Objectives To assess the malignancy risk of peripheral lung lesions with non-diagnostic percutaneous transthoracic needle biopsy (PTNB) findings and to evaluate contrast-enhanced ultrasound (CEUS) guidance for reducing non-diagnostic outcomes. Materials and methods This retrospective study included patients who underwent PTNB at three institutions between October 2018 and March 2023. PTNB results were categorized as diagnostic (malignancy or specific benignity) or non-diagnostic (nonspecific benignity, atypical epithelia, insufficient samples, or sampling failure). The risk factors for malignancy and the effectiveness of CEUS for guiding PTNB were analyzed. Results This study included 1591 peripheral lung lesions from 1558 patients (median age: 63 y; range: 18–87 y). Among these patients, 1072 were male, and 486 were female. Approximately 40% of PTNBs yielded non-diagnostic results. Malignancy risk increased with increasing lesion size (p < 0.001). Granulomatous inflammation/organizing pneumonia was a protective factor. Compared with atypical cells of undetermined significance, atypical cells suspicious of malignancy conferred a higher malignancy risk (p < 0.001). No significant difference in malignancy rates was observed between insufficient samples and sampling failures (p > 0.05). Compared with non‑contrast enhanced US guidance, CEUS guidance demonstrated a significantly greater sampling success rate, higher diagnostic accuracy, and higher sensitivity, particularly for lesions measuring 3.1–5.0 cm (all p < 0.05). Conclusion In terms of non-diagnostic PTNB results, lesions with atypical epithelia have the highest malignancy risk, whereas nonspecific benign lesions have the lowest risk. This study suggests that CEUS-guided PTNB is significantly effective for diagnosing lesions ranging from 3.1 to 5.0 cm in size, aiding the selection of imaging guidance. Key Points <Emphasis Type="BoldItalic">Question</Emphasis> What is the malignancy risk in peripheral lung lesions of non-diagnostic PTNB results, and can CEUS guidance effectively improve diagnostic accuracy and reduce inconclusive outcomes? <Emphasis Type="BoldItalic">Findings</Emphasis> Malignancy risk varies significantly across different non-diagnostic pathological categories, while CEUS guidance demonstrated improved overall diagnostic performance, particularly for lesions measuring 3.1 to 5.0 cm. <Emphasis Type="BoldItalic">Clinical relevance</Emphasis> This study provides a risk-stratification framework for managing non-diagnostic biopsies and demonstrates that integrating CEUS can optimize sampling success, reduce repeated procedures, and ensure timely, accurate diagnosis for patients with peripheral lung lesions. Graphical Abstract

Malignancy risk and contrast-enhanced ultrasound guidance in non-diagnostic biopsies of peripheral lung lesions: a multicenter study

期刊论文
发表日期：

2026年7月29日

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Qi Li,
Xueliang Yan,
Fang Nie,
Tiantian Dong,
Dan Yang,
Ting Liu,
Yanfang Wang,
Tiangang Li,
Bingzheng He

摘要

Objectives

To assess the malignancy risk of peripheral lung lesions with non-diagnostic percutaneous transthoracic needle biopsy (PTNB) findings and to evaluate contrast-enhanced ultrasound (CEUS) guidance for reducing non-diagnostic outcomes.

Materials and methods

This retrospective study included patients who underwent PTNB at three institutions between October 2018 and March 2023. PTNB results were categorized as diagnostic (malignancy or specific benignity) or non-diagnostic (nonspecific benignity, atypical epithelia, insufficient samples, or sampling failure). The risk factors for malignancy and the effectiveness of CEUS for guiding PTNB were analyzed.

Results

This study included 1591 peripheral lung lesions from 1558 patients (median age: 63 y; range: 18–87 y). Among these patients, 1072 were male, and 486 were female. Approximately 40% of PTNBs yielded non-diagnostic results. Malignancy risk increased with increasing lesion size (p < 0.001). Granulomatous inflammation/organizing pneumonia was a protective factor. Compared with atypical cells of undetermined significance, atypical cells suspicious of malignancy conferred a higher malignancy risk (p < 0.001). No significant difference in malignancy rates was observed between insufficient samples and sampling failures (p > 0.05). Compared with non‑contrast enhanced US guidance, CEUS guidance demonstrated a significantly greater sampling success rate, higher diagnostic accuracy, and higher sensitivity, particularly for lesions measuring 3.1–5.0 cm (all p < 0.05).

Conclusion

In terms of non-diagnostic PTNB results, lesions with atypical epithelia have the highest malignancy risk, whereas nonspecific benign lesions have the lowest risk. This study suggests that CEUS-guided PTNB is significantly effective for diagnosing lesions ranging from 3.1 to 5.0 cm in size, aiding the selection of imaging guidance.

Key Points

Question What is the malignancy risk in peripheral lung lesions of non-diagnostic PTNB results, and can CEUS guidance effectively improve diagnostic accuracy and reduce inconclusive outcomes?

Findings Malignancy risk varies significantly across different non-diagnostic pathological categories, while CEUS guidance demonstrated improved overall diagnostic performance, particularly for lesions measuring 3.1 to 5.0 cm.

Clinical relevance This study provides a risk-stratification framework for managing non-diagnostic biopsies and demonstrates that integrating CEUS can optimize sampling success, reduce repeated procedures, and ensure timely, accurate diagnosis for patients with peripheral lung lesions.

Graphical Abstract