Breast papillomas are a variety of lesions in the breast that are characterized by a papillary configuration on gross or microscopic examination (or both). Papillomas consist of a few broad fronds, abundant stroma, and an epithelium containing both luminal and myoepithelial cells 1. These include solitary intraductal papillomas, multiple papillomas, papillomatosis, and juvenile papillomatosis (JP). Solitary intraductal papillomas are tumours of major lactiferous ducts, most frequently observed in women 30 to 50 years of age. They commonly cause a serous or sero-sanguinous discharge. The discharge is bloodstained in approximately one half of women with these papillomas 2. Pathological nipple discharge (PND) is a relatively common symptom accounting for approximately 5% of all women attending symptomatic breast clinics 3. Papilloma is the commonest pathological finding in women with PND accounting for 40% to 70% of cases 34, followed by adenomatous or papillary epithelial proliferations (14%). However the incidence of malignancy (invasive or in situ) as a cause of PND varies between 1 and 23% depending upon the series studied 3. A solitary papilloma is not thought to be a pre-malignant lesion 5 and is considered by some to be an aberration rather than a true disease process 6.

Multiple intraductal papillomas occur in approximately 10% of cases of intraductal papillomas. Compared to solitary intraductal papillomas, multiple intraductal papillomas tend to occur in the younger patients, are less often associated with nipple discharge, more frequently peripheral, and more often bilateral. Essentially, these lesions appear to be susceptible to the development of carcinoma 1. Carter 7 reported that 2 of 6 patients with multiple papillomata developed cancer, while only 4 of 58 with solitary papilloma developed cancer. Haagensen et al. 5 found that 5 of 51 patients with multiple papillomata developed cancer, which was a marked contrast to those with a solitary papilloma, where only 4 of 174 developed cancer. In Haagensen's series of 68 patients with multiple papillomas, simultaneous or subsequent carcinoma of the apocrine papillary and cribriform types was observed in 22 patients (32%) 8. These findings were confirmed by another study, in which surgically excised specimens from patients with intraductal papillomas were subjected to three dimensional reconstruction 9. All 16 cases of multiple papillomas in the series were found to originate in the most peripheral portion of the duct system; the terminal duct lobular unit. Furthermore, malignancy was associated with these multiple peripheral papillomas in six cases (37.5%). In contrast, no cases of carcinoma were found to be associated with solitary papillomas involving the large ducts. These findings suggest that peripheral papillomas, on the contrary to solitary central papillomas, may be highly susceptible to malignant transformation.

Papillomatosis is a term used to describe microscopic foci of intraductal hyperplasia that have papillary architecture and are, therefore included by Dupont and Page in the category of proliferative lesions without atypia 10. JP is a rare condition that affects women between the ages of 10 and 44. Patients typically present with a painless mass that, on physical examination, is circumscribed, easily mobile, and most often thought to be a fibroadenoma 11. Follow up studies have suggested that JP is associated with an increased risk of breast cancer in the patient's female relatives, and the patient herself may be at increased risk for developing carcinoma, particularly if the lesion is bilateral and the patient has a family history of breast cancer 11121314.

Intraductal papillary lesions of the breast continue to be one of the most difficult diagnostic and therapeutic problems for the surgeon as they may be histologically benign, borderline, or malignant. Subsequent surgical treatment depends largely on the histological appearance of the lesion.

Deciding on the appropriate surgery for intraductal papilloma is problematic due to the difficulty in discriminating between intraductal papilloma and breast cancer. Moreover, the significance of intraductal papilloma as a pre-cancerous lesion is controversial to surgeons. Patients with multiple papillomas do have an increased risk of developing breast cancer and should be kept under annual review with regular digital mammography if treated conservatively. In view of the high sensitivity of MRI, the absence of enhancement typical of malignancy in women with multiple papillomas can be reassuring and supportive of conservative management 24. Because the risk is small, long term and affecting both breasts, long-term follow-up is more appropriate than prophylactic mastectomy. Patients who prove to have a solitary duct papilloma have insufficient increase in the risk of subsequent malignancy to justify routine follow-up.

From a historical perspective the philosophy of management of serous or sero-sanguineous nipple discharge changed radically in the last 50 years. Opinion regarding the likelihood of it being due to cancer was sharply divided early in the last century. Judd, 36 in 1917, reported a 57% incidence of cancer in 100 cases at the Mayo Clinic. In 1930, Adair reported 108 cases from the Memorial Hospital, with 47% malignant. In 1931, Cheatle and Cutler 37 argued strongly from pathological evidence that benign papillomas could progress to papillary carcinoma. This led to the simple mastectomy being the standard treatment for blood-stained discharge in many clinics.

