Focused ultrasound ablation surgery for multiple breast fibroadenomas: pathological and follow-up results

Abstract

Objective

To investigate the histopathological findings and follow-up outcome of focused ultrasound ablation surgery (FUAS) treatment of multiple fibroadenomas (FA).

Methods

A total of 20 patients with 101 multiple FAs were enrolled. After one session FUAS ablation, 21 lesions (≥15.0 mm) were surgically removed within one week for histopathological analysis, including 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, H&E staining, nicotinamide adenine dinucleotide (NADH) -flavretin enzyme staining, Transmission electron microscope (TEM) and scanning electron microscope (SEM). The remaining 80 lesions were followed up at 3, 6 and 12 months after treatment.

Results

All ablation procedures were performed successfully. Pathologic findings showed that irreversible damage of FA was confirmed. TTC, H&E and NADH staining and TEM/SEM demonstrated tumor cell death and tumor structural destruction at the gross, cellular, and subcellular levels, respectively. The median shrinkage rate at 12 months post-FUAS was 66.4 (43.6, 89.5) %.

Conclusion

Histopathological analysis for FAs after FUAS treatment proved that FUAS could effectively induce irreversible coagulative necrosis of FA, and the tumor volume would gradually shrink in follow-up. FUAS was safe and effective to treat multiple FAs with good cosmesis.

Key points

• This study was the first study of detailed histopathological analysis for FAs after FUAS treatment.

• FUAS can effectively induce irreversible coagulative necrosis of fibroadenoma cells.

• FUAS ablation of multiple fibroadenomas is safe and effective.

Keywords:

• Multiple fibroadenomas
• focused ultrasound ablation surgery
• histopathology
• coagulative necrosis
• shrinkage rate

1 Introduction

Fibroadenoma (FA) is the most common benign tumor of the breast and is commonly seen in young women between the ages of 20 and 30 years [1]. In 20% of cases, patients have multiple FAs in unilateral or bilateral breasts [2]. The exact cause of multiple FAs is not known and is believed to be related to dysregulated hormone levels [3]. Although FA grows slowly and has a low rate of malignant change potential (0.02–0.125%) [4], due to the location of FA is usually superficial and easy to be touched, it may cause anxiety of patients for both physical discomfort and cosmesis concern. Therefore, active clinical intervention is recommended to symptomatic and stressed patients instead of observation by regular physical examination and ultrasound imaging [5].

At present, the treatment of FA includes open surgery (OS), vacuum-assisted mammotomy (VAM) and energy ablation (including cryoablation and thermal ablation) [6]. OS is suitable for large FA, but it may lead to scar formation, breast deformity, breast duct injury, and may increase the incidence of complications, such as postoperative infection, hematoma, and abscess [7]. VAM treatment, with small skin incision, is used as a cosmetic surgery for the treatment of FA with a diameter no more than 3 cm. However, repeated cutting and vacuum suction of the lesion during the treatment process may cause some complications: large internal injury leads to skin dimpling, residual tumor, loss of surrounding normal breast tissue, postoperative hematoma and pain [8]. What’s more, postoperative pressure bandaging may lead to limited mobility and difficult breathing. Since multiple FAs have the characteristics of multiple lesions with scattered distribution, the treatment of multiple FAs is challenging for both OS and VAM. For open surgical resection, treatment of multiple lesions requires multiple incisions or extended incisions, while for VAM, increased number of skin incisions and disposable vacuum probes may also be not acceptable by patients concerning cosmesis as well as cost issues. Thus, minimally invasive and noninvasive energy ablation may become the most reasonable choice for patients with multiple FAs. The aim of treating multiple FAs by energy ablation was to cause necrosis of tumor cells, reduce the size of the lesion or control the growth of the lesion, take the safety and cosmetic effect into account, and avoid the psychological pressure caused by pain and scar.

