What are the diagnostic steps for Paget's disease?

Diagnostic Approach to Paget's Disease

The diagnosis of Paget's disease requires a surgical biopsy of the affected area (nipple areolar complex for breast Paget's disease) or specific laboratory and imaging studies (for Paget's disease of bone), depending on which form of the disease is suspected. 1, 2

Paget's Disease of the Breast

Clinical Presentation

• Eczema of the nipple or areola
• Bleeding or ulceration of the nipple
• Itching of the nipple
• Nipple excoriation and scaling

Diagnostic Algorithm

1. Complete history and physical examination

   • Focus on breast examination and assessment of skin changes
   • Note that diagnosis is often delayed due to confusion with other dermatologic conditions 1

2. Bilateral diagnostic mammogram with or without ultrasound imaging

   • Even if mammogram is normal, further workup is needed
   • Pure Paget's disease is frequently occult on mammography 1

3. Surgical biopsy of the nipple areolar complex

   • Must include full thickness of the epidermis
   • Include at least a portion of any clinically involved nipple areola complex 1
   • Punch biopsy of the skin or nipple biopsy is recommended 1

4. Breast MRI

   • Recommended when biopsy of the nipple areola complex is positive for Paget's disease
   • Helps define the extent of disease and identify additional disease 1

Important Considerations

• Associated cancer is present elsewhere in the breast in up to 80-90% of cases 1
• These cancers may not be located adjacent to the nipple areolar complex
• May be either DCIS (ductal carcinoma in situ) or invasive cancer

Paget's Disease of Bone

Clinical Presentation

• Bone pain
• Bone deformities
• Pathological fractures
• Hearing loss (if skull involvement)
• Often asymptomatic and discovered incidentally

Diagnostic Algorithm

1. Laboratory Tests

   • Serum total alkaline phosphatase (ALP) - recommended as first-line biochemical screening test
   • Must be combined with liver function tests to rule out liver disease 2
   • Consider specific markers of bone formation or resorption when warranted 3

2. Imaging Studies

   • Plain radiographs of suspected regions - initial diagnostic test 3
   • Radionuclide bone scan - recommended to determine the full extent of metabolically active disease 2, 3
   • MRI may be needed in complex cases 1

3. Bone Biopsy

   • Generally not required unless diagnosis is uncertain
   • May be considered to rule out other conditions like malignancy

Differential Diagnosis

Important conditions to rule out include:

• Infectious osteomyelitis
• Malignant bone tumors
• Fibrous dysplasia
• Osteoarthritis (especially with sternoclavicular involvement)
• Osteomalacia
• Hypophosphatasia 1

Monitoring Disease Activity

• Serum total alkaline phosphatase is the preferred marker for monitoring disease activity and response to treatment 2, 4
• Urinary markers (hydroxyproline) are sensitive but present technical difficulties in collection and measurement 4

Common Pitfalls to Avoid

1. Delayed diagnosis due to confusion with other dermatologic conditions (for breast Paget's) or asymptomatic presentation (for bone Paget's)
2. Incomplete evaluation - failing to perform breast MRI after positive nipple biopsy for breast Paget's disease
3. Missing associated cancers in breast Paget's disease
4. Relying solely on normal alkaline phosphatase to rule out Paget's disease of bone in monostotic disease
5. Failure to distinguish between the two distinct forms of Paget's disease (breast vs. bone)

Remember that early diagnosis is crucial for both forms of Paget's disease to prevent complications and improve outcomes.