The lactiferous ducts develop from epithelial buds and are affected by the hormonal milieu. The ducts drain the parenchyma and are the conduits of milk in the lactating woman. The duct system is the site of development of most benign and malignant epithelial lesions, and some of these may be associated with nipple discharge.
The evaluation of patients who present with an abnormal nipple discharge includes clinical examination and a variety of tests, such as cytologic analysis, mammography, ultrasound, magnetic resonance imaging (MRI), galactography, and ductoscopy. This chapter will focus on the role, technique, and interpretation of galactography.
Nipple discharge in a nonlactating breast can be produced by a variety of conditions, including duct ectasia, fibrocystic change, inflammation, intraductal papilloma, and intraductal carcinoma. The most common cause of a bloody or discharge at all ages is an intraductal papilloma (1). Galactography or ductography can be useful in the evaluation of a spontaneous nipple discharge, particularly when there are no mammographic or physical findings to account specifically for the etiology of the leakage.
Evaluation of Nipple Discharge
Clinical assessment of the patient who presents with nipple discharge is the first step in determining the potential significance of the symptom and the next step in management. Important clinical history includes the duration of symptoms, the color of the discharge, history of trauma, the laterality (unilateral vs. bilateral) and spontaneity of the discharge, and the history of medications, including hormones or hormonal imbalances (2). Clinical examination should include a general examination of the breast with expression of the discharge. A trigger point that when compressed produces the discharge may be identified. This point may indicate the orientation of the abnormal duct. Observation of the color of the discharge and the location of the orifice are important in planning the management and identifying the potential etiology of this symptom. The determination of whether the discharge is uniorificial is an important step in determining whether galactography is necessary.
Nipple discharge from the nonlactating breast may be white, creamy, yellowish, clear, green, serosanguineous, or bloody. Guaiac testing may be useful to analyze for blood in nipple discharge. The most suspicious discharges are those that are uniorificial and serous, serosanguinous, or bloody. The exceptions are bloody discharge related to pregnancy or to trauma. The absence of blood in nipple discharge, however, does not exclude carcinoma (3,4). Ciatto et al. (5) found that a bloody discharge was more frequently associated with cancer than other patterns of discharge. However, serous discharge that is heme negative may be found with carcinoma.
In most cases, yellow, white, or green discharge is related to a systemic etiology and occurs bilaterally and from multiple ducts. This type of discharge is usually not spontaneous and is associated with duct ectasia, fibrocystic change, or hormonal or medicinal causes (6). Discharges that are not spontaneous and are expressible only are usually of benign origin and related to fibrocystic change (7).
The frequency of malignancy in a patient with bloody nipple discharge has been found to be 5% to 28% (1); however, the frequency of carcinoma is 1.6% to 13% in patients with serous discharge (1,8). In a study of 174 women with uniorificial discharge (31% serous and 69% bloody), Tabar et al. (1) found carcinoma in 18 of 174 (10%) patients. Serous discharge was present in 3 of 18 (17%) patients with cancer; 15 of 18 (83%) patients with cancer had bloody discharge. In this study, cytologic analysis of the discharge was not sensitive, with only 2 of 18 of the cancers having suspicious cytology.
Occasionally pregnant women may develop nipple discharge that is bloody. LaFreniere (9) found that both mammography and cytology were negative in five pregnant women with unilateral bloody multiorificial discharge. In all cases, the discharge resolved within 2 months of onset. Table 14.1 describes the etiologies of nipple discharge based on color.
In the presence of a suspicious nipple discharge, further evaluation beyond mammography is indicated. This
may include cytology of the discharge, galactography, MRI, ductoscopy, or duct excision. Cytology has shown variable results with a sensitivity ranging from 11% to 31% (10,11). Therefore, the presence of negative cytology does not confirm that an intraductal malignancy is not present. Galactography is the only method to determine preoperatively the nature, location, and extent of the lesion producing the discharge, and it allows for more precise and limited surgical excision of the area of abnormality. Galactography was first described in the 1930s (12,13) but was not commonly used until mammography became established. If a duct excision without a prior contrast study is performed, the surgery may be unnecessary or more extensive than needed. Also, a blind duct excision has the potential to miss an intraductal lesion in a small peripheral duct. As many as 40% of ductal tumors have been found to lie in a nonsubareolar location, which may cause a lesion to be missed at surgery if a duct excision without preoperative galactography is performed (14).
