Galactocele

Etiology

The presence of the triad of secretory breast epithelium, prolactin stimulus, and ductal obstruction is needed to form a galactocele (see Image. Triad of Secretory Breas Epithelium).[2] 

Secretory breast epithelium: The most common demographic patient group that presents with galactocele are women in the 3rd trimester of pregnancy, during lactation, or sometimes seen even after cessation of lactation. Ductal proliferation is predominantly controlled by estrogen, whereas acinar differentiation is a progesterone effect facilitated by estrogen. These hormones contribute to mammogenesis. The hormonal influence of chorionic gonadotropin forms lobules that have acini with larger size and number of epithelial cells. Small amounts of milk can be secreted as early as week 16 of gestation.[3] Factors that predispose to galactocele formation are:

1. Difficulty in breastfeeding - For example, infants with cleft palate
2. If breastfeeding is contraindicated and breastmilk is not emptied[4]
   1. For infants with phenylketonuria, rare amino acidurias, and classic galactosemia
   2. For infants with an untreated congenital diaphragmatic hernia, Oesophageal atresia, tracheo-oesophageal fistula, intestinal obstruction, etc
   3. For infants whose mothers have diseases such as human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV), or Ebola
   4. For infants whose mothers are taking medications or radioactive agents that might be harmful to the infant
3.  The oral contraceptive pill has also been implicated in the formation of galactocele due to excessive stimulation of the breast epithelium.[2]

Prolactin stimulus: Thirty cases of galactoceles to date have also been reported in male infants due to trans-placental passage of prolactin or with previous cases citing a pituitary adenoma as the cause associated with chronic galactorrhoea.[5][6] Rarely, galactocele can occur in adult males resulting from hyperprolactinemia.[7] Hyperprolactinemia is caused by prolactinomas, which may be associated with MEN1 or with hypogonadotropic hypogonadism

Ductal obstruction: Recently, post-breast-augmentation galactoceles have also been reported, with periareolar incisions being a significant risk factor as they can cause ductal injury and, subsequently, ductal obstruction. However, breast augmentation procedures via the inframammary approach, which is usually considered a protective approach in terms of risk factors for induction of postoperative galactorrhea, also has been demonstrated to cause galactocele in some cases reported in the literature.[8][9] There were 13 cases reported after breast augmentation and 9 cases reported following breast reduction.[10]

The proposed theory is that intercostal nerves are stimulated from surgery, leading to autonomic control over central neurogenic paths, diminishing dopamine output into hypophysis’s portal circulation, increasing prolactin levels and milk secretion, and subsequently causing an increase in prolactin levels.[9] There is no genetic basis for the causation of galactocele, and no genetic risk factors have been identified to date.

Epidemiology

Benign diseases of the breast are seen during the 2nd to 5th decade of life, with a peak in the 4th to 5th decades. This is in contrast to malignant breast conditions, where the incidence increases with the patient's age. Breast lump was the most common presentation of benign breast diseases, accounting for 87% of the cases.

Literature estimates that the incidence of galactocele in women presenting with benign breast conditions to the out-patient department was 4%, accounting for approximately 4% to 5% of breast imaging reporting and data system (BI-RADS) category four lesions when core needle biopsies are performed.[11] However, galactocele is not so uncommon. Presumably, cases of galactocele have not been reported frequently in the literature due to its benign and asymptomatic nature.

Pathophysiology

The main predisposing factor for galactocele development is mammary duct obstruction in the lactating breast, most likely due to trauma, inflammation, nipple abnormalities, or a tumor in rare cases. Distal obstruction of the terminal duct lobular unit causes proximal focal ductal dilatation, forming a galactocele.[1]

Transplacental passage of prolactin does not explain the development of galactocele in male infants, who present with a new-onset breast swelling after a period of dormancy of a few months after birth. To explain this phenomenon, it is hypothesized that neonates develop small retention cysts that remain silent, and their secretory activity eventually ceases with time normally. However, trauma precipitates an inflammatory reaction, which leads to galactocele formation.