Focused ultrasound ablation surgery (FUAS), also known as high intensity focused ultrasound (HIFU), the concept of which proposed by Lynn, can focus ultrasonic energy on the target tissue and rapidly heat the target tissue to more than 60 °C within 1 s, leading to protein degeneration and irreversible coagulation necrosis, while the surrounding normal tissue and the skin are not damaged [9,10]. FUAS has been effectively used in the treatment of various solid tumors, such as uterine fibroids, liver cancer, and bone tumors. For its advantages of noninvasiveness, no bleeding risk, satisfactory cosmetic effect, short hospital stay, and short recovery time, FUAS has been increasingly used to treat breast cancer and fibroadenoma. In recent years, Wu et al. first performed a randomized clinical trial of FUAS treatment for breast Cancer [11]. Long-term follow-up, pathologic and immunohistochemical stains were performed to assess the therapeutic effects on tumor. Pathologic findings revealed that FUAS-treated tumor cells underwent complete coagulative necrosis, and tumor vascular vessels were severely damaged. Immunohistochemical staining showed that the treated tumor cells lost the abilities of proliferation, invasion, and metastasis. In 2015, Beatrice et al. first used ultrasound-guided FUAS for the treatment of FA. They demonstrated that FUAS could safely and effectively induce satisfactory ablation of benign breast lesions [12]. In recent years, a few studies have also confirmed the efficacy and safety of FUAS in the treatment of FA [13].

Although the pathological results of breast cancer after FUAS treatment have been discussed in the previous literature, there was a lack of reports on the pathological results of FUAS treatment of FA. Therefore, the aim of this prospective study was to investigate the histopathological findings and follow-up outcome of FUAS treatment of multiple FAs.

2. Patients and methods

2.1. Patient characteristics and enrollment

The study was approved by the ethics committee of Suining central hospital (LLSLH20210044). All patients signed written informed consent. From January 2021 to September 2021, twenty women with multiple FAs were included in the study. The inclusion criterion was as follows: (1) ≥ 16 years old, (2) Multiple FAs was evaluated by ultrasound, (3) FA was pathologically diagnosed by core needle biopsy. Exclusion criteria included: (1) pathological diagnosis of malignant tumor, (2) pregnant or lactating women, and (3) foreign body implantation in the treatment area. The flow chart of research process was shown in Figure 1.

Figure 1. Flow chart of research process.

2.2. Preparation of pre-FUAS

All patients underwent color Doppler ultrasonography (DC80, Mindary, China) before FUAS to measure diameters of FAs and to evaluate the blood flow signal of the tumor. The tumor volume was calculated by the following formula: V (mm³) = 0.5233 × a × b × c. After determining and marking the locations of the lesion, the patient underwent local anesthesia with 10–20 ml of 1% ropivacaine.

2.3. FUAS ablation

The procedure of FUAS was performed using the Focused Ultrasound Ablation System for Breast (Model JCQ-B, Chongqing Haifu Medical Technology Co. Ltd., China). Briefly, the patient was placed in prone position on the treatment bed, with the targeted breast immersed into a low-temperature degassed water. Real-time ultrasound was used for monitoring the target tumor and adjacent structure. The focus was put in the deep side of FA and the focused ultrasound energy was accumulatively given until the hyperechoic grayscale change emerging. And then, the focus was manually moved to the margin of hyperechoic grayscale, until this scale change covered the whole tumor, which was the termination criteria of the treatment (Figure 2). All the FA lesions visible under real-time ultrasound monitoring were treated one by one in a single FUAS session. After treatment, an ice bag was put on the breast skin for 0.5–2 h.

Figure 2. Changes of FA lesions treated with FUAS under real-time ultrasound monitoring. (A) Before treatment. (B) Hyperechoic scale changes occurred in the lesion during treatment. (C) Hyperechoic scale changed area covered the whole FA.

During treatment, following therapeutic indicators were recorded: treatment time (min), sonication time (s), time of hyperechoic grayscale change emerging (s), mean power (W), sonication energy. Energy efficiency factor (EEF, J/mm³), defined as the amount of acoustic energy required for ablating 1 mm³ of the biological tissue, were also recorded [14]. Visual analogue scale (VAS), scored from 0 to 10, was used to evaluate the pain feeling during treatment. Any adverse events, including skin burn, fever and pectoralis major injury, were recorded within 72h after FUAS treatment and in follow-up.

2.4. Open surgery

Within seven days after FUAS treatment, lesion with the largest diameter ≥ 15.0 mm was surgically removed. When a patient had two or more lesions needed to be surgically removed, one would be ablated followed by resection, while the other/others would be directly resected as a control. The removed tissue was kept in certain condition for the following experiments.

2.5. Histopathologic analysis

2.5.1 2, 3, 5-triphenyltetrazolium chloride (TTC) staining

As we reported before, cell viability of ablated and non-ablated FA samples was determined by TTC staining after gross specimens were retrieved [15].

