NIPPLE DISCHARGE

ADULT FEMALE, PHYSIOLOGIC NIPPLE DISCHARGE:

1.   Digital Mammography:

2.  If clinical findings are consistent with physiologic nipple discharge, routine screening mammography for patients 40 years of age or older is recommended. No further radiologic investigation is required and diagnostic breast imaging is unnecessary (3).

Remarks: Physiologic nipple discharge tends to occur with compression. Studies have proposed being mostly related to benign causes, with no association with insitu or invasive carcinoma (19-21).

Strong recommendation

High-Quality Evidence (studies well-designed and account for most common biases) (19-21).

3.  Image-guided Core Biopsy/ Fine Needle Aspiration:

We recommend against the use of image guided core biopsy or fine needle aspiration in these cases.

Strong recommendation

High-Quality Evidence (studies well-designed and account for most common biases) (20, 21).

ADULT FEMALE, 40 YEARS OF AGE OR OLDER, PATHOLOGIC NIPPLE DISCHARGE:

1.  Digital Mammography:

Mammography is the initial imaging modality in this age group. Both breasts should be imaged in two views; craniocaudal and mediolateral oblique views enabling the entire breast to be completely screened for any additional lesions. Additional mammographic views with spot compression and magnification are required for better evaluation of the retroareolar region when necessary (6).

Remarks: Despite its low sensitivity (15-68%) and positive predictive value (PPV) 42% for detection of malignancy as the cause of nipple discharge, mammography still plays an important role in breast imaging because of its high specificity (38-98%) and high negative predictive value (NPV) 90% (19-22).

Strong recommendation

High-Quality Evidence (studies well-designed and account for most common biases) (19-22).

2.  Digital Breast Tomosynthesis:

It is recommended as an initial diagnostic tool if available. Many studies have proposed the use of DBT in assessing nipple discharge (7). It has also been proven that the sensitivity of DBT is higher than that of mammography with better detection rate and diagnosis of breast cancer.

Remarks: This is possibly due to the reduced risk of obscuration of pathology by the overlapping breast tissues as the reconstructed DBT slices are demonstrated similarly to computed tomography reconstructed slices (5). DBT has the potential to increase workflow efficiency in a symptomatic setting by reducing benign biopsies (23).

Strong recommendation

High-Quality Evidence (studies well-designed and account for common biases) (7,23).

3. Breast ultrasound:

Breast US is recommended as a complementary tool for mammography in initial evaluation and assessing extent of involvement.

US is also an important tool to guide for biopsy and localization for surgical excision.

Remarks: Studies propose a sensitivity of 56%–80%, specificity of 61%–75%, PPV of 29%–39%, and NPV of 90%–91% for US alone in detecting underlying malignancy in patients with pathologic nipple discharge (5,19,23). False-positive results may be attributed to ductal wall volume averaging in a tortuous duct, intraductal/periductal fibrosis, blood clots, or inspissated secretions (24).

Strong recommendation

High-Quality Evidence (review and observational studies well-designed and account for common biases) (19-21, 24-26).

4.  MRI Breast:

MRI is not recommended as initial imaging for patients with pathologic nipple discharge. in patients with pathologic nipple discharge and negative mammography/ ultrasound, MRI is recommended to detect lesions of concern preoperatively. Imaging follow-up can be safely recommended for patients with normal MRI findings, thus avoiding unnecessary surgical duct excision (8).

Remarks: MRI should only be reserved for cases that are occult in mammography and US with failure to identify an underlying cause of pathologic nipple discharge (27,28).

Results shown by many studies with regards to breast MRI in the detection of the cause of pathologic nipple discharge revealed a sensitivity of 86-100% for invasive cancer and 40% to 100% for noninvasive disease (29-32).

Strong recommendation

High-Quality Evidence (systematic review and observational studies well-designed and account for common biases) (27)

5. Contrast enhanced mammography:

With CEM, lesions could be identified according to their density, morphologic as well as enhancement characteristics (9).  It is currently being used for diagnostic purposes especially in dense breasts, preoperative evaluation, assessment of extent of disease and MRI contraindication. Ongoing studies also propose future directions in breast cancer screening (10). It may be considered in patients with pathologic nipple discharge and negative mammography/ ultrasound according to its availability.

Remarks: Recent studies have proposed that the level of radiation exposure from CEM is similar to and within the range of radiation doses that patients are exposed to from other mammography examinations (33).

A study by Fakhry et al., 2022 in role of CEM for evaluation of pathological nipple discharge revealed a higher diagnostic accuracy of 79.3% compared to mammography and ultrasound 76.3% (34).

