Revised 2022

American College of Radiology
ACR Appropriateness Criteria®
Evaluation of Nipple Discharge
Variant 1:

Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male).
Physiologic nipple discharge. Initial imaging.
ProcedureAppropriateness Category

Relative Radiation Level

US breast

Usually Not Appropriate

Digital breast tomosynthesis diagnostic

Usually Not Appropriate

O

Ductography

Usually Not Appropriate

Mammography diagnostic

Usually Not Appropriate

Image-guided core biopsy breast

Usually Not Appropriate

VariesImage-guided fine needle aspiration breast

Usually Not Appropriate

Varies

MRI breast without and with IV contrast

Usually Not Appropriate

MRI breast without IV contrast

Usually Not Appropriate

O

Sestamibi MBI

Usually Not Appropriate

FDG-PET breast dedicated

Usually Not Appropriate

Variant 2:

☢☢
☢☢
☢☢

O

☢☢☢
☢☢☢

Adult male or female 40 years of age or older. Pathologic nipple discharge. Initial imaging.
ProcedureAppropriateness Category

Relative Radiation Level

US breast

Usually Appropriate

Digital breast tomosynthesis diagnostic

Usually AppropriateO

Mammography diagnostic

Usually Appropriate

☢☢
☢☢
☢☢

Ductography

Usually Not Appropriate

Image-guided core biopsy breast

Usually Not Appropriate

VariesImage-guided fine needle aspiration breast

Usually Not Appropriate

Varies

MRI breast without and with IV contrast

Usually Not Appropriate

MRI breast without IV contrast

Usually Not Appropriate

O

Sestamibi MBI

Usually Not Appropriate

FDG-PET breast dedicated

Usually Not Appropriate

ACR Appropriateness Criteria®

1

O

☢☢☢
☢☢☢

Evaluation of Nipple Discharge

Variant 3:

Adult male or female 30 to 39 years of age. Pathologic nipple discharge. Initial imaging.
ProcedureAppropriateness Category

Relative Radiation Level

US breast

Usually Appropriate

Digital breast tomosynthesis diagnostic

Usually AppropriateO

Mammography diagnostic

Usually Appropriate

☢☢
☢☢
☢☢

Ductography

Usually Not Appropriate

Image-guided fine needle aspiration breast

Usually Not Appropriate

Varies

MRI breast without and with IV contrast

Usually Not Appropriate

MRI breast without IV contrast

Usually Not Appropriate

O

Sestamibi MBI

Usually Not Appropriate

FDG-PET breast dedicated

Usually Not Appropriate

Variant 4:

O

☢☢☢
☢☢☢

Adult male younger than 30 years of age. Pathologic nipple discharge. Initial imaging.
ProcedureAppropriateness Category

Relative Radiation Level

US breast

Usually Appropriate

Digital breast tomosynthesis diagnostic

Usually AppropriateO

Mammography diagnostic

Usually Appropriate

☢☢
☢☢
☢☢

Ductography

Usually Not Appropriate

Image-guided core biopsy breast

Usually Not Appropriate

VariesImage-guided fine needle aspiration breast

Usually Not Appropriate

Varies

MRI breast without and with IV contrast

Usually Not Appropriate

MRI breast without IV contrast

Usually Not Appropriate

O

Sestamibi MBI

Usually Not Appropriate

FDG-PET breast dedicated

Usually Not Appropriate

Variant 5:

O

☢☢☢
☢☢☢

Adult female younger than 30 years of age. Pathologic nipple discharge. Initial imaging.
Procedure

US breast

Appropriateness Category

Relative Radiation Level

Usually Appropriate

O☢☢

Digital breast tomosynthesis diagnostic

Usually Not Appropriate

Ductography

Usually Not Appropriate

Mammography diagnostic

Usually Not Appropriate

Image-guided core biopsy breast

Usually Not Appropriate

VariesImage-guided fine needle aspiration breast

Usually Not Appropriate

Varies

MRI breast without and with IV contrast

Usually Not Appropriate

MRI breast without IV contrast

Usually Not Appropriate

O

Sestamibi MBI

Usually Not Appropriate

FDG-PET breast dedicated

Usually Not Appropriate

ACR Appropriateness Criteria®

2

☢☢
☢☢

O

☢☢☢
☢☢☢
Evaluation of Nipple Discharge

Variant 6:

Adult transfeminine (male-to-female) patient 30 years of age or older. Pathologic nipple
discharge. Initial imaging.
ProcedureAppropriateness Category

Relative Radiation Level

US breast

Usually Appropriate

Digital breast tomosynthesis diagnostic

Usually AppropriateO

Mammography diagnostic

Usually Appropriate

☢☢
☢☢
☢☢

Ductography

Usually Not Appropriate

Image-guided core biopsy breast

Usually Not Appropriate

VariesImage-guided fine needle aspiration breast

Usually Not Appropriate

Varies

MRI breast without and with IV contrast

Usually Not Appropriate

MRI breast without IV contrast

Usually Not Appropriate

O

Sestamibi MBI

Usually Not Appropriate

FDG-PET breast dedicated

Usually Not Appropriate

Variant 7:

O

☢☢☢
☢☢☢

Adult transfeminine (male-to-female) patient younger than 30 years of age. Pathologic nipple
discharge. Initial imaging.
ProcedureAppropriateness Category