The hypothetical contributory factor behind galactocele is the wrong breastfeeding technique, for example, breastfeeding intermittently or in a lying position.[12]

Histopathology

Galactocele is an encysted collection of milk products lined by flattened cuboidal epithelium. The presence of milk is confirmed chemically by a positive mucic acid test. On histopathology, dilated anastomosing channels are lined by cuboidal epithelium, often with secretory activity. Sometimes, adjacent tissue may show evidence of adjacent pressure necrosis or the presence of foamy macrophages and chronic inflammatory changes if cyst contents leak into adjacent tissues.[13]

History and Physical

Typically, a lactating mother will present with a lump in her breast, which is insidious and gradually progressive. There is no history of pain or fever. Primipara, mothers who have difficulty breastfeeding, mothers who breastfeed intermittently, or mothers who use formula feed instead of breast milk are more likely to develop galactocele as there is an incomplete evacuation of milk in the lactiferous ducts. It is essential to ask about medication history, as drugs like metoclopramide and domperidone are known galactagogues that increase the risk of galactocele formation.[14] Domperidone is available with proton pump inhibitors as an over-the-counter medication used frequently for acid peptic disease and gastroesophageal reflux disease (GERD).

The clinical finding is usually a mass in the breast that varies in its degree of tenderness. The mass is usually solitary, non-tender, firm, discrete, and freely movable, may or may not be associated with a milky discharge from the nipple, usually does not demonstrate the findings of acute infection or inflammation, and gives the impression of a solid tumor in a woman in the reproductive span of life (see Image. Galactocele).

Evaluation

Any new palpable lump in the breast requires prompt investigation with a triple assessment, including clinical examination, imaging, and cytologic or histologic assessment when needed.[1] Galactocele is primarily a clinical diagnosis that may be confirmed with the help of investigations. 

Ultrasound

Patients are usually lactating mothers with dense breasts; hence, an ultrasound is ideal after clinical examination. Ultrasound finding of galactocele is generally a solitary, well-defined, anechoic lesion with thin, echogenic walls and some distal acoustic enhancement.[15]

The following findings are seen depending on the chronicity and the site of the lesion:[3]

1. Site:
   1. Central location - A simple cyst is more common, characterized by an absence of loculation and no echogenicity of the cyst. 
   2. Peripheral location - A thin-septated multilocular cyst is a typical feature.
2. Chronicity:
   1. Acute - As the internal contents of the galactocele are a fluid suspension, it appears more homogeneous with medium-level echoes.
   2. Chronic - As the contents are inspissated material, the appearance is heterogeneous, with internal fluid clefts and anechoic fluid rims. Internal echogenic foci with acoustic shadowing are also seen. The internal echogenicity results from their contents, milk products containing about 10% solids, fat, and desquamated epithelium. The distal acoustic enhancement is due to the fluid-filled cyst. The intensity of hypoechoic echo increases gradually due to the interface between the fat and water components.

Notably, a heterogeneously echoic, irregular margined collection is suspicious of abscess formation and should be correlated clinically with signs such as redness, tenderness, and warmth.[16]

Color Doppler investigation may be of some benefit in cases of galactocele. Complex cysts presenting as galactocele can be carefully differentiated from intracystic carcinoma or intraductal papilloma, as blood flow will be absent on the Color Doppler in the case of galactocele.[17] However, a definite diagnosis remains elusive in many cases without histopathological examination.

Mammogram

Mammography should only be used in certain circumstances as a problem resolving technique, limiting radiation exposure of the breast. Mammography may show an indeterminate or circumscribed mass with high radiolucency due to high fat content and water-fat level. The various mammographic findings of galactoceles are described below.[3]

1. Pseudolipoma: When galactocele has a high-fat ratio to protein in breast milk, the lump seen in a mammogram is radiolucent. Since it mimics a lipoma, it is called a pseudolipoma. 
2. Cystic mass with fat-fluid level: This is seen with a low concentration of fat content, which floats above, in the cyst filled with breastmilk. It is better appreciated in the mediolateral oblique view of mammography.
3. Pseudohamartoma: The radiodensity of fat and water is mixed, as the lipid and liquid are not separated. This is similar to the radiologic findings seen in a case of a hamartoma that contains the high viscosity of breast milk. Hence, a galactocele with such characteristics seen on mammograms is called pseudohamartoma.