Conditional recommendation

Moderate-Quality Evidence (observational study) (34).

6. Image-Guided Core Biopsy:

Image-guided core needle biopsy is not recommended for initial evaluation of patients with pathologic nipple discharge.

Biopsy procedures can be guided by stereotactic mammography, contrast enhanced mammography, or US, depending on the imaging modality which best depicts the abnormality detected.

Vacuum-assisted core biopsy (VAB) is useful in complete sampling/ removing of small intraductal papillary lesions which may be therapeutic and can lead to cessation of nipple discharge in 90-97.2% of cases (11).  Surgical major duct excision remains the gold standard for exclusion of malignancy in patients with unremarkable imaging.

Remarks: Core biopsy is preferred over FNA because the larger gauge needle improves sampling (12, 35). Studies have shown reported rates of papillomas upgrade to malignancy between 3% and 14% (36).

Strong recommendation

High-Quality Evidence (randomized controlled clinical trial and observational studies well-designed and account for common biases) (11,26,32,35-37)

7.  Image-Guided Fine Needle Aspiration:

It is not recommended as the initial examination for evaluation of pathologic nipple discharge. Studies have shown that core needle biopsy is superior to FNA regarding accuracy and precise histological grading of breast cancer (12).

Remarks: Breast FNA can be done to assess lesions difficult to access by core biopsy or lymph nodes. Hypocellular cystic and fibrotic lesions, degenerative changes, necrosis and epithelial hyperplasia make evaluating the smear difficult. False negative results are common in special types of carcinomas, like lobular and tubular, and false positive results may be seen with lactation and therapy (38).

Breast FNA is safe, fast, cost effective and almost complication free. However, it mostly doesn't give a definite diagnosis, can't differentiate between atypical ductal hyperplasia and low grade DCIS or between high grade DCIS and invasive cancer. Moreover, its accuracy is influenced by the expertise of the aspirator as well as the reader giving equivocal, false positive and false negative results. This is often due to poor sampling technique, poor tumor localization, small tumor size and nonpalpable breast lesions (39).

Conditional recommendation

Moderate-Quality Evidence (randomized controlled clinical trial, review and observational studies) (12,35,38,39).

 ADULT FEMALE, 30 to 39 YEARS OF AGE, PATHOLOGIC NIPPLE DISCHARGE:

Same guidelines as adult female 40 years or older with the following consideration;

US is recommended as the initial imaging modality in this age group with the addition of mammography when necessary.

Remarks: It has been proven that US has a higher sensitivity of 95.7% than that of mammography 60.9% for the detection of breast cancer in females 30 to 39 years of age (40,41).

However, mammography remains the gold standard owing to its ability to detect microcalcifications, taking into consideration that patients with DCIS commonly present with nipple discharge.

Strong recommendation

High-Quality Evidence (studies well-designed and account for common biases) (40,41).

ADULT FEMALE, YOUNGER THAN 30 YEARS OF AGE, PATHOLOGIC NIPPLE DISCHARGE:

1.  Breast ultrasound:

US is the initial imaging modality of choice in this age group.

Remarks: A study by Yue et al where US was done for 692 of 955 symptomatic females aged <25 years, showed that 21 patients only had indeterminate findings. No cancer was detected in this group after biopsy or clinical follow-up (42).

Strong recommendation

High-Quality Evidence (study well-designed and account for common biases) (42).

2.  Digital Mammography or Digital Breast Tomosynthesis:

Diagnostic mammography or DBT are beneficial if US shows a suspicious finding.

Remarks: DBT demonstrates the true extent of the lesion and exclude contralateral abnormalities particularly in young women with dense breasts (43).

Strong recommendation

High-Quality Evidence (study well-designed and account for common biases) (7,23,43).

3.   Contrast studies (contrast enhanced mammography/MRI):

Not recommended as initial imaging for patients with pathologic nipple discharge.

In women with dense breasts, CEM or contrast MRI should be recommended for proper staging and to exclude multicentricity/bilaterality.

Remarks: CEM provides superior imaging performance compared to standard mammography and is considered a relatively affordable accessible imaging tool with a sensitivity approaching MRI.

Conditional recommendation

Moderate-Quality Evidence (systematic review and observational studies) (44,45).

4.  Image-guided Core Biopsy

If an imaging abnormality is seen, US can be used to guide biopsy.

Remarks: To our knowledge, no relevant evidence in the literature exists for evaluation of pathologic nipple discharge in this age group.

Good practice statement