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Nipple inversion

Nipple inversion
Literature review current through: May 2024.
This topic last updated: Feb 07, 2024.

INTRODUCTION — The nipple is the central projection in the areola. When the nipple is pulled in and points inward instead of out, it is termed nipple inversion or retraction. Nipple inversion can affect one breast or both and can be congenital or acquired. Acquired nipple inversion can be due to benign or malignant causes. Benign nipple inversion is usually a gradual process, occurring over a few years. When nipple inversion occurs rapidly, the underlying cause can be inflammation, postsurgical changes, or an underlying malignancy [1].

The evaluation and management of nipple inversion will be reviewed here. Nipple discharge, common breast problems, and the diagnostic evaluation of a suspected breast cancer are discussed elsewhere. (See "Nipple discharge" and "Clinical manifestations, differential diagnosis, and clinical evaluation of a palpable breast mass" and "Diagnostic evaluation of suspected breast cancer".)

NIPPLE DEVELOPMENT — The breast and nipple begin to form during the second month of gestation from lines of thickened ectoderm running from the axilla to the groin (figure 1) [2,3]. The nipple is initially an epidermal pit and eventually everts as the fetus nears gestation. An inverted nipple may represent a failure of this eversion during development [2]. Breast development and Tanner staging are depicted in the figure and are discussed in detail elsewhere (picture 1). (See "Breast development and morphology".)

The color of the nipple and areola is initially imparted by blood vessels coursing near the skin. Melanin is deposited in the basal cells as part of the aging process, thereby darkening the nipple-areolar complex [2].

NIPPLE ANATOMY — The normal nipple projects from the central area of the areola (figure 2 and figure 3). The darkly pigmented areola, located in the center of the breast, contains dense collagen fibers and a thin layer of contractile muscle. While there is significant variation in color, shape, size, and projection of the nipple-areola complex, a study of morphologic characteristics in 300 women reported a mean nipple height of 0.9 cm [4]. Differences in nipple projection can be affected by age, race, weight, and hormonal changes.

In the normal nipple, areolar muscle contraction results in nipple projection. Nipple inversion occurs when the contractile forces of the areolar muscles are unable to overcome tension between the central ducts and the skin of the nipple.

On the surface of the nipple, approximately five to nine central ductal orifices extend posteriorly toward the pectoralis muscle. A smaller number of ducts originate within the areola itself. Below the level of the areolar skin, the ducts of the central bundle taper down to a narrowed area or "waist" at the level of the superficial fascia [5]. Each orifice communicates with a separate ductal system of the breast and connects to terminal duct lobular units within the breast parenchyma [6]. During lactation, milk produced in the terminal duct lobular units travels through lactiferous ducts and sinuses and is ejected from ductal orifices in the nipple papilla as shown in the figure (figure 4).

The vascular supply to the breast is derived from the external mammary artery, cutaneous perforators of the internal mammary and fourth and fifth intercostal arteries, and musculocutaneous perforators of the thoracoacromial artery. The vascular supply to the nipple-areolar complex is derived from branches of the internal mammary artery, with contributions from branches of both the anterior intercostal arteries and the lateral thoracic artery. These branches travel in the subcutaneous tissue and communicate transversely above and below the areola. Branches from the communicating vessels above and below the areola run toward the base of the nipple and give off smaller vessels to the areolar skin in a circular distribution [7-9].

CLASSIFICATION — The classification of nipple inversion is based upon appearance, whether the nipple can be pulled out manually, and how well projection is maintained.

Nipple retraction versus nipple inversion — Although the terms "nipple inversion" and "nipple retraction" are often used interchangeably, there is a distinct difference [10,11]:

Nipple retraction occurs when only a part of the nipple is drawn in because it is tethered by a single duct, resulting in a slit-like appearance (picture 2).

Nipple inversion occurs when the entire nipple is pulled in.

