Intraoperative Mass Spectrometry in Oncology: Technologies, Clinical Applications, and Challenges.

Surgical precision is critical in oncology, where complete tumor resection while preserving healthy tissue directly influences patient outcomes. Traditional intraoperative diagnostic tools, such as frozen-section analysis, are limited by time constraints, tissue sampling, and interpretative variability. Intraoperative mass spectrometry (MS) has recently emerged as a transformative approach, enabling rapid, label-free molecular profiling of surgical specimens in real time. Several technologies-including Rapid Evaporative Ionization Mass Spectrometry (REIMS, "iKnife"), Desorption Electrospray Ionization (DESI-MS), Matrix-Assisted Laser Desorption/Ionization (MALDI-MS) Imaging, Picosecond InfraRed Laser mass spectrometry (PIRL-MS), and novel devices such as the MasSpec Pen-offer unique strategies for intraoperative tumor characterization. Applications have been demonstrated across multiple cancer types, including brain, breast, gastrointestinal, and urogenital malignancies, where MS can improve margin assessment, tumor classification, and surgical guidance. Beyond its clinical promise, intraoperative MS faces technical and translational challenges, including high infrastructure costs, a lack of standardization, and the need for robust multicenter validation. Integration with artificial intelligence, imaging modalities, and multi-omics approaches may further enhance its clinical utility. This review summarizes current technologies, clinical applications, limitations, and future perspectives of intraoperative MS in oncology, highlighting its potential to reshape surgical oncology practice.