What is mammary Paget disease?
Mammary Paget disease is an uncommon form of breast cancer, comprising 1–3% of all breast cancer presentations. It is also called Paget disease of the breast or nipple.
Mammary Paget disease is nearly always associated with an underlying intraductal breast cancer located near the areola.
Mammary Paget disease is distinguished from extramammary Paget disease seen in the apocrine gland-rich anogenital skin and axillae.
Who gets mammary Paget disease?
Mammary Paget disease mainly affects women in their 50s and 60s, with a wide age range reported from adolescence to the elderly. Men can also be diagnosed with mammary Paget disease, although this is rare.
What causes mammary Paget disease?
There are two main theories proposed for the pathogenesis of mammary Paget disease.
- Epidermotropic theory — this theory proposes that Paget cells arise in an underlying intraductal carcinoma and migrate along the lactiferous ducts to the nipple epidermis.
- In situ malignant transformation theory — this suggests Paget cells are malignant keratinocytes of the nipple epidermis.
What are the clinical features of mammary Paget disease?
Mammary Paget disease typically starts as an eczema-like change of one nipple, extending with time over the areola, and often associated with an underlying breast lump. It is rarely bilateral. Ectopic and accessory nipples can be affected.
Common cutaneous features of mammary Paget disease include:
- Eczematous or psoriasis-like change
- Well-defined but irregularly shaped red patch that slowly enlarges and can reach up to 15 cm in diameter
- May be scaly and/or crusted
- Initially asymptomatic, the nipple can become itchy, painful, or feel a burning sensation
- With time, the nipple may become thickened and/or retracted
- Ulceration, bleeding, and discharge may develop.
A pigmented variant is well recognised in both males and females, although this presentation is very rare. It can be very difficult to clinically distinguish from melanoma.
Mammary Paget disease
See more images in Mammary and extramammary Paget disease of the skin images.
What are the dermoscopic features of mammary Paget disease?
Dermoscopy may be performed to distinguish the lesion from an inflammatory or infective dermatosis or, in the case of pigmented mammary Paget disease, from melanoma.
Dermoscopic features of typical mammary Paget disease have been rarely described, but can include:
- Irregular linear vessels
- White scar areas
- Blue-grey dots
- Chrysalis-like structure — shiny white streaks on polarised dermoscopy.
Dermoscopy of pigmented mammary Paget disease is reported to be almost indistinguishable from melanoma, with features including:
- Multiple colours
- Irregular dots and globules
- Grey-blue pepper granules corresponding to melanophages
- Scar-like depigmentation suggestive of melanoma regression.
What are the complications of mammary Paget disease?
Mammary Paget disease is almost always a skin sign of an underlying breast cancer. This may be an in-situ or invasive intraductal carcinoma. Metastases to lymph nodes and beyond may be present.
How is mammary Paget disease diagnosed?
Mammary Paget disease should be suspected clinically when a longstanding, slowly progressive, unilateral nipple change is seen.
A skin biopsy will show the typical foamy Paget cells in the epidermis. In pigmented mammary Paget disease, special stains (eg, CK-7, S-100, Melan A, HMB-45) are required to distinguish Paget cells from malignant melanocytes.
A wedge biopsy of the nipple extends more deeply into the breast tissue and aids diagnosis of the underlying cancer. Immunohistochemistry is used to determine hormone receptor status (oestrogen receptor, progesterone receptor) and human epidermal growth receptor 2 (HER2) that can influence treatment.
Investigations to determine the extent of the associated breast cancer may include ultrasound, mammogram, or MRI.
What is the differential diagnosis for mammary Paget disease?
Mammary Paget disease should be distinguished from:
- Inflammatory dermatoses including eczema and psoriasis
- Infective skin conditions such as tinea
- Erosive adenomatosis of the nipple
- Melanoma if pigmented.
What is the treatment for mammary Paget disease?
The usual treatment of mammary Paget disease is surgical excision. Although mastectomy was routine, especially in males, consideration is now given to breast-conserving surgery (removing the nipple, areola, and underlying breast tissue with a margin of healthy tissue). Sentinel lymph node biopsy assesses node involvement. Axillary lymph node dissection may be required if the breast cancer has spread to lymph nodes.
Further treatment may include:
- Radiotherapy, if the primary cancer was large or could not be completely excised, or lymph nodes were positive
- Tamoxifen, if oestrogen receptor positive
- Trastuzumab (Herceptin), if HER2 positive
- Chemotherapy, if the breast cancer is rapidly progressive or advanced.
What is the outcome for mammary Paget disease?
Despite the visible lesion, a delay in presentation or diagnosis is common. On average, diagnosis is made 12 months after onset in women and 8–9 months in men. Prognosis is therefore not as good as for more common forms of breast cancer. It is particularly poor for males, with a 20–30% five-year survival.