Treatment / Management

Management of galactocele is usually conservative. A galactocele is a sterile collection that resolves spontaneously on cessation of lactation after the hormonal change associated with pregnancy and lactation is ceased.

Lactating women - Ultrasound-guided fine-needle aspiration is both diagnostic and therapeutic in most cases.[18] This should be done under the gram-positive antibiotic coverage as the most common causative organism for breast abscesses is Staphylococcus aureus. Recurrence is unlikely to occur. Antenatal and postnatal breast massage are preventional and therapeutic, respectively. 

Post-augmentation galactocele - In cases of post-augmentation chronic galactorrhea causing galactocele, dopamine agonists such as Bromocriptine should also be prescribed to inhibit milk secretion as diminishing dopamine output is one of the proposed mechanisms of galactorrhea.

Prolactinoma - Most prolactinomas are treated with medical therapy only. Surgery and radiotherapy are recommended for refractory cases. Cabergoline and Bromocriptine are commonly preferred.[19] 

Role of surgery - Cyst resolution following aspiration can be a pathognomonic sign of a galactocele. However, an excisional biopsy is recommended as the definitive treatment of the chronically obstructed duct if it is rapidly enlarging, discordance in the triple assessment, or if the mass reoccurs after complete aspiration. All these are hallmarks of a galactocele caused due to breast malignancy, and hence, cytology or histopathology is warranted.

Differential Diagnosis

• Breast cyst
• Breast abscess
• Breast carcinoma
• Fibrocystic changes
• Fibroadenomas
• Lactating adenoma
• Traumatic fat necrosis
• Hematoma
• Hamartoma

Prognosis

Galactocele is a benign condition that resolves spontaneously on cessation of lactation, without any intervention. Thus, it has an excellent prognosis. No increased risk of subsequent breast cancer or fibrocystic disease after galactocele has been reported.[20]

Complications

Galactoceles usually resolve on their own in most cases as the hormonal changes linked to lactation settle down. However, in some cases, desquamated epithelial cells and the stagnated milk form an inspissated cyst, which further forms crystals. This leads to forming a crystalizing or solid galactocele, with at least ten reported cases in the literature.[21][22][23] It cannot be diagnosed easily on ultrasound as it does not have any typical features of a galactocele. It may even be mistaken for other benign or solid lesions of the breast. See Image. Inspissated Galactocele.

FNA shows thick, chalky white material with a gritty sensation during aspiration. Hematoxylin and eosin staining of the aspirate shows many well-defined purple crystals. Leishman's staining shows discrete and polymorphic refractile crystals. These crystals show positive birefringence. Amorphous proteinaceous material is seen around the crystals. This crystallized galactocele cannot be emptied by aspiration alone and may require further intervention, like excision.

The rich nutrient content of milk in galactocele with a possible unsterile technique of aspiration or excision may lead to acute mastitis, which can get further complicated by the formation of breast abscesses.[24] Clinically, it becomes swollen and tender, with signs of inflammation present. Staphylococcus aureus is the most common causative organism, followed by Streptococcus species. These common pathogens are present in the nose and throat of nursing babies and infect the breast via the damaged epithelial interface of the nipple-areola complex. It is seen on ultrasound as a complex cyst with thickened walls. Its treatment includes intravenous antibiotics and aspiration or surgical drainage. Sometimes, a breast implant, which is a known predisposing factor, may also get infected with an infected galactocele, necessitating implant removal along with incision and drainage of the abscess.[25] Breastfeeding should continue because it promotes drainage. A milk fistula is a rare complication of incomplete surgical excision of galactocele.