TABLE 14.1 Etiologies of Nipple Discharge
The sensitivity of galactography has been studied by several authors (11,15,16). In a comparison of galactography and exfoliative cytology, Dinkel et al. (11) found the sensitivities for malignancy for each procedure to be 83% and 31.2% and the specificities to be 41% and 99%, respectively. The authors (11) found that one half of the cancers in the study demonstrated no palpable, mammographic, or cytologic abnormality and were identified only by galactography.
Van Zee et al. (17) found that localizing the lesion causing nipple discharge by preoperative galactography increased the likelihood that a specific pathology was found at surgery. In this study, 67% of patients who did not undergo galactography preoperatively did not have a specific pathology on excision. Cardenosa (18) found that galactography was positive in 32 of 35 (91%) of patients with spontaneous nipple discharge. In another study, however, King et al. (19) suggested that patients with nipple discharge should have breast imaging, and if this is negative, should be offered duct excision. The authors found no role for ductography, cytology, or laboratory studies. Dawes et al. (20) found that in 91 women with nipple discharge, only 5% were due to cancers and that galactography did not confirm or refute the presence of an intraductal lesion.
Galactography is a contrast study that outlines the intraductal lumina. The purpose of galactography is to identify the presence and location of an intraductal lesion. The indication for galactography is the presence of a suspicious type of nipple discharge—that is, a spontaneous, uniorificial, serous, serosanguinous, or bloody discharge. Galactography depicts the course of the ducts and the location and extent of intraductal lesions. Preoperative galactography facilitates a more directed surgery and can avert unnecessary surgery when findings are benign (21).
Galactography is performed only when discharge is present. The breast interventionist must visualize the orifice from which the discharge is occurring in order to cannulate the correct duct. The discharge is expressed, and the orifice is visualized. Identifying a trigger point is helpful to determine the orientation of the duct (7) before attempting duct cannulation. The supplies for the procedure include a 27- to 30-g cannula with tubing, a 5-cc syringe, water-soluble contrast, sterile gauze, antiseptic solution, and Steristrips (Fig. 14.1).
The nipple areolar complex is cleansed with an antiseptic solution, and the breast is draped. Small amounts of discharge are expressed from the breast until the orifice of the duct is identified. A blunt cannula—such as a 27-gauge pediatric sialography cannula with a straight end, a right angle, or an olive tip—is filled with water-soluble radiographic contrast. It is important to remove any air bubbles from the catheter, because when injected, they
may simulate intraductal masses. The duct is cannulated, and a small amount of contrast is injected. The most difficult step is cannulation of the duct, particularly if it is not dilated. Very gentle placement of the cannula is necessary to avoid penetration of the duct wall and extravasation of contrast. The cannula is taped in place with Steristrips. The amount of contrast needed ranges from 0.1 to 3.0 cc and varies with the number of secondary ducts draining into the main lactiferous duct and the degree of dilatation.
Figure 14.1 Supplies for galactography: cannula, syringe, water-soluble contrast, antiseptic solution, Steristrips, and sterile gauze.
As the contrast is injected, the patient is asked to state when she feels tightness or pressure in the breast. At this point, the injection is terminated, the cannula is left in place, and images are obtained with mild compression. Should the patient experience pain, indicating possible extravasation of contrast, injection should be terminated immediately. The patient is positioned at the mammographic unit, and the craniocaudal (CC) view is obtained. If duct filling is incomplete, more contrast may be injected, and the CC view is repeated. With an obstruction of the distal duct, rapid backflow of contrast occurs.
