Overview

Paget's disease is an eponym applied to several distinct medical conditions first described by Sir James Paget in the 19th century. The name most commonly refers to Paget's disease of bone (osteitis deformans). It is also used for mammary Paget's disease of the nipple and for extramammary Paget disease (EMPD), an intraepithelial neoplasm of skin in genital or perianal areas. Although historically linked by name, these are separate disorders with different causes, investigations and treatments.

Main types and key features

  • Paget's disease of bone: a chronic focal disorder of bone remodelling in which increased osteoclast-mediated resorption and abnormal new bone formation lead to bone enlargement, deformity and weakness. Common sites include pelvis, skull, spine and long bones.
  • Mammary Paget's disease: an intraepithelial adenocarcinoma affecting the nipple–areola complex. It commonly presents with persistent eczematous change of the nipple and is frequently associated with an underlying ductal carcinoma of the breast.
  • Extramammary Paget disease (EMPD): a rare adenocarcinomatous process of the epidermis, most often occurring in the vulvar, perianal or scrotal regions. EMPD may be primary to the skin or reflect spread from an underlying malignancy.

Causes and pathophysiology

Bone Paget's is characterised by dysregulated bone remodelling with excessive activity of osteoclasts followed by disorganized bone formation. Genetic predisposition and environmental factors have been implicated; the exact initiating events are uncertain. Mammary and extramammary Paget disease represent malignant glandular cells within the epidermis; mammary Paget cells typically arise from underlying ductal carcinoma, while EMPD can arise from adnexal or mucosal glands or extend from adjacent tumours.

Clinical features and diagnosis

Presentations differ by type. Bone disease may cause bone pain, deformity, fractures, and hearing loss when the skull is involved; many people are asymptomatic and found incidentally. Mammary Paget's typically causes chronic nipple irritation, crusting, bleeding or discharge. EMPD presents as a long-standing, often itchy or sore erythematous patch in apocrine-rich skin. Diagnosis uses targeted assessment: for bone disease, radiographs show mixed lytic and sclerotic changes with bone enlargement and bone scintigraphy demonstrates increased uptake; serum alkaline phosphatase is a useful marker of activity. For mammary and extramammary disease, biopsy is essential to identify Paget cells and to assess for underlying invasive carcinoma; immunohistochemistry (for example cytokeratin profiles or HER2 status in mammary Paget's) helps classification and planning of therapy.

Treatment and prognosis

Treatment depends on the specific form. Paget's disease of bone is managed primarily with antiresorptive therapy (bisphosphonates or, in some cases, calcitonin) to reduce bone turnover and relieve pain; orthopaedic treatment addresses fractures, deformity or joint involvement. Mammary Paget's typically requires surgical management of the nipple–areola complex with assessment and treatment of any underlying breast carcinoma; adjuvant radiotherapy or systemic therapy may be indicated based on tumour staging. EMPD is often managed by wide local excision or Mohs micrographic surgery; topical treatments or systemic therapies may be used when surgery is not appropriate. Prognosis varies: many patients achieve symptom control, but outcomes depend on extent of disease and presence of associated malignancy.

Complications, follow-up and differential diagnosis

Complications of bone Paget's include deformity, secondary osteoarthritis in affected joints, increased fracture risk and, rarely, sarcomatous transformation. Mammary and extramammary forms require evaluation for underlying or associated malignancies; delayed diagnosis can allow local progression. Follow-up is tailored to disease type and may include periodic imaging and laboratory monitoring for bone disease and clinical surveillance after treatment of mammary or extramammary lesions.

History and clinical significance

Sir James Paget's original descriptions led to the eponym; the grouping under one name reflects historical association rather than a single pathological process. Modern practice distinguishes the conditions clearly because each requires a different diagnostic pathway and therapeutic approach. Ongoing research addresses causes of bone Paget's and optimal management strategies for EMPD and Paget's disease associated with breast cancer.