Sarah Tang and Gerald Gui

Introduction

After breast lumps and mastalgia, spontaneous nipple discharge forms the next most common symptom, comprising 3–8% of referrals to symptomatic breast clinics.^1,2 The majority of nipple discharge is benign, with up to 20% being associated with an underlying malignancy.³ Conventional methods of investigating nipple discharge include mammography, ultrasound and smear cytology, each of which have recognised limitations. Standard operations such as microdochectomy and major duct excision are undirected procedures that carry a risk of leaving undiagnosed pathology in the breast.

Mammary ductoscopy allows direct visualisation of the duct epithelium to locate the lesion precisely and to map the three-dimensional anatomy. Endoscopic instruments for diagnostic biopsy and therapeutic excision are available. The ability to visualise normal or benign ductal structures may facilitate conservative management of symptomatic nipple discharge and enable targeted excision of visualised lesions or indeterminate areas.

Causes of nipple discharge

The causes of nipple discharge are wide ranging. The majority of discharge is physiological, hormone related or results from benign breast change. A recent meta-analysis that included over 3000 women with nipple discharge demonstrated an overall incidence of underlying breast malignancy of 18.7%,³ which is higher than the figure reported in many individual series.

Bilateral multiduct discharge can be stimulated by nipple manipulation in the majority of premenopausal women. The production of such physiological fluid is exploited by researchers of the intraductal approach for cytological, molecular and protein-based studies. This fluid is more likely to be released from the ducts if the nipples are repeatedly stimulated by chafing against clothing and during physical activities such as jogging. Squeezing of the nipples to elicit such discharge perpetuates symptoms. This is because the nipple ducts are plugged by keratin and repeated stimulation or squeezing removes the keratin plugs and allows the fluid that is normally present in the ductal tree to leak on to the surface of the nipple. The fluid in physiological discharge ranges from clear to white to yellow to green to black.

The most common physiological nipple discharge is lactation. Ongoing milky discharge may occur up to 2 years following a pregnancy and is a normal phenomenon. Galactorrhoea can also result from prolactin-secreting pituitary adenomas, medication that influences the oestrogen, progesterone or prolactin pathways, hypothyroidism and recreational drugs such as marijuana. Commonly prescribed medical drugs that may cause nipple discharge are summarised in Table 3.1.

Duct ectasia and benign breast change are common causes of multiduct discharge. In duct ectasia, the breast ducts become tortuous and dilated, predisposing to fluid accumulation. This fluid may discharge spontaneously or upon manipulation when the sphincters distal to the lactiferous sinuses relax and the keratin plugs are displaced. Common situations that may trigger loss of these keratin plugs and sphincter relaxation include massage and warm comfortable environments such as in a bath or under bedsheets. Cysts do not usually communicate directly with breast ducts. It has been suggested that inflammation related to a cyst may result in erosion into a duct system but this is unproven. The colour of nipple discharge associated with duct ectasia and fibrocystic change can vary from clear to white, yellow, grey, green, brown or black. This is the same colour range seen in physiological discharge. Nipple discharge arising in relation to inflammation and irritation of the lining of the ducts may be blood stained and contain acute inflammatory cells.

Persistent spontaneous discharge from a single nipple orifice is usually indicative of specific pathology involving that duct. Benign intraductal papillomas account for about 80% of single-duct bloodstained nipple discharges.^2,4,5 Papillomas give rise to nipple discharge of varying colour but as these structures can bleed intermittently, papillomas are often associated with blood staining. Recent bleeding may manifest as frank blood, but stagnant bloodstained fluid can be dark red, brown or black.

Periductal mastitis is a chronic and recurrent inflammatory condition associated with smoking in younger women. Purulent nipple discharge can be seen in later stages when the duct ruptures and an abscess or mammary duct fistula has developed.

Invasive breast cancer is an uncommon cause of spontaneous nipple discharge as the proliferating mass usually obliterates the duct lumen. Ductal carcinoma in situ or an extensive area of in situ disease in association with an invasive breast cancer may predispose to bloodstained nipple discharge. Bloodstained nipple discharge should be distinguished from bleeding from the nipple surface that may occur with Paget’s disease.

Assessment

A thorough breast problem orientated history is taken including a drug history, and a complete clinical examination should also be performed.

Bilateral physiological multiduct discharge aggravated by manipulation in younger patients usually resolves when the triggering factors are removed. Bilateral and profuse milky discharge in the younger population should be investigated by measuring serum prolactin and if elevated, supplemented by magnetic resonance imaging (MRI) of the pituitary gland. Thyroid function tests may be indicated if there are appropriate clinical features.

The colour of nipple discharge is not a reliable method of distinguishing between physiological, benign or malignant aetiologies.

Mammography is indicated in women over the age of 35 years and may demonstrate a mass or microcalcification in association with nipple discharge of malignant aetiology. Even in younger women with bloodstained discharge, mammography can demonstrate calcification in women with widespread ductal carcinoma in situ (DCIS). Other mammographic features may also be evident in patients with benign nipple discharge. Duct ectasia may occasionally be visible on mammography. The sensitivity of mammography in detecting pathology in nipple discharge is 57.1% (positive predictive value (PPV) of 16.7% and negative predictive value (NPV) of 91.4%).⁷ In a study of 306 patients with nipple discharge who had normal mammography and ultrasound, 10% were subsequently found to have underlying malignancy.⁷

Ultrasound can reliably diagnose duct ectasia and can identify discrete intraductal lesions. Papillomas below a threshold size of 1–2 mm may not be visible on ultrasound imaging. Ultrasound-guided core biopsy can be used to obtain a tissue diagnosis of any lesions visualised but papillary lesions are often assessed as an indeterminate B3 lesion and so usually still require excision for a definitive tissue diagnosis. A vacuum-assisted ultrasound-guided mammotome biopsy can be both diagnostic and therapeutic. Fine-needle aspiration of papillary lesions is usually unhelpful as cytology rarely resolves diagnostic uncertainty.

Ductography is less widely used but is an investigation that gives clear delineation of the breast anatomy. A small amount of radio-opaque contrast is instilled into a cannulated nipple duct. Accurate detection of small filling defect(s) caused by papillomas and duct narrowing or obstruction from malignant change can be recognised. However, ductography does not provide a tissue diagnosis and the precise position of the area of interest within the breast is not usually available to the surgeon, although it is possible to target the area of abnormality with a wire localisation procedure. The use of MRI to evaluate the ductal tree is gaining interest but is not a standard investigation of nipple discharge. In a comparative study of 163 patients with nipple discharge who had normal mammography and ultrasound, ductography was found to have a PPV of 19% and an NPV of 63%. MRI was performed in 52 patients and found to have a PPV of 56% and an NPV of 87%.⁷