Relative Radiation Level

US breast

Usually Appropriate

Digital breast tomosynthesis diagnostic

Usually AppropriateO

Mammography diagnostic

Usually Appropriate

☢☢
☢☢
☢☢

Ductography

Usually Not Appropriate

Image-guided core biopsy breast

Usually Not Appropriate

VariesImage-guided fine needle aspiration breast

Usually Not Appropriate

Varies

MRI breast without and with IV contrast

Usually Not Appropriate

MRI breast without IV contrast

Usually Not Appropriate

O

Sestamibi MBI

Usually Not Appropriate

FDG-PET breast dedicated

Usually Not Appropriate

ACR Appropriateness Criteria®

3

O

☢☢☢
☢☢☢

Evaluation of Nipple Discharge

EVALUATION OF NIPPLE DISCHARGE
Expert Panel on Breast Imaging: Matthew F. Sanford, MD a; Priscilla J. Slanetz, MD, MPHb;
Alana A. Lewin, MDc; Arnold M. Baskies, MDd; Laura Bozzuto, MDe; Susan A. Branton, MDf;
Jessica H. Hayward, MDg; Huong T. Le-Petross, MDh; Mary S. Newell, MDi; John R. Scheel, MD, PhD, MPHj;
Richard E. Sharpe Jr., MD, MBAk; Gary A. Ulaner, MD, PhDl; Susan P. Weinstein, MDm; Linda Moy, MD.n
Summary of Literature Review
Introduction/Background
Nipple discharge is common with a prevalence of 4.8% to 7.4%, with 50% to 80% of reproductive age womenexperiencing at least one episode during their lifetime [1-3]. Nipple discharge is the third most common breast
complaint after pain and a lump. It is reported by 5% to 10% of women at the time of routine medical examinations[4-7]. Nipple discharge can be characterized as physiologic or pathologic. Physiologic discharge is often provoked,
originates from multiple duct orifices, is bilateral and white, green, or yellow in color [2]. In a study of 13,443
women with nipple discharge, 316 (2.3%) had nonspontaneous discharge, only 1 (0.3%) of whom had carcinoma[8]. Similarly, a retrospective review of 273 women who underwent diagnostic and therapeutic surgery for nipple
discharge found no malignancies in those presenting with physiologic nipple discharge [9]. Pathologic nipple
discharge demonstrates at least one of the following features: spontaneous from a single-duct orifice, unilateral,
serous, or bloodstained. The most common causes of pathologic nipple discharge are benign, such as intraductal
papilloma/papillomatosis (35%–48%) and duct ectasia (17%–36%) [5,6,10]. Most nipple discharge is not associatedwith an underlying breast malignancy but may provoke concern by the patient and their provider [5,6,10]. The rateof malignancy associated with pathologic nipple discharge varies widely from 3% to 29% depending on the type ofdischarge, patient population studied, the intervention undertaken, and histopathologic classification [5,11]. Larger
studies estimate the rate of malignancy or high-risk histopathologic lesions to be closer to 11% to 16% of patientswith pathologic nipple discharge [5,6,12-18]. Even though nipple discharge in males is rare, it has a strong
association with an underlying malignancy based on a recent study of 430 consecutive men with nipple discharge
revealing malignancy in 57% [19]. In men with a palpable mass and nipple discharge, the rate of breast cancer has
been reported to be as high as 75% [20,21]. Of the approximately 8 to 25 million persons worldwide identifying astransgender [22], it is unknown how many will develop nipple discharge, and there are no specific studies addressing
the imaging of this population.
The standard evaluation for nipple discharge includes a detailed clinical history and physical examination that
directs the need for and type of breast imaging [11]. In patients with inconclusive breast imaging, the patient andprovider may elect for surgical consultation. Historically, major duct excision has been the reference standard for
defining the causative lesion of the nipple discharge and eliminating symptoms. However, this approach may not
be optimal for all, because the lesion may not be identifiable on pathology, the procedure may impair a patient’s
ability to breast feed, and peripheral breast lesions may not be amenable to excision [17,23,24]. If a target is
identified by imaging, excision by diagnostic vacuum-assisted percutaneous core needle biopsy (CNB) may offer
an alternative to surgery.
Special Imaging Considerations
In 2018, Schulz-Wendtland et al [25] first described a technique combining digital breast tomosynthesis (DBT) andductography and evaluated 5 women with pathologic nipple discharge. They found that DBT-ductography
performed comparably to high-resolution ultrasound (US) in identifying suspicious imaging lesions. In 2020
Moschetta et al [26] used this nascent technique on 49 consecutive patients with spontaneous, unilateral, singlepore discharge and inconclusive conventional digital mammography and US. In this series, they compared DBTa
Sanford Health of Northern Minnesota, Bemidji, Minnesota. bPanel Chair, Boston University School of Medicine, Boston, Massachusetts. cPanel Vice-Chair,
New York University School of Medicine, New York, New York. dVirtua Willingboro Hospital, Willingboro, New Jersey; American College of Surgeons.
eUniversity of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; American College of Obstetricians and Gynecologists. fUPMC,
Pittsburgh, Pennsylvania; American College of Surgeons. gUniversity of California San Francisco, San Francisco, California. hThe University of Texas MD
Anderson Cancer Center, Houston, Texas. iEmory University Hospital, Atlanta, Georgia. jUniversity of Washington, Seattle, Washington. kMayo Clinic,
Phoenix, Arizona. lHoag Family Cancer Institute, Newport Beach, California. mPerelman School of Medicine of the University of Pennsylvania, Philadelphia,
Pennsylvania. nSpecialty Chair, NYU Clinical Cancer Center, New York, New York.
The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR AppropriatenessCriteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final
document by individual contributors or their respective organization.
Reprint requests to: publications@acr.org

ACR Appropriateness Criteria®

4

Evaluation of Nipple Discharge

ductography with conventional full-field galactography and found improved sensitivity (95% versus 77%) andaccuracy (96% versus 80%) with identical specificity (80%).
Initial Imaging Definition
Initial imaging is defined as imaging at the beginning of the care episode for the medical condition defined by thevariant. More than one procedure can be considered usually appropriate in the initial imaging evaluation when:•

There are procedures that are equivalent alternatives (ie, only one procedure will be ordered toprovide the clinical information to effectively manage the patient’s care)
OR•

There are complementary procedures (ie, more than one procedure is ordered as a set or
simultaneously where each procedure provides unique clinical information to effectively manage
the patient’s care).

