International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationRole of Radiotherapy as Curative Treatment of Extramammary Paget’s Disease
Introduction
Extramammary Paget’s disease (EMPD) is a comparatively rare malignancy that often develops in the genital areas, including the vulva, scrotum, penis, and perineal and perianal regions, and less frequently in the axilla and umbilicus, in women aged 50–80 years. This neoplasm is considered to derive from the apocrine gland, but its etiology is still unclear. In 1874, Sir James Paget reported an intraepithelial neoplasm of the areola in the breast that was termed “Paget disease” (1). EMPD, which involved similar intraepithelial lesions in the skin of the scrotum and penis, was first described by Crocker (2) in 1888.
The disease sites generally present as relatively well-defined erythematous eczema or erosions, with or without leukokeratotic plaques, together with complaints of pruritus, irritation, or burning 3, 4, 5. However, EMPD will be asymptomatic in approximately 10% of patients. EMPD limited to the epidermis, so-called carcinoma in situ, is usually slow growing, with no change in the disease status for a period of ≥10 years in some cases. The diagnosis can accordingly be delayed, and the average interval between the onset of symptoms and diagnosis has been reported to be 2 years 4, 6. However, once the tumor invades into the dermis, it frequently makes rapid progress, resulting in lymph node and distant metastases. No well-established cures exist to treat patients with distant metastases of EMPD, and early detection and treatment while the disease is limited to the epidermis are of great importance. Additionally, EMPD frequently coexists with other internal malignancies; thus, a through examination to identify other malignancies should be performed before treatment 3, 4, 5, 6. Racial differences in the frequency of malignancies coexisting with EMPD have been reported, with the coexistence rate lower for Asian patients than for white patients (0–13% vs. 15–30%) (7).
Microscopically, Paget’s cells classically show abundant clear cytoplasm and large round-to-oval nuclei. They are distributed as single cells, strands, nests, or gland-like structures within the epidermis and epithelium of adnexal structures, with infiltration into the dermis at more advanced stages. However, the epidermal spread of other invasive cancers, such as genitourinary, colorectal, or anal canal carcinoma, or other intraepithelial neoplasms, such as squamous cell carcinoma in situ or intraepithelial melanoma, can occasionally mimic EMPD. Immunohistochemistry has been reported to be useful for differentiating between EMPD and these other malignancies and has been routinely used to definitively diagnose EMPD at our institution 8, 9, 10. Paget’s cells are generally positive for sweat gland markers such as cytokeratin 7 and gross cystic disease fluid protein 15 but are usually negative for markers of the epithelium and mucous membrane, such as cytokeratin 20 and cytokeratin 34βE12.
Wide surgical excision is currently the standard and most reliable curative treatment of EMPD 3, 4. However, surgical excision is sometimes not possible owing to the high incidence of elderly patients and the difficulties associated with aggressive surgery in the areas where the tumors are usually located. Although radiotherapy (RT) is applied to these medically inoperable patients and to patients who refuse surgery, few reports have been published of the results of RT. Therefore, we performed a retrospective review of patients with EMPD treated with RT with curative intent. We present the treatment outcomes and discuss the role of RT in EMPD.
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Patients
Between October 1998 and January 2007, a total of 22 patients with EMPD underwent RT with curative intent at our institution. The exclusion criteria included distant metastases and poor general condition (Eastern Cooperative Oncology Group performance status ≥3) (11). Of these patients, 4 were men and 18 were women, and their age at RT was 52–94 years (median, 72). The primary tumor sites were the vulva in 10 patients, perineum in 7, and scrotum in 5. The maximal diameter of the visible tumors
Tumor control and failure patterns
All irradiated tumors had macroscopically disappeared by 2–9 months after RT, and the initial complete response rate was 100%. Photographs of the tumor site in 2 patients before and after RT are shown in Fig. 1, Fig. 2. However, 13 of the 22 patients had developed recurrence 3–43 months after RT. Of these 13 patients, 3 had developed local progression within the radiation field and 10 had developed lymph node or distant metastases outside the radiation field, during a follow-up period of 8–133
Discussion
Although the most standard and reliable curative treatment of EMPD is surgery, and wide excision is usually performed as the first choice treatment, the incidence of positive surgical margins and local recurrence is high, reaching 36–71% and 15–61%, respectively, after surgery 4, 14, 15, 16, 17, 18. Accordingly, Mohs micrographic surgery, in which frozen sections from all surgical margins are evaluated during surgery, is considered a useful strategy for EMPD. Several investigators have reported
Conclusions
Radiotherapy was effective and safe in our patients with EMPD and appeared to contribute toward prolonged survival as a result of good tumor control. The optimal radiation dose for EMPD remains unknown; however, a total dose of ≥60 Gy may be required to control gross tumors. EMPD with tumor invasion into the dermis frequently leads to lymph node metastasis, and prophylactic RT of the inguinal and pelvic lymph nodes is recommended for these patients. Microscopic diseases such as potential lymph
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Vulvar extramammary Paget disease
2023, Diagnosis and Treatment of Rare Gynecologic CancersPaget's disease of the vulva: A challenge for the gynaecologist
2021, Journal of Gynecology Obstetrics and Human ReproductionCitation Excerpt :In the case of lymph node extension, radiation therapy of the inguinal, pelvic or lumbo-aortic regions should also be considered. Hata [32] reported a total dose ranging from 59.4–70.2 Gy for a median dose of 60.6 Gy in 12 cases of PDV treated with radiotherapy: overall survival at 2 years was 100 %, dropping to 53 % at 5 years. The side effects of radiotherapy included medium- and long-term desquamation and atrophy as well as acute dermatitis which can be prevented and treated with moisturizing creams [33].
Invasive Vulval Paget's disease treated with primary radiotherapy: A rare case report and literature review
2020, Gynecologic Oncology ReportsRadiation therapy for extramammary Paget's disease: Treatment outcomes and prognostic factors
2014, Annals of OncologyCitation Excerpt :Radiation therapy is considered as a possible treatment option for these patients, but there have been few studies that have presented treatment results to date. We have previously reported on radiation therapy for EMPD, but the number of patients involved in our study was too small to sufficiently define its role [4–6]. Therefore, data from our EMPD patients that were treated with radiation therapy have been arranged and thoroughly updated to reveal treatment efficacy and toxicity.
Conflict of interest: none.