Abstract
Background: Peripheral pulmonary lesions are increasingly detected through widespread computed tomography use, incidental imaging, and low-dose CT lung cancer screening programs. Diagnostic techniques have advanced substantially, including radial endobronchial ultrasound (rEBUS), virtual and electromagnetic navigation bronchoscopy, ultrathin bronchoscopy, cryobiopsy, cone-beam CT (CBCT), augmented fluoroscopy, and robotic-assisted bronchoscopy. Despite this rapid technological evolution, the interpretation of benign or non-malignant biopsy results remains one of the most consequential and underappreciated clinical challenges in pulmonary medicine. Summary: A benign biopsy result from a peripheral pulmonary lesion must not be interpreted as a single, unambiguous entity. Specific benign diagnoses, nonspecific benign findings, atypia, suspicious results, and nondiagnostic samples each carry a distinct residual probability of malignancy and different implications for subsequent management. Recent consensus recommendations mandate a strict definition of diagnostic yield, in which only specific malignant diagnoses and specific benign diagnoses sufficient to inform patient care are counted as truly diagnostic. Follow-up data are essential for calculating diagnostic accuracy, sensitivity for malignancy, negative predictive value, and false-negative rates — but should not retroactively reclassify nonspecific or nondiagnostic index results as diagnostic. We propose that the diagnostic process be understood as a chain: tool/access → navigation → position confirmation → sampling → pathology → final clinic-radiologic diagnosis. Failure at any link may create a diagnostic gap and produce a falsely reassuring result. Newer technologies address different links: robotic bronchoscopy primarily narrows the access and stability gap, while CBCT and augmented fluoroscopy primarily narrow the position confirmation gap. Neither technology — alone or combined — closes the sampling, pathology, or clinical concordance gaps.