Discussion of Procedures by Variant
Variant 1: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male).
Physiologic nipple discharge. Initial imaging.
Physiologic nipple discharge is defined as bilateral, originating from multiple ducts, white/green/yellow in color,or milky in appearance [27]. It tends to occur only when provoked [8]. Many studies have shown physiologic nipple
discharge to be benign, with no association within situ or invasive carcinoma [9,28,29].
Mammography Diagnostic
If patient history and physical examination demonstrate physiologic nipple discharge and routine screening
mammography is up to date, no further radiologic investigation is needed [28,29].
Digital Breast Tomosynthesis Diagnostic
If patient history and physical examination demonstrate physiologic nipple discharge and routine screening
mammography is up to date, no further radiologic investigation is needed [28,29].
US Breast
If patient history and physical examination demonstrate physiologic nipple discharge and routine screening
mammography is up to date, no further radiologic investigation is needed [28,29].
Ductography
If patient history and physical examination demonstrate physiologic nipple discharge and routine screening
mammography is up to date, no further radiologic investigation is needed [28,29].
MRI Breast
If patient history and physical examination demonstrate physiologic nipple discharge and routine screening
mammography is up to date, no further radiologic investigation is needed [28,29].
FDG-PET Breast DedicatedIf patient history and physical examination demonstrate physiologic nipple discharge and routine screening
mammography is up to date, no further radiologic investigation is needed [28,29].
Image-guided Core Biopsy Breast
Image-guided core biopsy is not required for the evaluation of physiologic nipple discharge in the female patient.
Image-Guided Fine Needle Aspiration Breast
Image-guided fine-needle aspiration (FNA) is not required for the evaluation of physiologic nipple discharge in thefemale patient.
Sestamibi MBI
If patient history and physical examination demonstrate physiologic nipple discharge and routine screening
mammography is up to date, no further radiologic investigation is needed [28,29].
Therefore, if the clinical findings are consistent with physiologic nipple discharge and a women’s healthmaintenance, including screening mammography, is current, diagnostic breast imaging is likely unnecessary [6,7].

ACR Appropriateness Criteria®

5

Evaluation of Nipple Discharge

Variant 2: Adult male or female 40 years of age or older. Pathologic nipple discharge. Initial imaging.
Mammography Diagnostic
Mammography is the first-line imaging modality for evaluation of pathologic nipple discharge in male and female
patients in this age group [30]. Although 3% to 29% of pathologic nipple discharge is due to an underlying breast
cancer, full-field mammography often does not demonstrate these lesions because they may be very small, containno calcifications, or are completely intraductal [1-3]. To better evaluate the subareolar breast in patients with anasymmetry/focal asymmetry or suspicious microcalcifications, additional mammographic views with spot
compression and magnification may be needed [31].
Most cases of pathologic nipple discharge are due to a benign intraductal papilloma [32]. When visible on
mammography, imaging findings of papilloma include asymmetrically dilated ducts, a circumscribed benignappearing subareolar mass, or grouped microcalcifications [1]. Up to 12% of patients with ductal carcinoma in situ
(DCIS) present with nipple discharge [33]. DCIS is usually detected mammographically as fine, linear,discontinuous, and branching microcalcifications in linear, ductal, or segmental distribution and less often as a mass,
asymmetry/focal asymmetry, or architectural distortion on mammography [11]. The mammographic features ofinvasive carcinomas are well known, including a mass of various margin characteristics with or without
microcalcifications or an asymmetry, focal asymmetry, or architectural distortion [34].
For detection of malignancy (DCIS and invasive cancer), the reported sensitivity of mammography varies widely
between 15% and 68%, with a specificity between 38% and 98% [3,9,23,28]. In one study, the positive predictive
value (PPV) was 42%, and the negative predictive value (NPV) was 90% [23]. Malignant and high-risk lesions are
identified by mammography with a reported sensitivity of 10% to 26%, specificity of 94% to 95%, PPV of 18%,
and NPV of 88% [3,16]. The possible causes of the wide variation in reported sensitivity include differences inimaging technology (digital versus film-screen mammography) and varied breast density among different cohortsof patients.
In a study of 106 patients >30 years of age with pathologic nipple discharge, Gray et al [28] showed the risk ofcarcinoma to be 3% with a negative mammogram and 0% when both mammogram and subareolar US were
negative. Although low in sensitivity and PPV, mammography remains useful in the evaluation of pathologic nipple
discharge because of its high specificity and high NPV.
Digital Breast Tomosynthesis Diagnostic
Although there is no relevant literature to support the use of DBT alone in assessing nipple discharge,
mammography is useful for evaluating pathologic nipple discharge in male and female patients in this age group[30]. Early studies with DBT demonstrate promise is assessing the symptomatic breast [35,36].
US Breast
US is useful in identifying invasive cancer and assessing extent of disease but has a diminished sensitivity for
detecting DCIS [9,12,37,38]. In patients with pathologic nipple discharge, US identifies lesions not visible on
mammography 63% to 69% of the time [30,39]. US adds specificity for some lesions when compared withmammography if it identifies the mammographic finding as a simple cyst or duct ectasia. US expands on
ductography in its ability to visualize and detect abnormalities in multiple rather than single ducts [24].
US alone has a reported sensitivity (56%–80%), specificity (61%–75%), PPV (29%–39%), and NPV (90%–91%)
for detection of underlying malignancy in patients with pathologic nipple discharge [3,9,23]. The wide variation inreported performance can be explained by differences in the definition of pathologic nipple discharge and variationin US technique [9].
Although more sensitive than mammography, US suffers from lower specificity in differentiating benign versus
malignant lesions [9]. False-positive US results may be due to volume averaging with the ductal wall in a tortuous
duct, intraductal and periductal fibrosis, adherent blood clots, or inspissated debris [31]. Previous studies have also
reported mammography and US to be unreliable in predicting histology in patients with pathologic nipple discharge,
which underscores the necessity of histological diagnosis [17,23]. In male and female patients, US is useful in
identifying and assessing lesions and for biopsy guidance [40].
Ductography
Ductography may demonstrate small lesions and localize the duct responsible for the nipple discharge. Ductography
is minimally invasive, may be uncomfortable, and can be time-consuming. The procedure is technically challenging
with 10% to 15% of cases resulting in inadequate or incomplete results [41,42]. The discharge must be present on
ACR Appropriateness Criteria®