Routine images include CC and mediolateral (ML) views. Magnification views are often helpful in the observation of small filling defects (21), and digital imaging is helpful to expedite the study. At the completion of imaging, the catheter is withdrawn with the breast still in compression, and a final image of the distal aspect of the duct is made. After the procedure, the patient is asked to express the residual contrast from the breast.
Figure 14.2 HISTORY: Patient who presents with serous nipple discharge.
MAMMOGRAPHY: Left ML view from a galactogram shows dense contrast in the subareolar area consistent with extravasation of contrast. There is filling of two tubular serosanguineous structures that are nonbranching and that extend from the areolar area toward the axilla.
IMPRESSION: Extravasation of contrast with lymphatic intravasation.
Figure 14.3 Anatomy of the major lactiferous duct system.
Complications of galactography include duct rupture with extravasation of contrast, lymphatic intravasation (Fig. 14.2), contrast reaction, and infection. In the patient with purulent discharge or signs of infection, galactography should not be performed, because the infection can be spread via retrograde injection.
The normal ducts converge toward the nipple into dilated ampullae, the lactiferous sinuses, which are then drained by thin 2- to 3-mm-diameter (1) collecting ducts (Fig. 14.3). As the ducts arborize back into the breast, the caliber gradually decreases. The walls of the lumina are smooth, and no beading, angulation, or abrupt narrowing should be present (Fig. 14.4).
In duct ectasia or secretory disease, the ducts are dilated, may be tortuous, and may contain filling defects from inspissated secretions (16). Cystic areas of dilatation may be present, particularly in the subareolar area, and a contrast-fluid level may be seen on the ML view (Figs. 14.5 and 14.6). The ducts may be up to 8 mm in diameter, and there may be some beading present (1). In fibrocystic
change, the ducts may be slightly irregular in diameter, and there may be filling of multiple tiny or even large cysts (16) (Fig. 14.7). In intraductal hyperplasia, multiple small filling defects may be seen within the ductal lumen (Fig. 14.8).
Figure 14.4 HISTORY: A 39-year-old woman with yellowish nipple discharge.
MAMMOGRAPHY: Right CC view from galactography shows the cannula in place and contrast filling the duct system drained by the collecting duct. Minimal dilatation in the collecting duct is seen (arrow). The ducts arborize normally, and no filling defects are present.
IMPRESSION: Normal galactogram.
Figure 14.5 HISTORY: A 40-year-old woman who presents with serous right nipple discharge.
MAMMOGRAPHY: Right CC view from galactography shows marked distension of the subareolar collecting and segmental ducts. There is cystic dilatation noted as well (arrow). Posterior to the subareolar region, the ducts appear pruned. No intraluminal filling defects were seen.
IMPRESSION: Marked duct ectasia.
Intraductal filling defects may be solitary or multiple. Filling defects identified on galactography may be iatrogenic (air bubbles), pseudolesions (clot, debris), or true epithelial lesions, including papilloma, papillomatosis, duct adenoma, intraductal hyperplasia, and ductal carcinoma. The etiologies of filling defects on galactography are listed in Table 14.2.
TABLE 14.2 Etiologies of Filling Defects on Galactography
Figure 14.6 HISTORY: Spontaneous serous left nipple discharge.
MAMMOGRAPHY: Left ML view from a galactogram shows marked distention of the collecting and segmental ducts in the subareolar area. There is filling of a small cyst, with a contrast fluid level being noted. No filling defects to suggest intraductal pathology were noted.
IMPRESSION: Cystic duct ectasia.
The etiology of a solitary defect is most often an intraductal papilloma, and these more commonly occur near the nipple-areolar complex (1). Hou et al. (8) found that 88 of 113 (77.9%) of benign intraductal lesions on galactography were located in main lactiferous ducts. It is important that the most terminal portion of the duct be filled during galactography to avoid bypassing a small papilloma in the nipple or subareolar area with the cannula. The borders of the papilloma are usually rounded or lobulated, and if the lesion is large, it may completely obstruct the duct (Figs. 14.9,14.10,14.11,14.12,14.13,14.14,14.15,14.16). Papillomatosis, which is a form of intraductal hyperplasia, produces multiple small defects and may appear as an irregularity of the luminal wall of the affected duct (16) (Fig. 14.17).
