Embryology
Breast development begins at approximately the 5th to 6th embryonic week. It proceeds from a single ectodermal bud and begins developing along the ventral side of the embryo as paired longitudinal bands of thickened ectoderm called milk lines (mammary ridges). The latter extend from axilla to groin. The majority of the mammary ridge involutes by the 9th week of gestation except for a focus of epithelial cells at the fourth intercostal space that subsequently form a single pair of mammary buds. Failure of complete involution results in polythelia/polymastia along the mammary ridge. The primary buds form the secondary buds as ectodermal cells begin to invade the underlying mesenchyme by the 12th week of gestation. While the epithelial cells grow downward as mammary ducts, terminating in lobular buds, the mesenchymal cells differentiate into smooth muscle of the nipple and areola. This specialized epithelium differentiates into 15–20 branches that first consist of solid epithelial columns and then, by the 20–24th week of gestation, develop inner lumens and eventually canalize to form the lactiferous ducts and their branches. These branched epithelial tissues are stimulated to canalize by the placental hormones that enter the fetal circulation during the third trimester. The ends of these branches differentiate into lobulo‐alveolar structures that contain colostrum , which is a yellow, sticky, and serous fluid. This colostral milk, stimulated by the placental hormones, can be expressed for 4–7 days after birth in both male and female newborns (“witch’s milk”). Sebaceous glands, sweat glands, and specialized apocrine glands (Montgomery glands) develop in the second trimester. During the final weeks of gestation, the mass of the mammary gland increases consistently and the nipple–areola complex (NAC) develops and becomes pigmented. With the withdrawal of placental hormones after birth, the secretion of colostrum stops and the breast begins to involute. The supporting structure of the breast, composed of connective tissue and fat, originates from the mesenchyme that invades and surrounds the epithelial system. Failure of some of these stages in breast development to take place can result in congenital abnormalities of the breast.
After birth, circulating maternal estrogens may cause breast enlargement. Thereafter, maternal estrogens are metabolized resulting in involution of breast tissue and a period of quiescence during childhood. At puberty, hormonal flux results in breast growth or thelarche , with estrogens affecting ductal and stromal tissue proliferation and progesterone causing alveolar budding and lobular growth. Thelarche occurs at an average of 11 years of age (range, 8–15). The Tanner Scale describes breast development as proceeding through five stages, with growth generally reaching completion at 16–18 years of age.
Polythelia and Polymastia
Polythelia or presence of supernumerary nipples or nipple–areola complexes are often noted at birth, with the majority located along the embryonic milk line ( Fig. 37.1 ). These form due to failure of regression of the mammary ridge. However, uncommon locations include the back, thigh, neck, and face. The condition usually occurs sporadically, but may be familial, and has a reported incidence as high as 5.6%. , The supernumerary nipple is most commonly located in the inframammary region. There is little evidence to support an association with other congenital anomalies or syndromes nor is there any correlation with gender or predilection for the right or left side, however, it has been suggested that the prevalence is higher on the left side and in males. The clinical significance of supernumerary nipples is the possibility of growth and development of similar pathologies as a normal breast, including breast neoplasia. Traditionally, the management of polythelia has been observation. However, pigmented lesions along the embryonic lines are routinely excised before puberty in order to avoid wider tissue excision secondary to glandular growth, which may be necessary after the onset of puberty in girls. , If multiple nipple–areola complexes are present on the breast proper, magnetic resonance imaging may be required to determine the complex associated with glandular/ductal tissue. Changes to the pigmented lesion should be treated as for any melanocytic nevus, with early excision and histopathological assessment. An oncologist should evaluate nipple growth that occurs at a time other than childhood, puberty, or pregnancy.
Polymastia occurs due to failure of the mammary ridge to completely regress in utero, leading to the development of breast tissue following hormonal stimulation. Ectopic breast tissue may or may not have an overlying NAC, but it is not uncommon for the nipple and areola to be absent or rudimentary. Polymastia has an even lower incidence than polythelia (1–2%), and also occurs along the embryonic milk line. Unlike polythelia, polymastia may only be noticed during puberty, pregnancy or lactation. A common location is the axilla and unusual locations include the vulva, lower extremities and dorsal trunk. Like polythelia, it is usually sporadic, but can have familial inheritance. Unlike polythelia, polymastia can be associated with other congenital anomalies, particularly congenital renal anomalies. Treatment of polymastia is variable and depends on the size and location of the supernumerary breast gland and nipple.
