Breast Imaging in Nipple Discharge Evaluation

Updated: Oct 06, 2022
  • Author: Edward Azavedo, MD, PhD; Chief Editor: Eugene C Lin, MD  more...
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Practice Essentials

Nipple discharge is the third most frequent complaint of women attending rapid diagnostic breast clinics. [1]  Nipple discharge accounts for 2-10% of the symptoms that women report when they seek care at breast clinics, causing anxiety in patients because it can be a presenting sign of breast cancer. [2]  However, it is usually benign in origin (papillomas and galactophore duct ectasia), with a 5-21.3% risk of an underlying malignant lesion, mostly due to in situ carcinomas. [3, 4]  If the discharge is considered to be physiologic on the basis of clinical information and characteristics of the nipple discharge, no further imaging studies of the breast are warranted. 

Although approximately 80-90% of patients with pathologic nipple discharge have been reported to have benign conditions, [2] breast imaging enables the localization of the breast abnormalities causing the pathologic nipple discharge, which helps minimize the number of operations and/or the extent of surgery. In addition, localizing the origin of pathologic nipple discharge enables percutaneous biopsy under imaging guidance, which allows clinicians to be more confident when deciding upon management and when choosing whether to perform minimally invasive percutaneous vacuum-assisted excision in these patients. [3]

Nipple smear cytology remains the single most used diagnostic method for investigating fluid content, but pooled data from studies examining nipple discharge fluid assessment suggest that the diagnostic accuracy of nipple smear cytology is limited. In a meta-analysis by Jiwa et al on the examination of nipple discharge fluid, nipple flow cytology had a sensitivity of 75% and a specificity of 87% for benign breast disease. For breast cancer, it had a sensitivity of 62% and a specificity of 71%. Patients presenting with blood-stained discharge yielded an overall malignancy rate of 58%, with a positive predictive value of 27%. [1]

Imaging modalities

Mammography or digital breast tomosynthesis (DBT) is the first-line study for a pathologic discharge in most patients. Mammography is limited because of its poor sensitivity of 20-25%. [5]  A negative mammogram in the context of nipple discharge does not therefore exclude any underlying disease, and ultrasound is performed immediately after mammography even if the mammogram is normal. It can be difficult to identify a source/cause when mammography is performed due to its poor sensitivity, and variable results have been reported with ultrasound. Advanced imaging such as magnetic resonance imaging (MRI) is increasingly utilized, limiting the need for ductography for diagnosis. [6]

According to the American College of Radiology (ACR), for women 30 to 39 years of age, either mammography or ultrasonography may be used as the initial examination. For women aged 30 years or younger, ultrasound should be the initial examination, with mammography/DBT added when ultrasound shows suspicious findings or if the patient is predisposed to developing breast cancer. For men aged 25 years or older, mammography/DBT should be performed initially, with ultrasound added as indicated, given the high incidence of breast cancer in men with pathologic nipple discharge. Although MRI and ductography (galactography) are not usually appropriate as initial examinations, each may be useful when the initial standard imaging evaluation is negative. ACR Appropriateness Criteria are summarized in Table 1 below. [7]

Table 1. ACR Appropriateness Criteria for Evaluation of Nipple Discharge (Open Table in a new window)

Indications

Mammography

Digital breast tomosynthesis

Ultrasound

Comments

Physiologic discharge in women of any age

1

1 1  
Pathologic discharge in men or women aged 40 years or older 9 9 9 US is usually complementary to mammography. It can be an alternative to mammography if the patient had a recent mammogram or is pregnant.
Pathologic discharge in men or women aged 30-39 years 9 9 9 US can be used as an initial examination in place of mammography in women in this age range. For men, it is complementary to mammography. 
Pathologic discharge in  women aged 29 years or younger 5 5 9

Mammography and/or DBT may be complementary when initial US shows a suspicious finding or the patient is BRCA positive or has another genetic mutation predisposing to breast cancer.

Pathologic discharge in men aged 29 years or younger 8 8 9 When the patient is younger than 25 years, US may be the initial examination, with mammography added as indicated. Mammography or DBT should be performed as the initial study in men older than 25 years, given the high incidence of cancer in men with pathologic nipple discharge.

Scales are designated 1-9, where 1, 2, 3 = usually not appropriate; 4,5,6 = may be appropriate; and 7,8, 9 = usually appropriate.   

