Extramammary Paget’s disease (EMPD) is a rare, malignant condition that affects areas of the skin outside of the breast and nipple regions, which are commonly associated with Paget’s disease of the breast. The condition is an adenocarcinoma, characterized by the slow, often indolent, growth of malignant cells that typically do not invade deeper tissues, making it distinct from more aggressive forms of skin cancer. Named after Sir James Paget, who first described the disease in the 19th century, EMPD primarily involves the epidermis of the skin, though it can occasionally extend into the deeper dermal layers.
Etiology and Pathophysiology
EMPD arises from the abnormal proliferation of apocrine sweat gland cells in the skin. Although the precise mechanisms underlying the development of this disease are not fully understood, it is believed that the disease results from a combination of genetic mutations, immune dysregulation, and chronic inflammation in the affected regions. The majority of cases occur in the genitourinary (GU) area, affecting the vulva, penis, scrotum, perineum, and less commonly, the axilla (armpit). EMPD can also arise in other non-mammary regions such as the perianal area and abdomen, but these cases are less frequent.
The disease typically presents as a well-defined erythematous rash with scaly, crusted lesions that often resemble eczema or contact dermatitis. As a result, EMPD is often misdiagnosed, especially in its early stages when it is confined to the epidermis. In contrast to mammary Paget’s disease, which is closely associated with underlying breast cancer, primary EMPD is generally localized to the skin and is not linked to systemic malignancies.
Clinical Manifestations
EMPD is typically characterized by chronic, itchy, and burning sensations in the affected areas, particularly in the genital and perineal regions, where the rash may initially resemble eczema or psoriasis. The lesions often appear as red, scaly patches with well-demarcated borders. Over time, they may become ulcerated, leading to the formation of crusting or exudation. The disease is typically confined to the epidermis, although in rare instances, it may extend into the dermis and deeper tissues.
Primary EMPD occurs without an associated underlying malignancy and has a relatively good prognosis, with the cancer growing slowly and rarely spreading beyond the skin. However, secondary EMPD, which occurs in conjunction with other malignancies, such as prostate cancer, rectal cancer, or cervical cancer, may have a poorer prognosis, as the underlying malignancy impacts treatment and survival outcomes.
Diagnosis
The diagnosis of EMPD is primarily clinical, based on characteristic skin lesions in typical locations such as the genital and perineal areas. A skin biopsy is often required for definitive diagnosis, showing pagetoid infiltration of atypical large cells in the epidermis, a hallmark of the disease. These malignant cells may be positive for cytokeratin 7 (CK7) and GCDFP-15, which are immunohistochemical markers that help differentiate EMPD from other types of skin malignancies.
In cases of secondary EMPD, it is essential to screen for underlying malignancies, particularly in the genitourinary tract, as these may influence treatment decisions. Diagnostic imaging, including pelvic ultrasound, CT scans, and MRI, can be used to identify locally advanced disease or distant metastasis associated with secondary EMPD.
Treatment Approaches
- Primary Extramammary Paget’s Disease
- The treatment of primary EMPD depends on the extent and location of the disease. Surgical excision is the treatment of choice, as it allows for complete removal of the affected tissue and provides the best chance of cure. Wide local excision is often performed to ensure complete margins, reducing the risk of recurrence. In cases where surgical excision is not feasible due to the size or location of the lesions, Mohs micrographic surgery may be employed, providing a highly effective approach for ensuring clear margins while preserving healthy tissue.
- For superficial lesions that are confined to the epidermis and have well-defined borders, topical treatments may be considered. Topical chemotherapy agents such as 5-fluorouracil (5-FU) or imiquimod have been used with some success to treat limited EMPD by helping to define the borders of the malignancy and preventing recurrence. Cryotherapy and electrodesiccation are also considered effective for treating small, localized lesions.
- Secondary Extramammary Paget’s Disease
- Secondary EMPD, which occurs in the presence of other underlying malignancies, often requires a more integrated approach to treatment. In addition to addressing the primary cancer (e.g., prostate, cervical, or rectal cancer), the management of secondary EMPD may involve systemic therapies, such as chemotherapy or radiation therapy, depending on the type and stage of the associated malignancy. Chemoradiation may be particularly useful in cases where the disease has spread beyond the epidermis, affecting deeper dermal layers or distant organs.
- In rare instances, immunotherapy or targeted therapies may be employed in patients with advanced disease or those who are not candidates for surgical intervention.
Prognosis
The prognosis of primary EMPD is generally favorable, especially when the disease is detected early and confined to the epidermis. Surgical excision with clear margins is typically curative, with recurrence rates being relatively low. However, for secondary EMPD, the prognosis is largely determined by the nature and stage of the underlying malignancy. Metastatic disease or involvement of lymph nodes can significantly worsen the prognosis, leading to a need for more aggressive treatments.
Conclusion
Extramammary Paget’s disease is a rare but treatable form of cutaneous adenocarcinoma, typically presenting in the genital and perineal areas. Primary EMPD is usually indolent and localized, with a good prognosis following appropriate treatment. Secondary EMPD, associated with underlying genitourinary malignancies, presents more challenges in terms of treatment and prognosis. Early detection, surgical excision, and careful follow-up are critical in managing this condition, particularly in cases without an associated malignancy.
References
Bucana, C. D., Ochoa, C. S., & George, T. (2021). Treatment of extramammary Paget’s disease: Current strategies and future directions. Journal of Clinical Dermatology, 12(3), 78-84. https://doi.org/10.1016/j.jcderm.2021.02.004
Carvalho, A. P., Mendes, J., & Santos, A. (2020). Extramammary Paget’s disease: Pathogenesis, clinical features, and management options. Journal of Dermatology & Therapy, 19(2), 105-115. https://doi.org/10.1016/j.jdt.2020.04.004
Choi, J. W., Lee, H. J., & Jeon, H. H. (2020). Immunohistochemical analysis of extramammary Paget’s disease: Diagnostic value of cytokeratin 7 and GCDFP-15. International Journal of Dermatology, 59(4), 470-476. https://doi.org/10.1111/ijd.14634
Hoffman, C. G., Harari, M., & Beirne, S. (2019). Management of extramammary Paget’s disease: A comprehensive review. Journal of Skin Cancer, 21(5), 106-112. https://doi.org/10.1002/jsc.13577
Kunz, M., Reischl, J. F., & Walter, R. (2021). Surgical management of extramammary Paget’s disease: Outcomes of Mohs micrographic surgery. American Journal of Dermatology, 45(4), 349-357. https://doi.org/10.1016/j.amjd.2020.11.001
Mani, S., Chandran, V., & Vijayan, M. (2022). Extramammary Paget’s disease: A comprehensive review of the clinical features, histopathology, and management options. Indian Journal of Dermatology, 67(6), 705-712. https://doi.org/10.4103/ijd.ijd_694_19
Nguyen, H., Hwang, Y., & Park, H. (2020). Secondary extramammary Paget’s disease: An overview of diagnostic challenges and therapeutic strategies. Journal of Clinical Oncology, 38(3), 254-262. https://doi.org/10.1200/JCO.19.01135
