Paget’s disease of the breast is a rare form of breast cancer that primarily affects the skin of the nipple and areola. Named after Sir James Paget, who first described the condition in 1874, Paget’s disease is often associated with an underlying breast cancer, typically ductal carcinoma in situ (DCIS) or invasive ductal carcinoma. In this blog post, we will delve into the characteristics of Paget’s disease, exploring its clinical presentation and focusing on the vital role of immunohistochemistry (IHC) in its diagnosis.
Clinical characteristics:
Paget’s disease of the breast is characterized by a range of symptoms, including itching, redness, and scaling of the nipple and areola. Patients may also experience nipple discharge, sensitivity, or pain. These symptoms are often misdiagnosed as dermatitis or eczema, leading to delayed detection and treatment. It is crucial for both healthcare professionals and individuals to be aware of these signs and seek prompt medical attention for a thorough evaluation.
Histology: Unveiling the Cellular Picture
The hallmark of Paget’s disease lies in the presence of Paget cells. These malignant, intraepithelial adenocarcinoma cells reside within the epidermis of the nipple and areola. Histologically, they stand out with their:
- Large size: Often larger than surrounding normal cells, Paget cells appear singly or in clusters.
- Shape: Variable, ranging from ovoid and round to signet-ring forms.
- Cytoplasm: Pale to clear, sometimes containing vacuoles, indicating the presence of mucin.
- Nuclei: High-grade with prominent nucleoli, hinting at their aggressive nature.
Beyond Paget cells, the surrounding epidermis might show:
- Hyperplasia: Increased number of cells in the outer layer of the skin.
- Spongiosis: Widening of intercellular spaces.
- Exocytosis: Migration of inflammatory cells into the epidermis.
Immunohistochemistry: Painting a Molecular Portrait
Immunohistochemistry utilizes antibodies to target specific molecules within cells, aiding diagnosis and classification. In Paget’s disease, key findings include:
- Cytokeratin (CK) expression: Paget cells typically express low molecular weight CKs like CK7,similar to breast ductal carcinomas. This differentiates them from normal skin cells, which express high molecular weight CKs.
- GATA3 positivity: This marker, associated with breast development, is positive in most Paget cells, further supporting their mammary origin.
- HER2 status: Overexpression of HER2, a potential therapeutic target, is seen in a significant portion of Paget’s disease cases.
- Estrogen and progesterone receptor (ER/PR) expression: These markers are less frequently positive in Paget’s disease compared to other breast cancers.
- CK 5/6: These markers are negative on Paget’s cells and are positive in surrounding keratinocytes.
A video summary
The Importance of the Microscopic Landscape
Understanding the histological and immunohistochemical features of Paget’s disease is crucial for:
- Accurate diagnosis: Differentiating it from other skin conditions like eczema or psoriasis.
- Determining the underlying breast cancer: Identifying the associated carcinoma and its characteristics.
- Guiding treatment: Informing decisions about surgery, radiation therapy, and targeted therapies based on molecular markers.
Try this MCQ on the topic
Which of the following IHC is in image B, in this 55- year old patient with eczema like lesion on the right breast.
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Correct answer is Her-2-neu. Note the membranous staining pattern.
Additional Resources:
- National Cancer Institute: https://www.cancer.gov/types/breast
- Sternberg Diagnostic surgical pathology 7th edition.
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