What are the diagnostic tests for Paget's disease?

Diagnostic Testing for Paget's Disease

Critical Distinction: Two Different Diseases

The diagnostic approach depends entirely on whether you are evaluating Paget's disease of the breast (nipple-areolar complex) or Paget's disease of bone (metabolic bone disorder)—these are completely separate conditions requiring different testing strategies.

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Paget's Disease of the Breast

Initial Clinical Assessment

• Examine the nipple-areolar complex specifically for eczema, bleeding, ulceration, and itching 1
• Perform bilateral diagnostic mammography with or without ultrasound as the first imaging study, regardless of age 1
• Critical pitfall: Pure Paget's disease can be occult on mammography—a negative mammogram does NOT exclude the diagnosis 1

Biopsy Strategy (Algorithm-Based Approach)

If imaging shows BI-RADS 1-3 (negative/benign/probably benign):

• Perform punch biopsy of the skin or nipple 1

If imaging shows BI-RADS 4-5 (suspicious/highly suggestive of malignancy):

• Perform core needle biopsy (preferred) with or without punch biopsy 1

For definitive diagnosis:

• Full-thickness surgical biopsy of the nipple-areolar complex including epidermis and any clinically involved tissue is the gold standard 1

Advanced Imaging After Diagnosis

• Breast MRI is strongly recommended once biopsy confirms Paget's disease to define disease extent and identify additional occult malignancies 1, 2
• This is critical because 80-90% of cases have associated cancer elsewhere in the breast (DCIS or invasive), which may not be adjacent to the nipple 1, 2

Common Pitfall to Avoid

• Do not mistake Paget's disease for benign eczema or dermatitis—when in doubt, biopsy 1
• If a benign skin biopsy result conflicts with clinical suspicion, reassess clinical-pathologic correlation, consider breast MRI, perform repeat biopsy, and consult a breast specialist 1

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Paget's Disease of Bone

Initial Diagnostic Tests

When Paget's disease of bone is suspected (incidental finding or symptomatic patient):

Laboratory evaluation:

• Measure serum total alkaline phosphatase (ALP) as the first-line biochemical screening test, combined with liver function tests 3
• Measure calcium, 25-hydroxy-vitamin D, phosphate, and parathyroid hormone levels to exclude other metabolic bone diseases 4
• Elevated serum ALP is the most common biochemical finding and serves as the primary marker 5, 6

Imaging approach:

• Plain radiography is the imaging modality of choice for diagnosis, showing characteristic features 3, 7
• Radiographic findings vary by phase: osteolytic lesions with well-defined margins (early phase), cortical thickening, trabecular coarsening, bone marrow sclerosis, and deformities (mixed and late-sclerotic phases) 7
• Radionuclide bone scan is recommended to fully and accurately define the extent of metabolically active disease 3
• The bone scan helps stage disease extent and assess treatment response 5

Most Commonly Affected Sites

• Pelvis, spine, skull, and long bones (femur) are preferentially affected 6, 7
• Any bone may be involved 6

Clinical Context

• Most cases are diagnosed incidentally on radiographs or as isolated elevation of serum ALP 5, 6
• Symptomatic patients present with bone pain, fractures, arthritis, or compression neuropathy features 5, 6
• The disease typically affects adults over age 55 years, with men at higher risk than women 6

Role of Advanced Imaging

• MRI and CT are important for assessing complications and surgical planning, but are not primary diagnostic tools 7