Paget disease of the breast

by Jason Wasserman MD PhD FRCPC
September 2, 2023

What is Paget disease of the breast?

Paget disease is a type of breast cancer that involves the nipple and surrounding skin.

What are the symptoms of Paget disease of the breast?

The most common symptom of Paget disease is a red, scaly rash involving the nipple and surrounding skin. These changes can look very similar to eczema. Other symptoms include bloody discharge from the nipple and retraction (pulling inwards) of the nipple and surrounding skin.

What causes Paget disease of the breast?

Paget disease shares risk factors with other more common types of breast cancer. These risk factors include female sex, advancing age, and early onset of menarche.

What type of cancer is Paget disease of the breast?

Paget disease is considered a non-invasive type of breast cancer because the tumour cells are limited to a layer of the skin called the epidermis.

Where does Paget disease of the breast start?

Most cases of Paget disease are believed to start in channels called ducts that run from the nipple to glands deep in the breast. The growth of abnormal cells within the ducts leads to a disease called ductal carcinoma in situ (another type of non-invasive breast cancer). Over time, the abnormal cells spread from the ducts into the overlying nipple and skin. In rare cases, however, where no underlying ductal carcinoma in situ is found, Paget disease is believed to start from specialized Toker cells that are normally found in the nipple.

Does Paget disease mean that there is cancer in the breast under the nipple?

Examination of the breast will show that most patients with Paget disease also have breast cancer in the underlying breast tissue. The underlying breast cancer is typically invasive ductal carcinoma or ductal carcinoma in situ (DCIS). However, for a small number of patients, no underlying cancer will be found.

How is Paget disease of the breast diagnosed?

The diagnosis of Paget disease of the breast can only be made after tissue is examined under the microscope by a pathologist.

What does Paget disease of the breast look like under the microscope?

When examined under the microscope, Paget disease of the breast is made up of large abnormal-looking tumour cells. The tumour cells spread through the epidermis, a thin layer of tissue on the surface of the skin, as single cells or in small groups. Because the tumour cells are found in the epidermis, the process is commonly described as intraepidermal. The cells usually contain a large amount of pale pink cytoplasm while the nuclei are typically enlarged and pleomorphic. A substance called mucin is frequently seen inside some of the tumour cells.

What other tests are performed to confirm the diagnosis of Paget disease?

Pathologists often perform a test called immunohistochemistry (IHC) to confirm the diagnosis of Paget disease of the breast. This test helps pathologists differentiate Paget disease from other conditions that can look similar under the microscope. When IHC is performed, the tumour cells in Paget disease are usually positive for low molecular weight keratins including cytokeratin 7 and CAM5.2. Most tumours also overexpress HER2 (they produce more HER2 than normal cells). Just under half of all tumours are positive for estrogen receptor (ER) and progesterone receptor (PR).

What does it mean if microinvasion is seen with Paget disease?

Microinvasion means that the tumour cells in Paget disease have spread from the epidermis into the dermis (the layer of tissue just below the epidermis). Microinvasion alone is not associated with more aggressive disease.

What stage is Paget disease of the breast?

If only Paget disease is found in the breast (or Paget disease with ductal carcinoma in situ) the pathologic tumour stage is Tis (‘is’ stands for in situ or non-invasive). If Paget disease is found with an underlying invasive cancer such as ductal carcinoma, the tumour stage is based on the invasive cancer.