Matrix-assisted laser desorption/ionization mass spectrometry imaging for spatial clinical oncopathology: diagnosis, margins and therapy.

Clinical oncology increasingly depends on molecular information, but many assays still detach analytes from the histological coordinates in which diagnostic decisions are made. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is being investigated as a spatial molecular adjunct that can measure lipids, metabolites, peptides, proteins, glycans and drugs directly from tissue sections. This review evaluates applications in which spatial molecular evidence may refine, rather than replace, conventional oncopathology: molecularly resolved tumor histology, margin and adjacent-tissue assessment, tumor microenvironment interpretation and therapeutic-response prediction. We emphasize that clinical value requires alignment with hematoxylin and eosin (H&E) morphology, expert annotation, quality control, molecular-identification confidence and patient-level validation. The literature shows progress from visual ion-map comparison toward multimodal registration, machine-learning classification, spatial proteomics and spatial pharmacology. However, routine adoption remains constrained by pre-analytical variability, incomplete metabolite annotation, batch effects, validation leakage in pixel-level models and limited prospective evidence. The most realistic near-term role for MALDI-MSI is therefore a spatial molecular adjudicator for selected, decision-relevant problems such as difficult classification, uncertain margins, field effects, microenvironment-associated risk and heterogeneous drug exposure.