Diagnostic Testing for Paget Disease
Context Clarification: Two Distinct Diseases
The term "Paget disease" refers to two completely different conditions that require different diagnostic approaches: Paget disease of bone (a metabolic bone disorder) and Paget disease of the breast (a malignancy of the nipple-areolar complex). The diagnostic workup differs entirely between these entities.
Paget Disease of Bone
Initial Diagnostic Tests
Plain radiographs of the suspected skeletal regions should be obtained as the first-line investigation, which typically show a mixed osteolytic and osteosclerotic appearance. 1
Serum total alkaline phosphatase (ALP) is the primary biochemical screening test and should be measured in combination with liver function tests to confirm the diagnosis and exclude hepatic causes of elevated ALP. 1, 2, 3
Additional laboratory tests should include calcium, 25-hydroxy-vitamin D, phosphate, and parathyroid hormone levels to exclude other metabolic bone diseases. 2
More specific bone turnover markers such as procollagen type I N-terminal propeptide (PINP) or C-terminal telopeptide (CTX) can be used when needed for additional confirmation. 1
Determining Disease Extent
Once the diagnosis is confirmed radiographically and biochemically, radionuclide bone scintigraphy should be performed to determine the full extent of skeletal involvement. 1, 3 This is critical because Paget disease is often multifocal, and bone scan shows marked increased uptake in all affected sites. 4
Key Diagnostic Features
The diagnosis is strongly supported by: 1
- Family history of Paget disease
- Typical localization to pelvis, spine, skull, or long bones
- Elevated alkaline phosphatase with normal liver function
- Bone deformities on examination
- Age over 50 years
Paget Disease of the Breast
Initial Clinical and Imaging Evaluation
A full-thickness surgical biopsy of the nipple-areolar complex (including epidermis and involved tissue) is required for definitive diagnosis. 5
Perform a complete history and physical examination focusing on the nipple-areolar complex, specifically looking for eczema, bleeding, ulceration, and itching. 6, 5
Bilateral diagnostic mammography with ultrasound as necessary should be obtained as the first imaging study, regardless of patient age. 6, 5
Critical pitfall: Pure Paget disease can be occult on mammography—a negative mammogram does not exclude the diagnosis. 5
Biopsy Strategy Based on Imaging
If imaging shows BI-RADS category 1-3 (negative, benign, or probably benign): Perform punch biopsy of the skin or nipple. 5
If imaging shows BI-RADS category 4-5 (suspicious or highly suggestive of malignancy): Perform core needle biopsy (preferred) with or without punch biopsy of any breast lesion identified. 6, 5
Advanced Imaging After Diagnosis
Breast MRI is strongly recommended once biopsy confirms Paget disease to define the extent of disease and identify additional occult malignancy, as 80-90% of cases have associated DCIS or invasive cancer elsewhere in the breast. 5
Critical Clinical Pitfall
Do not mistake Paget disease for benign eczema or dermatitis—when in doubt, biopsy immediately. 5 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 definitive diagnostic evaluation. 5
If a skin biopsy returns benign but clinical suspicion remains, reassess clinical-pathologic correlation, consider breast MRI, perform repeat biopsy, and consult a breast specialist. 5