Surgical management of pathologic nipple discharge

INTRODUCTION — Nipple discharge is the third most common breast-related complaint, after breast pain and breast mass. During their reproductive years, up to 80 percent of women will have an episode of nipple discharge [1], and 6.8 percent of women referred to a surgeon because of symptoms of a breast disorder have nipple discharge [2].

Nipple discharge is categorized as normal milk production (lactation), physiologic nipple discharge (galactorrhea), or pathologic (suspicious) nipple discharge. The most common causes of pathologic nipple discharge are benign intraductal papilloma (35 to 48 percent), ductal ectasia (17 to 36 percent), and carcinoma (5 to 21 percent) [1]. (See "Nipple discharge".)

The surgical evaluation and management of pathologic nipple discharge is discussed here. The evaluation and treatment of physiologic nipple discharge is presented elsewhere. (See "Clinical manifestations and evaluation of hyperprolactinemia" and "Management of hyperprolactinemia".)

DEFINITION OF PATHOLOGIC NIPPLE DISCHARGE — Pathologic nipple discharge, defined as secretory production of fluids other than milk due to pathological process in the breast, should be suspected by the presence of one or more of the following [3,4]:

●Unilateral nipple discharge

●Bloody nipple discharge

●Nipple discharge associated with a mass or skin changes

Grossly bloody or sanguineous nipple discharge simply means that a lesion in the duct is bleeding. The bleeding can be caused by an intraductal carcinoma (in situ or invasive), a bleeding papilloma, or benign fibrocystic changes with an active intraductal component (eg, plasma cell mastitis, ductal ectasia, intraductal hyperplasia, or papillomatosis). A meta-analysis of eight studies including 3110 patients showed that patients with bloody nipple discharge had a higher risk of breast cancer (52 percent) than patients with nonbloody nipple discharge (19 percent) [5]. (See "Nipple discharge", section on 'Pathologic (suspicious) nipple discharge'.)

Bilateral bloody nipple discharge is rare but has been reported in association with benign duct ectasia, papilloma, or carcinoma. It should be treated as pathologic discharge.

EVALUATION OF PATHOLOGIC NIPPLE DISCHARGE — After clinical evaluation, all patients presenting with pathologic nipple discharge should undergo breast imaging to search for any underlying abnormality in the duct (or elsewhere in the breast) and direct surgical intervention (algorithm 1).

Palpable breast mass — Patients with pathologic nipple discharge who are found to have a concomitant palpable breast mass by clinical evaluation should undergo evaluation and treatment of the breast mass as described elsewhere. (See "Diagnostic evaluation of suspected breast cancer".)

No palpable breast mass — Patients presenting with pathologic nipple discharge but no palpable mass should first undergo either diagnostic mammography, focused breast ultrasonography, or both, depending on their age and sex [6,7]. Breast magnetic resonance imaging (MRI) usually follows if mammogram and ultrasound are negative. Suspicious lesions should undergo core needle biopsy with clip placement. (See "Nipple discharge", section on 'Pathologic discharge'.)

TREATMENT OF PATHOLOGIC NIPPLE DISCHARGE — Further treatment of pathologic nipple discharge depends upon the core needle biopsy result (algorithm 1):

Breast cancer — Biopsy findings of breast cancer (eg, invasive ductal cancer, papillary cancer, or ductal carcinoma in situ [DCIS]) mandate oncologic resection, which is described in detail elsewhere. (See "Overview of the treatment of newly diagnosed, invasive, non-metastatic breast cancer", section on 'Early-stage breast cancer'.)

Benign lesions — The surgical management of patients with pathologic nipple discharge associated with benign lesions is controversial.

Treatment of lesions — Removing a lesion is the same as performing a lumpectomy. (See "Breast-conserving therapy", section on 'Lumpectomy'.)

Benign lesions with high-risk features — Biopsy findings of intraductal papillomas, atypical ductal hyperplasia, atypical lobular hyperplasia, and radial scar are benign but high-risk lesions. For these patients, the primary concerns are the known rates of carcinoma associated with these specific lesions found on core needle biopsy and the risk of sampling error that may occur with needle biopsy. Because there does not appear to be a group in which surgical excision can be omitted, we suggest that all benign lesions with high-risk features be surgically excised to rule out concomitant malignancy as well as to alleviate the nipple discharge. (See "Atypia and lobular carcinoma in situ: High-risk lesions of the breast".)

