Image-guided biopsy of clinically occult nipple lesions: techniques and learning points
Brief Report

Image-guided biopsy of clinically occult nipple lesions: techniques and learning points

Lijuan Jasmine Chan ORCID logo, Haiyuan Shi

Department of Radiology, Changi General Hospital, Singapore, Singapore

Correspondence to: Lijuan Jasmine Chan, BMed, MD. Department of Radiology, Changi General Hospital, 2 Simei St 3, Singapore 529889, Singapore. Email: jasmine.chan@mohh.com.sg.

Abstract: Percutaneous biopsy is the standard of care for breast lesions, except nipple lesions which are primarily biopsied by excision due to perceived risks of pain and bleeding. However, excisional biopsy of nipple lesion inevitably leads to disfigurement and possible loss of the nipple-areolar complex (NAC), highlighting the need for minimally invasive biopsy techniques. We present our experience of seven patients who underwent ultrasound-guided core biopsy or vacuum-assisted biopsy (VAB) for sampling of clinically occult nipple lesions. All patients tolerated the biopsy procedures well with minimal to mild pain. A patient was complicated by a subcentimetre skin laceration which was sutured with good wound healing and cosmesis. Radiopathological concordance was achieved in all patients. Five out of 7 patients did not require further surgical management after biopsy, avoiding the unnecessary disfigurement from conventional excisional biopsy of nipple. The remaining two patients were diagnosed with pre-malignant lesions and further surgical treatment was performed. This study highlights the important pre-procedural preparation, biopsy techniques and learning points derived from our experience. Learning points that increase the efficacy of obtaining suitable tissue samples, such as enhancing lesion visualisation, appropriate biopsy needle selection and optimising analgesia were discussed. Potential complications and common pitfalls, such as mimics of nipple calcifications, were also included. In conclusion, image-guided percutaneous biopsy techniques are feasible minimally invasive alternatives to excisional biopsy of the nipple.

Keywords: Nipple lesion; ultrasound-guided; biopsy; percutaneous


Submitted Jun 12, 2024. Accepted for publication Nov 19, 2024. Published online Dec 23, 2024.

doi: 10.21037/qims-24-1190


Introduction

The nipple is a unique structure of the breast with intricate anatomy that can be affected by a wide range of benign and malignant entities (1). Percutaneous biopsy is the standard of care for breast lesions, except nipple lesions which are primarily biopsied by excision due to perceived risks of pain and bleeding (2,3). While clinically observable nipple-areolar complex (NAC) changes can be sampled by ‘nipple-sparing’ core biopsy technique, sampling of clinically non-observable nipple lesions remain a challenge (4,5). Excisional biopsy of nipple lesion inevitably leads to disfigurement and possible loss of the NAC that could emotionally affect patients, highlighting the need for minimally invasive biopsy techniques. A few technical modifications have been described for percutaneous sampling of intra-nipple calcifications (6).

We present our experience of 7 patients who underwent core biopsy or vacuum-assisted biopsy (VAB) for sampling of clinically occult nipple lesions.


Methods

A total of 7 patients who underwent percutaneous biopsy of nipple lesions are summarised in Table 1. Four patients had intra-nipple nodules and 3 patients had nipple calcifications. Two patients were symptomatic with nipple discharge and 1 patient presented with nipple lump. The nipple lesions in the remaining four patients were detected on breast screening or incidentally on imaging done for unrelated complaints. Prior to biopsy, all patient underwent standard two-dimensional mammograms and breast ultrasounds. Two patients with nipple calcifications had additional magnification mammographic views. All targeted nipple lesions were visualised on ultrasound.

