From Cells to Targeted Therapy: Cytopathology as the Starting Point of Precision Oncology in the Molecular Tumor Board Workflow

Precision oncology is often portrayed as a story of genes and drugs, yet it begins with a cell on a slide. This paper positions cytopathology as the front door to Molecular Tumor Boards (MTBs), showing how minimally invasive specimens can reliably be a source for comprehensive genomic profiling and guide targeted therapy decisions. We summarise current evidence and international recommendations to outline a practical MTB workflow, from case selection and sample triage to technical and clinical validation of molecular alterations, structured reporting, and outcome monitoring. Emphasis is placed on pre-analytic variables and cytomorphologic assessment as determinants of next-generation sequencing success, as well as on the use of cytology-derived preparations, such as cell blocks, smears, body fluids, and supernatants, as site-specific "liquid biopsies", for example from CSF in advanced tumours and as alternative to surgical biopsy in some cases. We also discuss some operational bottlenecks and discuss how integrative pathology, can enhance MTB efficiency. Integrating cytopathology samples into MTB workflows, is increasingly recognized as a viable strategy to clinical decision-making using minimally invasive specimens. This integrative approach finds its most dynamic expression in the redefinition of the Molecular Tumor Board.