Umbilicated versus invaginated nipples — Umbilicated nipples can be pulled out from beneath the alveolar surface without maximal force, while invaginated nipples cannot be extracted [8].

Grading system — The clinical grading system for nipple inversion is based upon how difficult it is to pull the nipple out manually and how well projection is subsequently maintained [12]:

Grade I – The nipple is easily pulled out with gentle squeezing of the areolar skin. Nipple projection is well maintained for several minutes, but then the nipple reverts to an inverted state (picture 3).

Grade II – Forceful manipulation is required to pull the nipple out, and inversion recurs quickly as shown in the figure (picture 4). The majority of patients with nipple inversion have grade II inversion.

Grade III – There is no projection of the nipple, and the papilla is buried below the level of the skin. Despite maximal manipulation, the nipple cannot be pulled out and is described as invaginated (picture 5) [13,14].

CONGENITAL NIPPLE INVERSION — A congenitally inverted nipple is present in approximately 3 percent of women ages 19 to 26 without a history of infection, inflammation, trauma, tumor, periareolar surgery, or pregnancy [13-15]. Congenital nipple inversion is benign and usually bilateral (87 percent of cases in one report) [15].

The cause of congenital nipple inversion is a failure of the underlying mesenchymal tissue to proliferate and project the nipple papilla outward [13]. In the majority of cases, the inverted nipple is umbilicated (96 percent) rather than invaginated [15].

Genetic disorders associated with nipple inversion — While most cases of congenital inverted nipples are sporadic, some are associated with inherited genetic disorders:

Chromosome 2q37 deletion – Terminal deletions of chromosome 2 with breakpoints at or within band 2q37 result in mild-to-moderate level of intellectual disability, a degree of autism, prominent forehead, deficient nasal alae, thin upper lip, and abnormal nipples, including inverted nipples [16].

Ulnar mammary syndrome – Ulnar mammary syndrome is a rare pleiotropic autosomal dominant disorder resulting from a loss of critical levels of a T-box gene called TBX3. T-box genes encode for a family of developmental transcription factors. Ulnar mammary syndrome is characterized by ulnar defects, mammary and apocrine gland hypoplasia, inverted nipples, genital abnormalities, and short stature [17,18].

Congenital disorders of glycosylation – Nipple inversion may result from congenital disorders of glycosylation (CDG). CDG delineates a number of inherited disorders characterized by defective glycoprotein biosynthesis [19]. CDG-1a is the most common deficiency in this heterogeneous group of autosomal recessive disorders. This defect is associated with inverted nipples, abnormal distribution of fat, and dysmorphic facial features.

ACQUIRED NIPPLE INVERSION — Whereas congenital nipple inversions often have been present for what the patient will claim to be their whole life, acquired nipple inversions are new to the patient (either not yet worked up or for which there is no obvious explanation [eg, postsurgical change]). Acquired nipple inversion can be a result of inflammation, malignancy, or surgery. Each of these is discussed below.

Inflammation — Nipple inversion is commonly associated with mammary-duct-associated inflammatory disease sequence [20]. This disorder is a progression of inflammatory changes from normal breast ducts to duct ectasia, followed by periductal mastitis, subareolar abscess, and periareolar fistula formation. Chronic inflammation of the duct wall and periductal tissue may be sterile or bacterial and can lead to subsequent fibrosis of the duct wall and nipple inversion.

The etiology of ductal inflammation is unclear, although a number of hypotheses have been proposed [21-25]. However, no single mechanism clearly explains the pathogenesis of ductal inflammation, and a number of processes probably occur independently or together and are modified by age, anatomy, and smoking history [21].

Duct ectasia — Nipple inversion associated with duct ectasia usually involves the nipple but not the areola, as shown in the figure (picture 6) [23]. The nipples are usually easily everted. In contrast, nipple inversion from a carcinoma tends to distort the areola when the breast is examined in different positions. Duct ectasia presents with a longstanding history of bilateral symmetrical central nipple inversion and a creamy or greenish nipple discharge. Progressive inflammatory changes are associated with noncyclical mastalgia, a subareolar breast mass, and localized infection and/or fistula.

