNSL cases.
• Integration of FS and intraoperative genotyping significantly improved diagnostic accuracy for gliomas.

Conclusions:

• The i-ID system offers a reliable method for the integrated diagnosis of adult malignant CNS tumors.
• This approach facilitates rapid and accurate classification, supporting prompt therapeutic decision-making.
• The i-ID system represents a significant advancement in intraoperative neuro-oncology diagnostics.