What are the clinical presentation, diagnostic work‑up, and treatment options for Paget’s disease of the breast?

Paget's Disease of the Breast: Clinical Presentation, Diagnosis, and Treatment

Clinical Presentation

Paget's disease presents with characteristic nipple-areolar changes including eczema-like scaling, erythema, ulceration, bleeding, and pruritus of the nipple, but the critical point is that 80–90% of cases harbor an underlying invasive or in situ breast cancer that may be located anywhere in the breast, not just adjacent to the nipple. 1

Key Clinical Features to Identify

• Nipple-centric skin changes: excoriation, scaling, crusting, bleeding, ulceration, and itching specifically involving the nipple-areolar complex 1, 2
• Associated palpable mass is present in approximately 44% of cases (30 of 68 patients in one series), and these patients have significantly worse prognosis 3
• Rapid symptom onset within months, which helps distinguish from chronic benign dermatologic conditions 2

Critical Diagnostic Pitfall

• Do not mistake Paget's disease for benign eczema or dermatitis—if clinical suspicion exists, proceed directly to biopsy rather than empiric topical steroid trials 1
• The presentation mimics benign conditions, leading to frequent diagnostic delays 2

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Diagnostic Work-Up Algorithm

Step 1: Initial Imaging (Mandatory)

• Obtain bilateral diagnostic mammography with or without ultrasound as the first imaging study, regardless of patient age 1
• Recognize that pure Paget's disease can be occult on mammography—negative mammography does not exclude the diagnosis and is negative in up to 50% of cases 1, 4
• Ultrasound is required because it evaluates for underlying masses, fluid collections, and regional lymph-node involvement that mammography cannot reliably detect 2

Step 2: Tissue Diagnosis (Tailored to Imaging Results)

When Imaging Shows BI-RADS 1–3 (Negative/Benign/Probably Benign)

• Perform full-thickness surgical biopsy or punch biopsy of the nipple-areolar complex that includes the epidermis and at least a portion of any clinically involved tissue 1
• Obtain at least two specimens if clinical suspicion is high 2

When Imaging Shows BI-RADS 4–5 (Suspicious/Highly Suggestive of Malignancy)

• Core needle biopsy (preferred) of the breast lesion with or without concurrent punch biopsy of the nipple skin 1, 2
• Surgical excision is an acceptable alternative for obtaining diagnostic tissue 2

If Initial Biopsy Returns Benign

• Do not accept a benign result when clinical suspicion remains high—reassess clinical-pathologic correlation, obtain breast MRI, perform repeat biopsy, and refer to a breast specialist 1, 2

Step 3: Post-Diagnosis Staging

• Breast MRI is mandatory after biopsy confirmation to define the full extent of disease and identify additional occult malignancies, as the associated cancer is not necessarily adjacent to the nipple-areolar complex 5, 1
• Up to 80–90% of cases have associated breast cancer elsewhere in the breast 5, 1
• MRI is particularly useful because it can identify disease missed by mammography and ultrasound 4

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Treatment Algorithm

Surgical Options

Breast-conserving surgery with complete nipple-areolar complex excision plus whole-breast radiation therapy achieves local control and survival comparable to mastectomy and should be offered as the preferred option when feasible. 5

For Paget's Disease Without Associated Cancer (Pure Paget's)

• Remove the entire nipple-areolar complex with negative margins of underlying breast tissue 5
• Follow with mandatory whole-breast radiation therapy 5
• Consider a radiation boost to the site of the resected nipple-areolar complex 5

For Paget's Disease With Associated Cancer

• Remove the entire nipple-areolar complex with negative margins 5
• The nipple-areolar complex and peripheral cancer do not need to be removed in continuity or through a single incision 5
• Perform axillary surgery according to standard staging guidelines if underlying invasive cancer is present 5
• Sentinel lymph node biopsy should be performed in invasive disease; even in pure Paget's or DCIS-associated disease, positive sentinel nodes have been documented 6
• Follow with mandatory whole-breast radiation therapy 5

Mastectomy Indications

• Mastectomy remains an option when breast conservation is not feasible due to extent of disease, patient preference, or contraindications to radiation 6, 7
• Historically, 71 of 114 patients (62%) underwent mastectomy even when conservation was possible 6

Radiation Therapy

• Whole-breast radiation is mandatory for all patients treated with breast conservation 5
• Consider a radiation boost to the site of the resected nipple-areolar complex and any associated cancer site 5

Systemic Therapy

• Base systemic therapy decisions on the stage and biologic characteristics of the underlying cancer, not on the presence of Paget's disease itself 5
• Women with associated invasive cancer have substantial risk of metastases and should receive adjuvant systemic therapy according to cancer stage 5
• Paget's-associated invasive cancers are more commonly estrogen receptor–negative, progesterone receptor–negative, and high histologic grade 7

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Expected Outcomes and Prognostic Factors

• Breast-conserving surgery with radiation achieves similar ipsilateral breast cancer recurrence rates as standard breast-conserving surgery for typical invasive or in situ cancers 5
• Patients with Paget's disease who underwent breast conservation had outcomes equivalent to those who underwent mastectomy 7
• Presence of a palpable mass significantly worsens prognosis: median survival 42 months with mass versus 126 months without mass (p = 0.007) 3
• Patients with Paget's and underlying invasive cancer have 57% positive axillary nodes when a mass is present, versus 21% when no mass is present 3

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Critical Pitfalls to Avoid

• Do not delay biopsy with empiric topical steroid trials when Paget's disease is suspected 1
• Do not rely on mammography alone—ultrasound is mandatory, and MRI is required after diagnosis 1, 2
• Do not assume negative imaging excludes disease—up to 50% of Paget's cases have negative mammography 1, 4
• Do not perform only central excision without MRI staging—29% of patients without a palpable mass have peripherally located tumors that could be missed 3
• Do not omit radiation therapy when performing breast conservation—it is mandatory for local control 5