What is the appropriate workup for a 70‑year‑old woman with unilateral persistent nipple hardening (retraction) and skin changes but no palpable breast mass?

Workup for 70-Year-Old with Unilateral Prolonged Hard Nipple, No Masses, Other Skin Changes

This patient requires immediate diagnostic mammography with ultrasound and nipple scrape cytology to exclude Paget's disease of the nipple, which presents with persistent unilateral nipple changes and is associated with underlying breast cancer in over 80% of cases. 1, 2

Clinical Significance and Differential Diagnosis

Any persistent unilateral nipple lesion should be viewed with suspicion and Paget's disease must be considered. 1 The combination of unilateral nipple hardening (likely retraction), skin changes, and age 70 years places this patient at high risk for malignancy—the cancer risk in patients over 60 years with nipple abnormalities reaches 32%. 3

Key Differential Diagnoses to Consider:

• Paget's disease of the nipple: A rare variant of ductal carcinoma in situ (DCIS) that presents with persistent unilateral nipple changes, erythema, erosion, or retraction 1, 2
• Underlying invasive breast cancer with cutaneous extension: Should be suspected when nipple retraction and/or fixation is present 1
• Erosive adenomatosis of the nipple: A benign process that may simulate Paget's disease but is isolated to the nipple 1
• Eczema: Characterized by bilateral presentation, absence of nipple deformity, flare-ups, and favorable response to steroids—unlikely given unilateral presentation 1

Immediate Diagnostic Workup

1. Nipple Scrape Cytology

The diagnosis of Paget's disease is established by nipple scrape cytology, which should be performed immediately. 1 This is the definitive diagnostic test for Paget's disease and should not be delayed.

2. Diagnostic Mammography

Diagnostic mammography is the first-line imaging modality for patients 40 years or older with nipple abnormalities. 3

• Include retroareolar magnification views to better evaluate the subareolar region 3
• Sensitivity for detecting underlying malignancy ranges from 15-68%, so negative mammography does not exclude cancer 3
• Over 80% of Paget's disease cases have an underlying breast malignancy, which may be multifocal 1, 2

3. Breast Ultrasound

Ultrasound should be performed as a complementary examination to mammography. 3

• Ultrasound has higher sensitivity (63-100%) than mammography for detecting intraductal lesions 4
• Use peripheral compression technique, 2-handed compression, and rolled nipple technique to increase detection of subareolar abnormalities 3
• Ultrasound can identify masses not visible on mammography due to dense tissue 3

Advanced Imaging Considerations

Breast MRI

If Paget's disease is confirmed and breast-conserving surgery is contemplated, preoperative MRI is useful due to the high rate of occult malignancy on mammograms and ultrasound. 1, 2

• MRI shows sensitivity up to 96% for detecting underlying malignancy in nipple abnormalities 4
• MRI is particularly valuable for detecting multifocal disease, present in over 80% of Paget's cases 1, 2
• MRI should be performed after initial diagnosis but before surgical planning 2

Management Based on Imaging Results

If Imaging Shows Suspicious Findings (BI-RADS 4 or 5):

• Proceed immediately to image-guided core needle biopsy for tissue diagnosis 3
• Core biopsy is superior to fine needle aspiration for sensitivity, specificity, and correct histologic grading 3

If Imaging is Negative or Shows Only Benign Findings (BI-RADS 1-3):

• Surgical duct excision is still indicated if Paget's disease is confirmed on cytology, even with negative imaging 3, 4
• The presence of persistent unilateral nipple changes with skin involvement warrants tissue diagnosis regardless of imaging findings 1, 2

Critical Pitfalls to Avoid

• Do not dismiss persistent unilateral nipple changes as benign eczema without biopsy—eczema is bilateral and responds to steroids, whereas Paget's disease is unilateral and progressive 1
• Do not rely solely on mammography—sensitivity is low (7-26%) for detecting the underlying cause of nipple abnormalities 4
• Do not delay cytology or biopsy while waiting for imaging results—the diagnosis of Paget's disease requires histologic confirmation 1, 2
• Do not assume absence of a palpable mass excludes malignancy—over 80% of Paget's disease cases have underlying cancer that may not be palpable 1, 2

Timeline for Workup

All diagnostic studies should be completed within 1-2 weeks given the high suspicion for malignancy in this clinical scenario. 3 The combination of age >60 years, unilateral presentation, and persistent nipple changes with skin involvement represents a high-risk presentation requiring urgent evaluation.