Introduction

Breast cancer (BC) is the most common malignancy worldwide reported. It was reported that over one-third of excised breast lesions are clinically occult and non-palpable. Therefore, the current challenge for the optimal management of these patients is the accurate intraoperative localization of non-palpable breast lesions (NPBL) [1]. For many years, wire-guided localization (WGL) represented the gold standard method, even if several disadvantages, such as migration, breakage, increased patient anxiety, and logistical difficulties were identified [2]. Many alternatives to WGL were proposed, including radio-guided occult lesion localization (ROLL), radioactive seed localization (RSL) using iodine-125 seeds, magnetic seeds (Magseed), and SCOUT (an infrared radar technique) [3]. LOCalizer™ is the most recent method and represents a promising localization system for the identification of NPBL [4]. It is based on a radiofrequency transmission able to indicate the distance from the tagged lesion.

Patients

We presented the first Italian experience of a double localization with LOCalizer™ occurring in 45-year-old women affected by two suspected breast cancers (BC), in the same breast but in two opposite quadrants. In January 2021, 45-year-old women referred to our Surgical Department for the evidence during the annual screening mammography of two suspicious lesions, confirmed to ultrasound (US) exam: one into the external upper quadrant (EUQ) of the right breast was associated with BIRADS 4c with a risk of BC of 50–94% [5]. Another 4 mm lesion was at the union of the lower quadrants (ULQ) and was associated to BIRADS 4a (risk of malignancy of 4–10%). Breast magnetic resonance imaging (MRI) showed an early enhancement followed by a plateau for the EUQ lump and low vascular signals for the ULQ lesion, although it was classified as doubtful (BIRADS 3). The two lesions were 50 mm distant. The case was discussed in a multidisciplinary oncological meeting, and the patient was a candidate to for core biopsy for each lesion. Unexpectedly, she refused the proposed procedure, preferring surgical removal. So, the multidisciplinary oncological meeting candidate took the patient for a double excisional biopsy with an extemporaneous exam. Because both the lesions were non-palpable, she was addressed to a double preoperative localizing procedure with LOCalizer™. Considering the unknown origin of the lesions, the patient was accurately informed about the eventual sentinel lymph node biopsy and nipple-sparing mastectomy in the case of single or multicentric BC, respectively. The patient accepted the conditions and signed informed consent for the treatment and the publication of this case report. She underwent an innovative surgical technique consisting of double tunneling into breast parenchyma in two opposite directions through a peri-areolar external incision and LOCalizer™ system.

Materials

LOCalizer™ (Hologic, Santa Carla, CA, USA) is a radiofrequency identification (RFID) system approved by the Food and Drug Association (FDA) in 2017 and proposed to replace the traditional WGL method. The marker is named tag, and it is a centimetric chip coated with a biocompatible shell. It can be placed under the US or mammographic guide by a specific 12 gauge applicator under local anesthesia. The console station, called reader, can enable the chip and activate the radiofrequency circuit. The reader’s display can report the millimeters (mm) between the chip and the reader or the surgical probe. This latter is named pencil and can be introduced into the surgical incision and into the breast parenchyma. Each tag is associated with a univocal code, allowing the direct identification of each NPBL.

Surgical Technique

The surgical technique performed is aimed to realize a multiple excision of NPBLs into opposite breast quadrants through a peri-areolar incision. A double preoperative localizing procedure by LOCalizer™ under US guide. Each NPBL was associated with a univocal code that was recorded. In our case, the tag marking the EUQ was associated with code #78,286 and the other lump to code #52,745. LOCalizer™ reader was used to identify the skin of each lesion, and a sign with a sterile pen was realized. The external peri-areolar incision was preferred to perform two tunnels toward the desirable directions of each lesion, making an intra-mammary tunnel and maximizing the cosmetic result. The orientation of the tunneling was indicated by the dedicated pencil, through the sound and the reported distance on the display. Each NPBL was removed using a specific intramammary tunnel. No draining tubes were positioned after an accurate hemostatic control.

Results

After the lumpectomy of the EUQ, the extemporaneous examination showed a BC of 8 mm. The excision resulted oncologically safe. The pathological extemporaneous exam for the other NPBL concluded a benign tumor, a fibroadenoma. The breast specimens were sent to the definitive pathology, indicating the specific Tag code apart from the site description. The patient was discharged the same day, after 6 h of observation. The postsurgical period was regular (Fig. 1), without any complications. The definitive pathological evaluation confirmed the intraoperative diagnosis: the lesion in EUQ corresponding to code #78,286 was a no special type of BC with an intermediate differentiation grade. It was hormonal responsive, with a low proliferative index (Ki-67 = 5%). The c-ERB evaluation with immunohistochemistry gave a score of 0. After 3 months, the patient appeared very satisfied with the cosmetical results, shown in Fig. 2, and the therapeutic strategy.