6

Evaluation of Nipple Discharge

the day of ductography so that a cannula can be placed in the appropriate duct. Failure to cannulate the discharging
duct may lead to a false negative [43]. Ductography is not recommended in lactating women or patients with active
mastitis. Known hypersensitivity to iodinated contrast agents is a relative contraindication. Findings on ductographysuggestive of malignant or papillary lesions include intraductal filling defect, partial or complete obstruction of aduct, duct expansion or distortion, and duct wall irregularity [1].
In patients with pathologic nipple discharge and a negative mammogram and US, Morrogh et al [44] reported the
PPV and NPV of ductography for detection of cancer and high-risk lesions to be 19% and 63%, respectively. In thesetting of negative standard evaluations, ductography localized 76% of otherwise occult malignant/high-risk lesions
and 91% of benign lesions [39]. When the standard evaluation is positive, ductography facilitated preoperative
localization of the causative lesion in 78% of cases [39]. For detection of cancer in patients with pathologic nipple
discharge, 2 studies showed the sensitivity, specificity, PPV, and NPV of ductography to be 75% to 100%, 6% to49%, 16% to 18%, and 93% to 100%, respectively [16,23]. For detection of high-risk lesions, Adepoju et al [16]reported the sensitivity, specificity, PPV, and NPV of ductography to be 75%, 53%, 22%, and 92%, respectively.
Ductography is more sensitive than mammography and US but has lower specificity than both modalities. A
negative ductogram does not reliably exclude an underlying cancer or high-risk lesion, with the false-negative ratereported to be as high as 20% to 30% [44]. As such, the primary value of ductography is to localize intraductal
lesions and assist in surgery [45]. A study found that patients who underwent ductography-guided operations or any
other surgical procedure with image guidance of the lesion were significantly more likely to have a specificunderlying lesion identified than patients who underwent central duct excision alone [23,42].
MRI Breast
The sensitivity of breast MRI for detecting invasive breast cancer is high, ranging from 93% to 100%. Breast MRI
specificity ranges from 37% to 97% and relies on analysis of a lesion’s morphology and enhancement kinetics [46].
Malignant lesions may appear as a mass or nonmass enhancement in a ductal or segmental distribution on MRI.
Noncontrast MRI, although useful for evaluation of implant integrity, has little value in the detection of malignant
or high-risk lesions in patients with nipple discharge [47].
Contrast-enhanced breast MRI has high sensitivity for detecting benign papillary lesions as well as in situ andinvasive carcinoma [3]. Furthermore, MRI allows identification of index lesions in peripheral ducts that are beyond
the area normally encompassed by terminal duct excision, ductography, or targeted US [44]. Index or synchronous
lesions found on MRI alone can be percutaneously biopsied with MRI guidance to allow for single-stage definitive
surgical management (if malignant) or potentially to avoid unnecessary surgical excision for some benign lesions.
In general, MRI may be considered in cases in which mammography and US have failed to identify an underlying
cause of pathologic nipple discharge [3,44,48-50]. The sensitivities of breast MRI for detecting the cause of thepathologic nipple discharge are 86% to 100% for invasive cancer and 40% to 100% for noninvasive disease[3,12,44,49,51,52]. Bahl et al [52] reported the sensitivity, specificity, PPV, and NPV of MRI for detecting
malignancy in patients with pathologic nipple discharge to be 100%, 68%, 37%, and 100%, respectively. Several
studies have shown that MRI has higher sensitivity and specificity than US and ductography for lesion detection
and may be an alternative to ductography [12,32,48,49]. However, a study by van Gelder et al [51] asserted that
MRI has limited added value in patients with unilateral bloody nipple discharge who showed no signs of amalignancy on conventional diagnostic examinations, because malignancy was demonstrated in <2% of their cases.
Despite the high sensitivity of breast MRI, it is not indicated as initial imaging in a patient with pathologic nipple
discharge.
FDG-PET Breast DedicatedHigh-resolution cameras specifically designed for breast imaging have improved detection of small and noninvasive
carcinomas. However, specific research evaluating women with nipple discharge is lacking [41,53]. Currently, there
is no relevant literature for the use of fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET in the evaluation of amale or female patient with pathologic nipple discharge.
Image-Guided Core Biopsy Breast
Previous studies showed that mammography, US, and ductography are unreliable in predicting histology in patientswith pathologic nipple discharge [17,23,44], which underscores the importance of histological diagnosis of lesions
identified on imaging. The biopsy procedures may be guided by stereotactic mammography, US, ductography, or
MRI, depending on the imaging modality that best depicts the lesion. CNB is preferred over FNA because the larger
gauge needle improves sampling [54,55]. Placement of a tissue marker at the end of the biopsy allows for needle
ACR Appropriateness Criteria®

7

Evaluation of Nipple Discharge

localization and excision if the biopsied lesion yields malignant or high-risk histology. Vacuum-assisted CNB is
particularly useful in assuring complete sampling of small intraductal papillary lesions [24]. Although biopsy is adiagnostic procedure, the process of removing enough of the intraductal papillary lesion during vacuum-assisted
core biopsy may be therapeutic and will lead to permanent cessation of nipple discharge in 90% to 97.2% of patients[24,56]. However, Reiner et al [57] cautioned that ductography-guided 11-gauge vacuum-assisted stereotactic
biopsy should not be used as a substitute for surgical duct excision in cases of pathologic nipple discharge withabnormalities on ductography because of the high underestimation rate (50%) for high-risk lesions and DCIS, falsenegative rate (7%), and histopathological detection of lesion remnants in every case.
Papillomas are historically considered high-risk lesions, with reported rates of upgrade to malignancy between 3%
and 14% [58,59]. The management of papillomas diagnosed on CNB is controversial and varies by institution [60].
Because papillomas diagnosed on CNB are often excised, excisional biopsy instead of CNB may be useful when apapillary lesion is anticipated based on imaging findings. A recent study suggests that patients with nonbloody
pathologic nipple discharge, a benign CNB, or normal imaging (cancer risk <2%) may be considered fornonoperative management if they do not have risk factors such as prior ipsilateral breast cancer, BRCA mutation,
or atypia on CNB [61].
According to the surgical literature, major duct excision remains the reference standard to exclude malignancy inpatients with unremarkable imaging, when even a negative ductogram (NPV 63%–82%) [17,30] or MRI (NPV
87%–100%) [44,52] does not exclude an underlying cancer or high-risk lesion [13,39,44].
In addition, US does not reliably distinguish between benign and malignant small intraductal lesions [9]. Therefore,
the decision to perform percutaneous biopsy versus major duct excision should involve the patient and their healthcare provider.
Image-guided CNB is equally useful in male patients for obtaining tissue diagnosis and assisting in patientmanagement [40]. Image-guided CNB is not indicated as the initial examination to evaluate pathologic nipple
discharge.
Image-Guided Fine Needle Aspiration Breast
Once a suspicious lesion that is likely responsible for the pathologic nipple discharge is identified on imaging,
image-guided FNA or CNB can be performed for histological diagnosis. Although some institutions demonstrate
good results using FNA, larger series have shown that core biopsy is superior to FNA in terms of sensitivity,
specificity, and correct histological grading of a lesion [54,55]. Image-guided FNA is not indicated as the initial
examination to evaluate pathologic nipple discharge.
Sestamibi MBI
There is no relevant literature to support the use of molecular breast imaging (MBI) in the evaluation of a male orfemale patient with pathologic nipple discharge.
Variant 3: Adult male or female 30 to 39 years of age. Pathologic nipple discharge. Initial imaging.
The risk of breast cancer is relatively low (≤1.4%) for women in their fourth decade [62]. There are scant data on
the risk of breast cancer in women 30 to 39 years of age presenting with pathologic nipple discharge. In one study,
no malignancy was recorded among patients 30 to 39 years of age with pathologic nipple discharge and no palpablemass [9]. However, a study of 19 patients <40 years of age with pathologic nipple discharge [23] found 2 cancers.
There is no other relevant literature that addresses the appropriateness of imaging in women 30 to 39 years of age
with the specific symptom of pathologic nipple discharge.
Mammography Diagnostic
The sensitivity of US for palpable or nonpalpable breast cancer is higher than that of mammography (95.7% versus
60.9%) for women 30 to 39 years of age [63,64]. Either mammography or US may be used as the initial imaging
modality, on the basis of institutional preference and case-by-case consideration. However, mammography has its
value in detecting suspicious microcalcifications, given the high incidence of patients with DCIS presenting withnipple discharge.
Because of the high incidence (23%–57%) of breast cancer in male patients with nipple discharge [19,65], imaging
with mammography is indicated as an initial study per the ACR Appropriateness Criteria® topic on “Evaluation of
the Symptomatic Male Breast” [40].

