Nipple discharge

Nipple discharge is fluid leaving the nipple outside normal lactation. Most discharge is physiological or benign, and the key judgement is whether it is pathological, defined as spontaneous, persistent, unilateral, from a single duct, and bloody, serous or clear, because this pattern carries a risk of intraductal papilloma or malignancy.

Clinical relevance. Discharge is the presenting symptom in about 3 to 5% of breast clinic attendances. Intraductal papilloma explains most pathological discharge, and cancer is found in a minority of cases, rising with age and with bloody discharge.

Anatomy and physiology. Each breast has 15 to 20 lactiferous ducts opening at the nipple. Prolactin from the anterior pituitary drives milk production, and dopamine from the hypothalamus inhibits it. Classification.

• Physiological: bilateral, multiple duct, non-spontaneous (expressed), milky, green, brown or yellow, common after nipple stimulation, and in the postpartum year or longer.
• Galactorrhoea: milky bilateral discharge outside pregnancy and lactation, caused by hyperprolactinaemia or drugs.
• Pathological: spontaneous, unilateral, single duct, bloody, serosanguinous, serous or clear watery.
• Purulent: infection.

Key distinctions. Colour does not reliably separate benign from malignant discharge, but blood, spontaneity and single duct origin do. Discharge in a man is rarely physiological and needs imaging.

History.

• Duration, side, number of ducts, colour, consistency, spontaneity versus on pressure, and stains on clothing or bedding.
• Associated lump, pain, nipple retraction, skin change, fever and axillary swelling.
• Pregnancy, breastfeeding, recent weaning (discharge can persist for up to 2 years), menstrual history, previous breast surgery, trauma and nipple piercing.
• Galactorrhoea features: amenorrhoea or oligomenorrhoea, infertility, reduced libido, hot flushes, headache, visual disturbance, symptoms of hypothyroidism.
• Drugs: antipsychotics (risperidone, haloperidol), metoclopramide, domperidone, methyldopa, verapamil, opioids, oestrogens, tricyclic antidepressants, SSRIs, H2 blockers, cannabis, and herbal products.
• Breast cancer risk factors and family history, previous breast biopsy.

Examination.

• Inspect the nipple and areola for eczematous change, ulceration, retraction, crusting and a blood stained spot on the bra.
• Identify the discharging duct by pressing sequentially around the areola, and note colour and whether it is a single orifice. Test for blood with a urine dipstick.
• Palpate both breasts and axillae. Check for a retroareolar mass.
• Visual fields to confrontation for suspected pituitary disease, thyroid examination, and signs of hypothyroidism, chronic kidney disease or cirrhosis.
• Examine the chest wall and dermatomes for a herpes zoster rash or neurological irritation.

Red flags.

• Spontaneous bloody or serosanguinous discharge from a single duct.
• A palpable mass, skin change, nipple retraction or Paget type eczema of the nipple.
• Age over 50 years with new unilateral discharge.
• Discharge in a man.
• Axillary nodes.
• Headache with visual field loss (pituitary tumour).
• Purulent discharge with fever and a tender swelling (abscess).

Special groups. Pregnancy: bloody discharge (rusty pipe syndrome) is common in the third trimester and usually benign, but persistent discharge needs assessment. Neonates may have transient milky discharge from maternal hormones. Men with galactorrhoea need prolactin, testosterone and pituitary assessment.

Breast ductal causes (usually unilateral, single duct).

• Intraductal papilloma (commonest), papillomatosis.
• Duct ectasia with periductal mastitis (often green, brown or cheesy, multiple ducts, ageing).
• Fibrocystic change.
• Papillary carcinoma, ductal carcinoma in situ, invasive ductal carcinoma, Paget disease of the nipple.
• Mammary duct fistula, trauma and post surgical.

Physiological and hormonal. Pregnancy, lactation and postpartum persistence, nipple stimulation, neonatal discharge, cyclical change, menopause.