In view of the fact that ectopic breast tissue is subject to the same pathology as normal breast parenchyma, complete resection is recommended. Simple mastectomy is the option of choice in patients who present with a third distinct breast mound; however, disruption of the inframammary fold and soft tissue envelope of the remaining breast should be prevented when possible. In cases where the accessory breast is adjoined to the native breast, tissue-sparing techniques with skin de-epithelialization and accessory nipple excision can usually restore the mound to a normal appearance and location. Corrective surgery for polymastia should be performed when breast development is complete and final breast tissue volumes have been achieved. It is often difficult to predict the form and position of the accessory breast mound or nipple and early excision may ultimately compromise the eventual outcome. Delaying excision until the final shape and position of the native breast tissue is complete will prevent eventual deformities from inadvertent iatrogenic insult to the developing breast.
Gynecomastia
Gynecomastia, or abnormal benign proliferation of the male breast tissue, affects up to 65% of boys, peaking between the ages of 13 and 14 years ( Fig. 37.2 ). , Physiological pubertal gynecomastia is attributed to a disruption of balance between testosterone and estrogen, where there is a lag between rising testosterone and estradiol levels through puberty. This transient period of excess estradiol promotes glandular proliferation of the breast. Gynecomastia should not be confused with pseudogynecomastia, defined as adipose tissue giving the appearance of a female breast, without the presence of glandular tissue. Only 5–10% of gynecomastia persists beyond one year and spontaneous resolution occurs in the majority of patients. If the condition persists beyond one year, fibrosis and hyalinization occur, with regression of epithelial proliferation. These changes render the condition less amenable to medical therapy and increase the necessity for surgical intervention. Timing of surgical correction is based on the absence of a secondary cause for gynecomastia (e.g., endocrine), persistence of breast enlargement for greater than one year, as well as psychosocial impact on the patient. Simon proposed a classification system for gynecomastia, with grade 1 characterized by slight breast enlargement without skin redundancy, grade 2a moderate breast enlargement without skin redundancy, grade 2b moderate breast enlargement with marked skin redundancy, and grade 3 both marked breast enlargement and skin redundancy. Albeit physiological in the majority of cases, secondary gynecomastia must be ruled out by performing a thorough physical exam and history. Drug-induced gynecomastia is the most common secondary cause. A breast and testicular exam is recommended to rule out any rare secondary causes such as testicular malignancies. Other secondary causes include tuberous sclerosis, adrenal malignancies, and steroid hormone synthesis abnormalities. Preoperative evaluation by endocrinology should be considered if endocrinopathy is suspected on history or physical examination (such as galactorrhea, abnormal testicular examination, features of Klinefelter syndrome, abnormal visual field or funduscopic testing, rapid progression). Routine workup by an endocrinologist in patients with suspected physiological gynecomastia lasting less than a year with no suspicious findings is likely not necessary. Some authors suggest a more selective evaluation, recommending referral to endocrinology if gynecomastia persists beyond 16 years of age.
Management consists of excising the breast tissue and removing excess skin, if present. A semicircular periareolar incision is commonly used for breast tissue excision. Liposuction (traditional suction-assisted or ultrasonic-assisted) is used to remove the surrounding stromal hypertrophy or fibrofatty accumulation around the breast. The breast bud is often too firm and liposuction alone is difficult, however it could be used to fragment the breast tissue, facilitating subsequent excision through a limited excision (pull-through technique). , Arthroscopic shavers have been used to remove the firm fibrous breast tissue, obviating the need for a periareolar incision in certain cases. Mild skin excess may resolve after gland excision due to skin contraction. In view of the capacity for contraction of the skin envelope with the exception of dramatic skin excess, a staged approach may be considered with volume reduction as an initial treatment, followed by revision surgery if necessary 6–12 months later. When skin resection is necessary, an algorithm similar to that implemented for mastopexy may be applied. In cases of significant skin excess, a circumareolar, circumvertical, or wise-pattern skin resection can be considered depending on the severity.
Virginal Hypertrophy
Virginal hypertrophy or gigantomastia is defined as massive enlargement of the breast, usually defined as a breast volume requiring a reduction of at least 1800 g per side. The condition is usually bilateral and is associated with rapid and disproportionate growth of the breast, which typically commences shortly after puberty. The growth is so rapid that it often outgrows the existing blood supply. There is no association with endocrine abnormalities. Gigantomastia is generally sporadic and secondary to abnormally sensitive glandular tissue to normal levels of pubertal hormones. The standard treatment is breast reduction. Continued growth following breast reduction of the hypertrophied breast is frequent and also reported to occur years later during pregnancy. Some authors have recommended skin and nipple-sparing mastectomy in order to control an aggressive process in patients who demonstrated continued regrowth following a reduction. Pharmacological treatment with tamoxifen (antiestrogen medication) has been reported to control breast growth and/or ablate recurrence but its use is still controversial considering the significant side effects. Clinically, unilateral virginal hypertrophy should be distinguished from excessive breast growth secondary to a mass such as phyllodes tumor or fibroadenoma.