2.5.2. Hematoxylin and eosin (H&E) staining

The resected FA tissue was placed in 4% paraformaldehyde for sample fixation. After that, the sample was dehydrated with alcohol, embedded in paraffin and sectioned. Slides were stained with hematoxylin and eosin. Nonablated FA samples were stained by H&E as negative control.

2.5.3. Immunohistochemistry

The excised FA tissue was frozen and cut into sections, and the specimens were stained with reduced nicotinamide adenine dinucleotide (NADH) flavretin enzyme according to the manufacturer’s instructions (GM80039.2, GENMED, USA). Nonablated FA samples were prepared as negative control.

2.5.4. Transmission electron microscope (TEM) and scanning electron microscope (SEM)

Three to five tissue samples of approximately 1 mm³ (1 mm × 1 mm × 1 mm, for TEM) or 125 mm³ (5 mm × 5 mm × 5 mm, for SEM) in volume were cut from the ablated or non-ablated FA tissue. The samples were fixed in 2.5% glutaraldehyde solution (pH 7.4) at 4 °C for more than 2 h, followed by fixing in 1% osmium tetroxide solution, dehydrating in ethanol gradient, and embedding in epoxy resin. Semi-thin and ultrathin sections were examined with light microscopy to locate the ablated area. After double staining with uranyl acetate and lead citrate, the ultrastructural changes of cells after FUAS were observed under TEM (Hitachi-7500796, Hitachi Koki Co, Ltd, Tokyo, Japan) or SEM (Hitachi-S3000N, Hitachi Koki Co, Ltd, Tokyo, Japan).

2.6. Follow-up

Patients were followed up at 3, 6 and 12 months post-FUAS with physical examination and ultrasound imaging. Tumor volume were calculated as mentioned before. The shrinkage rate of tumor volume was calculated using the following formula: shrinkage rate = (Volume pre-FUAS – Volume in 3, 6, 12 months follow-up)/Volume pre-FUAS × 100%.

2.7. Statistical analysis

SPSS software (SPSS 25.0, IBM, USA) was used for statistical analysis. After one-sample Kolmogorov-Smirnov test, normally distributed data were reported as mean ± SD. Skewly distributed data were reported as median and inter-quartile range (P25, P75). Nonparametric test was used to compare the results before treatment with those at follow-up. Statistical significance was defined as a p value < 0.05.

3. Results

3.1. Baseline characteristics of patients with FAs

A total of 20 patients with 101 FAs were treated by FUAS. As shown in Table 1, the median age of the patients was 25.0 (21.5, 31.0) years. The average number of multiple FAs was 5.2 ± 2.4. Among the patients, nine had previously received other treatments of FA, including OS and VAM. As shown in Table 2, the median size of FA was 14.0 (11.0, 20.1) mm. The median distance from shallow margin of FA to skin and the median distance from deep margin of FA to pectoralis major were 5.5 (3.0, 9.0) mm and 2.9 (0.0, 5.4) mm, respectively. The lesions were distributed in all quadrants of the breast.

Table 1. Baseline characteristics of patients (N = 20).

Variables	Value
Age (y)	25.0 (21.5, 31.0)
BMI (kg/m^2)	20.5 ± 2.6
Mean number of lesions	5.5 ± 2.4
History of previous breast surgery
No history of surgery	11 (55.0%)
OS	5 (25.0%)
VAM	1 (5.0%)
Two or more surgical methods	3 (15.0%)

BMI: body mass index; OS: open surgery; VAM: vacuum-assisted mammotomy.

Table 2. Characteristics of FA lesions (n = 101).

Variables	Value
Size of FA (mm)	14.0 (11.0, 20.1)
FA volume (mm^3)	530.7 (310.8, 1690.3)
Distance between the shallow margin of FA and skin (mm)	5.5 (3.0, 9.0)
Distance between the deep margin of FA and pectoralis major (mm)	2.9 (0, 5.4)
Lesion location
Outer upper quadrant	28 (32.1%)
Upper inner quadrant	29 (24.7%)
Lower inner quadrant	20 (19.8%)
Outer lower quadrant	24 (23.5%)

FA: fibroadenoma.

3.2. Outcomes of FUAS ablation

Every tumor received only one session of FUAS treatment. As shown in Table 3, median treatment time, sonication time, time of hyperechoic change emerging were 13.0 (6.0, 23.0) min, 57.5 (32.0, 108.0) s, 11.5 (4.0, 28.0) s, respectively. Mean power was 149.0 (120.0, 189.0) W, and median sonication energy was 7.8 (4.4, 18.0) kJ. Median EEF was 10.6 (6.9, 20.3) kJ/mm³.

