Author Lisa Wiechmann MD

Historical notes

The first documentation of paget’s disease was carried out by John of Ardenne in 1307 who described nipple ulceration in a male priest that evolved into breast cancer. In 1874 Sir James Paget documented the association of the ulceration of the nipple with an underlying breast cancer in 15 patients, but erroneously speculated that the skin condition was benign. Such a conclusion was then rectified in 1881 by Thin who concluded that the skin condition was a malignancy.

Pathogenesis

There are two main theories for the origin of Paget’s disease of the nipple: the epidermotropic theory ( Paget cells arise in breast ducts and migrate to the epidermis) and the intraepidermal transformation theory ( Paget cells arise from the terminal portion of the lactiferous duct). The first theory is supported by the fact that more than 97% of patients with Paget’s disease of the nipple have an underlying breast carcinoma.

Clinical presentation

Paget’s disease typically presents as erythema and scaling of the nipple skin that progresses to crusting, skin erosion and ulceration if left untreated. Symptoms may include pruritus, tingling, hypersensitivity, burning or pain. Many diseases must be included when differentiating Paget’s disease from other conditions that lead to erythema and scaling of the skin. The differential diagnosis therefore includes: eczema, contact dermatitis, postradiation dermatitis, and Paget’s disease. Bilateral changes are most consistent with eczema and contact dermatitis. Less common differential diagnoses include nipple adenoma and a variety of skin cancers ( melanoma, Merkel cell carcinoma, basal cell carcinoma, squamous cell carcinoma).

Diagnosis

Diagnosis is obtained in a variety of ways including scrape cytology, shave biopsy, 2mm punch biopsy, wedge incisional biopsy or nipple excision. Immunohistologic staining is useful in the differentiation of Paget’s ( + for keratins- CK-7, CAM-5.2, + for S100) from other malignancies.

The typical histologic appearance of the Paget cell is that of a large pale-staining cell with round or oval nuclei and prominent nucleoli ( as shown below). Paget cells are between the normal keratinocytes of the nipple epidermis ( single cells in superficial layers and clusters near the basement membrane.

Incidence

Paget’s disease is diagnosed pathologically more frequently than it is clinically . Its clinical incidence ranges from 0.5% to 2.8% (mean 1.3%) whereas its pathological incidence is approximately 4%.

Treatment

Treatmetn of Paget’s disease varies depending on the presence of underlying breast carcinoma or DCIS. Mammogrephic evaluation looking for evidence of breast cancer is therefore part of the routine evaluation of patients with Paget’s disease (bilateral mammograms). If available, preoperative MRI of the breast can identify occult disease. When possible breast conserving surgical intervention should be considered. THe combination of radiation to breast conserving surgery has been shown to decrease recurrence rates. For patients undergoing mastectomy or breast preservation, the decision of evaluation and treatment of axillary nodes should be reserved for invasive breast cancers.