Disorders of the Breast


Disorders of the Breast

Monica Sifuentes, MD


A 2-year-old girl is brought to the office for bilateral breast swelling first noticed 3 weeks previously by her mother. The swelling is nontender and does not appear to be increasing in size. No history exists of galactorrhea. The child is otherwise healthy, takes no medications, and is not using any estrogen-containing creams or other over-the-counter products or supplements.

On physical examination, vital signs are normal, and the child is at the 50th percentile for height and weight. A 1.5-cm, firm, nontender mass is palpated below her left nipple. Below the right nipple, a 1-cm, nontender mass of similar consistency is present. There is no discharge from either nipple and no areolar widening. The abdomen is soft, with no masses palpated. The genitalia are those of a normal prepubescent female with no pubic hair and vaginal mucosa that appears red and not estrogenized.


1. What is premature thelarche, and how can it be differentiated from true precocious puberty?

2. What are the most common causes of breast hypertrophy in the infant?

3. When does pubertal breast development normally occur in females?

4. What are the most common causes of breast masses in adolescent females, and how should they be managed?

5. How can physiologic pubertal gynecomastia be differentiated from pathologic causes of gynecomastia in adolescent males?

Breast disorders occur in all pediatric age groups and can become a cause for significant concern for both patients and parents or guardians. A neonate may present to the pediatrician with bilateral breast hypertrophy and galactorrhea or mastitis. Bewildered parents or guardians might bring in their young prepubertal daughter because of what appears to be early breast development. An anxious adolescent female may notice for the first time that her breasts are asymmetric, or she may feel a lump beneath the skin. An adolescent male can present with unilateral or bilateral gynecomastia that makes him uncomfortable and causes severe psychological distress. Whatever the underlying cause, breast problems can be disconcerting at any age. Primary care physicians should be equipped to differentiate between normal variants of growth and pathologic conditions in newborns, infants, children, and adolescents. Significant disorders are rare, but diagnosis is important so that appropriate management can begin.


Breast problems range from congenital anomalies and benign disorders related to hormonal stimulation to breast masses and tumors. Serious disorders, such as primary breast cancer, are exceedingly rare in children and adolescents, although inappropriate breast enlargement or gynecomastia as a sign of another neoplastic process is not uncommon.

Benign breast hypertrophy can occur in 60% to 90% of newborns and occurs in both male and female term neonates. Presentation may be unilateral or bilateral. Occasionally nipple discharge occurs, particularly in the case of well-intentioned family members who try to extract the milk, inadvertently promoting the central secretion of prolactin and oxytocin via breast stimulation.

Congenital anomalies of the breast include polythelia, polymastia, amastia, and athelia. Polythelia, or extra accessory nipples, can occur anywhere along the embryonic mammary ridge (also called the “milk line”) from the axilla to the groin and occurs in 2% of the general population (Figure 62.1). Reportedly, abnormalities of the urologic and cardiovascular systems have been associated with polythelia. Polymastia refers to supernumerary breasts along the milk line and occurs less frequently than polythelia. The usual locations for supernumerary breasts are below the breast on the chest or the upper abdomen. Polythelia and polymastia may be familial and can occur bilaterally or unilaterally. Problems associated with breast development, such as a tuberous breast deformity, also can be thought of as a congenital anomaly, although it does not manifest until later in puberty when breast growth is noted to be underdeveloped or abnormal in appearance. The breasts have the appearance of a tuberous plant root, with an elevated inframammary fold, narrow breast base, and “herniation” of glandular tissue through the areolae, which are unusually large.

Amastia (congenital absence of glandular breast tissue) and athelia (absence of a nipple) are rare, but their presence often is associated with other anomalies of the chest wall, such as pectus excavatum. Amastia also is seen in Poland syndrome, which includes absence of the ipsilateral pectoral muscles, various rib deformities and upper limb defects (eg, syndactyly [webbed fingers]), and radial nerve aplasia (Figure 62.2).

Premature thelarche is isolated unilateral or bilateral breast development in girls between 1 and 4 years of age without other signs of sexual maturation (eg, pubic hair, estrogenized vaginal mucosa, acceleration of linear growth). An estimated 60% of cases occur between 6 months and 2 years of age, and a diagnosis after 4 years of age is uncommon. In contrast, precocious puberty is the appearance of any sign of secondary sexual maturation before age 8 years in girls with a normal body mass index or age 9 years in boys. In young females, this involves breast or pubic hair development, and in males it involves pubic hair development or testicular enlargement. Despite well-documented ethnic variation among children, 7 years is considered the lower acceptable age limit for the onset of puberty in non-Hispanic black and Mexican American girls.


Figure 62.1. Polythelia. Supernumerary nipples along the embryonic mammary ridge (milk line).


