What is Mammary Paget Disease?
In 1874, Sir James Paget discovered a link between chronic nipple conditions and breast cancer in 15 of his female patients. These patients had chronic sores on their nipples that looked like eczema or blisters with a clear, yellowish fluid. Initially, these sores were thought to be harmless, but later, they were found to contain cancer cells. These sores typically appear on the nipple and the darker skin around the nipple, also known as the areola.
This condition, which involves the presence of cancer cells in the nipples, was named after Paget and thus, became known as mammary Paget’s disease (MPD) or Paget’s disease of the breast (PDB).
A similar condition was discovered in the external genital area of both men and women, and it was given the name extramammary Paget’s disease. While the two conditions have similar appearances under a microscope (referred to as having the same ‘histological features’), they are caused by different factors (or have different ‘pathogenesis’).
What Causes Mammary Paget Disease?
Paget’s disease is widely recognized to be linked with some kind of underlying breast cancer, usually what’s known as ductal carcinoma in situ (cells that appear abnormal but haven’t spread) or invasive ductal carcinoma (cancer that started in a milk duct and has spread to the surrounding tissue). It’s thought this happens when harmful breast cells move towards the skin through milk ducts and smaller branches.
It’s a bit unclear what specifically puts someone at risk for Paget’s disease, but the usual risk factors for other types of breast cancer seem to apply.
These risk factors include being older (over 50 years old), having a history of certain breast abnormalities like lobular carcinoma in situ (abnormal cells in breast lobules) or atypical hyperplasia (a build-up of abnormal cells in the breast), having a family history of breast or ovarian cancer, having dense breast tissue (seen through a mammogram), exposure to radiation (especially in the chest), carrying inherited gene mutations (like BRCA1 and BRCA2) which can raise the risk of breast or ovarian cancers, using hormone replacements like estrogen therapy after menopause, belonging to a high-risk ethnicity group for breast cancer (white women are more likely than black or Hispanic women), and drinking a lot of alcohol.
Risk Factors and Frequency for Mammary Paget Disease
Paget’s Disease of the Breast (PDB) is less common compared to other symptoms of breast cancer such as noticeable lumps or mammography findings. It accounts for just 1-4 percent of overall breast cancer symptoms. Although mostly found in women, men can also experience this. It is typically seen in people aged 26 to 88 years old, with the most common occurrence in women after menopause, in their 60s.
Even though PDB is not a common symptom, anyone with a persistent skin rash on the nipple should be checked for this disease. Some research indicates that fewer people have been getting diagnosed with PDB over time. The total rate of PDB diagnosis was high from 1988 to 2002. However, according to the ‘surveillance, epidemiology, and end results (SEER)’ database, the diagnosis rate has dropped by 45% afterwards for reasons that are not known. This drop was most pronounced in cases of PDB linked to invasive cancer or DCIS (Ductal Carcinoma In Situ).
Signs and Symptoms of Mammary Paget Disease
When assessing a skin lesion on the breast, it’s important to ask about the duration of the condition and any associated symptoms. These might include fluid coming from the nipple, pain, bleeding, burning sensation, redness, flaking, and itching. A persistent, itchy lesion could suggest a possible underlying breast cancer. Early signs of this condition, called Paget’s disease of the breast (PDB), may include scratching due to itchiness and the repeated appearance and disappearance of tiny blisters within the skin lesion. It’s also vital to consider the personal risk factors for breast cancer, such as a personal or family history of breast or ovarian cancer, use of hormone replacement therapy, and lifestyle factors.
A thorough breast examination should be conducted to identify any additional breast abnormalities. PDB usually affects one breast, while eczema typically affects both, but it’s not uncommon for both breasts to be affected in PDB. On examination, you might typically find a red, scaly, crusty, and thickened area of skin on the nipple that extends to the surrounding area. This area of red skin is well-defined and tends to be much thicker than you’d typically see in eczema, but it can be difficult to tell the difference between PDB, eczema, and melanoma.
The skin lesions may appear around the nipple but can sometimes be found further out. They tend to range in size from a pinpoint to about 6 inches in diameter and can produce a bloodstained discharge. An underlying cancer is present in up to 88 percent of cases with these skin changes. Half of the people may also have a lump that can be felt in the breast. Other changes to the nipple, such as retraction or invagination, can suggest that the cancer has spread into the breast tissue.