Periductal mastitis — Periductal mastitis is an inflammatory condition of the subareolar ducts. The majority of patients who develop periductal mastitis are smokers. It is likely that smoking leads to damage of the subareolar ducts with subsequent tissue necrosis and later infection [26,27]. Details of the management of periductal mastitis are discussed elsewhere. (See "Nonlactational mastitis in adults", section on 'Periductal mastitis'.)

Subareolar abscess and periareolar fistula — Nipple inversion can be associated with subareolar abscess and fistula formation. In a study of 60 patients with recurrent abscesses, nipple inversion was noted in 8 percent of patients after their first abscess, in 22 percent with recurrent disease, and in 47 percent with a fistula [28]. (See "Primary breast abscess".)

Tuberculous mastitis — The clinical presentation of tuberculosis (TB) of the breast is usually with a solitary, ill-defined, unilateral hard mass [29]. TB can also present with nipple inversion, discharging sinuses in the breast or axilla, skin thickening, or a decrease in breast size (picture 7) [30]. (See "Nonlactational mastitis in adults".)

Other inflammatory causes — Periductal fibrosis can develop from inflammation due to fat necrosis, thrombophlebitis of the thoracoepigastric vein (Mondor's disease), or idiopathic granulomatous mastitis. (See "Overview of benign breast diseases", section on 'Fat necrosis' and "Nonlactational mastitis in adults", section on 'Idiopathic granulomatous mastitis'.)

Malignancy — Nipple inversion can occur with subareolar or central malignancies. The incidence of associated malignancy in patients with acquired nipple inversion ranges from 5 to 50 percent [31]. Nipple inversion associated with a malignancy tends to be asymmetric and distorts the areola as shown in the figure (picture 8).

A complete breast examination and radiologic evaluation with mammogram and ultrasound should be performed to look for the underlying cause. (See "Breast imaging for cancer screening: Mammography and ultrasonography" and "Diagnostic evaluation of suspected breast cancer".)

Patients with a centrally located tumor and associated nipple inversion may be eligible for breast conservation therapy. The 10 year actuarial survival, distant disease-free survival, and breast recurrence-free survival for central tumors are not significantly different from patients who present with breast cancer elsewhere in the breast [32-34]. (See "Breast-conserving therapy", section on 'Not a contraindication for BCT'.)

Postoperative nipple inversion — Postoperative inversion of the nipple can occur after reduction mammoplasty or a breast biopsy [35]. The breast may pull on the nipple-areolar complex, leading to inversion, particularly if the nipple was inverted or flat initially (picture 9).

ASSESSMENT OF NIPPLE INVERSION — A thorough evaluation is required for new-onset or acquired nipple inversion. This workup should include physical examination, imaging, and biopsy of any suspicious findings.

Mammogram — Acquired nipple inversion in an adult woman requires evaluation by physical examination and imaging studies, starting with diagnostic mammography [36]. Retroareolar breast cancers, within 2 cm of the nipple-areolar complex, are most likely to be associated with nipple inversion, as shown in the radiograph (image 1). However, retroareolar breast cancers are more difficult to identify with mammography than tumors elsewhere in the breast due to dense retroareolar tissue. It is important that the radiologist is informed that the patient has inverted nipples because the nipple can be erroneously identified as a subareolar mass. If nipple inversion is discovered within six months of completely normal imaging, and there is no new mass found on physical examination, repeat imaging is not necessary; otherwise, breast imaging should be repeated. Nipple inversion in men should be worked up in the same fashion as that in women. (See "Breast imaging for cancer screening: Mammography and ultrasonography", section on 'Diagnostic mammogram'.)