Figure 62.2. Amastia. Unilateral (left) complete absence of breast tissue.

Gynecomastia may occur in adolescent males as they progress through puberty and is often called “transient pubertal gynecomastia” or “physiologic pubertal gynecomastia.” An estimated 60% to 70% of adolescent males are affected, with a peak incidence between ages 13 and 14 years or approximately 1 year after the onset of puberty. This generally corresponds to sexual maturity rating (SMR) (ie, Tanner stage) 3 to 4 genital and pubic hair development in the young male. Like breast development in the pubertal female, transient pubertal gynecomastia may be asymmetric and painful, although concurrent or sequential involvement of both breasts can occur. It is uncommon for pubertal gynecomastia to occur beyond age 17 or 18 years in the adolescent male.

In the adolescent female, breast masses are not uncommon; however, clinically significant lesions are rare. Breast cancer has an estimated annual incidence of 0.1 in 100,000 adolescents. In most studies of patients through age 20 years, the most common benign breast tumor is a fibroadenoma, which has been reported in 60% to 95% of biopsied lesions. Two-thirds of these lesions are located in the lateral quadrants of the breast, with most in the upper outer quadrant. The peak incidence of these lesions is in late adolescence (17–21 years of age), and they tend to occur more commonly in black females. Reportedly, 10% to 15% of cases are bilateral. Additionally, 25% of cases involve multiple fibroadenomas.

Fibrocystic changes are the second most common histologic diagnosis after fibroadenomas. Other breast masses include solitary cysts, abscesses, lipomas, and the phyllodes tumor (also known as cystosarcoma phyllodes), an extremely rare, rapidly growing, painless breast tumor that is nearly always benign and clinically can be confused with fibroadenoma, except for its aggressive growth. If malignant, however, cystosarcoma phyllodes can metastasize hematogenously to the lungs.

Malignancy is reported in less than 1% of excised lesions. Fewer than 50 cases of primary breast cancer in children and adolescents have been reported in the literature to date. Rhabdomyosarcoma and fibrosarcoma are among the other rarely reported primary tumors of the breast in adolescents. Metastatic cancer of the breast is more common than primary breast cancer and has been reported in children with primary hepatocellular carcinoma, leukemia, Hodgkin and non-Hodgkin lymphoma, neuroblastoma, and rhabdomyosarcoma. Of note is the increased lifetime risk for radiation- induced breast cancer in girls and adolescents who undergo mantle/chest wall irradiation during peak breast development (10–16 years of age); such irradiation typically is administered during treatment for Hodgkin lymphoma. The breast cancer risk for women who are survivors of Hodgkin disease is 75 times that of the general population. According to the literature, the cumulative risk for breast cancer during their lifetime exceeds 40% for girls who undergo chest irradiation for treatment of Hodgkin lymphoma.

Normal Breast Development

In the adolescent female, the first sign of puberty is breast development or thelarche. This begins with the appearance of a breast bud beneath the areola. Under the influence of estrogen, there is an increase in the adipose tissue along with the beginning of ductal and stromal growth. Progesterone initiates alveolar budding and lobular growth and contributes to the development of secretory lobules and alveoli. The alveoli are later lined by milk-secreting cells under the influence of prolactin when full maturation occurs during the first pregnancy.

The normal progression of breast growth is divided into 5 stages or SMRs. These descriptions are used to follow normal breast development, which occurs in parallel with and generally precedes pubic hair development. It usually takes 2 to 4 years for the completion of breast development, although, as in all aspects of puberty, variations do occur. The practitioner should keep in mind that many females remain in SMR 3 or 4 breast development until pregnancy. Additionally, especially between SMR 2 and 4, significant breast asymmetry can be quite common in the adolescent without indicating a pathologic process. After both breasts are fully mature and reach SMR 5, adequate catch-up growth usually has occurred.

Clinical Presentation

Neonates with breast disorders usually present in the first few weeks after birth with bilateral breast enlargement that may be asymmetric (Box 62.1). They may present with associated clear or cloudy nipple discharge. If an infection is present, the overlying skin may be warm and erythematous. Fever or other nonspecific symptoms, such as poor feeding and irritability, also may be present because mastitis involves the entire breast bud; although rare, septicemia can occur as well.

In prepubertal females, benign premature thelarche presents as unilateral or bilateral nontender subareolar swelling without the appearance of other secondary sexual characteristics. In contrast, girls with precocious puberty may have axillary hair, nipple and areola enlargement and thinning, and pubic hair in addition to early breast

development. Adolescent females with a breast problem often report a unilateral breast lump noted incidentally by the teenager. It may be tender, fluctuant, firm, rubbery, or nodular. The adolescent also may report painful breasts (mastalgia) that can be cyclic in nature. For most breast masses, the overlying skin is normal, but occasionally skin changes do occur. Rarely, an associated nipple discharge may be present.

