Paget disease of the nipple

Definition

• Eczema-like change of the nipple and areola caused by large intraepidermal carcinoma cells (Paget cells), associated in over 90% with underlying DCIS or invasive breast cancer.

Occurrence & epidemiology

Epidemiology

• About 1–3% of breast cancers present in this way; mainly postmenopausal women aged 50 to 60 are affected, and rarely men.

Aetiopathogenesis

Aetiology and pathogenesis

• According to the most widely accepted epidermotropic theory, Paget cells migrate from an underlying carcinoma along the lactiferous ducts into the epidermis of the nipple.
• The transformation theory instead regards Paget cells as malignantly transformed keratinocytes of the nipple epidermis.

Clinical features

• Typical is a well-defined, irregularly shaped, red, scaly or crusted patch that starts on the nipple and spreads to the areola; usually only one side is affected.
• Pain, itching and burning occur in 15–25% and often precede the visible changes; ulceration, bleeding and discharge tend to occur in advanced stages.
• A palpable mass may be present and indicates a high probability of invasive cancer.

Histology

• Paget cells are large cells with abundant pale cytoplasm, pleomorphic nuclei and prominent nucleoli and lie singly or in clusters within the epidermis.
• On immunohistochemistry they are typically positive for low-molecular-weight cytokeratins such as CK7 and CAM5.2; HER2 is overexpressed in 80–90%, and oestrogen and progesterone receptors are positive in about 40% and 30%, respectively.

Diagnosis

Typical imaging findings

• Clinical finding: The nipple itself is destroyed and replaced by a sharply demarcated, eroded, reddish, scaly surface that was confirmed on biopsy to show Paget cells.
• Clinical finding: The nipple itself is replaced by a sharply demarcated, red, eroded surface that extends onto the areola. The surface is crusted and the nipple body partly destroyed.

• The diagnosis is confirmed by a full-thickness biopsy of the nipple-areola complex with histology and immunohistochemistry, while mammography, ultrasound and MRI look for a lesion within the breast.
• Invasive cancer may be present even when imaging is unremarkable.

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Further reading (selection)

1. National Cancer Institute: Paget Disease of the Breast
2. A Pictorial Exploration of Mammary Paget Disease: Insights and Perspectives (Cancers (Basel) 2023, PubMed Central)
3. DermNet: Mammary Paget disease

Cross-references