Table 1

Summary of patients who underwent ultrasound guided percutaneous biopsy of occult nipple lesions

Patients No. Clinical presentation Pre-procedural imaging Biopsy needle Specimen radiograph Post-procedural imaging Diagnosis Treatment Follow-up imaging
Mammogram Ultrasound Additional imaging Presence of calcifications
1 Nipple discharge Mass with pleomorphic microcalcifications Intra-nipple nodule 18-G core Yes Atypical papillary proliferation, at least atypical ductal hyperplasia Excision biopsy (histology: solid papillary carcinoma in-situ)
2 Nipple lump Nil Intra-nipple nodule 14-G core Intraductal papilloma without atypia Surveillance 2-year follow-up ultrasound shows less prominent intra-nipple nodule
3 Nipple discharge Nil Intra-nipple nodule 14-G core Adenoma with low grade ductal carcinoma in-situ Bilateral mastectomy for ductal carcinoma in-situ/invasive ductal carcinoma
4 Asymptomatic (detected on breast screening) Nil Intra-nipple nodule 16-G core Adenoma Surveillance 2-year follow-up ultrasound shows stable intra-nipple nodule
5 Asymptomatic (incidental finding on CT study) Coarse heterogenous calcifications Calcific foci 14G co-re No Mammogram Normal tissue, blood clot High-risk surveillance for contralateral carcinoma 1-year follow-up mammogram shows stable nipple calcifications
6 Asymptomatic (detected on breast screening) Coarse heterogenous calcifications Calcific foci Magnification views 12-G vacuum assisted Yes Focal adenosis; focal osseous metaplasia with microcalcifications Nil
7 Asymptomatic (detected on breast screening) Pleomorphic microcalcifications Calcific foci Magnification views 12-G vacuum assisted; 14-G core No Tomosynthesis Fibrocystic change Nil

CT, computed tomography.

Prior to procedure, all patients were counselled by the breast surgeons and breast radiologists on the pros and cons of percutaneous biopsy compared to conventional excision biopsy. Procedural consent was taken and all patients were agreeable to proceed with percutaneous biopsy. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by Singhealth Centralised Institutional Review Board (No. 202312-00101) with informed consent taken from all patients.

Pre-procedural preparation

Compared to the typical biopsy for breast lesions, there were specific points highlighted to patients during the consent process for nipple biopsy. Firstly, patients were counselled for the potential pain and discomfort during nipple biopsy as the NAC is a highly sensitive structure with abundant nerve endings (7). Secondly, they were also counselled for bloody nipple discharge that is expected to last for a few days post-procedure due to the vascular nature of the NAC and the inadvertent traversal of lactiferous sinuses and ducts by the biopsy needle (8). Lastly, the risk of non-diagnostic sampling as with all biopsies was communicated.

Biopsy techniques

All biopsies were performed under ultrasound guidance. Adequate local anaesthesia was achieved with periareolar infiltration using at least 10–15 mL of 1% lignocaine with or without adrenaline.

For intra-nipple nodules, core biopsies were performed with 14 to 18 G needles. A co-axial system was used as biopsies could be performed via a single skin entry and trajectory, while offering stability for the biopsy needle. Biopsies were performed using semi-automatic and no-throw technique. Before releasing the cutting cannula, it was essential to visualise the needle trough and ensure the target lesion was situated within the trough (Figure 1).

Figure 1 Ultrasound-guided core biopsy of intra-nipple nodule. (A) Ultrasound image showed an echogenic intra-nipple nodule demonstrating internal vascularity on power doppler. (B) Core biopsy was performed using a 14-G needle with the target lesion (arrow) situated within the needle trough, followed by release of cutting cannula. Histopathology showed nipple adenoma involved by low-grade ductal carcinoma in-situ.

For nipple calcifications, either a 14-G core biopsy needle or 12-G VAB needle was used. A 1mm periareolar incision was made for needle insertion. Core biopsy was performed using a co-axial system. For VAB, the needle was inserted inferior to the target lesion and tilted up to optimise trough positioning. Specimen radiographs were performed for nipple calcifications or intra-nipple nodule containing calcifications to document retrieval. Figure 2 illustrates the process of nipple calcifications biopsy. After biopsy, direct compression was performed for all cases to secure haemostasis.

Figure 2 Steps involved in the biopsy of nipple calcifications. (A) Magnification view showed coarse heterogenous calcifications within the nipple. (B) Echogenic foci on ultrasound corresponds to the nipple calcification (solid arrow) visualised mammographically. (C) Generous periareolar infiltration of local analgesia. (D) A tiny periareolar incision may be made for biopsy needle insertion if necessary. (E) Ultrasound image demonstrated the echogenic calcification positioned within the biopsy needle trough. (F) Specimen radiograph confirmed the retrieval of calcifications (dotted arrow). Histopathology showed focal adenosis and focal osseous metaplasia with microcalcifications.

