Transbronchial Cryobiopsy in the Era of Precision Thoracic Diagnostics: Histopathology, Omics, Radiomics, and AI Converge

Transbronchial cryobiopsy (TBCB) represents one of the most significant innovations in recent years in the diagnosis of diffuse lung diseases and thoracic malignancies. This technique, which involves the use of a cryoprobe introduced endoscopically, enables the collection of large, well-preserved tissue samples free from compression artifacts, thus overcoming the limitations of traditional forceps biopsies and providing a less invasive alternative to surgical lung biopsy. The retrieved tissues are ideal not only for histopathological evaluation but also for advanced molecular analyses, including next-generation sequencing (NGS), transcriptomics (RNA-seq), epigenomics, and proteomic profiling, positioning TBCB as a key tool in thoracic precision medicine. In light of current evidence, TBCB emerges not only as a high-value biopsy technique but also as a strategic technological platform for integrated morphological and molecular diagnosis, paving the way for a more equitable, timely, and personalized approach to the management of complex pulmonary diseases. This paper provides a critical and multidimensional review of the emerging applications of TBCB, encompassing its role in the integrated diagnosis of interstitial lung diseases (ILDs), in the molecular characterization of non-small cell lung cancer (NSCLC), in the identification of emerging biomarkers, and in synergy with advanced technologies such as radiomics and artificial intelligence. Particular attention is given to the use of TBCB in clinically fragile populations, including children, the elderly, and patients with severe comorbidities, highlighting its favourable safety profile, risk mitigation strategies, and the high quality of tissue samples obtainable even in these delicate clinical settings.