By Jeyashree Sundaram (MBA)

Extramammary Paget's disease or EPMD is a rare disease characterized by the appearance of a chronic skin rash, resembling eczema, in the genital areas.

A microscopic view of the condition reveals it to be composed of cells similar to those seen in mammary Paget disease, with the primary difference between EPMD and mammary Paget disease being the location in which the rashes appear. In the former, the scrotum, vulva, axilla, penis, and perianal region are affected, whereas in the latter the rash is seen around the areolar skin and nipple area.

Although women in the age group of 50–60 (postmenopausal women) are found to be most prone to EPMD, men of the same age group may also be affected. In some instances, individuals below 50 years of age have also been diagnosed with it. The prognosis of the disease depends upon early detection, diagnosis, treatment, and its association with any underlying cancer.

Disease Types

EPMD is categorized into three types, depending on the location of the origin of the disease.

• Type 1 (a) primary cutaneous EMPD: when the disease arises in the apocrine glands of the epidermis or the underlying skin appendages
• Type 1(b): about 15–25% of EMPD is found in association with adenocarcinoma in situ or invasive Paget disease
• Type 2 EMPD: cutaneous manifestation of underlying rectal or anal adenocarcinoma
• Type 3 EMPD: skin lesion associated with bladder adenocarcinoma

Symptoms and Causes

Patients typically report itchy  lesions in the anal and genital regions. The itching sensation may be mild or intense. When the lesions are scratched, pain or bleeding may result. The lesions may become scaly, red, crusty, flaky, or thick. Other frequent symptoms include irritation, burning sensation, inflammation, pimples, subtle changes in the skin, or inflamed hair follicles.

Some patients may not have any symptoms, while others may have multiple symptoms.

In women, the vulva is the most common area to be affected. However, the disease may spread to the vagina, mons pubis, labia, and thighs; perianal lesions may even extend up to the anal canal.

Around 25% of EPMD is associated to an underlying cancer. To accurately predict the risk of cancer  in a given case of EMPD, the location of the disease is important. About 25–35% of the disease identified in the anal region is linked with underlying colorectal cancer.

The cause of EMPD is not known. Around 25% of patients show the presence of an underlying tumor such as carcinoma of the bladder, urethra, cervix, vagina, Bartholin glands, prostate, endometrium, cutaneous adnexal carcinoma, and in particular apocrine carcinoma; in patients with genital EMPD, around 4–7% have associated carcinoma.

The disease progresses slowly, and in some cases, the cancer may not be noticeable even if it has been present for 10–15 years.

Diagnosis and Treatment

Often, EMPD is mistaken for eczema, moniliasis, or psoriasis due to the rash and itching it causes. It is also misdiagnosed as chronic dermatitis, jock itch, intertrigo, Bowen’s disease, or fungal infections.

Tests are required, such as needle biopsy or ultrasound scanning of regional lymph nodes, and search for other tumors by techniques such as colonoscopy, cervical smear, or mammography. When physicians suspect EMPD, a skin biopsy of the lesion is performed for disease confirmation. Special stains are used to differentiate EMPD and melanoma in situ.

Usually, surgery is the treatment option of choice for EPMD. Advanced surgical techniques such as Mohs micrographic surgery, excisional biopsy, and vulvectomy are available for treating EMPD.

The use of reflectance confocal microscopy avoids causing damage to the skin while enabling the examiner to visualize the cancer cells in real time. The use of this technique may enable EMPD patients to avoid or minimize the number of skin biopsies to see if the disease still exists and to confirm the need for further treatment.

It is often difficult to determine how much tissue to remove, especially when the lesions are spread across the anogenital area. As recurrence is common in 30–50% of patients after surgery, the standard practice is to re-examine patients once every 3 months. This is continued for 2 years, with follow-ups on a yearly basis thereafter.

In some patients, due to the location or recurrent disease, surgery may not be a possibility. Other treatment methods such as radiation therapy, aminolevulinic acid based photodynamic therapy, laser ablation, chemotherapeutic agents (for example, paclitaxel, 5-fluorouracil, docetaxel, imiquimod, and trastuzumab) are then chosen. The success levels vary across the different treatment methods and disease grades.

Being a rare disease and due to the unavailability of clinical trials, chemotherapy is seldom used to treat EMPD. However, with the progress of research into identifying tumor cell mutations (next-generation genome sequencing), it is expected that newer and more effective drugs will be developed in the future.

References

1. https://www.myempd.com/about/
2. https://stanfordhealthcare.org/medical-conditions/cancer/extramammary-pagets-disease/diagnosis.html
3. https://stanfordhealthcare.org/medical-conditions/cancer/extramammary-pagets-disease/treatments.html
4. https://rarediseases.info.nih.gov/diseases/4192/paget-disease-extramammary
5. https://stanfordhealthcare.org/medical-conditions/cancer/extramammary-pagets-disease.html
6. https://www.dermnetnz.org/topics/extramammary-paget-disease/
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949369/
8. https://www.myempd.com/empd-symptoms/

Further Reading

• All Extramammary Paget's Disease Content
• Extramammary Paget’s Disease Treatment
• Extramammary Paget’s Disease Classification and Diagnosis