Prepared by Cristina I. Campassi, MD and Wendie A. Berg,
MD, PhD at the Department of Radiology, University of Maryland
School of Medicine, Baltimore, MD
A 66-year-old woman presented with onset of bloody nipple
discharge from the right breast.
Mammograms revealed a dilated duct in the 6 o'clock position of
the right breast extending over an approximately 6-cm length
(figure 1). The adjacent nodule proved to be a cyst. Sonography of
the periareolar right breast confirmed a dilated duct in the 6
o'clock axis containing a 5-mm intraductal hypoechoic mass (figure
2) in the juxta-areolar location, within a centimeter of the
nipple. No additional filling defects were dem-onstrated along the
course of the duct. At this time, bloody nipple discharge was
demonstrated to emanate from the orifice in the 6 o'clock position.
Ductography was performed to confirm cor-respondence of the
discharging duct with the ectatic duct seen on ultrasound and
mammography and verify the presence of a single intraluminal
lesion. The discharging duct was cannulated with a 30-gauge
Jabszenski ductogram cannula a (Cook, Bloomington, IN) and
approximately 0.3 cc of water-soluble contrast (Omnipaque 300,
Nycomed Amersham Inc., Princeton, NJ) was instilled. Mag-nification
mammograms then confirmed a central, lobulated 7-mm filling defect
in the ectatic duct seen at the 6 o'clock position of the right
breast (figure 3).
Solitary intraductal papilloma (figure 4).
This case provides the opportunity to review the diagnostic
work-up, outcome, and management of nipple discharge, as well as
the opportunity to discuss papillary lesions of the breast.
Nipple discharge is a common and frightening complaint; however,
it is an infrequent sign of breast carcinoma. It can be physiologic
or pathologic. Briefly, the latter can be related to conditions
with elevated prolactin or breast pathology, including benign
breast diseases and, rarely, malignancy. A thorough clinical
history and breast examination is fundamental. The type of nipple
discharge is extremely important: except for galactorrhea,
bilateral and multiple-duct discharge is typically due to a benign
breast process and no diagnostic work-up is indicated. Discharge is
considered significant if it is unilateral, bloody, or spontaneous
serous. In this instance, a diagnostic work-up and pathologic
diagnosis is required, as this type of discharge can be secondary
The diagnostic evaluation of significant nipple discharge
includes imaging, surgical consultation, and biopsy. Clinical
breast examination provides characterization and location of the
discharge, as well as testing of serous discharge for occult
hemoglobin. Imaging includes mammography, sonography, and
galactography. A mammogram, though typically negative in these
patients, should be obtained to look for dilated ducts (as in this
case), nonpalpable masses, and microcalcifications.
Microcalcifications within a duct portend malignancy.
Ultrasound can depict dilated ducts, intraductal solid lesions (as
in this case), and masses. A ductogram is typically performed to
locate the abnormality and evaluate the extent of the disease.
Galactography is limited by its lack of specificity and inability
to be performed unless discharge is present at the time of the
study. MRI has recently been advocated as an alternative.
The causes of significant discharge are usually benign. Their
frequency varies in different series, however, solitary intraductal
papilloma is the most common cause of bloody discharge (44% to
The vast majority of the remaining etiologies are benign, including
fibrocystic changes and severe ductal ectasia. The reported
incidence of breast malignancy ranges between 2% and 13%.
The likelihood of nipple discharge being due to breast carcinoma
increases as patient age increases and in the presence of an
associated palpable or mammographic abnormality. If an occult
cancer is found, it is usually an intraductal lesion.
Papillary lesions of the breast are characterized by a papillary
growth pattern supported by a fibrovascular stalk.
They are classified as benign, including solitary and multiple
papillomas; or malignant lesions, including intraductal and
invasive papillary carcinoma. Benign papillary lesions of the
breast are proliferative lesions associated with an increased risk
of developing invasive breast cancer with relative risk of 1.5 to
2, and up 4- to 5-fold if atypia coexists.
Solitary intraductal papilloma is usually located within a major
duct in the subareolar region. They are usually nonpalpable and
mammographically occult due to their small size. On ultrasound, a
solid nodule or a dilated duct with an intraductal solid lesion can
be demonstrated. Typically a central, retroareolar filling defect
can be identified on galactography. Multiple papillomas are usually
asymptomatic; however, nipple discharge can be seen in 20% of
patients. They develop in terminal ducts and, therefore, are
usually peripherally located. Imaging findings are similar in
appearance to solitary papilloma, however, multiple and
peripherally located. Galactography is especially helpful in
defining the extent of the process. In one series, 43% of multiple
papillomas had adjacent atypical ductal hyperplasia, ductal
carcinoma in situ (well- to moderately differentiated), or lobular
neoplasia at excision and, therefore, they can be considered a
Papillomatosis is a different entity characterized by marked
intraductal epithelial proliferation and is therefore part of the
spectrum of fibrocystic changes. Papillary carcinoma is extremely
rare, representing 1% to 2% of all breast cancers and usually
presents as a subareolar mass. Nipple discharge is seen in 22% to
34% of cases. Most papillary carcinomas are intraductal in a
dilated duct. Unfortunately, imaging features do not distinguish
papillary carcinoma from intraductal or intracystic papilloma.
Management of women with bloody or serous nipple discharge is
controversial. Surgical duct excision is advocated in any case of
bloody discharge or those with intraductal masses on imaging.
Since galactography has a low false-negative rate, others advocate
follow-up in the absence of clinical, cytological, and
Recently, imaging-guided, vacuum-assisted biopsy (Mammotome,
Ethicon Endo-Surgery, Cincinnati, OH) has been used as a minimally
invasive method for obtaining an accurate diagnosis with a high
probability of excising the papilloma responsible for the nipple
discharge and eliminating the symptomatic discharge.
If there is an associated palpable or non-palpable mass, it
should be biopsied under ultrasound guidance or excised.
Core-needle biopsy can differentiate between a two-layer epithelial
lining, seen in benign papillary lesions; and a single epithelial
lining, without myoepithelial cells, typical of papillary
carcinoma. Even with results of benign solitary papilloma on core
biopsy, we have observed adjacent atypical ductal hyperplasia or
ductal carcinoma in situ in 13% of cases.
In addition, if nuclear atypia or atypical ductal hyperplasia is
present within a benign papillary lesion, surgical biopsy is
necessary due to the risk of associated ductal carcinoma in situ,
as reported in 30% of cases in one series.
In summary, nipple discharge is secondary to benign disease in
the vast majority of cases. The most common cause of spontaneous,
single-duct discharge is solitary intraductal papilloma, which is a
benign proliferative disease of the breast associated with
increased relative risk of invasive carcinoma ranging from 1.5- to
5-fold, depending on the presence of nuclear atypia. Benign
fibrocystic changes and ductal ectasia account for the majority of
the remaining cases; however, nipple discharge can be due to breast
carcinoma in up to 13% of cases. Surgical excision of the
discharging duct can be done through a circumareolar incision under
local anesthesia with good cosmetic results, providing a definitive
diagnosis and usually definitive treatment of papillary benign,
high-risk, or malignant lesions.
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