DBT = digital breast tomosynthesis; US = ultrasound.

Note:  The following modalities were rated 1 for initial examination in all indications: ductography, MRI breast without and with IV contrast, fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission mammography (FDG-PEM ), Tc-99m sestamibi molecular breast imaging (MBI).  

Modern, high-resolution ultraasonographic 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).

A 45-year-old woman with serosanguineous discharge A 45-year-old woman with serosanguineous discharge from her right nipple presented with no other clinical symptoms. Mammography was unrevealing. Ultrasonography revealed a 3-mm dilated duct with an intraluminal lesion (arrow) located close to the nipple. Cytology revealed epithelial cell fragments in a papillary formation. Histopathology confirmed the presence of a papilloma.
Additional ultrasonogram obtained in the same pati Additional ultrasonogram obtained in the same patient as in the immediately preceding image.

A meta-analysis by Berger et al reported a higher diagnostic performance for MRI than ductography (galactography) in the detection of any kind of lesion in patients with pathologic nipple discharge. Moreover, high sensitivity and very high specificity for cancer by MRI could be confirmed in this clinical setting. [8]

Contrast-enhanced mammography (CEM) is an emerging breast imaging modality that is useful in evaluating patients with nipple discharge who have a negative galactogram, especially if they are not good candidates for contrast-enhanced MRI. [9]

Limitations of techniques

Ductography (galactography) is not indicated unless the nipple discharge is spontaneous, unilateral, and expressed from a single pore. Ductography is occasionally technically impossible because of failed catheterization of the pore because of the need to reproduce the discharge on the day of the investigation. It is invasive, with a risk of extravasation and complications due to allergy to the iodinated contrast medium, or mastitis. [5]  According to a systematic review by Waaijer et al, ductoscopy detects about 94% of all underlying malignancies in patients with pathologic nipple discharge, but it does not permit reliable discrimination between malignant and benign findings. [10]

The major disadvantage of MRI is that it often detects additional images or false positives, which result in MRI monitoring or biopsies being taken that are unrelated to the pathologic nipple discharge. It appears to be more difficult with this technique to characterize an endoductal lesion and therefore guide the diagnosis toward a benign or malignant lesion, which then necessitates repeat ultrasound. [5]

High-resolution ultrasonography is not available at all breast-imaging centers. In addition, it is operator dependent and requires expertise for the identification of small intraductal structures.

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Radiography

Mammography is the standard initial step in evaluation of most patients with pathologic nipple discharge. The mammogram needs to include only the symptomatic breast if the patient has undergone recent bilateral screening mammography within the past 6 months. It usually consists of craniocaudal and mediolateral oblique views of the symptomatic breast, with additional views if indicated. [7]

Digital breast tomosynthesis (DBT) is a 3-dimensional technique based on digital mammography (DM) that is known to improve breast cancer detection rates and to reduce recall rates. On DBT, partial 3-D reconstruction of the breast is obtained from a finite number of 2-D projections, which are acquired as the x-ray tube moves along an arc. This reduces the summation of overlapping breast tissues and may increase detection of architectural distortion. [11]  DBT can be useful in improving characterization of noncalcified lesions, as compared to conventional mammographic workup, and could therefore be useful in the setting of nipple discharge evaluation. [7]

Ostojic et al performed a retrospective study comparing DBT with mammography, ultrasound, and MRI in evaluating patients with nipple discharge and found that DBT exhibited higher specificity than MRI (82.9% vs 61.9%). DBT and MRI both exhibited high sensitivity (100%) and high negative predictive value (100%) for the detection of breast cancer in patients with nipple discharge. Sensitivity and specificity for mammography were 83.3% and 76.6%, respectively. Breast ultrasonography had a sensitivity of 66.7% and a specificity of 57.5%. [4]

Ductography, also known as galactography, is historically the procedure of choice in identifying and localizing intraductal lesions in patients with pathologic nipple discharge. Repeat ductography can be used to guide preoperative wire localization once a suspicious target lesion is identified. [7]  Ductography has been used in the past to visualize the number, location, and extent of the involved milk ducts in women with pathologic nipple discharge, but it is an invasive imaging method that requires iodinated contrast-medium injection and also has low diagnostic accuracy, because the differential diagnosis of the causative lesion cannot be completed based on ductographic findings alone. [3]

Ductography 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). 