Table 3. FUAS treatment results for FA lesions (n = 101).

Variables	Value
Sonication time (s)	57.5 (32.0, 108.0)
Treatment time (min)	13.0 (6.0, 23.0)
Time of hyperechoic change emerging (s)	11.5 (4.0, 28.0)
Mean power (W)	149.0 (120.0, 189.0)
Sonication energy (kJ)	7.8 (4.4, 18.0)
EEF (kJ/mm^3)	10.6 (6.9, 20.3)
Average VAS score	2.0 (1.0, 3.0)
Pain intensity*
Painless	12.9% (13/101)
Mild pain	72.3% (73/101)
Moderate pain	14.8% (15/101)
Severe pain	0% (0/101)

EEF: energy efficiency factor.

*Pain intensity is expressed by VAS score, 0 is no pain, no pain sensation, 1–3 is mild pain, does not affect work and life, 4–6 is moderate pain, affects work, does not affect life, 7–10 is severe pain, pain severely affects work and life.

Under local anesthesia, all of patients had well tolerance for the procedure, during which the median VAS score was 2.0 (1.0, 3.0) and mostly were mild pain (72.3%, Table 3). No skin burn, fever or pectoralis major injury was found during and within 72h after FUAS treatment (Figure 3).

Figure 3. Skin safety after FUAS. (A) A 23-year-old woman with 8 FAs in the left breast. Left: pre-FUAS, skin marks of FA lesions were made under ultrasound imaging. Right: post-FUAS, the breast skin became a little pale after immersed in cold water, with no skin burn found after treatment. (B) A 35-year-old woman with a history of OS had 4 FAs in the right breast. Left: pre-FUAS, skin marks of FA lesions were made under ultrasound imaging. Right: post-FUAS, the breast skin became a little pale after immersed in cold water, with no skin burn found around the old scar (red arrow).

3.3. Outcomes of histologic analysis

3.3.1. TTC staining

Coagulative necrosis change was revealed in the gross specimen of the ablated FAs by TTC staining, which was presented as pale non-pigmented areas, while the non-ablated FAs showed red TTC staining area (Figure 4(A)).

Figure 4. Pathological results of FA under light microscope or electron microscope. (A) TTC staining of FA. Left: Nonablated FA, red color indicating the viability of tumor cells. Right: Ablated FA. pale color indicating the occurrence of coagulation necrosis. (B) H&E staining. Upper row: Nonablated FA. Tumor tissue was composed of collagen and fibroblasts in rich stroma and distorted lobules, squeezed catheter. A thin line branching structure and fractured appearance lacuna was formed. Fibroadenomatoid changes were considered without signs of necrosis. Lower row: Ablated FA. Signs of coagulate necrosis were found, including nuclear pyknosis, karyorrhexis and karyolysis of tumor cells, unclear cell contour, and swollen collagen fibers with eosinophilic changes. (Magnification: Left, 40×; Middle, 100×; Right, 400×) (C) NADH staining. Upper row: Nonablated FA. Blue-stained spots suggested the viability of tumor cells. Lower row: Ablated FA. No blue- stained spot suggested the absence of vital cells. (Magnification: Left, 40×; Middle, 100×; Right, 400×) (D) TEM images. Upper row: Nonablated FA. The integrity of cell membrane and nuclear membrane, and morphology and distribution of organelles were observed. Lower row: Ablated FA. Destroyed cell membrane and nuclear membrane, damaged organelles were observed. (Magnification: Left, 5000×; Middle, 10000×; Right, 40000×) (E) SEM images. Upper row: Nonablated FA. Proliferative fibrous tissue could be seen on the surface of nonablated FA. Lower row: Ablated FA. Surface features of FA completely disappeared and the fibrous tissue structure of the tumor was destroyed. (Magnification: Left, 5000×; Middle, 10000×; Right, 40000×)

3.3.2 H&E Staining

As demonstrated in Figure 4(B), destroyed structures of the ablated tissue were found with H&E staining. Morphological changes of the nucleus were observed in ablated tissues, which manifested as nuclear pyknosis, karyorrhexis and karyolysis. Furthermore, the cell contour was not clear, and the cytoplasm disappeared as well. The collagen fibers surrounding the mesenchymal cells were swollen and liquefied, represented by eosinophilic changes. All these microscopic characteristics suggested cell death and tissue necrosis after FUAS ablation. However, there was no such signs of coagulative necrosis in the non-ablated specimens.