The appearance of intraductal carcinoma on galactography may be a solitary irregular mass, multiple intraluminal filling defects, encasement and abrupt areas of narrowing and dilatation of the duct, distortion of the arborization, and obstruction of the duct lumen (7) or multiple filling defects (Figs. 14.17,14.18,14.19,14.20). Multiple filling defects are suspicious for ductal carcinoma in situ, papillomatosis, or multiple papillomas. Encasement of the ducts, areas of abrupt termination, or multiple small filling defects are findings suspicious for intraductal malignancy. If these findings are present, it is important that multiple biopsies or needle localization with bracketing wires be performed to identify the extent of the disease. Rongione et al. (15) found that galactographic findings associated with carcinoma included multiple irregular filling defects, ductal irregularity, ductal obstruction, and contrast extravasation. Hou et al. (8), in a review of 37 patients with cancers identified on galactography, found that 70.3% of these lesions were located in the smaller peripheral ducts.
Figure 14.7 HISTORY: Premenopausal patient who presents with uniorificial yellowish clear discharge.
MAMMOGRAPHY: Left CC view from the galactogram shows the cannulated duct system filled with contrast. The duct system is not dilated, and the ducts arborize normally. There is filling of small distal cystic structures consistent with mild fibrocystic change.
IMPRESSION: Mild fibrocystic changes.
Ciatto et al. (16) found that galactographic findings associated with malignancy in 200 patients with bloody
nipple discharge were multiple filling defects; no solitary intraluminal-filling defect was malignant on excision. Funovics et al. (22) reported the following sensitivities/specificities in detecting cancer in 134 galactography cases: filling defect (55.6%/62.1%), duct ectasia (22.2%/94%), and obstructed duct (5.6%/77.6%). Normal galactograms had a sensitivity of 78% and a specificity of 93% in predicting the absence of disease (22). Dinkel et al. (23), however, found no statistically significant relationship between the galactographic filling defect and the presence of malignancy.
Figure 14.8 HISTORY: A 72-year-old gravida 3, para 3 woman with a bloody left nipple discharge.
MAMMOGRAPHY: Left galactogram ML (A) and magnification (2X) (B) views. The left breast is very dense for the patient's age. No abnormalities were noted on routine mammography. Galactography was performed because of the nipple discharge, but only a small amount of contrast could be injected without retrograde flow. On galactography, there are at least three intraductal filling defects(arrows). There is incomplete filling of the duct system drained by this major duct. The filling defects are rather smooth, and there is no encasement present, suggesting more likely a benign etiology. However, the termination of the duct lumen is of some concern. The differential diagnosis includes papillomas, papillomatosis, duct hyperplasia, and intraductal carcinoma.
IMPRESSION: Intraluminal filling defects of uncertain nature, favoring a benign process.
HISTOPATHOLOGY: Atypical ductal hyperplasia.
Figure 14.9 HISTORY: A 52-year-old woman with unilateral brownish nipple discharge.
MAMMOGRAPHY: Right CC (A) and enlarged CC (B) images from a galactogram show a dilated duct with minimal ramifications. There is a solitary intraluminal filling defect present (arrows) that, based on the imaging, most likely represents a papilloma.
IMPRESSION: Intraductal papilloma.
HISTOPATHOLOGY: Sclerotic ductal papilloma.
Figure 14.10 HISTORY: A 48-year-old woman with left spontaneous serous nipple discharge.
MAMMOGRAPHY: Left ML (A) and CC (B) views from a galactogram demonstrate an obstructed duct in the subareolar area. The enlarged image (C) shows an irregular intraluminal filling defect (arrow). Posterior to this obstruction is a bifurcating distended duct(arrowheads). Needle localization and excision were performed.
IMPRESSION: Filling defect, likely papilloma.
HISTOPATHOLOGY: Intraductal papilloma.
Figure 14.11 HISTORY: A 64-year-old woman with uniorificial heme-positive right nipple discharge.
