Paget's disease of breast

Synonyms: Paget's disease of the nipple, mammary Paget's disease

What is Paget's disease of breast?^{1 2}

Paget’s disease of the breast, or mammary Paget’s disease, was first described by Sir James Paget in 1874 as an eczematous lesion of the nipple associated with underlying breast cancer.

It is now recognized as a rare cutaneous intraepithelial malignancy characterised by large epidermal adenocarcinoma cells, called Paget’s cells, within the squamous epithelium of the nipple, which may extend into the areola and adjacent skin. Paget’s disease may also develop on ectopic breasts and accessory nipples.

Mammary Paget's disease is nearly always associated with an underlying intraductal breast cancer located near the areola. The underlying breast lesion is usually a ductal carcinoma in situ (DCIS) but can be invasive cancer.

How common is Paget's disease of breast? (Epidemiology)^{1 2}

Mammary Paget’s disease is reported in 1–3% of all primary breast cancers. Between 93–100% of cases are associated with underlying breast cancer.

Mammary Paget's 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's disease, although this is rare. See also the article on Male Breast Cancer.

Pathophysiology

Malignant cells infiltrate into the epidermis via the mammary duct epithelium.³ The cells proliferate leading to thickening of the affected skin.

Paget's disease of breast symptoms (presentation)^{1 2}

• It is usually unilateral but can occur bilaterally.

• Some cases may occur following mastectomy despite no breast tissue being present.⁴

• It usually involves the nipple but can extend to involve other areolar skin.

• It presents as chronic eczematous change of the nipple with:
  

  • Itching.

  • Erythema.

  • Scale formation.

  • Erosions.

  • Nipple discharge including bleeding.

• An underlying palpable breast lump (usually indicates an invasive nature).

Differential diagnosis¹

• Skin disorders - eg, eczema (always consider Paget's disease of the breast first).

• Melanoma of the nipple.

• Nipple adenoma.

Investigations

• Biopsy with immunohistochemistry and special stains.

• Investigation of a breast lump, if palpable.

• Investigations looking for underlying malignancy if there is no lump palpable - eg, mammography or MRI (may be more useful).⁵

Paget's disease associations⁶

Presence of Paget's disease is associated with the following:

• Higher histological grade.

• Oestrogen receptor-negative breast cancer.

• Progesterone receptor-negative breast cancer.

Staging

Paget's disease of the nipple with no associated tumour is staged as carcinoma in situ. Otherwise, these are classified according to the size of the underlying tumour.

Paget's disease treatment and management

The surgical treatment of Paget's disease is controversial. Mastectomy with or without axillary lymph node dissection has been regarded as the standard therapy for Paget's disease, even in the absence of other clinical signs of malignancy. The National Institute for Health and Care Excellence (NICE) recommends that breast-conserving surgery with removal of the nipple-areolar complex should be offered as an alternative to mastectomy for people with Paget's disease of the nipple that has been assessed as localised.⁷

Further breast cancer treatment may include radiotherapy and chemotherapy.

Prognosis²

Delay in presentation or diagnosis is common, with diagnosis 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. Prognosis is particularly poor for males, with a 20-30% five-year survival.

Extramammary Paget's disease⁸

Extramammary Paget's disease of the skin is an uncommon intraepithelial adenocarcinoma, usually of the anogenital or axillary skin. Extramammary Paget's disease is classified into primary and secondary disease:⁹

• Primary: cutaneous origin.

• Secondary: associated with a primary adenocarcinoma elsewhere in the body.

Approximately 25% of the cases are associated with an underlying in-situ or invasive neoplasm, particularly an adnexal apocrine carcinoma. Other associated malignancies include carcinomas of Bartholin's glands, urethra, bladder, vagina, cervix, endometrium and prostate.

It is a rare condition with only several hundred cases in the world reported. It most commonly appears in those aged 50-60 years and is more common in women.

It usually presents as chronic dermatitis of the groin, genitalia or perianal area, which is resistant to treatment. It is often associated with intense pruritus and long-standing lesions may cause pain and bleeding.