Testing for Mammary Paget Disease
Your doctor might start investigating your symptoms by conducting either mammography (an x-ray of the breast) or a biopsy (a procedure where a small sample of tissue is removed for examination). A technique known as scrape cytology is a quick, easy, and non-invasive method of checking for nipple eczema in the doctor’s office. Mammography of both breasts must be performed to search for an underlying lump. Approximately half of the cases of nipple eczema often have abnormal findings on the mammogram. In one-fifth of the cases, abnormalities are seen on the mammogram even if no lump can be felt.
Negative mammograms do not always mean that there is no cancer. For instance, in a clinical study, mammography failed to detect a type of breast cancer known as Ductal Carcinoma in Situ (DCIS) in 17 women, of which 5 had extensive disease spread over a wider area. Whole breast ultrasound can sometimes assist in further investigations, however, it doesn’t significantly increase detection of underlying problems when used with mammography.
Magnetic Resonance Imaging (MRI) is a sensitive tool for diagnosing invasive breast cancer. MRI is sometimes recommended as the cancer may be scattered in various parts of the breast. Around 12 to 15 percent of cases might not manifest as a palpable lump or abnormal findings in a mammogram. MRI might reveal hidden cancer in some women with nipple eczema, even if no such indications are seen on the mammogram or physical examination. This can allow for a more targeted treatment of the breast area affected. However, even MRI is not 100% reliable in excluding hidden cancer.
Biopsy, the removal and examination of tissue, is crucial. This method investigates not only the nipple but also any underlying lumps or abnormalities seen in the mammogram, to assist in further planning of the management and treatment. If there is nipple discharge, a sample of it may be collected and examined to detect the presence of abnormal cells.
Immunohistochemistry staining for nipple biopsy is very useful for differentiating the disease from other similar conditions. This diagnostic panel includes tests such as CK7 and CK20, Carcinoembryonic Antigen (CEA, a type of protein), Estrogen receptor (ER, a type of protein that can bind to estrogen), HER2 (a type of protein that plays a significant role in breast cancer), S-100, and MART-1 or HMB-45 (if melanoma is suspected). These help in identifying if the condition is a type of skin cancer or breast cancer and guide the treatment accordingly.
Treatment Options for Mammary Paget Disease
Paget’s disease of the breast is categorized and arranged using the TNM classification system, just like other types of breast cancer. This means that the presence of Paget’s disease doesn’t change the stage of any existing breast cancer. If there’s no other type of breast cancer found, Paget’s disease is classified as Tis (Paget) disease. One key element that impacts treatment plans is if there is any underlying breast cancer present.
Traditionally, a simple mastectomy, or removal of the entire breast, has been the standard treatment for Paget’s disease of the breast, both with and without an underlying mass or lump. But recently, breast-conserving treatment (BCT) has become the preferred option for a certain type of breast cancer known as ductal carcinoma in situ (DCIS). No guidelines exist yet for Paget’s disease co-existing with invasive breast cancer.
When Paget’s disease is present alongside a palpable mass or a noticeable change in a mammogram, the associated breast cancer is usually at a more advanced stage. This also increases the chances of finding multiple or invasive tumors or finding cancer in the lymph nodes under the arm.
Women with multiple areas of cancer or widespread calcium deposits in the breast are usually treated with a mastectomy along with an examination of the underarm lymph nodes, often through a procedure known as a sentinel lymph node biopsy (SLNB).
In cases where there’s no visible lump, there’s still a high probability of an underlying condition, such as DCIS. The chances of finding underlying invasive cancer range from 25 to 33 percent. Both mastectomy and BCT, followed by radiation therapy, are considered acceptable treatment options. If the patient has Paget’s disease and there’s no palpable mass or change in the mammogram, removal of the nipple-areolar complex with a targeted lumpectomy and then radiation therapy to the whole breast is considered a reasonable alternative to mastectomy, if it results in a good cosmetic outcome and cancer-free margins.
The risk of cancer spreading to the underarm lymph nodes is higher if there’s a palpable mass or invasive cancer. In these cases, an examination of the lymph nodes is needed. Patients with DCIS don’t require investigation of the lymph nodes unless the disease is widespread enough to warrant a mastectomy.
If a mastectomy is planned, a sentinel lymph node (SLN) biopsy is usually done to avoid having to remove all the lymph nodes under the arm if any invasive cancer is found.
