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Review
. 2024 Apr 16;13(8):2302.
doi: 10.3390/jcm13082302.

The Role of Contrast-Enhanced Ultrasound in the Differential Diagnosis of Malignant and Benign Subpleural Lung Lesions

Andrea Boccatonda  1   2 , Maria Teresa Guagnano  3 , Damiano D'Ardes  3 , Francesco Cipollone  3 , Luigi Vetrugno  4 , Cosima Schiavone  5 , Fabio Piscaglia  2   6 , Carla Serra  7
Affiliations
Review

The Role of Contrast-Enhanced Ultrasound in the Differential Diagnosis of Malignant and Benign Subpleural Lung Lesions

Andrea Boccatonda et al. J Clin Med. .

Abstract

Background: The application of transthoracic contrast-enhanced ultrasound (CEUS) to the study of peripheral lung lesions is still a topic of debate. The main objective of this review was to evaluate the diagnostic accuracy of CEUS in the diagnosis of malignant subpleural pulmonary consolidations and, therefore, differentiate them from benign ones. Methods: Papers published before December 2023 were detected through a search of PubMed, Cochrane library, and Embase. The pooled specificity and sensitivity, summary receiver operating characteristic (SROC) curve and diagnostic odds ratio (DOR) were used. Results: CEUS is characterized by a pooled sensitivity of 0.95 (95% CI: 0.93-0.97) and a pooled specificity of 0.93 (95% CI: 0.90-0.95) in differentiating benign and malignant subpleural lung diseases; the AUC of SROC was 0.97. Homogeneous CE was characterized by a pooled sensitivity of 0.43 (95% CI: 0.40-0.45) and the pooled specificity of 0.49 (95% CI: 0.46-0.52). Non-homogeneous CE displayed a pooled sensitivity of 0.57 (95% CI: 0.55-0.60) and a pooled specificity of 0.51 (95% CI: 0.48-0.54). The lack of CE displayed a pooled sensitivity of 0.01 (95% CI: 0.00-0.06) and a pooled specificity of 0.76 (95% CI: 0.64-0.85). Marked CE displayed a pooled sensitivity of 0.41 (95% CI: 0.37-0.44) and a pooled specificity of 0.54 (95% CI: 0.50-0.58). Non-marked CE displayed a pooled sensitivity of 0.59 (95% CI: 0.56-0.63) and a pooled specificity of 0.46 (95% CI: 0.42-0.50). The early AT displayed a pooled sensitivity of 0.04 (95% CI: 0.02-0.08) and a pooled specificity of 0.83 (95% CI: 0.77-0.87). The early wash out displayed a pooled sensitivity of 0.61 (95% CI: 0.48-0.72) and a pooled specificity of 0.98 (95% CI: 0.92-1.00). The delayed wash out displayed a pooled sensitivity of 0.15 (95% CI: 0.10-0.20) and a pooled specificity of 0.69 (95% CI: 0.62-0.75). Conclusions: CEUS is characterized by excellent diagnostic accuracy for the diagnosis of the malignancy of subpleural lung lesions. By separately analyzing the CEUS findings, the diagnostic accuracy values are considerably lower and not significant in some cases. The simultaneous evaluation of multiple CEUS features allows us to reach an excellent diagnostic accuracy. Non-homogeneous CE with early wash out are the most indicative features of malignancy of a lung lesion.