ACR Appropriateness Criteria®

8

Evaluation of Nipple Discharge

Digital Breast Tomosynthesis Diagnostic
Although there is no relevant literature to support the use of DBT alone in assessing nipple discharge,
mammography is useful for evaluating pathologic nipple discharge in male and female patients in this age group[30]. Early studies with DBT demonstrate promise is assessing the symptomatic breast [35,36].
US Breast
The sensitivity of US for palpable or nonpalpable breast cancer is higher than that of mammography (95.7% versus
60.9%) for women 30 to 39 years of age [63,64]. Hence, US may be useful as the initial imaging modality, withmammography added when necessary.
Ductography
Ductography may demonstrate small lesions and localize the duct responsible for the nipple discharge. Ductography
is minimally invasive, may be uncomfortable, and can be time-consuming. The procedure is technically challenging
with 10% to 15% of cases resulting in inadequate or incomplete results [41,42]. The discharge must be present on
the day of ductography so that a cannula can be placed in the appropriate duct. Failure to cannulate the discharging
duct may lead to a false negative [43]. Ductography is not recommended in lactating women or patients with active
mastitis. Known hypersensitivity to iodinated contrast agents is a relative contraindication. Findings on ductographysuggestive of malignant or papillary lesions include intraductal filling defect, partial or complete obstruction of aduct, duct expansion or distortion, and duct wall irregularity [1].
In patients with pathologic nipple discharge and a negative mammogram and US, Morrogh et al [44] reported the
PPV and NPV of ductography for the detection of cancer and high-risk lesions to be 19% and 63%, respectively. In
the setting of negative standard evaluations, ductography localized 76% of otherwise occult malignant/high-risk
lesions and 91% of benign lesions [39]. When the standard evaluation is positive, ductography facilitatedpreoperative localization of the causative lesion in 78% of cases [39]. For detection of cancer in patients withpathologic nipple discharge, 2 studies showed the sensitivity, specificity, PPV, and NPV of ductography to be 75%
to 100%, 6% to 49%, 16% to 18%, and 93% to 100%, respectively [16,23]. For detection of high-risk lesions,
Adepoju et al [16] reported the sensitivity, specificity, PPV, and NPV of ductography to be 75%, 53%, 22%, and92%, respectively.
Ductography is more sensitive than mammography and US but has a lower specificity than both modalities. A
negative ductogram does not reliably exclude an underlying cancer or high-risk lesion, with the false-negative ratereported to be as high as 20% to 30% [44]. As such, the primary value of ductography is to localize intraductal
lesions and assist in surgery [45]. A study found that patients who underwent ductography-guided operations or any
other surgical procedure with image guidance of the lesion were significantly more likely to have a specificunderlying lesion identified than patients who underwent central duct excision alone [23,42].
At this time, there is no relevant literature available for use of ductography for evaluation of a male patient withnipple discharge.
MRI Breast
The sensitivity of breast MRI for detecting invasive breast cancer is high, ranging from 93% to 100%. Breast MRI
specificity ranges from 37% to 97% and relies on analysis of a lesion’s morphology and enhancement kinetics [46].
Malignant lesions may appear as a mass or nonmass enhancement in a ductal or segmental distribution on MRI.
Noncontrast MRI, although useful for evaluation of implant integrity, has little value in the detection of malignant
or high-risk lesions in patients with nipple discharge [47].
Contrast-enhanced breast MRI has a high sensitivity for detecting benign papillary lesions as well as in situ andinvasive carcinoma [3]. Furthermore, MRI allows for the identification of index lesions in peripheral ducts that are
beyond the area normally encompassed by terminal duct excision, ductography, or targeted US [44]. Index orsynchronous lesions found on MRI alone can be percutaneously biopsied with MRI guidance to allow for singlestage definitive surgical management (if malignant) or potentially to avoid unnecessary surgical excision for somebenign lesions.
In general, MRI should be considered in cases in which mammography and US have failed to identify an underlying
cause of pathologic nipple discharge [3,44,48-50]. The sensitivities of breast MRI for detecting the cause of thepathologic nipple discharge are 86% to 100% for invasive cancer and 40% to 100% for noninvasive disease[3,12,44,49,51,52]. Bahl et al [52] reported the sensitivity, specificity, PPV, and NPV of MRI for detecting
malignancy in patients with pathologic nipple discharge to be 100%, 68%, 37%, and 100%, respectively. Several
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studies have shown that MRI has a higher sensitivity and specificity than US and ductography for lesion detection
and may be an alternative to ductography [12,32,48,49]. However, a study by van Gelder et al [51] asserted that
MRI has limited added value in patients with unilateral bloody nipple discharge who showed no signs of amalignancy on conventional diagnostic examinations, because malignancy was demonstrated in <2% of their cases.
At this time, there is no relevant literature available for use of MRI for evaluation of a male patient with nipple
discharge.
FDG-PET Breast DedicatedHigh-resolution cameras specifically designed for breast imaging have improved detection of small and noninvasive
carcinomas. However, specific research evaluating women with nipple discharge is lacking [41,53]. Currently, there
is no relevant literature for the use of FDG-PET in the evaluation of a male or female patient with pathologic nipple
discharge.
Image-Guided Core Biopsy Breast
Previous studies showed that mammography, US, and ductography are unreliable in predicting histology in patientswith pathologic nipple discharge [17,23,44], which underscores the importance of histological diagnosis of lesions
identified on imaging. The biopsy procedures may be guided by stereotactic mammography, US, ductography, or
MRI, depending on the imaging modality that best depicts the lesion. CNB is preferred over FNA because the larger
gauge needle improves sampling [54,55]. Placement of a tissue marker at the end of the biopsy allows for needle
localization and excision if the biopsied lesion yields malignant or high-risk histology. Vacuum-assisted CNB is
