Paget disease of the nipple

Paget disease presents as a unilateral eczema-like change of the nipple that spreads to the areola: scaling, redness, itching, crusting, discharge or nipple retraction, often treated as dermatitis for months before biopsy. Under the microscope the epidermis contains Paget cells, large pale cells with abundant cytoplasm that stain for cytokeratin 7 and, in most cases, overexpress HER2; they are thought to migrate from an underlying ductal carcinoma along the lactiferous ducts into the nipple skin. A full-thickness punch or wedge biopsy of the nipple makes the diagnosis, and bilateral mammography with breast MRI then looks for the disease behind it, which is present in the large majority of cases as ductal carcinoma in situ, invasive ductal carcinoma or both; a palpable mass makes invasion and node involvement more likely. Paget disease confined to the nipple without an underlying carcinoma is the exception, and extramammary Paget disease of the vulva or perianal skin is a different condition.

Mastectomy was the standard for a century because the underlying disease is often extensive or multicentric. The EORTC 10873 study of 61 women treated with excision of the nipple-areola complex and underlying tumour followed by whole-breast radiotherapy reported a five-year local recurrence rate of about five percent, and population analyses show survival matched by stage is the same after breast conservation with radiotherapy as after mastectomy, so central lumpectomy with radiotherapy is now offered when the underlying disease is limited and the margins are clear. Sentinel node biopsy is performed when invasive disease is present or when mastectomy is planned, because the nipple cannot be re-sampled afterwards. Systemic treatment, endocrine, chemotherapy and HER2-directed, follows the stage and receptors of the underlying carcinoma, not the nipple.

Prognosis is set by what lies beneath. Paget disease with in situ disease alone is cured in almost all cases, and Paget disease with an invasive tumour behaves like that tumour, with node status the strongest factor. The frequent HER2 overexpression of Paget cells has made the disease a model for HER2 biology in the skin and an occasional candidate for topical or HER2-directed approaches, but there are no randomised trials of anything in a condition this rare, and delay in diagnosis remains the main avoidable harm.