Benign lesions without high-risk features — Generally speaking, benign breast lesions without high-risk features, such as usual ductal hyperplasia and fibroadenoma, do not require surgical excision. It is controversial whether surgical excision is necessary for all intraductal papilloma diagnosed by core needle biopsy [8-18]. There is emerging literature that supports nonsurgical management of radiologic-pathologic concordant papillomas without atypia [19-26]. Currently, some UpToDate contributors excise all lesions associated with pathologic nipple discharge, while other UpToDate contributors do not excise lesions that are biopsy-proven to be benign without high-risk factors and concordant with imaging studies.

A prospective trial that will hopefully definitively answer this question has been initiated by the Breast Cancer Research Consortium (TBCRC 034) seeking to find the upgrade rate of adjacent invasive carcinoma and/or DCIS for patients diagnosed with intraductal papilloma without atypia. (See "Overview of benign breast diseases", section on 'Proliferative lesions without atypia'.)

Treatment of the discharging duct — The technique of terminal duct excision is described below. (See 'Single-duct excision' below.)

After core needle biopsy or surgical excision of the lesion, the nipple discharge often ceases, in which case some UpToDate contributors perform no further intervention. These contributors argue that pathologic nipple discharge is most often caused by lesions such as papilloma or duct ectasia, excision of which should stop the nipple discharge/bleeding, in which case a true duct excision would not be necessary. However, if the nipple discharge persists, the discharge duct should then be excised for symptomatic relief.

Other UpToDate contributors suggest that all discharging ducts associated with pathologic, especially bloody, discharge should be surgically excised with a terminal duct excision because there are no prospective data that support not excising the duct [27,28]. A directed terminal duct excision still leaves the vast majority of ducts in place.

No identifiable lesion — Patients who have pathologic nipple discharge but do not have any identifiable lesion on mammography, ultrasound, or magnetic resonance imaging (MRI) should undergo excision of the discharging duct(s) for symptomatic relief and to definitively exclude a lesion [29]. (See 'Single-duct excision' below.)

PREOPERATIVE PREPARATION

Surgical anatomy — Breasts are located within the superficial fascia of the anterior chest wall, with the majority of the breast tissue resting on the pectoralis major fascia (figure 1) [30]. Breasts are primarily composed of fatty tissue and breast parenchyma.

Anatomical cross-sectional studies reveal 18 to 25 ducts behind the nipple, but lactational studies show only 8 to 12 ductal orifices that produce milk. Thus, many of the ducts are truncated without developing into formal lactiferous ducts with branching glands. These truncated ducts usually terminate around the areolar edge. The remaining larger ducts branch widely and into differing quadrants.

Most nipples contain five to nine ductal orifices arranged in a central and a peripheral group [31]. The central ducts have a branching pattern shaped like a tear drop located directly behind the nipple and course posteriorly toward the chest wall, while the peripheral ducts branch widely and cover large areas in a radial manner [31]. Three-dimensional reconstruction of the breast reveals that the typical breast contains 15 to 20 mammary ductal/lobular systems (picture 1) [32].

The majority of intraductal lesions (especially papillomas) are in a subareolar position [33], although they can occur in a more peripheral location [34]. Careful dissection reveals that most ducts increase in diameter as they traverse deeper into the breast and that not all orifices are located within the very top section of the nipple [35]. A thorough understanding of ductal anatomy will assist surgeons in optimizing their surgical approaches.

Anesthesia considerations — Performance of duct excision surgery under general anesthesia may be better for some patients due to the sensitivity of the nipple-areolar complex. Appropriate risk screening should be performed in patients prior to undergoing general anesthesia [36]. (See "Preoperative medical evaluation of the healthy adult patient".)

For motivated patients, duct excision can be performed under local anesthesia with intravenous sedation. A nipple block is generally performed by infiltrating local anesthetic along the superior and inferior aspect of the nipple-areolar complex. This can be done initially superficially and then at deeper levels. Avoid infiltration directly at the nipple duct core to maintain the anatomy and visualization in this area. Typically, local anesthesia without epinephrine should be used to minimize the theoretical risk of necrosing small blood vessels near the nipple.

