Diagnostic Approach for Paget Disease

Paget Disease of Bone

The American College of Radiology recommends plain radiographs of the suspected skeletal regions as the first-line investigation, which typically show a mixed osteolytic and osteosclerotic appearance, in patients with suspected Paget disease of bone 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, with a strength of evidence level of moderate, in patients with suspected Paget disease of bone 1, 2
Additional laboratory tests should include calcium, 25-hydroxy-vitamin D, phosphate, and parathyroid hormone levels to exclude other metabolic bone diseases, with a strength of evidence level of low, in patients with suspected Paget disease of bone 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, with a strength of evidence level of moderate, in patients with suspected Paget disease of bone 1
Radionuclide bone scintigraphy should be performed to determine the full extent of skeletal involvement, with a strength of evidence level of high, in patients with confirmed Paget disease of bone 1

The National Comprehensive Cancer Network recommends a full-thickness surgical biopsy of the nipple-areolar complex (including epidermis and involved tissue) for definitive diagnosis, with a strength of evidence level of high, in patients with suspected Paget disease of the breast 3
A complete history and physical examination focusing on the nipple-areolar complex, specifically looking for eczema, bleeding, ulceration, and itching, should be performed, with a strength of evidence level of low, in patients with suspected Paget disease of the breast 3, 4
Bilateral diagnostic mammography with ultrasound as necessary should be obtained as the first imaging study, regardless of patient age, with a strength of evidence level of moderate, in patients with suspected Paget disease of the breast 3, 4
Breast MRI is strongly recommended once biopsy confirms Paget disease to define the extent of disease and identify additional occult malignancy, with a strength of evidence level of high, in patients with confirmed Paget disease of the breast 3