Galactorrhoea due to hyperprolactinaemia.

• Prolactinoma, other sellar and parasellar tumours or stalk compression, empty sella, acromegaly.
• Primary hypothyroidism.
• Chronic kidney disease, cirrhosis.
• Macroprolactinaemia (inactive form).
• Chest wall lesions, herpes zoster, burns or trauma, and breast or chest surgery.
• Ectopic prolactin from bronchogenic carcinoma or renal cell carcinoma.

Drug induced. Antipsychotics, metoclopramide, domperidone, methyldopa, verapamil, opioids, oestrogens, tricyclic antidepressants, SSRIs, proton pump inhibitors, H2 blockers, cocaine and cannabis, herbal products (fennel, fenugreek, anise).

Infective and inflammatory. Lactational mastitis, periductal mastitis, subareolar abscess, tuberculous mastitis (endemic regions), eczema and dermatitis of the nipple.

Step 1. Classify the discharge as physiological, galactorrhoea or pathological by history and examination. Discharge that is bilateral, multiple duct, non-spontaneous and not bloody needs no breast imaging when the examination is normal.

Step 2. Pathological discharge. Triple assessment: examination, ultrasound of the retroareolar region and mammography (age 40 and over; under 40 mammography is added only for suspicious features).

• Ultrasound shows dilated ducts, an intraductal mass or a papilloma, with sensitivity for a causative lesion of about 70 to 90%.
• Breast MRI with contrast for persistent pathological discharge with negative imaging; MRI sensitivity for a significant lesion is high, and a negative MRI allows reassurance and follow up.
• Ductography (galactography) is used less often and is replaced by MRI in many centres. Duct cytology has low sensitivity and is not relied on.
• Core biopsy of any mass or suspicious lesion. Nipple punch or wedge biopsy for nipple eczema that does not settle after 2 weeks of topical corticosteroid (Paget disease).
• Test for blood: a positive dipstick supports a ductal lesion, but a negative result does not exclude one.

Step 3. Suspected galactorrhoea. Pregnancy test, serum prolactin (take at least 1 hour after waking, without nipple stimulation or recent exercise), TSH, creatinine, liver tests, and review of drugs.

• Prolactin over 25 ng/mL (about 500 mIU/L) is raised, and repeat once to confirm if mildly raised (stress and sampling cause small rises).
• Values over 100 ng/mL suggest a pituitary cause, and over 200 ng/mL suggest a macroprolactinoma. Drug induced rises are usually under 100 ng/mL (antipsychotics can reach 200 ng/mL or more).
• Request macroprolactin (polyethylene glycol precipitation) when prolactin is raised in an asymptomatic patient.
• MRI of the pituitary with contrast for prolactin over 100 ng/mL, persistent hyperprolactinaemia without a cause, visual symptoms or headache. Visual field testing when a macroadenoma is suspected.

Step 4. Infection: swab or culture of purulent discharge, ultrasound for abscess, and mycobacterial testing (GeneXpert, acid fast stain, culture) when tuberculosis is possible.

Limitations. Imaging may miss small intraductal lesions. Negative cytology does not exclude cancer. Prolactin rises with sleep, stress, exercise, a recent breast examination and some meals.

Principles. Physiological discharge needs reassurance and avoidance of nipple stimulation. Pathological discharge needs specialist assessment and usually duct excision for diagnosis and cure. Galactorrhoea needs treatment of the cause and prolactin control.

Physiological discharge. Reassure, avoid nipple expression and stimulation, and reassess at 3 months if it persists.

Pathological discharge.

• Refer to a breast surgeon within 2 weeks.
• Microdochectomy (excision of the affected duct) for a persistent single duct discharge with a papilloma or negative imaging, which also gives a histological diagnosis. Total duct excision (Hadfield procedure) for multiple duct discharge in duct ectasia when symptoms are troublesome.
• Excision of intraductal papilloma with a core biopsy showing atypia, and cancer treatment decided by the multidisciplinary team.

