Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology

Molecular Testing in Solid Tumors: Best Practices from the Molecular Pathology and Precision Medicine Study Group of the Italian Society of Pathology (PMMP/SIAPeC)

Nicola Fusco — 2025-05-09

The Italian Society of Pathology’s Molecular Pathology and Precision Medicine Study Group (PMMP/SIAPeC) has released a three-part set of best practice guidelines to standardize and enhance molecular testing in solid tumors. Part I focuses on the pre-analytical phase, emphasizing proper tissue handling and quality control to preserve nucleic acid integrity. Part II addresses the analytical phase, outlining workflows for next-generation sequencing (NGS), from extraction to variant interpretation, with recommendations on platform choice, gene panels, and bioinformatics. Part III covers the post-analytical phase, offering guidance on structured, clinically meaningful reporting to support therapeutic decisions, including standards for both tissue and liquid biopsies. Together, these documents aim to harmonize molecular diagnostics across Italy, ensuring reliable, high-quality results that support precision oncology.

Part I – Pre-analytical phase

Caterina Marchiò — 2025-05-09

Precision oncology relies on pathology to integrate morphological and genomic data for tailored treatment selection. The preanalytical phase, covering all steps from specimen collection to processing before analysis, is one of the major determinants of the quality of downstream molecular analyses, which are essential for selection personalized therapeutic strategies. Strict adherence to protocols and specific quality control programs are essential to ensure the reliability and standardization of molecular testing. This document intends to guide the multidisciplinary team (pathologists, technicians, molecular biologists) in pathology laboratories during the preparation of samples for molecular analyses.

Part II – Analytical phase

Elena Guerini-Rocco — 2025-05-09

Next-generation sequencing (NGS) has become a cornerstone of precision oncology, requiring standardized workflows in molecular pathology laboratories. The analytical phase, which includes all procedures from nucleic acid quantification to variant interpretation, plays a central role in ensuring the accuracy and clinical utility of molecular results. This document aims at supporting pathology teams—comprising pathologists, technicians, and molecular biologists—during the implementation and execution of the analytical phase of NGS testing. Key topics include clinical indications, platform and gene panel selection, bioinformatics pipelines, quality assurance strategies, and organizational considerations. The goal is to promote standardized, high-quality molecular diagnostics to advance precision pathology.

Part III – Post-analytical phase

Simonetta Buglioni — 2025-05-09

Precision oncology requires standardized and clinically meaningful reporting of molecular test results to support therapeutic decision-making. Next-generation sequencing (NGS), increasingly used in routine diagnostics, must be accompanied by clear, structured, and up-to-date interpretative reports. This document provides updated guidance for the annotation, interpretation, and reporting of variants detected through NGS, encompassing both small targeted panels and large-scale comprehensive genomic profiling (CGP) assays. Emphasis is placed on structured reporting, clinical applicability, and harmonization across institutions. The recommendations also address critical aspects of quality assurance, standardization for both tissue and liquid biopsy samples, with the aim to streamline molecular report generation, improve multidisciplinary communication, and facilitate the integration of NGS into everyday oncology practice in Italy.