However, in the last 30 years, a more conservative approach has become accepted, resulting particularly from the studies of Haagensen in the USA and Atkins and Wolff 38 in the UK, who all recognized that those patients whose discharge was due to intraductal papilloma were cured by removing the papilloma. Atkins developed the operation of microdochectomy and Haagensen 8 used a procedure that is intermediate between the microdochectomy of Atkins and the major duct excision operation of Urban 39. If the discharge can be localized to a single duct, microdochectomy gives satisfactory results in younger patients with a minimal interference with the breast. In older patients where breast-feeding is not required, major duct excision may be preferable irrespective of whether the discharge is localized to one duct, both to avoid inconvenience of further discharge from a different duct and to provide a more comprehensive histology.

MD has recently revolutionised the management of PND and breast papillomas. The only reliable way to both establish the diagnosis and control the discharge is ductal excision, the success of which is dependant on identifying the correct origin of the discharge. When a specific duct cannot be identified then blind excision of the retro-areolar ductal system is usually performed. MD offers the advantages of accurate localisation of pathology, ductal lavage under direct visualization (figure 1), and intra-operative guidance especially for lesions deep within the ductal system 2030. Furthermore, MD can detect multiple lesions within the same duct. The technique has the potential to reduce the number of duct excision procedures and minimise the extent of surgical resection. It is important to note that in some clinical scenarios, MD-guided intraductal biopsy can be diagnostic and curative and the discharge can resolve following the procedure 16. This potential therapeutic role of MD-guided intraductal biopsy requires further evaluation and validation.

Simple light trans-illumination through the skin during MD can be used to guide duct excision. We have recently described a new technique involving ductoscopy and the use of a blue dye to perform microdochectomy 40. The procedure is performed in an outpatient surgical setting, under conscious sedation monitored control anaesthesia. Figures (2, 3, and 4) illustrate the operative technique used in MD guided microdochectomy. MD can also potentially reduce the need to perform duct excision in patients with PND due to benign disease thus resulting in cost savings.

Dietz et al 4 reported that duct cannulation was achieved in 105 (88%) of 119 patients with PND and ductoscopy directed duct excision could be performed in 104 (87%) of 119 cases. These authors also found that MD was more accurate than preoperative ductography (90% vs. 76%) in localising the relevant pathology. The pathological diagnoses were malignancy in 5 patients, papilloma in 84 cases, and hyperplasia in 16. In 22 patients, ductoscopy visualised multiple lesions or abnormalities beyond 4 cm. Such lesions would have been missed by blind duct excision.

Nevertheless, MD has recognised limitations. MD examines 1 – 2 ducts per breast and leaves the remaining 13 – 18 ducts that open at or just below the nipple surface unexamined. MD is also incapable of reaching the peripheral small branches of the ducts due to the scopes' diameter 2030. Thus it is unable to visualise the terminal duct-lobular unit (TDLU) where malignant lesions often originate. Furthermore complete occlusion of the duct by the lesion limits the role of MD in the management of PND.

If the papilloma is detectable on mammography and/or ultrasonography, then imaging-guided vacuum-assisted biopsy can be both diagnostic and curative (Figure 5).

Dennis et al evaluated the role of imaging-guided vacuum-assisted core biopsy as a minimally invasive method of obtaining a satisfactory diagnosis and eliminating the bothersome symptoms in patients presenting with nipple discharge. This study concluded that this technique allows safe and accurate tissue analysis and a high probability of terminating the symptomatic nipple discharge 41.

Finally if the discharge is not troublesome and all investigations show no evidence of malignancy, then the discharge can be managed conservatively with no need for surgical intervention.

Figure 6 shows a new proposed algorithm for the treatment of papillomas.

Current biopsy tools used with MD need further evaluation and validation, as the challenge of verifying endoscopic appearances with a histological diagnosis has not yet been overcome. The future development of reliable intraductal biopsy tools capable of obtaining tissue sample under direct visualisation sufficient for histological diagnosis can enhance further the role of MD in the management of PND and papillomas. The potential therapeutic role of MD-guided intraductal biopsy 16 requires further evaluation. MD can also complement other novel screening modalities such as molecular profiling including proteomics in differentiating benign papillomas from pre-malignant and malignant lesions 42.

Moreover, the addition of radiofrequency 43 to MD as a curative endoscopic procedure is worthy of investigation. These potential applications underscore the need to develop reliable methodology to mark the ducts harbouring pathology.

CAD: Computer-aided detection

DCIS: Ductal Carcinoma In-situ

JP: Juvenile Papillomatosis

MCC: Micro-calcifications

MD: Mammary Ductoscopy

MRI: Magnetic Resonance Imaging

PND: Pathological Nipple Discharge