Results

All patients tolerated the biopsy procedure well. On a pain scale of none, mild, moderate or severe, all patient rated pain scale ranging from minimal to mild. None of the patients requires additional analgesia other than the local anaesthesia. No uncontrollable bleeding or haematoma formation was observed. One patient had a subcentimetre skin laceration during the procedure which was closed using absorbable sutures with good wound healing and cosmesis (patient N7 in Table 1). All patient were discharged on the same day of the procedure. None of the patient required early or urgent clinic review at the breast centre for biopsy-related complications.

Five out of the 7 patients received benign histopathology results (Table 1). Three of these five patients were placed under surveillance while the other two were returned to routine screening. The remaining two patients were diagnosed with pre-malignant lesions and further surgical excision or resection were performed. All cases were discussed at multi-disciplinary meetings and radiopathological concordance was achieved in all patients. Follow-up imaging was available in the 3 out of the 5 patients who received benign histology and all the lesions remained stable (Table 1, Figure 3). No artefacts or architectural distortion is identified as a result of the percutaneous biopsy performed.

Figure 3 Stable ultrasound imaging findings before biopsy and at subsequent follow-up. (A) Intra-nipple nodule (arrow) at initial diagnosis. (B) Follow-up imaging after 2 years.

Discussion

Our study demonstrates the feasibility of using core biopsy and VAB for clinically occult nipple lesions. Five out of 7 patients did not require further surgical management after biopsy, avoiding the unnecessary disfigurement from conventional excisional biopsy of nipple. At the same time, we will like to highlight the following learning points.

Mimics of nipple calcifications

Benign dermal calcifications can occur in the nipple, similar to other areas of the breast. Specific to the nipple, which contains sebaceous and apocrine sweat glands, calcifications can result from chronic folliculitis or inspissated material within the sebaceous glands (9). Other factors including dystrophic calcifications from prior surgery and dermal lesions such as dermatosis, fibroepithelial polyp and neurofibroma can contribute to benign dermal calcifications of the nipple (1,10).

Skin calcifications may be difficult to differentiate from non-central intra-nipple calcifications on a two-view mammogram. Benign skin calcifications typically exhibit rounded morphology with a radiolucent centre, better demonstrated on tangential views (11). Occasionally, skin calcifications may also demonstrate radiologically indeterminate coarse heterogeneous or amorphous morphology (6). In such cases, either additional views or biopsy is necessary to confirm benignity.

One of our patients (patient N7) was initially thought to have eccentrically distributed calcifications in the upper outer corner of the nipple. However, upon encountering initial difficulties in retrieving the calcifications, a tomosynthesis revealed skin calcifications (Figure 4). Hence, we recommend troubleshooting with tomosynthesis when faced with difficulties in calcification retrieval during biopsy.

Figure 4 Mimic of nipple calcifications. (A) Magnification view showed initial diagnosis of eccentrically distributed pleomorphic microcalcifications in the upper outer corner of the nipple. (B) Tomosynthesis performed after encountering challenges in retrieving the calcifications during biopsy showed skin calcifications.

External factors such as deodorants, tattoos and talc powder can also mimic breast calcifications (11). Consequently, patients should be advised to not apply these skin products on the day of imaging, and radiographers should be vigilant in recognising these artifacts.

Optimise lesion visualisation

Ultrasound can visualise most intra-nipple lesions, including calcifications, with good techniques. Ultrasound is therefore the modality of choice for nipple biopsy (12). A few techniques can be adopted to improve the imaging quality of nipple lesions on ultrasound. Firstly, high frequency transducer should be used, between 10 to 15 MHz, to provide better spatial and soft tissue resolution (13). Secondly, ultrasound settings should be optimised such as depth and focal zone, considering the superficial location of nipple lesions (14). Colour doppler is also useful in detecting twinkling artefacts of subtle calcifications and vascularity in small solid lesions (14). Lastly, minimising air gaps through the generous application of gel, gentle transducer pressure and avoiding air bubbles from local analgesia injections can reduce acoustic shadowing, thereby improving lesion visualisation (6).