3.3.3. NADH staining

With NADH-diaphorase analysis, the absence of vital cells was observed in ablated tumors, which was characterized by areas without any blue-stained spot. Non-ablated tumor cells showed numerous blue-stained areas under light microscope, indicating the viability of tumor cells (Figure 4(C)).

3.3.4. TEM and SEM

The subcellular structure was further observed under electron microscope. It was found under TEM that the cell ultrastructure of FA without FUAS ablation was normal, including the integrity of cell membrane and nuclear membrane and normal distribution of mitochondria, Golgi apparatus and endoplasmic reticulum in the cytoplasm. After FUAS ablation, the integrity of cell membrane and nuclear membrane were destroyed. Furthermore, the chromatin in the nucleus were deconstructed and organelles in the cytoplasm were swollen, damaged and even disappeared, while a large number of lysosomes and liposomes appeared in the cytoplasm (Figure 4(D)).

SEM showed that the surface of non-ablated FA displayed numerous diffusely-distributed proliferative tumor fiber tissues in disordered arrangement, and tubule-like structures were formed after these proliferative tumor fiber tissues pressing mammary duct or acinar. However, on the surface of ablated FA tissue, the above-mentioned characteristics were completely disappeared, with no tumor fiber tissue left there (Figure 4(E)).

3.4. Follow-up results for FAs after FUAS ablation

As shown in Figure 5, The volumes of FA gradually and significantly shrank in follow-up (p < 0.05). The shrinkage rate at 3, 6, 12 months post-FUAS was 47.4 (20.0, 64.8) %, 53.7 (21.3, 80.0) % and 66.4 (43.6, 89.5) %, respectively. A typical ultrasound imaging in follow-up was shown in Figure 6.

Figure 5. Percentage of volume remaining during follow-up. Percentage of volume remaining of FA at 3-, 6-, and 12-month post-ablation, which indicated that the tumor volume gradually and significantly shrank over time. At 12-month follow-up, the median percentage of FA volume remaining was 33.6% (*p < 0.05; **p < 0.01)

Figure 6. A typical ultrasound imaging in follow-up. (A) Pre-ablation. (B) At 3-month follow-up, FA volume decreased by 87.5%. C. At 6-month- follow-up, necrotic FA tissue was 100% absorbed.

4. Discussion

With the increasing demand for FA treatment, FUAS is an excellent choice to meet the cosmetic needs of young patients. Whether FUAS can inactivate tumor cells is the key to the success of the technology. In the past two decades, with the continuous progress of FUAS technology and the increasing indications for treatment, the pathological results of a variety of tumors after FUAS ablation have been explored [16]. In 2001, to explore the pathologic impact of extracorporeal FUAS on malignant tumors, 30 patients with liver cancer, breast cancer, malignant bone tumor, soft tissue sarcoma and other malignant tumors underwent surgical removal after FUAS treatment. Pathologic findings showed that the treated tissues had homogenous coagulative necrosis with an irreversible tumor cell death and severe damage to tumor blood vessels at the level of microvasculature within the FUAS-targeted region [17]. Similarly, tumor coagulative necrosis was observed after FUAS treatment of benign tumor, such as uterine fibroids. Furthermore, the histopathological results demonstrated that tissues around the treated area were undamaged [18]. In our study, the histopathological results of FA ablated by FUAS were consistent with the above studies. TTC, H&E, and NADH staining confirmed coagulative necrosis of FA cells after ablation from both gross specimen level and cell level. TEM and SEM revealed that the nuclei and organelles in FA cells and the structure of proliferating fibrous tissue were destroyed, which proved the tumor cell death and tumor structure damage in subcellular structure level. Thus, irreversible damage of FA was confirmed by our pathological findings. This study fills the gap of pathological results after FUAS treatment of FA, and once again demonstrates that FUAS can effectively cause tumor necrosis.