particularly useful in assuring complete sampling of small intraductal papillary lesions [24]. Although biopsy is adiagnostic procedure, the process of removing enough of the intraductal papillary lesion during vacuum-assisted
core biopsy may be therapeutic and will lead to permanent cessation of nipple discharge in 90% to 97.2% of patients[24,56]. However, Reiner et al [57] cautioned that ductography-guided 11-gauge vacuum-assisted stereotactic
biopsy should not be used as a substitute for surgical duct excision in cases of pathologic nipple discharge withabnormalities on ductography because of the high underestimation rate (50%) for high-risk lesions and DCIS, falsenegative rate (7%), and histopathological detection of lesion remnants in every case.
Papillomas are historically considered high-risk lesions, with reported rates of upgrade to malignancy between 3%
and 14% [58,59]. The management of papillomas diagnosed on CNB is controversial and varies by institution [60].
Because papillomas diagnosed on CNB are often excised, excisional biopsy instead of CNB may be useful when apapillary lesion is anticipated based on imaging findings. A recent study suggests that patients with nonbloody
pathologic nipple discharge, a benign CNB, or normal imaging (cancer risk <2%) may be considered fornonoperative management if they do not have risk factors such as prior ipsilateral breast cancer, BRCA mutation,
or atypia on CNB [61].
According to the surgical literature, major duct excision remains the reference standard to exclude malignancy inpatients with unremarkable imaging, when even a negative ductogram (NPV 63%–82%) [17,30] or MRI (NPV
87%–100%) [44,52] does not exclude an underlying cancer or high-risk lesion [13,39,44].
In addition, US does not reliably distinguish between benign and malignant small intraductal lesions [9]. Therefore,
the decision to perform percutaneous biopsy versus major duct excision should involve the patient and their healthcare provider.
Image-guided CNB is equally useful in male patients for obtaining tissue diagnosis and assisting in patientmanagement [40]. Image-guided CNB is not indicated as the initial examination to evaluate pathological nipple
discharge.
Image-Guided Fine Needle Aspiration Breast
Once a suspicious lesion that is likely responsible for the pathologic nipple discharge is identified on imaging,
image-guided FNA or CNB can be performed for histological diagnosis. Although some institutions demonstrate
good results using FNA, larger series have shown that core biopsy is superior to FNA in terms of sensitivity,
specificity, and correct histological grading of a lesion [54,55]. Image-guided FNA is not indicated as the initial
examination to evaluate pathological nipple discharge.
Sestamibi MBI
There is no relevant literature to support the use of MBI in the evaluation of a male or female patient with pathologic
nipple discharge.
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Variant 4: Adult male younger than 30 years of age. Pathologic nipple discharge. Initial imaging.
For male patients presenting with nipple discharge, the incidence of cancer is high (23%–57%) [19,65]. Given thehigh pretest probability, imaging is appropriate for male patients <30 years of age.
Mammography Diagnostic
Diagnostic mammography is useful in distinguishing malignancy from benign breast conditions in symptomatic
male patients with nipple discharge [1,2]. Please refer to the ACR Appropriateness Criteria® topic on “Evaluationof the Symptomatic Male Breast” [40] for additional details.
Digital Breast Tomosynthesis Diagnostic
Although there is no relevant literature to support the use of DBT alone in assessing nipple discharge,
mammography is useful for evaluating pathologic nipple discharge in male and female patients in this age group[30]. Early studies with DBT demonstrate promise in assessing the symptomatic breast [35,36].
US Breast
In conjunction with mammography or DBT, US is often useful in assisting with management decisions and to
facilitate US core biopsy [3]. Please refer to the ACR Appropriateness Criteria® topic on “Evaluation of theSymptomatic Male Breast” [40] for additional details.
Ductography
There is no relevant literature to support the use of ductography for the evaluation of male patients with nipple
discharge.
MRI Breast
There is no relevant literature to support the use of MRI for the evaluation of male patients with nipple discharge.
FDG-PET Breast Dedicated
There is no relevant literature to support the use of FDG-PET for the evaluation of male patients with nipple
discharge.
Image-guided Core Biopsy Breast
There is no relevant literature to support the use of core biopsy for the evaluation of male patients with nipple
discharge. However, if an imaging abnormality is identified, US may be used to direct biopsy.
Image-Guided Fine Needle Aspiration Breast
There is no relevant literature to support the use of image-guided FNA for the evaluation of male patients withnipple discharge.
Sestamibi MBI
There is no relevant literature to support the use of MBI for the evaluation of male patients with nipple discharge.
Variant 5: Adult female younger than 30 years of age. Pathologic nipple discharge. Initial imaging.
The probability of a woman developing breast cancer over the next decade increases with age; the risk is 1 in 1,681
at 20 years of age, 1 in 232 at 30 years of age, and 1 in 69 at 40 years of age [62]. Breast cancer is rare in women<30 years of age, with the exception of those with a genetic predisposition or prior mantle radiation to the chest. In
a study by Seltzer et al [66] on the significance of age in patients with nipple discharge, malignancy was found in
1 of 10 patients <30 years of age. However, caution should be exercised interpreting these results given a very small
sample size and the possible inclusion of high-risk patients.
Mammography Diagnostic
Most breast lesions in young women are not visualized on mammography [67,68] because of the low incidence ofbreast cancer (0.4% or lower) in women <30 years of age. US is most useful for initial imaging in this population;
however, diagnostic mammography may be useful when US shows a suspicious finding.
Digital Breast Tomosynthesis Diagnostic
Although there is no relevant literature to support the use of DBT alone in assessing nipple discharge,
mammography is useful for evaluating pathologic nipple discharge in male and female patients in this age group[30]. Early studies with DBT demonstrate promise in assessing the symptomatic breast [35,36].

