by Jason Wasserman MD PhD FRCPC and Zuzanna Gorski MD
November 20, 2023
Paget’s disease is a non-invasive type of breast cancer that involves the nipple and surrounding skin. It is considered non-invasive because the tumour cells are limited to a layer of the skin called the epidermis. Most tumours 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, the tumour is believed to start from specialized Toker cells that are normally found in the nipple.
The most common symptom of Paget’s 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.
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.
Examination of the breast will show that most patients with Paget’s 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.
This diagnosis can only be made after tissue is examined under the microscope by a pathologist.
When examined under the microscope, Paget’s 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. The process is commonly described as intraepidermal because the tumour cells are found in the epidermis. 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.
Pathologists often perform a test called immunohistochemistry (IHC) to confirm the diagnosis. This test helps pathologists differentiate Paget’s disease from other conditions that can look similar under the microscope. When IHC is performed, the tumour cells 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).
Microinvasion means that the tumour cells in Paget’s 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.
If only Paget’s disease is found in the breast (or Paget’s disease with ductal carcinoma in situ) the pathologic tumour stage is Tis (‘is’ stands for in situ or non-invasive). If the disease is found with an underlying invasive cancer such as ductal carcinoma, the tumour stage is based on the invasive cancer.
This article was written by doctors to help you read and understand your pathology report. Contact us if you have any questions about this article or your pathology report. Read this article for a more general introduction to the parts of a typical pathology report.