Localization — If an intraductal lesion is not palpable or not clearly associated with nipple discharge, preoperative localization can be performed to facilitate excision. Localizing the target lesion ensures the surgeon can target the appropriate area of the breast for removal but has not been shown to decrease re-excision rate. It is particularly helpful for lesions that are not located in the immediate subareolar location.

Localization is typically performed with mammographic or ultrasound guidance. Commonly, localization is performed via placement of a thin wire into the lesion of concern [37,38]. Alternate methods of localization such as intraoperative ultrasound localization [39,40], hematoma-guided localization [41,42], seed localization [43,44], radiocolloid localization [45], and reflector-guided localization [46] have also become available. (See "Techniques to reduce positive margins in breast-conserving surgery".)

Another approach is to perform preoperative galactography with instillation of a mixture of methylene blue and radiopaque dye, which can provide a visual image of the course of the duct as well as aid in intraoperative identification of the targeted duct, which will be filled with blue dye. This can help limit the dissection to the area of the intraductal lesion and increase the likelihood of identifying a lesion at pathology [47]. (See 'Single-duct excision' below.)

SURGICAL TECHNIQUES — The breast surgeon may elect to excise a single duct or the entire ductal system, depending upon whether the pathologic nipple discharge can be traced to a single duct.

In either case, it is important to discuss with premenopausal women that any duct excision may preclude lactation in the future. Although some women can still breastfeed after a localized excision of a single duct, the scarring associated with healing can still make this difficult or impossible, and women should be counseled as to this possibility. Any duct excision can also change the sensitivity of the nipple, including hyposensitivity and hypersensitivity.

Single-duct excision — When a discharging duct can be identified with the assistance of a lacrimal duct probe, methylene blue injection, or another method, a single duct can be excised without injuring the other ductal elements. This is the preferred approach in patients who wish to preserve the ability to breastfeed and may preserve the ability of the nipple to respond to sexual stimulus [48].

An intraductal papilloma can be resected over a lacrimal duct probe gently placed in the duct [49]. Alternatively, a nipple flap duct resection can be performed. In this procedure, the areolar skin is dissected back with a gentle teasing dissection to the subareolar region where the abnormal duct can be identified as larger and darker than the other lactiferous ducts. The ductal abnormality can be confirmed by gentle occlusion of the duct with a hemostat, which will demonstrate that the nipple secretion no longer flows. The duct is then resected by ligation of its cutaneous end followed by dissection and excision of the length of duct that appears abnormal and its intraluminal lesion.

The discharging duct can also be identified with the assistance of methylene blue (movie 1). One study utilized a light-emitting wire to enhance visualization of the involved duct and reported shorter surgery times with smaller amounts of tissue volume excised when this technique was compared with methylene blue injection [50]. Dissection is then carried out to completely remove the duct without injuring the other nipple ductal elements. If the location of the lesion is not known, care should be taken to remove 2 to 3 cm of breast parenchyma deep to the nipple itself, thereby maximizing the chances of excising the target lesion [11,51,52].

It is important to orient the specimen to allow for directed excision of surgical margins if cancer is the final diagnosis. Additionally, a specimen radiograph should be obtained if localization was performed to ensure removal of the area of concern.

Complete subareolar duct excision — Occasionally, a complete subareolar duct excision, also called complete terminal duct excision, is performed for intractable discharge from multiple ducts that is causing significant distress to the patient; copious amounts of nipple discharge may be anxiety provoking and socially embarrassing.

In these patients, surgery is intended to alleviate nipple discharge as a symptom and is appropriate even without pathologic findings (eg, intraductal mass). A period of observation with no nipple stimulation is recommended prior to complete subareolar duct excision, which alone sometimes will alleviate the nipple discharge.

For patients who require complete subareolar duct excision, a periareolar incision along the lateral portion of the areola that circumnavigates no more than 30 percent of the circumference of the areola allows adequate access and minimizes the risk of nipple necrosis (picture 2) [53]. Dissection is carried toward the nipple duct elements with a combination of electrocautery and blunt dissection. The ductal elements are freed from their attachments to the nipple with sharp dissection, taking care not to injure the nipple itself. This can be done by placing the operator's nondominant hand on the skin side of the nipple.