Ultrasound — Ultrasound is a useful adjunct to mammography in the evaluation of nipple inversion and may identify a retroareolar mass that is not visible on mammography [37]. The use of a standoff pad moves the focal zone of the ultrasound beam by 1.5 cm and improves the detectability of a retroareolar mass [11]. (See "Breast imaging for cancer screening: Mammography and ultrasonography", section on 'Role of ultrasound'.)

Magnetic resonance imaging — Contrast-enhanced magnetic resonance imaging (MRI) would not be part of the usual evaluation of nipple inversion but may be useful when mammographic and sonographic findings are inconclusive [1,38]. Breast MRI can differentiate tumor confined to the retroareolar location from the nipple-areolar complex.

The normal appearance of the nipple on MRI consists of a "two-layered" effect with an intense 1 to 2 mm enhancement of the superficial layer and a nonenhancing layer deep to this zone [39]. The nipple with tumor involvement shows increased thickening and enhancement of the nipple-areolar complex and the retroareolar tissue with disruption of the "two-layered" rim. Comparing the morphology and enhancement pattern in the nipple pairs is important since normal nipples have a symmetrical enhancement. Nipple areolar enhancement and thickening of the nipple areolar complex are highly associated with invasion of cancer into the nipple [40]. False-positive retroareolar enhancement may be induced by benign inflammation. (See "MRI of the breast and emerging technologies".)

Biopsy — Nipple inversion and carcinoma are both common and can coexist. Thus, management of new nipple inversion should include a careful physical examination as well as mammography and ultrasound. Any suspicious abnormality should prompt a biopsy. (See "Breast biopsy" and "Diagnostic evaluation of suspected breast cancer".)

Follow-up — Patients who present with nipple inversion but have a negative workup should receive a six-month follow-up examination and mammogram. If the findings remain unchanged, they may be returned to their routine screening schedules.

SURGICAL CORRECTION OF BENIGN NIPPLE INVERSION — Although the majority of patients with nipple inversion have benign disease, some may wish to have correction of their inversion for cosmetic and/or hygienic reasons. For many women, inverted nipples can be a source of aesthetic and functional concern, leading to self-consciousness and psychological distress.

The goal of surgical correction is to restore projection while maintaining the ductal anatomy as much as possible. Some techniques preserve the underlying luciferous ductal anatomy, while others damage it. Because no one technique is convincingly superior to others [41], the choice is by surgeon preference.

Purse-string — One of the simplest techniques described is a purse-string suture that is placed around the neck of the nipple through a periareolar incision at the 6 o'clock position [12]. This technique tightens the neck of the nipple and works well for those with less severe cases of nipple inversion [42].

Selective ductal division — Selective division of ducts that restrict nipple projection involves blunt dissection through vertical spreading of fibrous tissue parallel to the lactiferous ducts through an inferior periareolar incision. The vertical dissection under the nipple is followed by two internal sutures, one from the 12 o'clock to the 6 o'clock positions and one from the 3 o'clock to the 9 o'clock positions, to reduce dead space and stabilize the nipple base [43].

The repair is completed by placing the nipple on traction for two to five days with a stent. The stent consists of a nylon suture placed through the skin of the nipple and affixed to a specimen cup over the nipple-areolar complex to maintain traction. In an observational series of 21 patients who underwent selective ductal division, there was no recurrence of nipple inversion at one-year follow-up [43].

Endoscope-assisted ductal division — An endoscope can be used as an adjunct for surgical correction of nipple inversion [44]. For this technique, a small incision is made at the 6 o'clock position and a 4 mm, 30 degree endoscope is advanced to better differentiate between subcutaneous normal ducts, contracted ducts, fibrous band, vessels, and nerves. With improved visualization, normal ducts can be preserved while successfully dividing fibrous bands and retracted ducts. In an observational series of 23 such procedures, the nipples were judged to have an excellent result, and there were no changes in sensation reported [44].

