Nipple discharge is a symptomatic problem that causes many women discomfort and anxiety. Tremendous advances have been made in the management of breast problems, mainly through advances in diagnostic breast imaging (see the images below). 
According to Kapenhas-Valdes and coworkers, mammary ductoscopy is useful in evaluating patients who have nipple discharge, revealing papilloma in 45% of patients (42 of 93), cancer in 6.5% (6 of 93), and atypia in 6.5% (6 of 93). They noted that in their study, mammary ductoscopy was helpful for accurate visualization, analysis, and excision of intraductal abnormalities, especially deeper intraductal abnormalities. [2, 3]
Vaughan et al, in a study of 89 patients with pathologic nipple discharge, found that the combination of visualization by ductoscopy and pathologic analysis of washings provided the highest predictive value for the diagnosis of papilloma. More than 90% of patients with pathologic nipple discharge were found to have a lesion on pathologic examination when this technique was used for directed duct excision. Cellular yields were excellent, with specimens yielding more than 5,000 epithelial cells/hpf and with evaluable ductal cells in 82% of specimens. 
Tokuda et al found that MRI (1.5-T system) provided clinically useful data in 47 patients with suspicious nipple discharge. The MRI images were evaluated for a signal of abnormal discharge, related abnormal enhancement according to the breast imaging-reporting and data system MRI descriptors, and the presence of clustered ring enhancement; they were compared with the histopathologic diagnoses established in 39 lesions. The most common finding was non-masslike enhancement, and 17 malignant lesions and 22 benign lesions were detected. The most frequent findings in the malignant lesions were segmental, heterogeneous, and plateau patterns. Clustered ring enhancement was found in 60% of the enhanced malignant lesions. 
Ultrasonography is not typically used unless the nipple discharge is accompanied by a palpable mass or a positive mammographic finding. Ultrasonography may be useful in presurgical localization if galactography reveals a dilated duct larger than a few millimeters in width. Modern, high-resolution ultrasonographic techniques are becoming more sensitive for the visualization of intraductal changes. Tiny, solitary papillomas can sometimes be visualized by using this sophisticated technology (see the images below).
Magnetic resonance imaging (MRI) may play an adjunctive role, aiding in the differentiation of benign ductal abnormalities from malignant ones. However, a prospective study comparing MRI with galactography and sonography will be necessary before MRI's role can be determined.
Fiber-ductoscopy is an experimental technique that may eventually play a role in the evaluation of nipple discharge. At this endoscopic examination, a thin, flexible, silica fiber-ductoscope is inserted into the duct through the secreting duct orifice at the surface of the nipple; the intraluminal findings are viewed on a television monitor. The technique is still in its infancy. Recent reports suggest that this imaging technology could be of help as a guide to surgery.  It is now possible to have not only cytology specimens but also tissue samples for histologic assessment of intraductal lesions visualized through ductoscopy. [2, 3, 4, 7, 6, 8, 9]
Limitations of techniques
Galactography is not indicated unless the nipple discharge is spontaneous, unilateral, and expressed from a single pore. If discharge cannot be expressed at the time of galactography, the affected duct cannot be identified or cannulated.
High-resolution ultrasonography is relatively new and expensive. This examination is not available at all breast-imaging centers. In addition, it is operator dependent and requires expertise for the identification of small intraductal structures.
Galactography involves the retrograde injection of contrast medium into a discharging duct, with subsequent mammographic imaging of the breast in at least 2 planes. The contrast agent–filled ducts should decrease in width from the nipple inward. An increase in duct diameter suggests duct ectasia.
A contrast-agent filling defect in an otherwise well-filled duct suggests an intraductal growth. Solitary papillomas are usually seen as single lobulated contrast-agent filling defects within a duct (see the first 4 images below). Occasionally, a continuous filling defect is present; this finding suggests papillomatosis (see the fifth and sixth images below).
In instances in which the passage of radiographic contrast medium stops abruptly, the ductal lumen is totally obstructed and visualization of its proximal portion is precluded. The obstruction could be due to a large papilloma, although malignancy cannot be excluded. Ductal carcinoma in situ is often apparent as irregular duct walls (see the images below), in contrast to the smooth walls associated with normal ducts. Hyperplasia also can appear as continuous, irregular duct walls. A ductogram that reveals irregular duct walls should always be investigated further, because the differential diagnosis includes hyperplastic micropapillary changes and malignancy.
Duct compression due to an extrinsic mass decreases the ductal diameter, which takes on the shape of a cone or funnel.
Degree of confidence
When radiographs show obvious contrast-agent filling defects in the examined ducts that are not due to artifact (eg, air bubbles), the findings always correspond with intraductal growths at pathology. The degree of confidence for other findings is more variable and corresponds to individual experience and the technical quality and success of a ductographic examination.
The absence of convincing visible pathologic findings on a ductogram does not exclude local pathophysiologic changes. Therefore, some physicians advocate close interval follow-up; however, others prefer surgical ductal excision.
To the author's knowledge, no large studies have been conducted to define the positive or negative predictive values of galactography. In the author's experience, which encompasses more than 2 decades, with approximately 100 ductograms performed annually, intraductal contrast-agent filling defects at ductography have always corresponded with intraductal epithelial growths at histopathology; therefore, ductography has no false-positive findings. Most defects (98%) represent solitary intraductal papillomas or papillomatosis. Less than 2% of pathologic findings on ductograms are associated with intraductal malignancies at surgery. In the few patients with biopsy-proven intraductal malignancies, galactography demonstrates irregular ducts and never solitary contrast-agent filling defects.
In the published data as well as in the author's experience, a negative galactographic finding does not exclude intraductal disease. In patients with clear or sanguineous discharge and negative ductographic findings, abnormalities may still be proven at surgery. In approximately 10% of patients with these findings, histopathology demonstrates micropapillary epithelial proliferations; the corresponding false-negative rate for pathologic findings at galactography is 10%. In less than 1% of cases, histopathology demonstrates atypical ductal hyperplasias or intraductal malignancies; the corresponding false-negative rate for neoplastic changes at galactography is less than 1%.
A meta-analysis about the association between the color of nipple discharge and breast cancer risk was published by Chen et al. Eight studies, including 3,110 patients, were eligible for this meta-analysis. Compared with patients in the nonbloody nipple discharge group, patients in the bloody nipple discharge group had a markedly higher breast cancer risk. 
Magnetic Resonance Imaging
Boisserie et al recently reported that MR galactography has been shown to be of diagnostic value. In a study that included 50 patients with nipple discharge, MRI showed excellent sensitivity, positive predictive value, and negative predictive value. The authors concluded that a negative result on MRI would support clinical follow-up as opposed to surgery. [11, 12]
Ultrasonography is indispensable as a complementary diagnostic tool in the investigation of breast abnormalities (see the images below). However, ultrasonography is not commonly indicated for the evaluation of nipple discharge. Ultrasonography is an adjunctive tool for breast evaluation when more specific indications, including an abnormal mammographic finding or a palpable clinical finding, are present. Technological advances in high-resolution ultrasonography mean that in the future this modality may have a role in breast ductal evaluation. [13, 14]