To assess the added value of contrast-enhanced ultrasound (CEUS) to conventional ultrasound (US) in differentiating benign soft-tissue tumors from malignant ones.

One hundred and night-seven soft-tissue tumors underwent US examination with confirmed histopathology were retrospectively evaluated. The radiologists classified all the tumors as benign, malignant, or indeterminate according to US features. The indeterminate tumors underwent CEUS were reviewed afterwards for malignancy identification by using individual and combined CEUS features.

US analysis classified 62 soft-tissue tumors as benign, 111 tumors as indeterminate and 24 tumors as malignant. There were 104 indeterminate tumors that underwent CEUS. Three CEUS features of enlargement of enhancement area, infiltrative enhancement boundary, and intratumoral arrival time difference were significantly associated with the tumor nature in both univariable and multivariable analysis in the indeterminate tumors (all p < 0.05). When at least one out of the three discriminant CEUS features were present, the best sensitivity of 100% for malignancy identification was obtained with the specificity of 66.7% and the AUC of 0.833. When at least two of the three discriminant CEUS features were present, the best area under the receiver operating characteristic curve (AUC) of 0.924 for malignancy identification was obtained. The combination of at least two discriminant CEUS features showed much better diagnostic performance than the optimal combination of US features in terms of AUC (0.924 vs 0.608, p < 0.0001), sensitivity (94.0% vs 42.0%, p < 0.0001), and specificity (90.7% vs 79.6%, p = 0.210) in the indeterminate tumors.

The combination CEUS features of enlargement of enhancement area, infiltrative enhancement boundary and intratumoral arrival time difference are valuable to improve the discriminating performance in indeterminate soft-tissue tumors on conventional US.

The combination of peritumoral and arrival-time CEUS features can improve the discriminating performance in indeterminate soft-tissue tumors on conventional US.