24th May 2025

Nipple Discharge

After breast pain and breast lumps, nipple discharge represents the 3rd most common breast-related complaint. As many as 80% of women of reproductive age, will experience at least one episode of nipple discharge. It can be further classified into lactational (normal), physiological or pathological, the majority of which is of a benign origin.

Intraductal Papilloma

Intraductal papillomas are the most common cause of pathological nipple discharge, classically seen in women between the ages of 40 and 50 years. They are characterised by the development of a wart-like lump within the milk ducts and are usually found in the vicinity of the nipple, though they can occur anywhere in the breast. Central intraductal papillomas, located in the subareolar region, arise from large lactiferous ducts and are usually solitary in nature. Peripheral intraductal papillomas meanwhile, involve the terminal duct lobular unit (TDLU) and are usually several in number, termed papillomatosis.

As papillomas can be asymptomatic, they are often noted incidentally during routine imaging. However, clinical examination may reveal a painless retroareolar mass. In instances of nipple discharge, papillomas are typically associated with unilateral, spontaneous and persistent discharge of bloody or serosanguinous fluid, often less than 6 months in duration. 

Mammography is usually normal, though findings may include a solitary or multiple dilated ducts, with an associated subareolar mass that is benign in appearance, with or without calcification. On ultrasound, a papilloma can be seen as a well-defined mass, partially outlined by fluid, with colour doppler demonstrating a vascular stalk. Further investigation is usually warranted, usually by way of an excision biopsy, which reveals a dual population of both epithelial and myoepithelial cells lining a fibrovascular core and set within a duct.

Papillomas are not associated with an increased risk of breast cancer, unless they are noted to contain atypical cells during histological assessment. Follow-up is typically reserved for those in which atypical cells have been identified, or those with multiple papillomas.

Mammary Duct Ectasia/Periductal Mastitis

Mammary duct ectasia and periductal mastitis are terms that are often used interchangeably, though some literature has described them as being two distinct entities. They are another common cause of benign nipple discharge, accounting for up to 30% of cases. Duct ectasia is typically seen in perimenopausal women over 35 years of age and is thought to arise due to age-related shortening and widening of the ducts, with subsequent obstruction secondary to inspissated secretions. Periductal mastitis, however, is more common in younger women and occurs when the ducts become inflamed and/or infected. The latter has a strong association with smoking.

Duct ectasia may be asymptomatic, but can present with thick, “cheesy” nipple discharge, but can also be watery in consistency, as well as brown, green or blood-stained. Occasionally, a lump may be felt behind the nipple and the nipple itself may become red, tender and retracted. At this point, periductal mastitis may be more appropriate terminology and the surrounding breast tissue may become painful, hot and erythematous. If left untreated, a pus filled abscess or fistula may also develop.

Mammography and ultrasound imaging reveal similar features, characterised by dilated, branching tubular structures in the subareolar region. X-ray may also show rod like calcifications pointing towards the nipple. Biopsy of the area shows dilated duct lumens containing foamy macrophages, with surrounding periductal chronic and/or granulomatous inflammation, particularly if there has been rupture. In the latter stages, periductal fibrosis and obliteration of the lumen may also be seen.

Duct ectasia will often resolve spontaneously and may only require simple analgesia for pain relief. Periductal mastitis will usually be treated with a course of antibiotics, though some cases will resolve on their own accord. In the presence of complications, such as an abscess or the development of a fistula, specialist input may be required for further management. This can include aspiration of the pus, or incision and drainage. Surgical intervention may be warranted in recurrent disease or in cases that do not respond to the aforementioned measures. However, neither duct ectasia or periductal mastitis are associated with an increased risk of developing breast cancer.

Galactorrhoea

Galactorrhoea is characterised by milky nipple discharge unrelated to pregnancy or breastfeeding and can be physiological or pathological in nature. It can affect as many as 1 in 4 women and can occur at any age, including after menopause. Raised serum prolactin levels are responsible for the discharge, of which there are many underlying causes.

Physiological nipple discharge can be attributed to several factors, one of which is excessive nipple stimulation. This can be through sexual activity, frequent breast examinations (including imaging) or high-impact exercise. Stress is also known to increase serum prolactin levels, which can result in galactorrhoea.

Pathological nipple discharge can be secondary to a wide variety of endocrine and iatrogenic factors. Hyperprolactinaemia can be associated with disorders of the hypothalamic-pituitary axis, of which lactotroph adenomas are the most common. Accounting for up to 40% of all pituitary adenomas, lactotroph adenomas are usually benign sporadic prolactin secreting tumours, though occasionally they may form part of an underlying Multiple Endocrine Neoplasia Type 1 (MEN 1) Syndrome. Disorders affecting the hypothalamus may also lead to increased prolactin levels, usually by way of reduced dopaminergic inhibition of the pituitary gland. These can include benign tumours (such as craniopharyngioma), malignancy (such as metastatic breast carcinoma), infiltrates (such as sarcoidosis) or trauma.

Drug induced hyperprolactinaemia is also a common cause of pathological galactorrhoea. The most common cause of pharmacologically induced hyperprolactinaemia is antipsychotic medication, typically due to their antagonistic effect on dopamine receptors. Other medications that have been associated with raised prolactin levels include selective serotonin reuptake inhibitors (SSRIs), the gastric motility drugs Metoclopramide and Domperidone, Methyldopa and Verapamil.

Other less common causes of galactorrhoea include familial hyperprolactinaemia (characterised by a germline, loss of function mutation in the prolactin receptor gene PRLR), hypothyroidism, macroprolactinaemia (aggregates of prolactin and antibodies) and chronic kidney disease.

Investigations and treatments for galactorrhoea are dependent upon the underlying cause. Evaluation usually requires an extensive history, coupled with clinical examination, serum prolactin levels and imaging, such as an MRI scan of the pituitary gland. The presence of galactorrhoea alone does not always necessitate treatment, unless it is bothersome to the patient. When indicated, the pharmacological treatment for lactotroph adenomas and idiopathic hyperprolactinaemia usually involves the introduction of a dopamine agonist, such as Cabergoline or Bromocriptine. Larger tumours that are unresponsive to initial medical therapy may require more invasive measures, such as transsphenoidal surgery and postoperative radiotherapy. Drug induced hyperprolactinaemia can be managed through patient counselling and education surrounding medication side effects. In some circumstances, dose tapering or discontinuing the medication may be required.