Fig. 1
figure 1

Non-palpable breast lesion marked by LOCalizer™-Tag

Fig. 2
figure 2

Cosmetic result after the multiple excision

Discussion

The appropriate and accurate localization is the cornerstone of breast-conserving surgery for NPBL Currently, two localization techniques are the most diffused: WGL, the actual gold standard, and RSL, despite many disadvantages known [5]. LOCalizer™ is a NPBL innovative localization system based on radiofrequency technology, with two interesting features: the exhibition of the exact distance in mm and the attribution of a univocal code for each tag [6, 7]. The latter aspect is suitable for multiple NPBLs [8]. In the reported case, the actual gold-standard localizing systems seemed less performing than LOCalizer™. Indeed, using WGL, we would have implanted two wires and it would have required a double incision. Moreover, the surgeon’s movements would have been very difficult with a high risk of dislocating the other wire [9]. In literature, multiple WGL procedures have been reported for the treatment of multifocal or large breast cancers. This technique, named “bracket breast localization” is under investigation for the possible decrease of mastectomies because it allows the localization of bulky tumors [10]. However, the aim of our surgery was to perform two mini-invasive asportation rather than a large breast conservative one. Therefore, the LOCalizer™ system seemed the most suitable technique for excellent lump localization, precise surgical excision, and the option of intraparenchymal tunneling with optimal cosmetic results. Recently, in literature, a great interest in RFDI localization systems in breast surgery is reported. A computer-aided literature review about the use of radiofrequency as a guide in the removal of NPBL, using the EMBASE, Medline, and PubMed databases, was performed up to December 2021. The final article was realized in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [11]. The following keywords and their combinations were used for the research: breast, LOCalizer™, RFID, and non-palpable breast lesions (NPBL), excluding the articles referring to ablation and experiences with axillary lymph node clipping. All the titles and abstracts of the studies resulting from the research were reviewed, avoiding articles not in English. To date, 11 studies were included in this review article. We considered partially the trials reporting data not categorized for Magseed and LOCalizer™ systems [12, 13]. This review evaluated 1342 patients who has undergone breast localization with RFID systems (Table 1). Almost 1093 breast lesions were cancers (Malter et al. have not precised the lump histology) [13]. The migration rate was neglectable: only Lamb et al. reported 7 cases (0.7%) [14]. The re-excision rate was between 0 and 27%: in McGugin et al., it has been reported a little increase using LOCalizer™ in confront to WGL (19.1 and 16.3%, respectively) [15]. Dauphine et al. described a precursor of LOCalizer™, named tag finder, reporting poor oncological outcomes considering that 20% of the patients required reoperation for the presence of tumor on the margins [16].

Table 1 LOCalizer™ experiences reported in literature

Firstly, the RFID system LOCalizer™ was tested in 2019 by DiNome ML et al. on 50 women, and the results were satisfying for the absence of migration and the successful removal of all tags. This trial valued patients’ and clinicians’ experiences, finding high satisfaction. The reoperation rate appeared to improve because only one patient needed reoperation for positive margins [6]. Many trials compared the new wireless radiofrequency system to the actual gold standard (i.e., WGL): Mc Gugin et al. verified a re-excision rate of 19.1% of the LOCalizer™ vs 16.8% of the WGL group, without any difference about mean operative time [15]. Another recent study compared two wireless systems, Magseed and LOCalizer™, to WGL, showing promising outcomes recommending them for future application and as a possible modern alternative to the gold standard method. Magseed is similar to the RFID system but is not able to offer the exact distance from the marker in mm, because it is based only on acoustic and visive information about the signal strength [12]. Both the systems are promising, and many studies encouraged the adoption of RFID breast localization for NPBL, particularly [15,16,17]. Wazir et al. [18] reported the experience of a double tag placement. Two tags were placed for the same patient: one of them marked a pT1cNo BC while the other localized a fibroadenoma, but it is not specified if the NPBLs affected the same breast or not. A previous clinical study on LOCalizer™ focalized its feasibility, highlighting two strengths of the system: its echogenicity and the precise mensuration of the distance between the tag and the pencil. This latter is a precious element for the surgeon, but it could be not sufficient because the most interesting information is the distance from the BC margin, which is essential to perform an oncological safe excision. So, it was proposed a combined localization with IOUS, evaluating the margins with 8 coordinates: the distances of the marker from upper, lower, medial, lateral, cranial and caudal margins, pectoral fascia, and skin. Considering these data and comparing them with the distance pencil tag, it is possible to increase the margin detection, performing good surgical excision with excellent cosmetic outcomes. These advantages appear of utmost importance, especially in patients with small breast or in case of multiple breast excision where the performance of mini-invasive operations are mandatory [7]. A limitation of the RDIF system is the evidence of MRI artifacts; they reduce the employment for neoadjuvant localization [14]. The larger retrospective study performed by Lamb et al. assessed consecutive patients who underwent NPBL localization with RFID in the period from July 2018 to July 2019, verifying the surgical success in 98.4% of the tags. It is the only study reporting migration episodes (0.7%). In 15.1% of the cases of breast cancers, the margins showed neoplastic cells, requiring surgical re-excision. However, the reoperation rate resulted in improvement in all cases [14]. So, LOCalizer™ appeared a safe and feasible technique, and an acceptable alternative to WGL, and the further possible application for the sentinel axillary lymph node biopsy is under investigation [18,19,20].

Conclusion

LOCalizer™ appears to be a promising system for breast localization, especially in multiple lesions. The described surgical technique allowed us to choose a particular cut, such as the peri-areolar access, that would be prohibitive using other localization techniques, except LOCalizer™. This technique is based on tunneling into breast parenchyma using peri-areolar access for NPBLs in opposite quadrants.