Drug induced galactorrhoea. Review the offending drug with the prescriber and, where safe, stop or change it. For antipsychotics, change to a prolactin sparing agent (aripiprazole, quetiapine) under psychiatric advice rather than stopping. Recheck prolactin 4 to 6 weeks after the change. Hypothyroidism.

Levothyroxine 25 to 50 micrograms orally once daily on an empty stomach (12.5 to 25 micrograms in older adults and in cardiac disease). Increase by 12.5 to 25 micrograms every 4 to 6 weeks to a TSH in the reference range. Usual maintenance 1.6 micrograms/kg daily; maximum about 2 micrograms/kg daily. Monitor TSH every 6 to 8 weeks after each change, then annually. Separate from iron, calcium and antacids by 4 hours.

Prolactinoma or idiopathic hyperprolactinaemia needing treatment (symptomatic galactorrhoea, amenorrhoea, infertility, macroadenoma).

• Cabergoline 0.25 mg orally twice weekly, increased by 0.25 mg twice weekly each month, directed by serum prolactin, to a usual 0.5 to 1 mg weekly (maximum 4.5 mg weekly); take with food at bedtime to reduce nausea and orthostatic hypotension.
• Cabergoline monitoring: prolactin every 4 weeks during titration, blood pressure, and an echocardiogram before treatment and every 6 to 12 months at doses over 2 mg weekly (cardiac valve fibrosis).
• Cabergoline cautions: avoid in uncontrolled hypertension, pre-eclampsia, pulmonary or cardiac fibrosis and psychosis; reduce the dose in severe liver impairment; stop in pregnancy unless tumour growth is a risk.
• Consider cabergoline withdrawal after 2 years if prolactin is normal and imaging shows no tumour.
• Bromocriptine as an alternative and when pregnancy is planned: 1.25 mg orally at night with food, increased by 1.25 mg every 3 to 7 days to a usual 2.5 mg two to three times daily (maximum 30 mg daily). Monitor blood pressure and nausea; avoid in uncontrolled hypertension and psychosis.
• Pituitary surgery for drug resistant or intolerant macroadenomas, and for visual loss or apoplexy.

Infection.

• Breast abscess: ultrasound directed aspiration or incision, flucloxacillin 500 mg to 1 g orally every 6 hours for 7 days (maximum 4 g daily; reduce in severe kidney impairment), or clindamycin 300 to 450 mg orally every 6 to 8 hours (maximum 1.8 g daily) if penicillin allergic.
• Breast abscess: send pus for culture and tuberculosis testing when risk factors are present.
• Periductal mastitis: amoxicillin with clavulanic acid 500/125 mg orally every 8 hours for 7 to 14 days (maximum 1.5 g amoxicillin daily; 500/125 mg every 12 hours for CrCl 10 to 30 mL/min; every 24 hours under 10 mL/min), plus smoking cessation advice.

Monitoring. Prolactin every 4 weeks during dose titration, then every 3 to 6 months. TSH after thyroid treatment starts. Repeat MRI of the pituitary at 6 to 12 months for macroadenomas.

Referral and escalation. Breast clinic within 2 weeks for pathological discharge, a breast mass or nipple change. Endocrinology for hyperprolactinaemia, prolactin over 100 ng/mL, pituitary mass or fertility needs. Urgent ophthalmology and neurosurgery for visual loss. Psychiatry for antipsychotic related discharge.

Admission criteria. Pituitary apoplexy (sudden headache, visual loss, ophthalmoplegia), severe visual compromise, breast abscess with sepsis, or abscess needing drainage under anaesthesia.

Discharge and safety netting. Discharge when the pattern is physiological or the cause is identified and a plan is in place. Patients return for new bloody discharge, a lump, skin or nipple change, headache or visual symptoms, and fever with breast redness.