What labs should be ordered for a patient presenting with nipple drainage?

Diagnostic Approach to Nipple Discharge

For patients presenting with nipple discharge, the diagnostic approach should first determine whether the discharge is physiologic or pathologic, as imaging is not indicated for physiologic discharge but is necessary for pathologic discharge based on age-specific protocols. 1, 2

Characterization of Nipple Discharge

Physiologic Discharge

• Bilateral, from multiple ducts, white/green/yellow in color, occurs only when provoked, and has no association with breast cancer 3
• No imaging workup is needed if routine screening is up to date 2, 3

Pathologic Discharge

• Spontaneous, unilateral, single duct involvement, and bloody/serous/serosanguineous in appearance 2, 4
• Associated with underlying malignancy in 3-29% of cases, with risk increasing with age 3
• Requires imaging evaluation based on age and gender 1

Imaging Workup Algorithm by Age and Gender

Women < 30 years

• Ultrasound should be the initial examination (rated 9/9 for appropriateness) 2
• Mammography/DBT should be added only when ultrasound shows suspicious findings or if the patient has high risk factors 1

Women 30-39 years

• Either mammography/DBT (rated 9/9) or ultrasound (rated 9/9) can be used as initial examination based on institutional preference 1, 2
• If mammography is chosen, ultrasound should be complementary 1

Women ≥ 40 years

• Diagnostic mammography or DBT should be the initial examination (rated 9/9) 1, 2
• Ultrasound is usually added as a complementary examination 1
• Mammography should be repeated if prior mammography was performed >6 months ago 1

Men < 25 years

• Ultrasound should be the initial examination (rated 9/9), with mammography added as indicated 2

Men ≥ 25 years

• Mammography/DBT should be performed as the initial study given the high incidence of cancer in men with pathologic nipple discharge (23-57%) 1, 2
• Ultrasound serves as a complementary examination 3

Secondary Imaging and Biopsy Considerations

• When initial standard imaging is negative but clinical suspicion remains high, MRI breast with contrast may be considered 2, 3
• MRI has a sensitivity of up to 96% for detecting underlying pathology 3
• A negative mammogram reduces the risk of carcinoma to 3%, while negative mammogram and ultrasound together reduce the risk to approximately 0% 3
• Image-guided core needle biopsy is preferred over fine-needle aspiration for suspicious lesions detected on imaging 3

Common Pathologies

• Benign intraductal papilloma is the most common cause of pathologic nipple discharge (35-48%) 3
• Ductal ectasia is the second most common cause (17-36%) 3
• Malignancy risk increases with:
  • Age: 3% in patients ≤40 years, 10% in patients 40-60 years, and 32% in those >60 years 2
  • Discharge characteristics: higher risk with serous, serosanguineous, sanguineous, or watery discharge 4
  • Gender: men have higher risk (23-57%) compared to women (16%) 2, 3

Clinical Pitfalls

• False-positive ultrasound results may occur due to volume averaging with ductal wall in tortuous ducts, intraductal and periductal fibrosis, or adherent blood clots 3
• Ductography, while historically used, has a technical failure rate of 10-15% and is increasingly being replaced by MRI 3
• Among patients with cancer presenting with nipple discharge, 11.9% had no palpable mass, 16.4% had negative cytologic findings, and 10.4% had a negative mammogram 4