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

Precision oncology is often portrayed as a story of genes and drugs, yet it begins with a cell on a slide. This review positions cytopathology as the front door to Molecular Tumor Boards (MTBs), showing how minimally invasive specimens can reliably power comprehensive genomic profiling and guide targeted therapy decisions.

We summarize current evidence and international recommendations to outline a practical, cytology-centered MTB workflow, from case selection and sample triage to technical and clinical validation of molecular alterations, structured reporting, and outcome monitoring. Particular emphasis is placed on pre-analytic variables, nucleic acid yield, 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" in advanced and difficult to biopsy tumors. We also revise some operational bottlenecks and discuss how integrative pathology can enhance MTB efficiency and equity.

Cytopathology is the front door to MTBs, enabling minimally invasive specimens to power comprehensive genomic profiling and guide targeted therapy decisions. Pre-analytic variables, nucleic acid yield, and cytomorphologic assessment is determinants of next-generation sequencing success. A practical, cytology-centered MTB workflow from case selection and sample triage to technical and clinical validation of molecular alterations, structured reporting, and outcome monitoring. By reframing cytology from a fallback option to a strategic starting point, this article proposes a model in which cytopathologists co-drive MTB deliberations, enabling timely, evidence-based, and patient-centered precision oncology from the least invasive samples available.