Keywords: CEUS; consolidation; lung; malignant lesion; ultrasound.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
Risk of bias and applicability concerns graph: review authors’ judgements about each domain presented as percentages across included studies.
Figure 3
Figure 3
Risk of bias and applicability concerns summary: review authors’ judgements about each domain for each included study [15,16,17,18,19,20,21,22,23,24].
Figure 4
Figure 4
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of CEUS in differentiating malignant vs. benign peripheral lung lesions. In particular, 970 patients with 536 malignant lesions were analyzed [15,17,22].
Figure 4
Figure 4
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of CEUS in differentiating malignant vs. benign peripheral lung lesions. In particular, 970 patients with 536 malignant lesions were analyzed [15,17,22].
Figure 5
Figure 5
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of homogeneous contrast enhancement in differentiating malignant vs. benign peripheral lung lesions. In particular, 8 studies for a total of 2623 patients and 1413 malignant lesions were examined [15,16,17,18,19,20,21,23].
Figure 5
Figure 5
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of homogeneous contrast enhancement in differentiating malignant vs. benign peripheral lung lesions. In particular, 8 studies for a total of 2623 patients and 1413 malignant lesions were examined [15,16,17,18,19,20,21,23].
Figure 6
Figure 6
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of non-homogeneous contrast enhancement in differentiating malignant vs. benign peripheral lung lesions. In particular, 8 studies for a total of 2623 patients and 1413 malignant lesions were examined [15,16,17,18,19,20,21,23].
Figure 6
Figure 6
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of non-homogeneous contrast enhancement in differentiating malignant vs. benign peripheral lung lesions. In particular, 8 studies for a total of 2623 patients and 1413 malignant lesions were examined [15,16,17,18,19,20,21,23].
Figure 7
Figure 7
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of a lack of contrast enhancement in differentiating malignant vs. benign peripheral lung lesions. In particular, 2 studies on 158 patients with 92 malignant lesions were included [18,20].
Figure 8
Figure 8
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of marked contrast enhancement in differentiating malignant vs. benign peripheral lung lesions. In particular, 4 studies on 1476 patients with 819 malignant lesions were examined [16,18,20,21].
Figure 8
Figure 8
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of marked contrast enhancement in differentiating malignant vs. benign peripheral lung lesions. In particular, 4 studies on 1476 patients with 819 malignant lesions were examined [16,18,20,21].
Figure 9
Figure 9
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of non-marked contrast enhancement in differentiating malignant vs. benign peripheral lung lesions. In particular, 4 studies on 1476 patients with 819 malignant lesions were examined [16,18,20,21].
Figure 9
Figure 9
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of non-marked contrast enhancement in differentiating malignant vs. benign peripheral lung lesions. In particular, 4 studies on 1476 patients with 819 malignant lesions were examined [16,18,20,21].
Figure 10
Figure 10
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of early arrival time of contrast enhancement in differentiating malignant vs. benign peripheral lung lesions. In particular, 2 studies involving 412 patients with 200 malignant lesions were analyzed [19,20].
Figure 10
Figure 10
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of early arrival time of contrast enhancement in differentiating malignant vs. benign peripheral lung lesions. In particular, 2 studies involving 412 patients with 200 malignant lesions were analyzed [19,20].
Figure 11
Figure 11
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of early wash out of contrast enhancement in differentiating malignant vs. benign peripheral lung lesions. In particular, 2 studies on 155 patients with 71 malignant lesions were analyzed [17,20].
Figure 11
Figure 11
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of early wash out of contrast enhancement in differentiating malignant vs. benign peripheral lung lesions. In particular, 2 studies on 155 patients with 71 malignant lesions were analyzed [17,20].
Figure 12
Figure 12
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of delayed wash out of contrast enhancement in differentiating malignant vs. benign peripheral lung lesions. In particular, 3 studies on 472 patients with 218 lesions were analyzed [17,19,20].
Figure 12
Figure 12
Sensitivity, specificity, diagnostic odds ratio, and SROC curve of delayed wash out of contrast enhancement in differentiating malignant vs. benign peripheral lung lesions. In particular, 3 studies on 472 patients with 218 lesions were analyzed [17,19,20].
Figure 13
Figure 13
Pooled SROC curve of different contrast-enhanced ultrasound features in differentiating malignant vs. benign peripheral lung lesions. Contrast enhancement, CE; arrival time, AT.
Figure 14
Figure 14
Evaluation of publication bias by contour-enhanced funnel plot.
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