Dermal/skin flaps — Triangular skin flaps can be mobilized to add bulk to the base of the nipple and, when closed, tighten the neck of the nipple. Another technique is to use two broad, triangular areolar skin flaps on opposite ends of the nipple [45]. The restricting subareolar fibrous bands and/or ducts are released, and the flaps are then advanced through a tunnel beneath the nipple to fill dead space created by the dissection. The tip of each flap is fixed with the base of the other flap, and the tissue is reapproximated to tighten the nipple neck. In their series of 14 cases, there were no recurrences at follow-up ranging from 3 to 18 months. Dermal flaps can also be used, which may decrease the appearance of scars [46].

External distraction — A plastic device can be placed on the base of the areola with or without ligation of lactiferous ducts. Placement of two subcutaneous wires crossing under the base of the nipple is performed, which exert gentle, continuous pressure on the tissue and can be tightened periodically over several months [47], with the goal of lengthening the central ducts and eliciting the growth of soft tissue to support the nipple in the everted position. This technique has a theoretical advantage of preserving the ability to breastfeed in younger women [48,49].

The "Pirelli" technique involves cutting the ducts through a perioareolar incision followed by placement of a bolster to maintain the nipple in the everted position for one week.

Percutaneous release — Percutaneous release of nipple inversion can be accomplished with a wire subcision technique or with a simple minimally invasive technique using a needle tip for lysis of retracted ducts:

Wire subcision — Subcision releases the dermis from the tissue below. In the wire subcision technique, entry and exit points are created at the 6 and 12 o'clock positions with the introduction of a wire scalpel (Diamond Wire scalpel) after placing the nipple on traction [50]. The wire scalpel is inserted inferiorly and directed around retracted tissue to exit superiorly at 12 o'clock. A second wire is placed through the same sites. By pulling the two ends back and forth, tethered tissue between the two wires is divided. The wires are removed, and a horizontal mattress suture with 4-0 chromic is placed to maintain the everted nipple in position [50].

Needle tip lysis — Needle tip lysis is a simple minimally invasive technique for lysis of retracted ducts. For this technique, an 18 gauge needle tip is inserted at the 6 o'clock position and used to lyse fibrous tissue and tethered glands until satisfactory nipple projection has been achieved [51]. Following this, a monofilament purse-string suture is placed, starting at the entry site, with entry and exit through the same stitch point every 3 to 5 mm around the nipple base. The suture is then tied under moderate tension. In a series of 58 inverted nipples in 31 patients, there were 13 recurrences, of which 11 were successfully treated with a second purse-string suture and two required a third procedure [51].

SUMMARY AND RECOMMENDATIONS

Definition of nipple inversion – The nipple is the central projection in the areola. When the nipple is pulled in and points inward instead of out, it is termed nipple inversion or retraction. Nipple inversion can affect one breast or both and can be congenital or acquired. (See 'Introduction' above.)

Grading system of nipple inversion – The clinical grading system for nipple inversion is based on how difficult it is to pull the nipple out manually and how well projection is subsequently maintained. (See 'Classification' above.)

Congenital versus acquired nipple inversion – Congenital nipple inversion is benign and usually bilateral. The cause of congenital nipple inversion is a failure of the underlying mesenchymal tissue to proliferate and project the nipple papilla outward. Acquired nipple inversion can be a result of inflammation, malignancy, or surgery. (See 'Congenital nipple inversion' above and 'Acquired nipple inversion' above.)

Evaluation of nipple inversion – A thorough evaluation is required for new-onset of acquired nipple inversion. This workup should include physical examination, imaging, and biopsy of any suspicious findings. (See 'Assessment of nipple inversion' above.)

Surgical correction of nipple inversion – Women with benign disease may wish to have correction of their inversion for cosmetic reasons. For many women, inverted nipples can be a source of aesthetic and functional concern, leading to self-consciousness and psychological distress. The goal of surgical correction is to restore projection while maintaining the ductal anatomy as much as possible. (See 'Surgical correction of benign nipple inversion' above.)

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References

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