Duct compression due to an extrinsic mass decreases the ductal diameter, which takes on the shape of a cone or funnel.

A 47-year-old woman with serous discharge from her A 47-year-old woman with serous discharge from her right nipple. Ductography reveals a contrast-agent filling defect approximately 3 cm from the nipple. Cytology revealed normal epithelial cells and cell debris. Histopathology after surgery revealed a solitary, lobulated intraductal papilloma.
Close-up view of the immediately preceding image. Close-up view of the immediately preceding image.
A 50-year-old woman with serous discharge from her A 50-year-old woman with serous discharge from her right nipple. Ductography reveals contrast-agent filling defect approximately 4 cm from her nipple. Cytology of the smears from her nipple discharge revealed normal epithelial cells. Histopathology after surgery revealed a solitary intraductal papilloma in a cystic lesion.
Close-up view of the immediately preceding image. Close-up view of the immediately preceding image.
A 48-year-old woman with serous discharge from her A 48-year-old woman with serous discharge from her right nipple. Ductography reveals contrast-agent filling defects approximately 1.5 cm from the nipple, extending to a depth of approximately 2.5 cm. Cytology demonstrated epithelial cells arranged in papillary fragments. Histopathology after surgery revealed extensive involvement of intraductal papillomas.
Close-up view of the immediately preceding image. Close-up view of the immediately preceding image.

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.

A 42-year-old woman with serous discharge from her A 42-year-old woman with serous discharge from her left nipple. Ductography reveals contrast-agent filling defects approximately 1.5 cm from her nipple. Cytology of smears of secreted fluid revealed malignant epithelial cells. Histopathology after surgery revealed intraductal carcinoma.
Close-up view of the immediately preceding image. Close-up view of the immediately preceding image.

 

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Magnetic Resonance Imaging

MRI is a valuable additional diagnostic tool for the evaluation of pathologic nipple discharge when conventional imaging is negative. A retrospective study of 118 women who underwent MRI for evaluation of nipple discharge reported that in women with negative or inconclusive mammography findings, the risk of malignancy is low, at 5.7%. With negative MRI findings, the risk of malignancy is less than 4%. A negative MRI in this symptomatic population may obviate the need for duct exploration and excision. [12, 13]  

The most common abnormality seen with a pathologic nipple discharge is enhancement without a mass (EWM) for malignant, atypical, or papillary lesions. In decreasing order of frequency, these are ductal EWM, focal regions, and segmentally or regionally distributed EWM. [14, 15] A ductal or segmental EWM can be seen in both papillomas and papillomatoses. In this situation, the segmental spatial distribution and micronodular or annular nature of the lesion are the EWM features, which have the greatest positive predictive value for malignancy. [5]

In a retrospective study of 320 patients presenting with nipple discharge, Chung et al found that the combination of mammography and ultrasonography detected 93% of breast malignancies associated with nipple discharge, with a 98% negative predictive value for malignancy. Contrast-enhanced MRI had a 100% sensitivity and a 100% negative predictive value for malignancy. [16]

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Ultrasonography

Ultrasonography (US) is used as an adjunct to mammography for breast imaging, enabling the further characterization of abnormalities detected on mammography and providing biopsy guidance. [17] US enables the visualization of ductal pathologies that are smaller than a centimeter, as well as associated ductal changes that cannot be detected on mammography, especially in women with dense breasts (see the images below). US can detect the causative lesion(s), along with orientation of the surrounding ductal structures involved, which is helpful in planning the method of biopsy or the extent of surgery. [3]

Adding US to diagnostic mammography can help detect additional cancers in women with pathologic nipple discharge. [18] Also, in a study by Park et al, the addition of US in patients with pathologic nipple discharge who had negative findings on mammography led to the detection of malignancies in 15.1% of these patients by US-guided core needle biopsy, without additional diagnostic surgery. [19]

A 45-year-old woman with serosanguineous discharge A 45-year-old woman with serosanguineous discharge from her right nipple presented with no other clinical symptoms. Mammography was unrevealing. Ultrasonography revealed a 3-mm dilated duct with an intraluminal lesion (arrow) located close to the nipple. Cytology revealed epithelial cell fragments in a papillary formation. Histopathology confirmed the presence of a papilloma.
Additional ultrasonogram obtained in the same pati Additional ultrasonogram obtained in the same patient as in the immediately preceding image.
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