At present, there is no evidence to suggest that hormone therapies, such as tamoxifen or aromatase inhibitors, can lower the risk of local disease recurrence in patients with Paget’s disease of the breast who have received breast-conserving therapy and who don’t have any underlying invasive carcinoma or DCIS. Recommendations for hormone therapy and other forms of additional treatment, like chemotherapy and trastuzumab, should be made based on the characteristics of any associated invasive carcinoma or DCIS.
Finally, a new procedure known as photodynamic therapy has been tested recently in clinical trials for the treatment of Paget’s disease. This method uses a drug called a photosensitizer along with special type of light that can destroy affected cells. Initial results suggest that photodynamic therapy is a safe, well-tolerated and possibly less invasive alternative to surgery, but more research is needed to validate its effectiveness and long-term safety.
What else can Mammary Paget Disease be?
It’s critical to correctly diagnose Paget’s disease of the breast and distinguish it from other similar conditions. These may include certain skin inflammation issues, pre-cancerous skin conditions, and other types of breast cancers. In order to conduct accurate examinations and treatments, doctors should consider a variety of potential diagnoses, which include:
- Various skin inflammation conditions like atopic dermatitis, factitious dermatitis, contact dermatitis or other types of eczema
- Different skin cancers such as malignant melanoma, squamous cell carcinoma, or basal cell carcinoma
- Pre-cancerous skin conditions like Bowen’s disease
- Erosive adenomatosis of the nipple, a benign (non-cancerous) tumor of the nipple ducts
- Nipple duct adenoma, a condition presenting as a noticeable nipple lump with skin erosion and sometimes a discharge in middle-aged women
- Benign Toker cell (clear cell of the nipple epidermis) hyperplasia – an overgrowth of normal cells
- Drug eruptions – reactions to medications
An inflammation of the nipples, known as eczematous dermatitis, is usually seen in both nipples. It doesn’t cause hardening and quickly responds to steroid creams. However, if this “eczema” lasts for more than three weeks even after treatment, Paget’s disease could be the underlying cause.
What to expect with Mammary Paget Disease
The outlook of Paget’s disease of the breast (PDB) depends on how it appears at first and if there is a deeper, invasive ductal carcinoma (a type of breast cancer) or if the cancer has spread to the axillary lymph nodes (small glands that filter substances in the body) under the armpits. If PDB starts with a noticeable lump, it usually suggests that the disease is more advanced compared to cases without a discernible lump.
When there isn’t a noticeable lump in the breast, about 92% of patients live for at least five years after having the lump removed; around 82% live for at least ten years. If there is a lump, the numbers drop down to 38% living for five years and 22% living for ten years. The outlook becomes worse if there is lymphadenopathy, which means the lymph nodes are abnormal in size or consistency.
Possible Complications When Diagnosed with Mammary Paget Disease
It’s not unusual for the detection of Mammary Paget disease, a type of breast cancer, to be delayed or even missed. The longer the delay, the more time the cancer has to spread, which could potentially result in spread to the lymph nodes, making the disease more serious. A more widespread disease will require more extensive removal of tissue.
The complications of treating breast cancer in patients with Mammary Paget disease are the same as those of any breast cancer surgery. Taking out the lymph nodes might cause long-term swelling called lymphedema. Chemotherapy and radiation treatment could potentially increase the likelihood of developing other types of cancers. Furthermore, hormonal treatments and radiation may also increase the risk of earlier menopause or infertility.
Common Risks from Delayed Detection & Treatment:
- Spread of breast cancer
- More widespread disease requiring extensive tissue removal
- Long-term swelling after removal of lymph nodes
- Increased risk of other cancers from chemotherapy and radiation treatment
- Earlier menopause or infertility from hormonal treatment and radiation
Preventing Mammary Paget Disease
Paget’s disease of the breast is a rare type of breast cancer. It often comes across as a skin rash, but this could actually be a warning sign of a potential tumor in the breast. So, if someone has this rash, they may need urgent medical testing.
Rashes on the nipple are not uncommon and are usually caused by skin infections or irritations. However, if a nipple rash doesn’t improve with creams or ointments that contain steroids, then further medical examinations, like high-tech scans or removing a small piece of the rash for testing (biopsy), might be necessary. These tests are needed to rule out serious conditions, such as malignant melanoma, a type of skin cancer, or Paget’s disease of the breast.
Treatment will vary depending on different factors. These include the stage of the disease, whether a tumor is present, whether lymph nodes are involved, the status of hormone and HER2 receptors (proteins), and the patient’s overall health condition.
Surgery, followed by radiation therapy for the entire breast, is usually the recommended treatment option. This offers the best chances of survival and recovery.
