In a patient with nipple erythema, scaling, ulceration, or persistent discharge, how should Paget disease of the breast be diagnosed, treated, and what complications are expected?

Paget Disease of the Breast: Diagnosis, Treatment, and Complications

Diagnostic Approach

Any patient presenting with nipple erythema, scaling, ulceration, or persistent discharge requires immediate full-thickness surgical biopsy of the nipple-areolar complex to confirm Paget disease, followed by breast MRI to identify the 80-90% of cases with associated underlying breast cancer. 1

Initial Clinical Evaluation

• Perform careful assessment of the nipple-areolar complex specifically looking for eczema, bleeding, ulceration, and itching of the nipple 1
• Do not mistake Paget disease for benign eczema or dermatitis—when in doubt, biopsy immediately rather than treating empirically 1
• A short trial of topical steroids may be considered only if clinical suspicion for Paget disease is low and suspicion for eczema is high, but this should not delay diagnostic evaluation 1

Mandatory Imaging Studies

• Order bilateral diagnostic mammography with or without ultrasound as the first imaging study, regardless of patient age 1
• Critical pitfall: Pure Paget disease can be occult on mammography in up to 50% of cases, and a negative mammogram does not exclude the diagnosis 1, 2

Biopsy Protocol Based on Imaging Results

• If imaging shows BI-RADS 1-3 (negative, benign, or probably benign): Perform punch biopsy of the skin or nipple 1
• If imaging shows BI-RADS 4-5 (suspicious or highly suggestive of malignancy): Perform core needle biopsy (preferred) with or without punch biopsy 1
• The gold standard is full-thickness surgical biopsy of the nipple-areolar complex that includes the epidermis and at least a portion of any clinically involved nipple-areolar complex 1

Post-Biopsy Confirmation Imaging

• Obtain breast MRI immediately after biopsy confirmation to define the full extent of disease and identify any additional occult malignancies 3
• This is critical because 80-90% of Paget disease cases have associated cancer elsewhere in the breast (either DCIS or invasive cancer), which may not be adjacent to the nipple-areolar complex 3, 1, 2

Management of Discordant Results

• If a benign skin biopsy result conflicts with clinical suspicion, immediately reassess clinical and pathologic correlation, consider breast MRI, perform repeat biopsy, and consult with a breast specialist 1

Treatment Algorithm

Breast-conserving surgery with complete nipple-areolar complex excision plus whole-breast radiation therapy achieves local control and survival comparable to mastectomy and is the recommended treatment approach. 3

Surgical Management for Paget Disease Without Associated Cancer

• Remove the entire nipple-areolar complex with negative margins of underlying breast tissue 3
• Follow with mandatory whole-breast radiation therapy 3
• Consider a radiation boost to the site of the resected nipple-areolar complex 3

Surgical Management for Paget Disease With Associated Cancer

• Remove the entire nipple-areolar complex with negative margins 3
• The nipple-areolar complex and peripheral cancer do not need to be removed in continuity or through a single incision 3
• Perform axillary surgery according to standard staging guidelines if underlying invasive cancer is present 3, 4
• Sentinel lymph node biopsy should be performed even in cases with only non-invasive underlying disease, as positive nodes have been documented 4

Radiation Therapy Requirements

• Whole-breast radiation is mandatory for all patients treated with breast conservation 3
• Consider a radiation boost to the site of the resected nipple-areolar complex and any associated cancer site 3

Systemic Therapy Decisions

• Base systemic therapy decisions on the stage and biologic characteristics of any underlying cancer, not on the presence of Paget disease itself 3
• Women with associated invasive cancer have substantial risk of metastases and should receive adjuvant systemic therapy according to cancer stage 3

Expected Complications and Outcomes

Oncologic Outcomes

• Breast-conserving surgery with radiation achieves similar ipsilateral breast cancer recurrence rates as standard breast-conserving surgery for typical invasive or in situ cancers 3
• Local recurrence occurs in a minority of patients when appropriate surgical margins and radiation are achieved 4
• Patients with underlying invasive cancer and lymph node metastases have risk of distant metastases 4

Disease Characteristics Affecting Prognosis

• More than 90% of Paget disease cases are associated with an additional underlying breast malignancy, most commonly DCIS in the underlying lactiferous ducts 2
• The underlying cancer may be located at least 2 cm away from the nipple-areolar complex 2
• Multicentricity is present in a significant proportion of cases 5
• Lymph node metastases occur in patients with invasive underlying disease 5, 4

Common Clinical Pitfalls to Avoid

• Never delay biopsy by treating presumed eczema or dermatitis with topical steroids when Paget disease is in the differential 1
• Never rely on mammography alone to exclude Paget disease, as imaging can be negative in up to 50% of cases 1, 2
• Never skip breast MRI after biopsy confirmation, as it is essential for identifying the high percentage of cases with additional occult disease 3, 1
• Never omit whole-breast radiation when performing breast conservation, as it is mandatory for local control 3