MAMMOGRAPHY: Right ML galactographic view shows a distended duct delineated by contrast. There is a large polypoid filling duct(arrow) nearly completely obstructing the duct.
IMPRESSION: Filling defect, likely a papilloma.
HISTOPATHOLOGY: Sclerotic intraductal papilloma.
Figure 14.12 HISTORY: A 57-year-old woman with spontaneous serous nipple discharge.
MAMMOGRAPHY: Left ML (A) and CC (B) views show a solitary duct that has been cannulated. In the immediate subareolar area is a round intraluminal filling defect, and just posterior to this are two other small filling defects.
IMPRESSION: Intraluminal filling defects, likely papillomas.
Figure 14.13 HISTORY: A 49-year-old woman reporting bloody left nipple discharge.
MAMMOGRAPHY: Left CC (A) and ML (B) views from a galactogram show the cannulated duct to be dilated. There is an intraluminal filling defect causing duct obstruction, seen best on the enlarged image (C).
IMPRESSION: Filling defect, possible papilloma.
HISTOPATHOLOGY: Papilloma, partially sclerotic.
Figure 14.14 HISTORY: A 39-year-old woman with bloody spontaneous left nipple discharge.
MAMMOGRAPHY: Left ML view (A) from a galactogram and enlarged CC image (B) show the cannulated duct containing contrast. There is nearly complete obstruction of the duct by an intraluminal filling defect (arrow). On the enlarged image, the polypoid filling defect with a multilobulated edge is noted.
IMPRESSION: Solitary defect, likely papilloma. Recommend biopsy.
HISTOPATHOLOGY: Intraductal papilloma with epithelial hyperplasia.
Figure 14.15 HISTORY: A 45-year-old woman with left bloody nipple discharge.
MAMMOGRAPHY: Left ML view (A) and enlarged image (B) from a galactogram show the cannulated duct containing contrast. There is nearly complete obstruction of the duct in the immediate subareolar area. An irregular filling defect is present within the duct (arrow).
IMPRESSION: Solitary defect, likely papilloma. Recommend biopsy.
HISTOPATHOLOGY: Sclerotic intraductal papilloma.
When an intraluminal filling defect is identified, biopsy or surgical excision is needed to diagnose its etiology. Stereotactic breast biopsy of the filling defect identified on galactography can be performed (24,25) (Figs. 14.21 and 14.22). With the catheter in place and contrast filling the duct, the lesion can be targeted stereotactically and biopsied. Guenin (25) found that nipple discharge ceased after vacuum-assisted biopsy of papillomas in five patients, suggesting a potential therapeutic value of needle biopsy.
Alternatively, needle localization with excision of the ductal abnormality duct is performed. The duct may be visible in retrospect on mammography, and if so, can be localized for excision based on mammographic findings. If the location of the lesion is uncertain, repeat galactography at the time of needle localization is performed to guide the procedure. Tabar et al. (1) described the use of
retrograde injection of methylene blue into the duct to guide surgical excision. With imaging guidance to identify and localize the lesion(s) preoperatively, surgical excision of the abnormalities is optimized.
Figure 14.16 HISTORY: A 38-year-old woman with a bloody left nipple discharge.
MAMMOGRAPHY: Left CC view from galactography (A) and enlarged (2X) CC view (B). The cannulated duct arborizes into mildly dilated lactiferous ducts. There is a solitary filling defect approximately 1 cm deep to the nipple (closed arrow). This defect expands the duct and is well circumscribed and persistent, consistent with an intraductal lesion. A second well-circumscribed defect is seen more peripherally in the medial aspect of the breast (open arrow) (B), and this was found to represent an air bubble. The differential diagnosis of the subareolar defect includes an intraductal papilloma, hyperplasia, or carcinoma (less likely).
HISTOPATHOLOGY: Intraductal papilloma. The histologic sections at low (C) and high (D) power shows the papilloma filling the duct lumen. The frondlike epithelium covers the papillary fibrovascular stalks.
Figure 14.17 HISTORY: A 50-year-old woman with bloody nipple discharge from the right breast.