After complete subareolar ductal system excision, some surgeons advocate closure of the orifice stumps from the underside of the nipple with 4-0 Prolene sutures to avoid potential formation of fistulas [51,53]. There are no studies to confirm the efficacy of this type of suture closure to reduce fistulas as opposed to simply letting the subareolar tissue scar in with time.

Skin closure can be performed with standard suture closure or with tissue adhesives, with no data to support one approach over the other [54]. Suture closure is typically performed with two layers of sutures, a deep dermal layer followed by a subcuticular skin layer. Due to the small amount of tissue excised, there is no need for placement of surgical drains, and patients normally heal without difficulty [27].

All excised tissue should still be appropriately oriented and sent for pathologic analysis, even if there is no concern for malignancy. Excellent rates of success and symptom relief have been reported with this approach [55,56]. Nevertheless, given the absence of identified pathology, routine imaging follow-up is recommended for early detection of any residual pathologic lesions.

POSTOPERATIVE CARE — Most standard duct excisions are performed as an outpatient procedure. Narcotic pain medications are prescribed for patients to take as needed. If a waterproof dressing such as Tegaderm is applied, the patient may shower while the primary dressing is maintained. The primary dressing is usually removed 48 to 72 hours after the operation.

All specimens removed are sent for pathological analysis. Further follow-up is dependent upon the specific pathology. (See "Approach to the patient following treatment for breast cancer".)

COMPLICATIONS — Complications such as infection, nipple necrosis, duct fistula, and hematoma have been reported [10,27,48], with the risk of any of these complications being less than 5 percent.

It is critical to remove the ductal tissue without causing injury to the nipple, and surgeons need to be continuously cognizant of the proximity of the blade to the nipple skin. Despite that, nipple necrosis or duct fistulas may form after subareolar duct excision [53], and additional operations may be required.

Although rare, and typically associated with subcutaneous injection, complications with methylene blue have been reported [57]. The surgical and anesthesia teams should be aware of this; complications, such as allergic reaction, need to be managed appropriately.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Breast surgery".)

SUMMARY AND RECOMMENDATIONS

●Nonlactating nipple discharge can be physiologic or pathologic. Physiologic nipple discharge is treated medically. Pathologic nipple discharge requires further evaluation and surgical treatment. (See 'Introduction' above and "Nipple discharge".)

●Pathologic nipple discharge is defined as nipple discharge that is unilateral, bloody, or associated with a mass or skin lesions. (See 'Definition of pathologic nipple discharge' above.)

●After clinical evaluation, all patients presenting with pathologic nipple discharge should undergo breast imaging, usually followed by core needle biopsy to search for any underlying abnormality in the duct (or elsewhere in the breast) and direct surgical intervention (algorithm 1). This is discussed elsewhere. (See "Nipple discharge", section on 'Pathologic discharge'.)

●Most nonlactating women and men with pathologic nipple discharge require surgical treatment, the extent of which is guided by biopsy results (algorithm 1):

•Patients with biopsy findings of invasive or in situ cancer should undergo appropriate oncologic treatment. (See "Overview of the treatment of newly diagnosed, invasive, non-metastatic breast cancer", section on 'Early-stage breast cancer'.)

•For patients with biopsy findings of benign lesions with high-risk features (eg, papilloma with atypia), we suggest surgical excision of the lesion (ie, lumpectomy) (Grade 2C).

•The decision to excise benign lesions without high-risk features associated with pathologic nipple discharge (eg, papilloma without atypia) is controversial, and there is a lack of consensus. Some UpToDate contributors excise benign lesions without high-risk features, while others do not. (See 'Treatment of lesions' above.)

•In addition, there is also lack of consensus as to whether or not the discharging duct(s) associated with the lesions should also be excised. Some UpToDate contributors routinely excise all discharging ducts associated with pathologic discharge, while others only excise the duct if the nipple discharge persists after biopsy or excision of the lesion. (See 'Treatment of the discharging duct' above.)

•Patients without identifiable lesions on imaging studies require excision of the discharging duct for symptomatic relief and to definitively exclude a lesion. (See 'No palpable breast mass' above.)

●Perioperative localization of the discharging duct allows for excision of a single duct. Alternatively, complete subareolar duct excision is performed for symptomatic patients in whom nipple discharge cannot be localized. (See 'Surgical techniques' above.)