What is Extramammary Paget Disease?
Extramammary Paget disease (EMPD) is a rare skin condition that often shows up in areas with a large number of sweat glands, like the vulva, although it can also occur on the scrotum, the anus, and the penis. The affected areas often appear as red, clearly defined patches that can become eroded, ulcerated, flaky, or resemble eczema. Most often, it affects women and usually happens between the ages of 60 to 80 years.
Many aspects of EMPD are still debated among medical professionals, such as how often it’s associated with cancer of the vulva or invasive EMPD, its link with cancers in nearby or distant parts of the body, and how often it comes back after surgery. Early detection is very important for this condition, due to delays in diagnosis and because it’s often associated with invasive disease.
What Causes Extramammary Paget Disease?
The exact cause of primary Extramammary Paget’s Disease (EMPD), a rare skin disorder, is still being discussed, but it is generally believed to start in the sweat glands. Secondary EMPD, on the other hand, usually spreads from a cancerous growth in nearby areas or comes from a more severe, hidden cancer somewhere else in the body.
For example, it can extend from a skin cancer that begins in oil or sweat glands (adnexal adenocarcinoma) or from an internal cancer like bladder or rectal cancer. In some cases, it may also originate from cervical, prostate, ovarian, or womb cancer.
Risk Factors and Frequency for Extramammary Paget Disease
Extramammary Paget’s disease (EMPD) is a rare condition. There are just several hundred cases reported globally and its exact count is unknown. EMPD makes up 6.5% of all skin-related Paget’s diseases. This condition typically affects people aged between 50 and 80, with those aged around 65 being the most affected. While Caucasians and women are commonly affected, in Asia, males are more likely to have this disease.
The disease often appears in the vulvar area – a fact that is reflected in the 65% of EMPD cases found there. However, it can also be found in places with specialized sweat glands such as the outer ear canal where it could be linked with a certain type of cancer, and even the eyelid where it might occur with Moll’s glands’ cancer. Other rare spots where EMPD can occur include the buttock, penis tip, knee, thigh, belly, belly button, lower part of the chest, and the scalp.
It’s worth noting that there is a significant association of EMPD with other kinds of cancers. In fact, between 10% and 30% of EMPD patients also have a different underlying cancer. Therefore, a thorough check to rule out cancer is very important.
Signs and Symptoms of Extramammary Paget Disease
Extramammary Paget’s disease (EMPD) is a skin condition that starts with red, flaky patches that are usually well-defined and cover a few centimeters of skin. Over time, these spots might develop into crusty sores, wet erosions, or even ulcers. Sometimes, the combination of eroded areas and white scale can make the skin look like a “strawberries and cream” pattern. These affected areas tend to grow slowly, with a clear boundary between healthy and affected skin.
It can be challenging to diagnose EMPD because its symptoms can look like other skin conditions like eczema, psoriasis, or candidiasis. As a result, many people try multiple skin treatments before they discover that they have EMPD. On average, people wait about two years before getting an accurate diagnosis.
The most common symptom of extramammary Paget’s disease is itchiness, but people might also experience a burning sensation, tenderness, or swelling. Some lesions display lighter or darker skin color. Lesions that have been present for a long time may show changes due to repeated scratching or secondary infections.
- Red, flaky patches
- Develop into crusty sores, wet erosions, or ulcers
- “Strawberries and cream” pattern
- Symptoms resemble other skin conditions
- Common symptom is itchiness
- May experience burning, tenderness, or swelling
Moreover, hard nodules and enlarged regional lymph nodes could indicate an underlying cancer. In cases where the disease starts in the groin area and spreads to other areas covered by underwear, this is known as an ‘underpants-pattern erythema’. This pattern might be due to cancer spreading through the lymphatic system, and it tends to have a poor prognosis since it is associated with rapidly spreading distant metastases. This spread of cancer could lead to fatality if not detected and treated early.
Testing for Extramammary Paget Disease
If your doctor suspects you have extramammary Paget’s disease (EMPD), which is a rare skin disorder, they will order some tests to check for underlying cancer. These tests could include a cervicovaginal smear, rectocoloscopy, cystoscopy, abdominal ultrasound or CT scan, gastroduodenal fibroscopy, mammography, intravenous urography, and serum tumor markers. The type of test they choose will depend on where your skin lesions are.