MAMMOGRAPHY: Right CC (A) and ML (B) views from a galactogram show contrast filling multiple ducts drained by the cannulated collecting duct. There are multiple small filling defects in the cannulated duct system (arrowheads). There is also a spiculated mass(arrow) located medially that is associated with narrowing encasement and abrupt termination of the ducts.
IMPRESSION: Multiple filling defects most consistent with ductal carcinoma in situ and invasive carcinoma.
HISTOPATHOLOGY: Ductal carcinoma in situ, intermediate nuclear grade, solid type. Invasive ductal carcinoma.
Figure 14.18 HISTORY: A 78-year-old gravida 4, para 4 woman with a bloody discharge from the left nipple.
MAMMOGRAPHY: Left CC (A) and magnification (2X) CC (B) views from a galactogram. The cannulated duct and its branches are dilated in the subareolar area. There are multiple areas of encasement (arrows) with narrowing and changes in caliber (A), as well as irregular filling defects (arrow) (B) and areas of abrupt termination of the lactiferous ducts. These findings are highly suggestive of intraductal carcinoma.
IMPRESSION: Extensive intraductal carcinoma.
HISTOPATHOLOGY: Intraductal carcinoma, solid and cribriform varieties.
Figure 14.19 HISTORY: A 39-year-old gravida 3, para 4 woman with a bloody right nipple discharge.
MAMMOGRAPHY: Right CC (A) and magnification (1.5÷) CC (B) views from a galactogram. On the initial film (A), a breast implant is noted, and the breast tissue is heterogeneously dense. On the galactogram (B), the injected ducts are mildly dilated. There are multiple irregular filling defects (straight arrows) and some areas of abrupt termination (curved arrow) of the ductal lumen. The filling defects could represent papillomatosis, hyperplasia, or carcinomas, but the finding of the abrupt terminations is more suspicious for intraductal carcinoma.
IMPRESSION: Multiple filling defects suspicious for intraductal carcinoma.
HISTOPATHOLOGY: Intraductal carcinoma.
Figure 14.20 HISTORY: A 33-year-old woman with a 2-cm palpable mass at the 6 o'clock position in the left breast and bloody left nipple discharge.
MAMMOGRAPHY: Left CC views with early filling (A) and with late filling (B) during galactography. On the initial film (A), the breast is very dense, consistent with the patient's age. There is multinodular mass (arrow) deep in the breast, corresponding to the palpable lesion and suspicious for carcinoma. It is important to evaluate the patient via galactography, because the lesion lies very deep in the breast, and the nipple discharge suggests the possibility of intraductal extension. On the galactogram (B), there is a straightening of the ducts, with multiple areas of narrowing and abrupt termination (arrows) suspicious for intraductal extension of tumor.
IMPRESSION: Probable carcinoma with extensive intraductal extension.
HISTOPATHOLOGY: Infiltrating ductal carcinoma, extensive intraductal carcinoma, and comedocarcinoma.
Figure 14.21 Patient in position for stereotactic biopsy of a galactographic finding. The galactography cannula is in place, taped to the nipple. The lesion has been targeted stereotactically on an upright unit. The vacuum-assisted probe has been inserted into the breast for lesion sampling.
Figure 14.22 HISTORY: A 36-year-old woman with bloody nipple discharge.
MAMMOGRAPHY: Enlarged right CC view from a galactogram shows the filled duct to be irregular in contour. There are numerous small irregular filling defects causing a cobblestone appearance of the duct wall. Areas of narrowing and obstruction are noted medially as well. These filling defects were biopsied stereotactically using vacuum assistance.
IMPRESSION: Highly suspicious for malignancy.
HISTOPATHOLOGY: Ductal carcinoma in situ.
In summary, galactography is performed to evaluate the patient with a suspicious type of nipple discharge. Galactography is not used to differentiate with certainty benign papillomas or papillomatosis from intraductal malignancy. Instead, galactography is important in identifying an intraluminal defect and its exact location for biopsy or surgical removal.