Paget disease of the breast

Paget disease (PD) is defined as the presence of neoplastic cells of glandular differentiation, interspersed between keratinocytes of nipple epidermis, and constitutes approximately 1% of breast cancer cases. More than 90% of cases are associated with an underlying in situ or invasive breast carcinoma. The most accepted explanation for the development of PD is that it results from the migration of cells from the underlying tumor via the duct system into the epidermis, the so-called epidermotropic theory. Migration may be mediated by keratinocyte-secreted heregulin-? through its binding to HER3 or HER4 receptors, dimerized to highly overexpressed HER2. The approximately 10% of cases of PD not associated with an underlying breast cancer may result from neoplastic transformation of Toker cells, benign cells with glandular phenotype frequently located in the normal nipple epidermis. The differential diagnosis of PD includes other eczematous conditions of the nipple, but any unilateral nipple abnormality in an adult woman should be considered malignant until proven otherwise. Pathologically, the differential diagnosis includes other neoplastic entities associated with atypical cells in the epidermis, as well as benign mimics. Up to two-thirds of patients presenting with PD without a palpable breast mass have a normal mammogram. Magnetic resonance imaging is recommended in cases with no findings on clinical examination, mammogram, or ultrasound. Despite data suggesting that breast conserving surgery plus radiotherapy is effective in treating PD, mastectomy continues to be the most popular treatment. Review of published data suggests a significant bias to perform mastectomy in PD, even in the presence of tumors that would likely be managed with breast conservation had they not presented with PD. Sentinel lymph node surgery is appropriate in PD patients with a clinically negative axilla and should be used in accordance with guidelines established for usual breast cancer.