What is the next step in workup for a 35-year-old female with left-sided nipple discharge, normal mammogram, breast ultrasound, and breast MRI, and normal Thyroid-Stimulating Hormone (TSH), Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), and prolactin levels?

Next Step: Ductography or Surgical Duct Excision

Given that this 35-year-old woman has pathologic nipple discharge with completely negative imaging (mammogram, ultrasound, and MRI) and normal laboratory workup, the next step is either ductography or proceeding directly to surgical major duct excision, with ductography being the preferred initial approach if the discharge is still present and can be cannulated. 1

Rationale for This Recommendation

Why Further Workup is Necessary

• Despite negative imaging, pathologic nipple discharge requires definitive evaluation because up to 20% of lesions associated with pathologic discharge are located >3 cm beyond the nipple and may not be detected even by MRI. 1

• The ACR Appropriateness Criteria specifically states that when mammography, ultrasound, and MRI are all negative in patients with pathologic nipple discharge, clinicians may proceed to major duct excision, but thorough preoperative imaging evaluation including ductography is beneficial. 1

Ductography as the Next Step

• Ductography can detect underlying abnormalities in 14% to 86% of cases when conventional imaging is negative. 1

• The procedure identifies and localizes intraductal lesions by cannulating the discharging duct and injecting contrast medium. 1

• Ductographic findings suggestive of malignant or papillary lesions include intraductal filling defects, partial or complete duct obstruction, duct expansion or distortion, and duct wall irregularity. 1

• Ductography is particularly valuable because it can guide surgical intervention with methylene blue dye injection immediately preoperatively, simplifying the surgical procedure. 2

Alternative: Direct Surgical Excision

• If ductography cannot be performed (discharge not present on procedure day, technical failure, or patient preference), proceeding directly to major duct excision is appropriate. 1

• Major duct excision without preoperative ductography has limitations: pathologists may not always identify a discrete causative lesion, and the procedure may be undesirable for a woman of childbearing age. 1

• Without prior ductography, central duct excision may result in incomplete removal of abnormal ductal tissue or understaging of disease extent. 3

Important Clinical Considerations

Confirming Pathologic Discharge Characteristics

Before proceeding, verify that the discharge is truly pathologic:

• Pathologic discharge is spontaneous, unilateral, from a single duct, and bloody, serous, or serosanguineous in appearance. 4
• The patient's left-sided nipple discharge meets the unilateral criterion. 4

Technical Aspects of Ductography

• The discharge must be present on the day of ductography for successful cannulation of the appropriate duct. 1, 3
• Technical failure occurs in 10% to 15% of cases due to inadequate or incomplete results. 1
• If extravasation occurs, ductography should be rescheduled for 7-14 days later. 3

Malignancy Risk in This Age Group

• The risk of breast cancer is relatively low (1.4%) for women in their fourth decade, but pathologic nipple discharge increases this risk. 1
• One study found no malignancy among patients 30-39 years of age with pathologic nipple discharge and no palpable mass, though another study of 19 patients <40 years found two cancers. 1

Common Pitfalls to Avoid

• Do not assume negative MRI excludes all pathology - MRI has limited added value in some studies, and small intraductal lesions may still be missed. 1

• Failure to cannulate the discharging duct during ductography leads to false-negative results - ensure the procedure is performed when discharge is actively present. 1

• Avoid "blind" major duct excision without attempting ductography first when technically feasible, as this may result in incomplete excision or understaging. 1, 3

Surgical Referral

• Regardless of whether ductography is performed, this patient requires referral to a breast surgeon for definitive treatment planning. 5

• The surgeon can determine whether ductography should be attempted first or whether to proceed directly to major duct excision based on clinical factors and patient preference. 1