Ipsilateral axillary diagnostic ultrasound is part of the initial staging for breast cancer to evaluate lymph nodes using a b-mode classification where certain aspects, when present, increase the level of suspicion for metastatic disease, such as cortical thickening and poor hilar visibility.1–3 Diagnostic ultrasound is also used as a method to guide biopsies of the suspicious lymph nodes.1
The majority of patients will have no suspicious lymph nodes findings at the time of diagnosis, the lymphatic system mapping after the injection of blue dye and/or a radioactive tracer followed by a surgical excision becomes the only way to determine the final stage of disease. However, these methods have limitations such as the use of radiation and lack of an imaging component.
In the past, ultrasound could not be used for lymphatic mapping, since mapping requires administration of a tracer. This changed with the use of contrast-enhanced ultrasound (CEUS) to detect lymph nodes after subcutaneous injections of microbubble-based ultrasound contrast agents (UCA), termed “lymphosonography”.4–6 The development of the lymphosonography technique addressed the limitations of the currently used lymphatic mapping techniques.
Our group conducted a clinical trial to evaluate the efficacy of CEUS lymphosonography in the identification of sentinel lymph nodes (SLN) in patients with breast cancer undergoing surgical excision following the injection of blue dye and radioactive tracer as part of their standard of care using pathology results for malignancy as a reference standard.6,7
In the clinical trial, 86 subjects were enrolled and 79 completed the study. The subjects received 4 subcutaneous injections of ultrasound contrast agent around the tumor, for a total of 1.0 ml. A clinical ultrasound scanner with CEUS capabilities was used to identify SLNs. After the ultrasound study examination, the subjects received blue dye and radioactive tracer for guiding SLN excision as part of their standard of care. The SLNs excised during the standard-of-care surgical excision were classified as positive or negative for presence of blue dye, radioactive tracer and UCA, and sent for pathology to determine presence or absence of metastatic involvement.
A total of 252 SLNs were excised from the 79 subjects. Of the 252 SLNs excised, 158 were positive for blue dye, 222 were positive for radioactive tracer and 223 were positive for UCA. Statistical comparison showed that compared with the reference standards, lymphosonography showed similar accuracy with radioactive tracer (p > 0.15) and higher accuracy (p < 0.0001). The pathology results showed that, of the 252 SLNs excised, 34 had metastatic involvement and were determined malignant by pathology. Of these 34 SLNs, 18 were positive for blue dye (detection rate of 53%), 23 were positive for radioactive tracer (detection rate of 68%) and 34 were positive for UCA (detection rate of 100%; p < 0.0001).
The conclusion of this study indicates that lymphosonography had similar accuracy as the standard-of-care methods for identifying SLNs in breast cancer patients, with the added advantage of an imaging component that allows for a preoperative evaluation of SLNs and that lymphosonography may be a more specific and precise approach to SLN identification in patients with breast cancer.6
Larger multicenter clinical trials are necessary to be able to translate this technique to the clinical setting and to be able to incorporate it as part of the breast cancer patients’ standard of care.
- Voit CA, van Akkooi ACJ, Schäfer-Hesterberg G, et al. Rotterdam Criteria for sentinel node (SN) tumor burden and the accuracy of ultrasound (US)-guided fine-needle aspiration cytology (FNAC): can US-guided FNAC replace SN staging in patients with melanoma? J Clinical Oncol 2009; 27(30):4994–5000.
- Dialani V, Dogan B, Dodelzon K, Dontchos BN, Modi N, Grimm L. Axillary imaging following a new invasive breast cancer diagnosis—A radiologist’s dilemma. J Breast Imaging 2021; 3:645–658.
- Chang JM, Leung JWT, Moy L, Ha SM, Moon WK. Axillary nodal evaluation in breast cancer: state of the art. Radiology 2020; 295:500–515.
- Goldberg BB, Merton DA, Liu J-B, Thakur M, et al. Sentinel lymph nodes in a swine model with melanoma: contrast-enhanced lymphatic US. Radiology 2004; 230:727–734.
- Goldberg BB, Merton DA, Liu J-B, Murphy G, Forsberg F. Contrast‐enhanced sonographic imaging of lymphatic channels and sentinel lymph nodes. J Ultrasound Med 2005; 24:953–965. doi: 10.7863/jum.2005.24.7.953.
- Machado P, Liu J-B, Needleman L, et al. Sentinel lymph node identification in patients with breast cancer using lymphosonography. Ultrasound Med Biol 2023; 49:616–625. Epub 2022 Nov 26.
- Machado P, Liu JB, Needleman L, et al. Sentinel lymph node identification in post neoadjuvant chemotherapy breast cancer patients undergoing surgical excision using lymphosonography. J Ultrasound Med 2023; 42:1509–1517. doi: 10.1002/jum.16164. Epub 2023 Jan 2.
Priscilla Machado, MD, FAIUM, is a Research Assistant Professor in the Department of Radiology at Thomas Jefferson University in Philadelphia, PA.
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