Long-term monitoring is needed once EMPD is diagnosed, as some people experience a return of the disease more than 15 years after their initial treatment. If your EMPD is not invasive, your doctor will check in on you twice a year for the first three years, then annually for the next ten years. However, if your EMPD is invasive or linked to a distant tumor, you’ll need to see your doctor more often – up to four times a year. Any suspicious skin lesions will be biopsied. For EMPD around the anus, you’ll undergo an annual comprehensive exam, punch biopsy of new lesions, and proctosigmoidoscopy, and also a colonoscopy every 2-3 years. For EMPD of the vulva, regular inspections, biopsies of any recurring lesions, and hysteroscopy or regular pelvic ultrasound scans will be performed.
Recently, doctors have been using a lymph node staging system to help them predict outcomes for EMPD patients. This system, proposed by Hatta and colleagues, categorises lymph node involvement into three stages: N0 (no involvement), N1 (unilateral involvement), and N2 (bilateral or distant site disease). According to this system, survival rates decrease as lymph node involvement increases.
Therefore, deciding how to manage a patient with confirmed EMPD and no signs of lymph node disease can be tricky. This has spurred some discussions among the medical community regarding two surgical procedures: the sentinel lymph node biopsy (SLNB) with or without complete lymph node dissection (CLND) and elective lymph node dissection (ELND). The aim of these procedures is to stop the spread of the disease by removing the lymph nodes through which metastases (cancer spread) are thought to pass initially, before spreading throughout the body.
Treatment Options for Extramammary Paget Disease
Surgery is generally considered to be the most effective treatment for EMPD. Over time, doctors have tried a variety of treatments to lessen the serious side effects often tied to the traditional surgical treatments. Given that EMPD is a rare condition, there’s limited experience in managing it. Due to frequent relapses after removal, additional therapies are often used.
Medical literature suggests that when removing the affected area, a safety margin of 2 centimeters should be left, but 1 centimeter might be enough for lesions with visibly clear margins. Lower recurrence rates have been reported when using a specific surgical procedure known as Mohs micrographic surgery (MMS). A study found that the recurrence rate was 23% for MMS compared to 33% for conventional removal with margin control.
There are also non-surgical treatments available. Systemic chemotherapy, which involves using drugs like vincristine, docetaxel, carboplatin, 5-FU, mitomycin-C, etoposide, can be used when surgery and radiation are not viable options. Radiation can also be used for lesions that can’t be operated on or as an additional treatment to surgical removal, such as in the case of recurrence after surgery. This method tends to have better results for primary in-situ EMPD (confined to its original place).
Some local cytotoxic drugs (like bleomycin, 5-fluorouracil), while not sufficient on their own, may help reduce the lesion’s margins or assist in making it more visible, making surgical removal more effective. Interferon, a type of protein, has shown promising results when injected directly into the lesion in some patients.
Imiquimod, a topical medication that enhances the immune response, has been used successfully in a small number of EMPD cases, and it appears to be helpful in superficial (surface level) forms. Imiquimod could be considered an alternative to surgery, an additional treatment before or after surgery or even part of a combination of treatments. While only individual case studies or small group studies have been published so far, the results for Imiquimod appear hopeful.
What else can Extramammary Paget Disease be?
Diagnosis and treatment sometimes get delayed because the symptoms are not specific and can be easily confused with other conditions, especially in older patients who often seek help later. EMPD, a type of skin cancer, can be mistaken for a range of different illnesses such as:
- Contact dermatitis (a type of skin irritation)
- Fungal infection
- Psoriasis (a skin condition that causes red, scaly patches)
- Seborrheic dermatitis (a skin condition that causes dandruff and red skin)
- Anogenital intraepithelial neoplasia (a precancerous condition affecting the anus and genitals)
- Lichen sclerosis (a skin condition causing white, thin patches)
- Melanoma (a serious type of skin cancer)
- Mycosis fungoides (a type of lymphoma affecting the skin)
- Histiocytosis (a disease involving an overproduction of certain cells)
- Leukoplakia (white patches in the mouth)
- Squamous cell carcinoma (a type of skin cancer)
- Basal cell carcinoma (another type of skin cancer)
- Condylomata acuminate (genital warts)
- Hidradenitis suppurativa (a skin condition causing lumps under the skin)
- Crohn’s disease (a type of inflammatory bowel disease)
Given these potential misdiagnoses, it’s essential for doctors to make thorough checks before deciding on the most appropriate treatment.
