Nipple discharge

Epidemiology and Demographics

• Most often benign: overall incidence cancer ~ 3-5%
• Risk of malignancy much increased if concurrent mass (~ 60%)
• Reported in 10-15% of women with benign breast disease
• Reported in 2.5-3% of women with breast cancer

Pathophysiology & Etiology

• Physiologic

• Discharge only with compression
• Multiple duct involvement
• Bilateral
• Fluid may be clear, yellow, white or dark green

• Pathologic

• Spontaneous discharge
• Bloody
• Unilateral
• Associated with a mass

• Physiologic / Endocrinologic Discharge

• Lactation

• Milk produced in presence of postpartum exocrin, parathyrin, thyroxine, cortisol, growth hormone and placental lactogen
• Milk secreted via stimulation of lobular and ductal epithelium by PRL
• Milk ejected via stimulation of muscular walls of lactiferous ducts by oxytocin
• Oxytocin and PRL secreted by pituitary in response to nipple stimulation

• Galactorrhea:

• Milk secretion unrelated to pregnancy/lactation
• Usually due to hyperprolactin state, though can be idiopathic with normal prolactin (PRL)
• Can occur via:

1. Chronic breast stimulation (nipple manipulation, rubbing on bra)
2. Oral Contraceptive Pills (OCPs) – E can stimulate PRL secretion
3. Drugs that inhibit dopamine (loss of tonic inhibition of PRL)
4. Hypothalamic/pituitary disease interfering with DA release
5. Prolactinoma
6. Hypothyroidism
7. Chronic renal failure
8. Chest wall injury – healing wound stimulates PRL release

• Pathologic Discharge

• Intraductal papilloma: monotonous proliferation of papillary cells growing into the lumen

• Fluid typically straw-colored, transparent, sticky

• Duct ectasia: distention of subareolar ducts
• Fibrocystic disease: associated irritation within the duct
• Papillomatosis: formation of multiple papillomas

• Associated with small increase in breast cancer risk

• Intraductal hyperplasia: increased number of epithelial cells lining the ducts

• Cells appear benign but associated with small increase in breast cancer risk

• Breast cancer: risk much increased if mass associated with abnormal discharge

History and Symptoms

• Description of Discharge

• Unilateral vs. bilateral (bilateral almost always due to endocrinologic cause)
• Spontaneous vs. provoked
• Bloody vs. nonbloody

• Endocrine Symptoms

• Irregular menses,
• thyroid symptoms,
• endo review of symptoms (& visual fields) if prolactinoma suspected

• Medical Conditions

• Renal failure,
• thyroid disease

• Medications

• Potential causes of hyperprolactinemia

Physical Examination

• Thorough breast exam to rule out palpable mass
• Skin exam for superficial lesions that might produce discharge mimicking nipple discharge

• (Eczema, Paget’s disease, local infections or irritation)

• Expression of discharge: firm pressure applied at base of areola of each breast

• Close observation to determine if discharge from > 1 nipple duct
• Guaiac testing for blood

• Cytology for bloody or G+ discharge:

• Express fluid along surface of glass slide
• Spray immediately with Pap smear fixative
• Prepare 4-6 slides for evaluation
• Low sensitivity, but high specificity for cancer

Other Imaging Findings

Mammogram

• Mammogram in all patients with pathologic discharge
• Mammogram in patients > 35 years old with physiologic or endocrinologic discharge:

• If negative mammogram, exam and endocrine evaluation, avoidance of nipple stimulation will often lead to resolution of discharge

Risk Stratification and Prognosis

Referral

• Unilateral, bloody or spontaneous discharge: all should be referred to breast surgeon

• Terminal duct excision diagnostic; may also be therapeutic if benign lesion

• Bilateral, non-bloody discharge with negative endocrine work-up: referral to breast surgeon if fails to resolve