Athelia and Amastia
The absence of nipple (athelia) and/or glandular breast tissue (amastia/amazia, respectively) is a rare occurrence. According to Lin and Nguyen, there are different presentations of amastia and each can be attributed to different underlying pathologies: (1) ectodermal defects may cause bilateral absence of breasts in males and females and is related to failure of development of the ectodermal layer and its appendages (abnormalities of the skin, teeth and nails); (2) bilateral amastia may be an isolated occurrence or be associated with other anomalies of the palate and upper extremities; (3) unilateral amastia may be a variant of Poland syndrome and should be treated accordingly ( Fig. 37.3 ). Treatment of amastia and athelia may follow the principles of post-oncologic breast reconstruction with special attention paid to the placement of the inframammary fold and nipple. However, reconstruction in patients with amastia should be performed keeping in mind potential aberrations of the blood supply to the skin. Very often, reconstruction for amastia is initiated prior to physical maturity with placement of a tissue expander, which is inflated commensurate with the growth of the normal contralateral breast or in bilateral cases, initiated at thelarche and continued proportionate with body habitus.
Tuberous Breast
Rees and Aston first described the tuberous breast deformity in 1976, after its resemblance in shape to a tuberous plant root. This deformity is characterized by constriction of the breast base, parenchymal hypoplasia, pseudoherniation of the breast tissue through the areolar region, skin deficiency in the subareolar region and superior malposition of the inframammary fold. Since their initial description, many similar breast deformities have been described, including herniated areolar complex , snoopy deformity , tubular breast , constricted breast , lower pole hypoplasia , and narrow-based breast. Indeed, most consider these deformities to be various degrees of the same pathology, with the commonality being breast base anomaly. Tuberous breast remains the most widely used nomenclature to describe the pathological condition of glandular hypoplasia with a deficiency in the circumferential skin envelope of the breast base. The incidence remains unknown and there is no evidence to suggest a familial association. The deformity can be unilateral or bilateral, and usually asymmetric.
The etiology remains unclear, although several authors have proposed developmental sequences to account for the deformity. Grolleau et al attribute the deformity to an anomaly of the superficial muscular fascia in the lower pole of breast, such that the superficial fascia is aberrantly adherent to the dermis and muscular plane. This restricts peripheral expansion, exaggerating forward growth resulting in a tubular breast shape and enlarged areola. Additionally, the deformity may arise secondary to involution of the mammary ridge, in light of the fact that the inferior portion of the deformed breast possesses a deficiency of milk ducts. Alternatively, Mandrekas and Zambacos proposed that the deformity is a result of a constricting ring at the base of the breast. The authors propose that this pathological process begins in puberty explaining why no anomaly is discernible prior to the onset of breast development. As a result of the ectodermal origin of the breast and its invagination into the underlying mesenchyme, the breast parenchyma is contained within a fascial envelope, the superficial fascia. This fascia consists of a superficial layer, which covers the breast parenchyma and a deep layer, which forms the posterior boundary of the parenchyma and lies on the muscular fascia of the pectoralis major and serratus muscles. The two layers of superficial fascia are joined by fibrous attachments (suspensory ligaments of Cooper) extending from the dermis to the pectoralis fascia. The region beneath the NAC is devoid of superficial fascia. Thus, the pathological constricting ring at the periphery of the NAC in the tuberous breast deformity is thought to represent a thickening of the superficial fascia, which coupled with the absence of superficial fascia beneath the areola inhibits inferior expansion of the breast and leads to herniation of the breast parenchyma through the areola. As a result, the authors proposed complete vertical transection along the inferior portion of the breast parenchyma. In 1996, von Heimburg et al proposed a classification system for the tuberous breast deformity, based primarily on the degree of breast hypoplasia and deficiency of skin in the lower pole, including Type I , hypoplasia of the lower medial quadrant, Type II , hypoplasia of the lower medial and lateral quadrants, with sufficient skin in the subareolar region, Type III , hypoplasia of the lower medial and lateral quadrants, with a deficiency of skin in the subareolar region, and Type IV , severe breast constriction with minimal breast base. Grolleau et al proposed a more simplified classification system, which is more commonly adopted. In type I deformity, only the lower medial quadrant is deficient. Both lower medial and lateral quadrants are deficient in a type II anomaly ( Fig. 37.4 ), and in type III deformity all four quadrants are deficient and the breast base is constricted both horizontally and vertically ( Fig. 37.5 ). Meara et al expanded on the latter classification system to aid in development of a specific treatment strategy.
