A patient with 6 months of nipple ulceration, crusting, oozing, and redness and negative ultrasound (US) and mammography results for bilateral breasts, what is the most appropriate next step?

Nipple Biopsy is the Most Appropriate Next Step

A patient presenting with 6 months of persistent nipple ulceration, crusting, oozing, and redness with negative imaging requires nipple biopsy to exclude Paget's disease of the breast, regardless of negative mammography and ultrasound results.

Clinical Reasoning

This presentation is highly suspicious for Paget's disease of the breast, which characteristically presents with:

• Nipple excoriation, scaling, and eczema 1
• Ulceration and bleeding of the nipple 2
• Persistent symptoms lasting months 2
• Frequently occult on mammography - a negative mammogram does not exclude Paget's disease 1

The 6-month duration of symptoms eliminates simple dermatologic conditions and demands tissue diagnosis.

Why Nipple Biopsy (Option A) is Correct

The NCCN explicitly states that when skin changes of the nipple are present with normal imaging (BI-RADS 1-3), punch biopsy of the skin or nipple biopsy should be performed 1. This is the definitive diagnostic standard for Paget's disease 2.

• Paget's disease is a rare but serious malignancy affecting the nipple-areolar complex, associated with underlying in situ or invasive carcinoma in most cases 3, 2
• Pure Paget's disease is frequently occult on mammography 1
• Surgical biopsy is the diagnostic standard and must be performed to confirm or exclude the diagnosis 2
• The malignancy risk with persistent nipple changes warrants tissue diagnosis even with negative imaging 1

Why Other Options are Inappropriate

Option B (Dermatology Consult): While nipple eczema can mimic Paget's disease 4, the diagnosis of Paget's disease is often delayed due to confusion with dermatologic conditions 1. After 6 months of persistent symptoms with negative imaging, tissue diagnosis takes priority over dermatologic management to exclude malignancy 1.

Option C (Steroid Ointment): Empiric steroid treatment without tissue diagnosis is dangerous when Paget's disease remains in the differential. The NCCN guidelines do not support empiric treatment of persistent nipple skin changes without histologic confirmation 1.

Option D (Follow-up in 2 months): An 8-month delay (6 months already elapsed + 2 more months) in diagnosing potential breast malignancy is unacceptable. The NCCN recommends biopsy after imaging, not prolonged observation 1.

Critical Management Algorithm

1. Immediate nipple/skin punch biopsy to establish histologic diagnosis 1
2. If biopsy shows Paget's cells, proceed to breast MRI to define extent of disease 3
3. If biopsy is benign, reassess clinical-pathologic correlation and consider repeat biopsy or breast MRI if clinical suspicion remains high 1
4. Antibiotics may be considered if infection is suspected, but should not delay diagnostic biopsy 1

Common Pitfalls to Avoid

• Never dismiss persistent nipple skin changes as benign dermatologic conditions without tissue diagnosis - Paget's disease diagnosis is frequently delayed due to this error 1, 2
• Never rely on negative mammography alone - Paget's disease is often mammographically occult 1, 3
• Never treat empirically with steroids without excluding malignancy first, as this can mask and delay cancer diagnosis 1
• Exfoliative cytology has limited utility - a negative finding does not exclude Paget's disease 2