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DOI: 10.1055/s-0045-1811697
Percutaneous Lung Biopsy: Evidence-Based Techniques to Reduce Complications

Image-guided percutaneous lung biopsy is a commonly performed procedure that provides cells or tissue for pathologic diagnosis, typically under computed tomography (CT) guidance. The most common indication is evaluation of a suspicious pulmonary nodule concerning for malignancy, for which percutaneous lung biopsy has a diagnostic yield of > 90%.[1] [2] These lesions may be found incidentally, during low-dose lung cancer screening, or as part of the evaluation of a symptomatic patient. Beyond primary malignancy, percutaneous lung biopsy may be used for staging in patients with lung nodules in the setting of known extra-thoracic malignancy, or in cases of persistent pulmonary infection despite empiric treatment.
During the procedure, fine needle aspiration (FNA), core needle biopsy, or both can be performed. While FNA provides cells for diagnosis, it omits cellular architecture and provides less tissue overall compared to a core biopsy. Over the past 15 years, lung biopsies have transitioned from predominantly FNA to predominantly core biopsy sampling in the United States.[1] This reflects increased use of molecular testing in the assessment of primary lung cancer, which requires greater quantities of tissue.
When comparing core needle biopsy and FNA, the former is associated with both higher rates of sufficient tissue for diagnosis (99% vs. 91%) and higher diagnostic accuracy (95% vs. 86%) overall.[3] Similar findings are confirmed by multiple smaller studies.[4] [5] Core needle biopsy is also associated with higher diagnostic accuracy in the setting of benign disease (91% vs. 52%),[6] ability to diagnose specific cancer subtypes, and the ability to complete molecular analysis.[5] Factors associated with lower diagnostic accuracy include target lesion size < 1 cm, subsolid lesions, a final diagnosis of benign disease or lymphoma, and use of FNA alone.[3] The Society of Interventional Radiology Quality Improvement Guidelines recommend a QI threshold success rate of at least 90% for percutaneous biopsy of lesions greater than 2 cm and at least 80% for lesions under 2 cm.[7] While core needle biopsy is associated with a higher rate of complications overall, meta-analysis demonstrates no difference in major complication rates between the two techniques.[8]
The most frequent diagnosis made from percutaneous biopsy is nonsmall cell lung cancer (NSCLC), which represents 85% of all lung cancer diagnoses. With the development of a number of targeted therapies over the past 15 years, molecular testing for driver mutations has become essential, particularly in the evaluation of adenocarcinoma, the most common NSCLC subtype.[9] These tests assess for the presence of common driver mutations in tyrosine kinases such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) and enable the use of targeted tyrosine kinase inhibitors (TKIs) when mutations are present. Currently, osimertinib is the preferred EGFR-TKI,[10] [11] [12] and alectinib, brigatinib, and lorlatinib are the first-line ALK-TKIs.[13] [14] [15] Additional targeted therapies are available for lung cancers driven by less common mutations in ROS-1, NTRK, MET, RET, and BRAF. Lung biopsy for molecular analysis demonstrates similar yield and safety compared to conventional indications, with the caveat that a core biopsy technique is recommended, as FNA alone does not typically provide an adequate amount of tissue for diagnosis.[16]
In addition to tissue testing, liquid biopsy has emerged as a useful tool for molecular characterization, particularly in the setting of lung adenocarcinoma. In liquid biopsy, patient serum samples undergo next-generation sequencing to identify circulating tumor DNA, allowing for the identification of driver mutations. Most importantly, this allows for a noninvasive method to assess for tumor clonal evolution after progression on targeted therapy to direct subsequent therapeutic options.[17] In addition, liquid biopsy can increase biomarker detection when used in concert with tissue biopsy at initial diagnosis, with studies reporting up to a 65% increase in the detection of actionable mutations.[18] Further, liquid biopsy is being explored as an acceptable initial approach for the assessment of driver mutations in the absence of available tissue. Finally, small-scale studies have proposed liquid biopsy as a screening tool to supplement low-dose lung cancer screening in high-risk populations, and as a screening tool after complete surgical resection in early lung cancer to predict the likelihood of recurrence.[19] The primary barrier to the widespread adoption of liquid biopsy as an initial screening tool is its low sensitivity in early disease, with a reported sensitivity of around 50% for stage 1 NSCLC.[20] [21]
Publication History
Article published online:
16 September 2025
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