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An English surgeon by the name of Sir James Paget reported on a condition of eczematous change of the nipple–areola complex associated with underlying breast malignancy in 1874.1 It is now recognized that Paget disease denotes an entity of intraepithelial adenocarcinoma within the epidermis of the nipple–areola complex that is associated with underlying in situ or invasive mammary carcinoma in 92% to 100% of cases.2-4 Paget cells, large cells with pale cytoplasm and prominent nucleoli, identified within nipple epidermis on histology confirm diagnosis. Ninety percent of these will overexpress Her-2/neu.

Paget disease represents only 0.5% to 5% of all breast cancer, with average age of onset in the 50s to 60s. The majority of patients are postmenopausal women; however, a few cases have been documented in men, with a ratio of 1:50-200 men to women.5,6

Paget disease usually presents as a scaling, erythematous, eczematous lesion of the nipple that can be mistaken as a benign condition leading to delayed diagnosis (Fig.19-1). Usually the disease is unilateral, beginning at the nipple, and may spread to the areola; however, there are instances where only the areola may be affected. Late stages may be associated with ulceration, crusting, serous or bloody nipple discharge, and nipple retraction or flattening (Fig. 19-2). Patients may complain of pain, burning, and/or itching. Physical exam may reveal an underlying breast mass in 30% to 50% of cases. Rarely, Paget disease will be identified on a mastectomy specimen without clinical signs of disease (no skin lesion).

Figure 19-1

Clinical presentation of early Paget disease. Note eczematous change of nipple–areola complex. (Courtesy of Kelly Hunt, MD, Department of Surgical Oncology, MD Anderson Cancer Center.)

Figure 19-2

More advanced stage of Paget disease. (Courtesy of Kelly Hunt, MD, Department of Surgical Oncology, MD Anderson Cancer Center.)

The pathogenesis of Paget disease has been long debated, with 2 main competing theories: the epidermotrophic theory and the transformation theory. The epidermotrophic theory, currently the more favored theory, states that neoplastic ductal epithelial cells migrate through the ductal system of the breast into the epidermis of the nipple. Evidence for this lies in the observation that both the underlying mammary carcinoma and the intraepithelial nipple lesion will have similar staining of markers such as CEA, c-erb-B2, and Her-2/neu,6,7 suggesting that the nipple lesion arose from the breast malignancy. In addition, there is some research pointing to the ability of the Her2/neu receptor acting as an agent that induces chemotaxis of tumor cells, allowing for migration of malignant cells to the nipple, thus giving a mechanistic explanation supporting the epidermotrophic theory.8,9

On the other hand, the transformation theory suggests that epidermal keritinocytes within the nipple transform into malignant Paget ...

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