To evaluate the value of multimodal ultrasound—including conventional ultrasound, elastography, and contrast-enhanced ultrasound—in the differential diagnosis of benign and malignant subcentimeter (≤1 cm) breast nodules with microcalcifications.

This retrospective study enrolled 120 patients with pathologically confirmed subcentimeter breast nodules with microcalcifications between January 2022 and March 2025. Using pathological results as the gold standard, the patients were divided into benign and malignant groups. Univariate analysis (χ² test and non-parametric test) was performed to compare sonographic features (conventional ultrasound, elastography, and contrast-enhanced ultrasound) between the two groups. Multivariate logistic regression analysis was used to identify independent risk factors. Receiver operating characteristic curves were plotted to evaluate the diagnostic performance of each independent risk factor alone and in combination. Nodules negative for all independent risk factors were further defined as "ultrasound-low-risk" nodules, and the remaining nodules as "ultrasound-high-risk" nodules. The negative predictive value of this risk stratification strategy was calculated.

A total of 120 nodules were included, comprising 75 benign and 45 malignant. Compared with the benign group, malignant nodules more frequently exhibited larger diameters [9.00 (7.00, 10.00) mm vs 7.00 (6.00, 10.00) mm], irregular shape (82.22% vs 61.33%), irregular margins (88.89% vs 24.00%), and clustered distribution of microcalcifications (40.00% vs 10.67%). Malignant nodules also showed higher elastography scores (grades 4-5: 55.56% vs 18.67%). On contrast-enhanced ultrasound, malignant nodules more commonly demonstrated high enhancement (95.56% vs 54.67%), irregular margins after enhancement (62.22% vs 29.33%), and enlarged lesion size after enhancement (82.22% vs 16.00%). All these differences were statistically significant (Z = –2.432, P = 0.015; Z = –5.754, P=0.016; χ²=47.422, P＜0.001; χ²=14.259, P＜0.001; χ²=17.446, P＜0.001; χ²=22.693, P＜0.001; χ²=12.517, P＜0.001; and χ²=51.051, P＜0.001, respectively). Multivariate logistic regression analysis identified irregular margins, clustered distribution of microcalcifications, and enlarged lesion size after enhancement as independent risk factors for malignant nodules (odds ratio [OR]=41.127, P＜0.001; OR=15.088, P=0.005; OR=9.622, P=0.009). The combination of these factors yielded higher diagnostic performance than any single factor, with an area under the curve of 0.940, accuracy of 90.83%, sensitivity of 88.89%, and specificity of 92.00%. After risk stratification, 44 nodules were classified as "ultrasound-low-risk" nodules, with a negative predictive value of 97.72% (43/44).

Multimodal ultrasound combined diagnosis demonstrates excellent discriminatory efficacy for subcentimeter breast nodules with microcalcifications. The "ultrasound-low-risk" stratification rule based on independent risk factors achieves a high negative predictive value, offering important support for avoiding unnecessary biopsies in such nodules.