Paget’s disease of the breast or nipple is an eczematous condition involving the nipple and areolar skin, which is histologically characterized by the presence of malignant cells interspersed within the keratinocytes of the epidermis (cells of the skin). In approximately 90% of cases, the condition is associated with an in situ or invasive breast carcinoma.
- Chronic eczematous lesion involving the nipple (most common presentation) [highlighted in the image]
- Nipple erythema or ulceration
- Nipple inversion
- Nipple discharge
- As many as 40% of women have a palpable mass on presentation, and some may present with enlarged axillary lymph nodes.
90% patients who present with an underlying breast lump along with Paget’s have abnormal findings on mammography but only 50% patients who present with Paegt’s without a breast lump show mammographic abnormalities. Magnetic resonance imaging (MRI) is increasingly being used, particularly in cases without a palpable mass. MRI is particularly useful to establish extent of disease in patients in which breast-conserving surgery is being contemplated.
Pathology: The hallmark of Paget’s is the presence of neoplastic cells within the epidermis that show abundant clear cytoplasm and tend to spread individually in between the native keratinocytes (Image). They tend to display prominent nucleoli and frequent mitoses. In addition, they commonly show intracytoplasmic mucin-filled vacuoles, which are stained with a periodic-acid-Schiff or mucicarmine stain.
Paget cells are usually positive for markers of breast epithelium differentiation like:
- Cytokeratin 7
- CAM 5.2
- Low-molecular-weight cytokeratins (negative for high-molecular-weight cytokeratins)
- Vast majority of cases show strong overexpression of the HER2/neu proteinion of the gene
- Positive for mucin
- 18-20% of Paget’s cells express S100 protein but contrary to melanoma cells, HMB45 is consistently negative.
Toker cells are immunophenotypically similar to Paget cells, sharing expression of cytokeratin 7 and CAM 5.2, absence of high-molecular-weight cytokeratin expression, and negative S100- and HMB45-expression. They differ in the negative expression of mucin, HER2/neu, and epithelial membrane antigen. The similarities between Toker and Paget cells have suggested that the former may represent the cell that undergoes malignant transformation in the initial phases of PD. Toker cells can be present in normal patients as well.
The most accepted explanation for the development of PD is that Paget cells result from the migration of cells from the underlying adenocarcinoma through the epidermis, the so-called epidermotropic theory. This theory is supported by the existence of an underlying carcinoma in about 90% of cases of PD, which usually shares phenotypic similarities with Paget cells.
- Eczema – tends to be bilateral and responds to topical steroids
- Nipple adenoma
- Wedge biopsy
- Punch biopsy
Management: Management of PD depends on the underlying breast lump. Traditionally, the surgical procedure of choice has been a mastectomy but there are numerous studies which show that breast conservation surgery can be carried out in patients with PD. Prognosis in PD is largely determined by the underlying breast tumor.
Source: 1. Bland & Copeland – The Breast. 4th Edition 2. Michael Sabel – Essentials of Breast Surgery