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US Breast
Yue et al [69] studied 955 women <25 years of age who presented with breast symptoms including palpable mass,pain, and nipple discharge. US was performed in 692 patients and was normal/negative in 671 patients andindeterminate in 21 patients. No cancer was found in this group via biopsy or clinical follow-up. However, it isunknown how many of these patients had pathologic or physiologic discharge.
Ductography
There is no relevant literature to support the use of ductography in women <30 years of age with symptoms ofpathologic nipple discharge.
MRI Breast
There is no relevant literature to support the use of MRI in women <30 years of age with symptoms of pathologic
nipple discharge.
FDG-PET Breast Dedicated
There is no relevant literature to support the use of FDG-PET in women <30 years of age with symptoms ofpathologic nipple discharge.
Image-guided Core Biopsy Breast
There is no relevant literature to support the use of image-guided core biopsy in women <30 years of age withsymptoms of pathologic nipple discharge. However, if an imaging abnormality is identified, US may be used todirect biopsy.
Image-Guided Fine Needle Aspiration Breast
There is no relevant literature to support the use of image-guided FNA in women <30 years of age with symptoms
of pathologic nipple discharge.
Sestamibi MBI
There is no relevant literature to support the use of MBI in women <30 years of age with symptoms of pathologic
nipple discharge.
Variant 6: Adult transfeminine (male-to-female) patient 30 years of age or older. Pathologic nipple discharge.
Initial imaging.
In cisgender men presenting with nipple discharge, the incidence of cancer is high (23%–57%) [19,65]. Therefore,
given the high pretest probability, imaging is appropriate in transgender women ≥30 years of age. Transgenderwomen who are taking gender-affirming hormone therapy are at an increased risk for breast cancer [70].
Endogenous or exogenous exposure to estrogen results in an increase in the lobules, ducts, and acini identical to thenatal female breast. As such, imaging maybe be considered regardless of the duration of hormone therapy.
Mammography Diagnostic
Diagnostic mammography is useful in distinguishing malignancy from benign breast conditions in symptomatictransfeminine patients [1,2]. Please refer to the ACR Appropriateness Criteria® topic on “Evaluation of theSymptomatic Male Breast” [40] for additional details.
Digital Breast Tomosynthesis Diagnostic
Although there is no relevant literature to support the use of DBT alone in assessing nipple discharge,
mammography is useful for evaluating pathologic nipple discharge in male and female patients in this age group[30]. Early studies with DBT demonstrate promise is assessing the symptomatic breast [35,36].
US Breast
In conjunction with mammography or DBT, US is often useful in assisting with management decisions and to
facilitate US core biopsy [3]. Please refer to the ACR Appropriateness Criteria® topic on “Evaluation of theSymptomatic Male Breast” [40] for additional details.
Ductography
There is no relevant literature to support the use of ductography for evaluation of transgender patients with nipple
discharge.
MRI Breast
There is no relevant literature to support the use of MRI for evaluation of transgender patients with nipple discharge.
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Evaluation of Nipple DischargeFDG-PET Breast Dedicated
There is no relevant literature to support the use of FDG-PET for evaluation of transgender patients with nipple
discharge.
Image-guided Core Biopsy Breast
There is no relevant literature to support the use of image-guided core biopsy for evaluation of transgender patientswith nipple discharge. However, if an imaging abnormality is identified, US may be used to direct biopsy.
Image-Guided Fine Needle Aspiration Breast
There is no relevant literature to support the use of image-guided FNA for evaluation of transgender patients withnipple discharge.
Sestamibi MBI
There is no relevant literature to support the use of MBI for evaluation of transgender patients with nipple discharge.
Variant 7: Adult transfeminine (male-to-female) patient younger than 30 years of age. Pathologic nipple
discharge. Initial imaging.
In cisgender males presenting with nipple discharge, the incidence of cancer is high (23%–57%) [19,65]. Therefore,
given the high pretest probability, imaging is appropriate in transgender women <30 years of age. Transgenderwomen who are taking gender-affirming hormone therapy are at an increased risk for breast cancer [70].
Endogenous or exogenous exposure to estrogen results in an increase in the lobules, ducts, and acini identical to thenatal female breast. As such, imaging maybe be considered regardless of the duration of hormone therapy.
Mammography Diagnostic
Diagnostic mammography is useful in distinguishing malignancy from benign breast conditions in symptomatictransfeminine patients with nipple discharge [1,2]. Please refer to the ACR Appropriateness Criteria® topic on“Evaluation of the Symptomatic Male Breast” [40] for additional details.
Digital Breast Tomosynthesis Diagnostic
Although there is no relevant literature to support the use of DBT alone in assessing nipple discharge,
mammography is useful for evaluating pathologic nipple discharge in male and female patients in this age group[30]. Early studies with DBT demonstrate promise is assessing the symptomatic breast [35,36].
US Breast
In conjunction with mammography or DBT, US is often useful in assisting with management decisions and to
facilitate US core biopsy [3]. Please refer to the ACR Appropriateness Criteria® topic on “Evaluation of theSymptomatic Male Breast” [40] for additional details.
Ductography
There is no relevant literature to support the use of ductography for evaluation of transgender patients with nipple
discharge.
MRI Breast
There is no relevant literature to support the use of MRI for evaluation of transgender patients with nipple discharge.
FDG-PET Breast Dedicated
There is no relevant literature to support the use of FDG-PET for evaluation of transgender patients with nipple
discharge.
Image-guided Core Biopsy Breast
There is no relevant literature to support the use of core biopsy for evaluation of transgender patients with nipple
discharge. However, if an imaging abnormality is identified, US may be used to direct biopsy.
Image-Guided Fine Needle Aspiration Breast
There is no relevant literature to support the use of image-guided FNA for evaluation of transgender patients withnipple discharge.
Sestamibi MBI
There is no relevant literature to support the use of MBI for evaluation of transgender patients with nipple discharge.