In addition to ultrasound, other imaging modalities such as tomosynthesis or magnification views may be considered for further characterisation of nipple lesions. The use of other imaging modalities is especially important when troubleshooting or faced with difficulties in either pre-biopsy planning or during the biopsy process. For post-biopsy of nipple lesions containing calcifications, specimen radiograph is recommended to increase confidence in the yielded specimen.

Biopsy needle selection

The core biopsy needle for intra-nipple nodules or calcifications should be of adequate size to maximise tissue yield per incision. We utilised core biopsy needles ranging from 14 to 18 G for intra-nipple nodules, yielding satisfactory tissue samples. A technical article describing core biopsy for nipple calcifications also recommended using similar sized needle and achieved satisfactory results (6). For nipple calcifications, we were able to obtain suitable tissue sample using the smallest available VAB needle in our institution which was 12 G.

As with majority of breast lesions, we do not advocate using fine needle aspiration for nipple lesions due to its low diagnostic yield and the lack of histological assessment which is essential for diagnosis of pre-malignant and malignant lesions (15,16).

Ensure adequate analgesia

NAC is particularly sensitive due to its multiple sensory nerve endings (7). Adequate analgesia is not only essential for patients’ comfort, it is also critical for technical success. We found pre-procedural counselling and intraprocedural reassurance to be important in managing patient’s expectations. All our patient rated pain score as none to mild, demonstrating the feasibility of performing nipple biopsy with minimal discomfort. The addition of sodium bicarbonate to local analgesia and warming the solution can be considered to minimise discomfort during infiltration (17). Upon discharge, simple oral analgesia, such as paracetamol, may be advised for patient to manage residual pain.

Minimise bleeding

NAC is a highly vascular structure with vascular supply from perforators that can arise from several different arteries forming anastomosis around the NAC (18). Manual compression should be applied immediately after biopsy needle removal to achieve haemostasis. Given the superficial location of nipple and limited potential space for haematoma formation, haemostasis can generally be achieved by direct compression. To further reduce bleeding risk, patients can continue Aspirin but dual antiplatelets, such as clopidogrel or ticargrelor, should be stopped 5 days before biopsy (19,20). Anticoagulation should be stopped according to local guidelines for low-risk procedures (19,20).

Possible complication

Skin laceration is a possible complication given the superficial location of the nipple, especially when the biopsy is performed near the sulcus. One of the problems associated with skin laceration is the loss of vacuum when performing VAB. We encountered such issue with patient N7 when using a 12-G VAB needle and a core biopsy had to be performed instead. A suitable sample was eventually obtained which yielded fibrocystic change. The subcentimetre skin laceration was stitched with absorbable sutures with good wound healing and cosmesis. The patient did not require additional follow-up in clinic for suture removal or wound review. She was discharged to routine screening via phone consult as per institutional practice.

We acknowledge the potential risk of skin laceration in percutaneous biopsy of nipple lesions. Nonetheless, when compared to excisional biopsy, percutaneous biopsy offers superior cosmesis without compromising the ability to obtain sufficient tissue sample for diagnosis.


Conclusions

In current clinical practice, nipple lesions are predominantly biopsied by excision due to the perceived technical difficulties and concerns around pain and bleeding risks. Our study demonstrated the application of percutaneous biopsy techniques for diagnosing clinically occult nipple lesions. Proficiency in sonographic skills is crucial for visualising both nipple calcifications and nodules. Radiologists conducting the procedure should also explore alternative imaging approaches to enhance the evaluation of target lesions and assess post-biopsy specimens. Admittedly there are potential risks like minor skin lacerations associated with percutaneous nipple biopsy, it is important to note that the overall procedural risks remain low. Therefore, percutaneous biopsy of nipple lesions presents as a viable alternative to excisional biopsy, while preserving the NAC and maintaining the ability to obtain diagnostic tissue specimens.


Acknowledgments

Funding: None.


Footnote

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1190/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by Singhealth Centralised Institutional Review Board (No. 202312-00101) with informed consent taken from all patients.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.


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Cite this article as: Chan LJ, Shi H. Image-guided biopsy of clinically occult nipple lesions: techniques and learning points. Quant Imaging Med Surg 2025;15(1):931-938. doi: 10.21037/qims-24-1190

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