What is the appropriate workup for a patient presenting with nipple discharge?

Workup for Nipple Discharge

The appropriate workup for nipple discharge should begin with determining if the discharge is physiologic or pathologic, with ultrasound being the first-line imaging for pathologic discharge in women under 30, and mammography/digital breast tomosynthesis (DBT) being first-line for women over 40 and men over 25. 1

Characterization of Nipple Discharge

• Physiologic discharge is typically bilateral, from multiple ducts, non-spontaneous (requires manipulation), and white, green, yellow, or clear in color 2
• Pathologic discharge is characterized by spontaneous occurrence, unilateral presentation, single duct involvement, and bloody, serous, or serosanguineous appearance 2, 3
• No imaging workup is needed for physiologic discharge if routine screening is up to date 1

Initial Imaging Workup for Pathologic Discharge by Age and Gender

Women under 30 years:

• Ultrasound should be the initial examination (rated 9/9 for appropriateness) 1
• Mammography or DBT may be complementary (rated 5/9) only when:
  • Initial ultrasound shows suspicious findings
  • Patient has BRCA mutation or other genetic predisposition to breast cancer 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
• If mammography is chosen first, ultrasound is complementary 1

Women 40 years and older:

• Diagnostic mammography or DBT should be the initial examination (rated 9/9) 1
• Ultrasound is typically performed as a complementary examination 1

Men under 30 years:

• For men under 25: Ultrasound should be the initial examination (rated 9/9), with mammography added as indicated 1
• For men 25-30: Mammography or DBT should be performed as the initial study (rated 8/9) given the high incidence of cancer in men with pathologic nipple discharge 1

Men 30 years and older:

• Mammography or DBT should be the initial examination (rated 9/9) 1
• Ultrasound is complementary to mammography in men 1

Secondary Imaging Considerations

• MRI breast with contrast may be considered when:

  • Initial mammography and ultrasound are negative but clinical suspicion remains high 1
  • MRI has higher positive and negative predictive values than ductography for detecting high-risk lesions and cancers 1
  • Note: MRI is rated as "usually not appropriate" (1/9) as an initial examination 1

• Ductography (galactography):

  • Historically used for identifying and localizing intraductal lesions 1
  • Can detect abnormalities in 14-86% of cases with pathologic discharge 1
  • Currently rated as "usually not appropriate" (1/9) as an initial examination 1
  • May be useful for preoperative wire localization once a suspicious target lesion is identified 1

Biopsy Considerations

• Image-guided core biopsy should be performed for suspicious masses detected on imaging 1
• In cases with persistent pathologic discharge and negative imaging, surgical duct excision may be considered 1, 4
• Surgical duct excision may be simplified by preoperative ductal injection of methylene blue 5

Risk Factors and Malignancy Rates

• Underlying malignancy can be found in 5-21% of patients with pathologic nipple discharge who undergo biopsy 1
• Risk for malignancy increases with age: 3% in patients ≤40 years, 10% in patients 40-60 years, and 32% in those >60 years 1
• Men with nipple discharge have a higher risk of malignancy (23-57%) compared to women (16%) 1
• Factors increasing likelihood of cancer include:
  • Discharge that is watery, bloody, pink, or yellow
  • Accompanying palpable mass
  • Unilateral discharge from a single duct
  • Patient age over 50 years 6

Common Pitfalls to Avoid

• Failure to distinguish between physiologic and pathologic discharge, leading to unnecessary imaging 2, 7
• Missing posterior lesions that may not be identified on ductography (>3cm beyond nipple) 1
• Underestimating the significance of nipple discharge in men, which has a higher association with malignancy 1
• Relying solely on clinical examination without appropriate imaging when pathologic discharge is present 1