In this study, a dedicated-designed focused ultrasound breast ablation system was used, to treat multiple fibroadenomas. The efficacy of this system in the treatment of FA was confirmed by histopathological findings. By the improvement of engineering technology and clinical protocol, the efficiency and safety were also improved for FUAS treatment of FA. Compared to the study by Hahn et al. [19], in which the average treatment time was 38 min, a median treatment time of only 13 min was needed in our study. In addition, the treatment was not restricted by lesion location, with the tumor almost evenly distributed in all the four quadrants. And the median distance between the deep margin of FA and pectoralis major was 2.9 mm, with median pain score of 2.0 and more than 85% of patients were being painless or felt mild pain. What’s more, no adverse events and complications occurred in the process of treatment. All the results in this study indicated that FUAS treatment for multiple FAs was effective and safe.

As a noninvasive treatment method, FUAS ablates the tumor tissue in situ. Thus, unlike being removed from body by surgical resection, the necrotic FA tumor tissue would be still inside patient’s body and be absorbed by immune cells, including granulocytes and macrophages. The extent and speed of shrinkage of the ablated FA tumor tissue is a common concern of clinical practitioners and patients. In our study, a 12-month follow-up was conducted to the patients. The results showed that lesions have a median shrinkage rate of 66.4% in 12 months after FUAS. In addition, some patients felt their palpable lesions becoming soft or even untouchable during the follow-up. In previous studies, the rate of FA volume reduction ranged from 43.2% to 72.5% at 1 year after FUAS treatment [20,21]. Our results were in accordance with their findings. In another study by Kovatcheva et al. [22], a second FUAS treatment in patients with poor tumor absorption resulted in an overall mean lesion reduction of 86.3%. They followed up the two groups of patients who received one treatment and two treatments for 24 months and found that the reduction rate of lesions in the two groups after 2 years of treatment was 77.3% and 90.5%, respectively. These studies indicated that after FUAS treatment for FA, the lesions were not only effectively ablated, but also gradually absorbed. In this study, the 12-month shrinkage rate seemed not as high as Kovatcheva’s group reported. The possible reason might be that all the patients in this study had multiple lesions, and the average number of lesions treated by FUAS was 5.5, with the distribution in unilateral breast or bilateral breasts. The proportion of multiple FAs necrotic tissues in the breast was relatively higher than that of single FA, which may affect the absorption rate of necrotic tumors after ablation. In Kovatcheva’s study, they chose to perform a second FUAS ablation if the reduction of FA volume was less than 50% at 6-month follow-up, and they observed a higher absorption rate than that after only one session of FUAS. However, in our study, a second FUAS was not routinely recommended at 6-month follow-up, based on the following reasons: Firstly, although the absorption rate might be slow in some patients, no blood supply was found in the ablated FA under Doppler ultrasound, which meant no sign of viability of tumor cells. A second FUAS conducted on these patients may cause excessive deposition of energy and then cause carbonization of FA tissue, which may not help but even hinder the absorption. Next, the interval of 6 months between two sessions of FUAS treatment might be slightly short. If there was no sign of relapse, including obvious enlargement of volume and color flow signal under Doppler ultrasound, the first active intervention timepoint recommended was at 12-month follow-up. Considering the natural course of slow growth of FA, it is better to leave enough time for the necrotic tissue to be absorbed and the relapse (usually from alive residue in situ) to be definitely diagnosed. At last, since only 35% (7/20) patients in Kovatcheva’s study were multiple FA and the average number of FA per patients was only 1.3, whether the improvement of absorption rate could be achieved in patients with multiple fibroadenoma who had a large amount of FA (average 5.5 in our study) was uncertain, which was worth further research.

There were some limitations of this study. Firstly, FUAS treatment was performed by different doctors, which may affect energy dose delivery and further affect shrinkage rate. Secondly, this study was conducted in a single center and the follow-up time was relatively short. Study of multiple centers with longer follow-up time should be performed in the future.

5. Conclusion

In conclusion, to the best of our knowledge, this study was the first study of detailed histopathological analysis for fibroadenomas after FUAS treatment. The pathological results showed that coagulation necrosis of fibroadenoma was caused by FUAS. From the intra-FUAS treatment and follow-up results, it was also demonstrated that with the characteristics of noninvasiveness and keeping cosmesis, FUAS was effective and safe for multiple fibroadenomas, especially suitable for the patient who was unwilling to have a surgery or was afraid of leaving scar on breast skin.

Disclosure statement

Zhibiao Wang is a senior consultant to Chongqing Haifu Medical Technology Co., Ltd. The other authors report no conflict of interest to declare. The authors alone are responsible for the content and writing of the paper.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Additional information

Funding

This work was partially supported by the Foundation of State Key Laboratory of Ultrasound in Medicine and Engineering [Grant No. 2021KFKT016].