Box 62.1. Diagnosis of Breast Disorder From Birth Through Adolescence

Neonates, Infants, Prepubescent Children, and Adolescent Males

Unilateral or bilateral subareolar mass

Possible associated nipple discharge

Overlying skin changes, such as erythema in neonates and infants

Adolescent Females

Firm, rubbery, freely movable mass

Possible tenderness

Breast asymmetry

Skin changes, such as shininess, venous distention, or dimpling (rare)

Possible associated nipple discharge

Because most breast masses occur in females, gynecomastia is particularly anxiety provoking in young adolescent males. It usually appears as a unilateral or bilateral 2- to 3-cm firm mass beneath the areola, which may or may not be tender. Irritation of the skin of the nipple may occur resulting from prolonged friction from clothing. Galactorrhea rarely accompanies pubertal gynecomastia and may be indicative of self-stimulation; illicit drug use, including cannabis, opiates, benzodiazepines, and amphetamines; or exposure to other medications, such as risperidone.


Neonatal breast hypertrophy seemingly is a response to maternal estrogen exposure in utero. Constant stimulation can result in persistent swelling, galactorrhea, and overt infection (ie, mastitis). Of note, if galactorrhea is present, it should not persist beyond the first few weeks after birth. Generally, preterm neonates are less responsive to maternal hormones and, therefore, breast hypertrophy occurs less often in this age group and its appearance may be delayed for weeks.

Benign premature thelarche is a variation of normal pubertal development with transient elevations in estrogen levels from functional ovarian cysts or fluctuations in pituitary gonadotropin secretion. Often, the breast enlargement occurs without other estrogen effects, such as an increase in uterine size or changes in the appearance of the external genitalia. Typically, no linear growth or bone age advancement is associated with this condition. Current research is examining the potential role of leptin and its influence on sex steroids in the development of premature thelarche as well as pubertal gynecomastia.

Central precocious puberty is the result of early activation of the hypothalamic-pituitary-gonadal axis and the secretion of gonadotropin-releasing hormone (GnRH)-dependent pituitary gonadotropins in a pulsatile pattern. Although a search may be undertaken for an underlying central nervous system (CNS) or gonadal abnormality, most cases in females are idiopathic. In contrast, less than 10% of males with precocious puberty do not have an identifiable cause, and it has been reported that approximately 50% of boys with precocious puberty have an identifiable intracranial process. Central nervous system tumors cause precocious puberty by impinging on the neuronal pathways that inhibit the GnRH pulse generator in childhood. Cranial irradiation, received as a part of tumor therapy, also can cause central sexual precocity. Pseudo-precocious puberty is GnRH-independent and is caused by the extrapituitary secretion of gonadotropins or the secretion of gonadal steroids independent of pulsatile GnRH stimulation. (See the article by Long in Selected References for a general review of precocious puberty.)

The cause of fibroadenomas in adolescent females is postulated to be an abnormal sensitivity to estrogen. Observations supporting this hypothesis include the presence of estrogen receptors in the tumor and an increased incidence of this type of tumor during late adolescence. Thus, prolonged exposure to estrogen may play a role in the development of fibroadenoma. Enlargement can occur during pregnancy or toward the end of the menstrual cycle.

The definition of gynecomastia is an increase in the glandular and stromal tissue of the male breast. Physiologic gynecomastia is thought to occur from a transient imbalance between estrogen and androgens during puberty. Alterations in the ratio of these hormones results in an increase in estrogen relative to testosterone. Certain medications can cause elevations in serum prolactin and lead to gynecomastia or galactorrhea (Box 62.2). Some illicit drugs, such as marijuana, contain phytoestrogens that can mimic estrogen or stimulate estrogen receptor sites. Specific medications, such as spironolactone and cimetidine, interfere with androgen receptors or induce inhibition of enzymes necessary for steroid synthesis.

Differential Diagnosis

The differential diagnosis of breast disorders in children and adolescents depends on sex and age at onset. In addition, the presence or absence of other secondary sexual characteristics is helpful to differentiate between a variation of normal pubertal development and a pathologic process.

Infants and Children Younger Than 9 Years

In prepubertal children, the differential diagnosis of isolated early breast development includes exposure to exogenous sources of estrogen, such as skin creams that may contain tea tree or lavender oil, makeup, and medications (eg, oral contraceptives).

Box 62.2. Causes of Galactorrhea

Mechanical stimulation of the nipple





Butyrophenones (haloperidol)








Tricyclic antidepressants

Illicit drugs



Hypothalamic-pituitary disorders

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Aug 28, 2021 | Posted by in PEDIATRICS | Comments Off on Disorders of the Breast
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