Transbronchial cryobiopsy in the era of precision thoracic diagnostics: Histopathology, omics, radiomics, and AI converge

In the era of precision medicine, transbronchial cryobiopsy (TBCB) has emerged as a significant technological advancement supporting the diagnosis of diffuse lung diseases and thoracic malignancies. The advent of targeted therapies, along with the increasing need to identify new diagnostic and prognostic biomarkers, has made it essential to adopt innovative surgical techniques capable of obtaining large, well-preserved tissue samples. This approach not only enables accurate histopathological assessment but also allows for comprehensive molecular analyses, while meeting the requirement for minimal invasiveness in particularly fragile patients or those with severe comorbidities. Tissue samples obtained via TBCB are immediately frozen, offering a precise snapshot of the disease at the time of collection. The sample size is generally sufficient for further molecular testing, thereby reducing the need for repeat biopsies and enabling prompt and accurate diagnosis—an essential element in the treatment pathway for patients with complex pulmonary conditions, both oncologic and interstitial. Although surgical lung biopsy remains the gold standard in terms of diagnostic accuracy, TBCB has demonstrated superiority over conventional forceps biopsy techniques, both in terms of sample quality and safety profile, with a significantly lower risk of serious complications. This review aims to critically evaluate the available evidence supporting TBCB compared to traditional techniques, with a particular focus on its role in the molecular characterization of thoracic tumors and interstitial lung diseases. Furthermore, we explore its integration into a forward-looking framework where TBCB contributes to radiomics and artificial intelligence training, fostering the development of predictive tools for diagnosis, prognosis, and therapeutic response.