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

CASE SUMMARY

A 66-year-old woman presented with onset of bloody nipple discharge from the right breast.

IMAGING FINDINGS

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).

DIAGNOSIS

Solitary intraductal papilloma (figure 4).

DISCUSSION

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 to malignancy.

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. ¹ 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. ²

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 46%). ^3,4 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%. ^4,5 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. ⁶ 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. ⁷ 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 high-risk lesion. ⁸ 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. ⁹ Since galactography has a low false-negative rate, others advocate follow-up in the absence of clinical, cytological, and galactographic abnormalities. ¹⁰ 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. ¹¹

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. ¹² 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. ¹³

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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