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Summary of Recommendations• Variant1: Diagnostic imaging is usually not appropriate for assessing physiologic nipple discharge in adultfemale, male, transfeminine (male-to-female), or transmasculine (female-to-male) patients.
•

Variant 2: DBT or diagnostic mammography is usually appropriate for the initial imaging of pathologic nipple
discharge in adult male or female patients 40 years of age or older. These procedures are equivalent alternatives(ie, only one procedure will be ordered to provide the clinical information to effectively manage the patient’scare). Breast US is complementary to DBT and diagnostic mammography and may be performed during thesame patient encounter or in close approximation to one another to better characterize the disease process.

•

Variant 3: DBT or diagnostic mammography is usually appropriate for the initial imaging of pathologic nipple
discharge in adult male or female patients 30 to 39 years of age. These procedures are equivalent alternatives(ie, only one procedure will be ordered to provide the clinical information to effectively manage the patient’scare). Breast US is complementary to DBT and diagnostic mammography and may be performed during thesame patient encounter or in close approximation to one another to better characterize the disease process.

•

Variant 4: DBT or diagnostic mammography is usually appropriate for the initial imaging of pathologic nipple
discharge in adult male patients younger than 30 years of age. These procedures are equivalent alternatives (ie,only one procedure will be ordered to provide the clinical information to effectively manage the patient’s care).
Breast US is complementary to DBT and diagnostic mammography and may be performed during the same
patient encounter or in close approximation to one another to better characterize the disease process.

•

Variant 5: Breast US is usually appropriate as the initial imaging of pathologic discharge in adult female
patients younger than 30 years of age.

•

Variant 6: DBT or diagnostic mammography is usually appropriate for the initial imaging of pathologic nipple
discharge in transfeminine (male-to-female) patients 30 years of age or older. These procedures are equivalentalternatives (ie, only one procedure will be ordered to provide the clinical information to effectively manage
the patient’s care). Breast US is complementary to DBT and diagnostic mammography and may be performed
during the same patient encounter or in close approximation to one another to better characterize the disease
process.

•

Variant 7: DBT or diagnostic mammography is usually appropriate for the initial imaging of pathologic nipple
discharge in adult transfeminine (male-to-female) patients younger than 30 years of age. These procedures areequivalent alternatives (ie, only one procedure will be ordered to provide the clinical information to effectively
manage the patient’s care). Breast US is complementary to DBT and diagnostic mammography and may be
performed during the same patient encounter or in close approximation to one another to better characterize thedisease process.

Supporting Documents
The evidence table, literature search, and appendix for this topic are available at https://acsearch.acr.org/list. The
appendix includes the strength of evidence assessment and the final rating round tabulations for each
recommendation.
For additional information on the Appropriateness Criteria methodology and other supporting documents go towww.acr.org/ac.

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Appropriateness Category Names and Definitions
Appropriateness Category Name
Usually Appropriate

May Be Appropriate

May Be Appropriate(Disagreement)

Usually Not Appropriate

AppropriatenessRatingAppropriateness Category Definition

7, 8, or 9

The imaging procedure or treatment is indicated in thespecified clinical scenarios at a favorable risk-benefit
ratio for patients.

4, 5, or 6

The imaging procedure or treatment may be indicatedin the specified clinical scenarios as an alternative toimaging procedures or treatments with a morefavorable risk-benefit ratio, or the risk-benefit ratio forpatients is equivocal.

5

The individual ratings are too dispersed from the panel
median. The different label provides transparency
regarding the panel’s recommendation. “May beappropriate” is the rating category and a rating of 5 is
assigned.

1, 2, or 3

The imaging procedure or treatment is unlikely to be
indicated in the specified clinical scenarios, or therisk-benefit ratio for patients is likely to be
unfavorable.

Relative Radiation Level Information
Potential adverse health effects associated with radiation exposure are an important factor to consider whenselecting the appropriate imaging procedure. Because there is a wide range of radiation exposures associated withdifferent diagnostic procedures, a relative radiation level (RRL) indication has been included for each imaging
examination. The RRLs are based on effective dose, which is a radiation dose quantity that is used to estimate
population total radiation risk associated with an imaging procedure. Patients in the pediatric age group are atinherently higher risk from exposure, because of both organ sensitivity and longer life expectancy (relevant to thelong latency that appears to accompany radiation exposure). For these reasons, the RRL dose estimate ranges forpediatric examinations are lower as compared with those specified for adults (see Table below). Additional
information regarding radiation dose assessment for imaging examinations can be found in the ACR
Appropriateness Criteria® Radiation Dose Assessment Introduction document [71].
Relative Radiation Level Designations
Adult Effective Dose Estimate
Range

Pediatric Effective Dose Estimate
Range

0 mSv

0 mSv

☢☢

<0.1 mSv<0.03 mSv

0.1-1 mSv

0.03-0.3 mSv☢☢☢☢

1-10 mSv

0.3-3 mSv

10-30 mSv

3-10 mSv

30-100 mSv

10-30 mSv

Relative Radiation Level*
O

☢

☢☢☢

☢☢☢☢☢

*RRL assignments for some of the examinations cannot be made, because the actual patient doses in these procedures varyas a function of a number of factors (eg, region of the body exposed to ionizing radiation, the imaging guidance that is used).
The RRLs for these examinations are designated as “Varies.”

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The ACR Committee on Appropriateness Criteria and its expert panels have developed criteria for determining appropriate imaging examinations fordiagnosis and treatment of specified medical condition(s). These criteria are intended to guide radiologists, radiation oncologists and referring physicians inmaking decisions regarding radiologic imaging and treatment. Generally, the complexity and severity of a patient’s clinical condition should dictate theselection of appropriate imaging procedures or treatments. Only those examinations generally used for evaluation of the patient’s condition are ranked.
Other imaging studies necessary to evaluate other co-existent diseases or other medical consequences of this condition are not considered in this document.
The availability of equipment or personnel may influence the selection of appropriate imaging procedures or treatments. Imaging techniques classified as
investigational by the FDA have not been considered in developing these criteria; however, study of new equipment and applications should be encouraged.
The ultimate decision regarding the appropriateness of any specific radiologic examination or treatment must be made by the referring physician andradiologist in light of all the circumstances presented in an individual examination.

ACR Appropriateness Criteria®

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Evaluation of Nipple Discharge