BACKGROUND: No consensus has been reached regarding the optimal chemotherapy for metastatic extramammary Paget\'s disease (EMPD), a rare cutaneous adenocarcinoma, because of the lack of solid evidence from prospective trials. However, the immunohistochemical profile of EMPD reportedly resembles that of breast cancer, particularly in terms of human epidermal growth factor receptor 2 (HER2) expression, suggesting that HER2 is a promising therapeutic target for advanced HER2-positive EMPD.
METHODS: In this phase II single-arm trial, 13 Japanese patients received intravenous trastuzumab (loading dose of 8 mg/kg and maintenance dose of 6 mg/kg) and docetaxel (75 mg/m2) every 3 weeks for up to 2 years. The docetaxel dose was reduced or discontinued according to its toxicity. The primary trial endpoints were objective response rate (ORR) after 3 cycles of treatment and safety throughout the study period.
RESULTS: All 13 patients completed 3 cycles of combination therapy. The median follow-up was 27.9 months. The ORR was 76.9% (n = 10/13; 90% CI, 50.5-93.4). Frequently observed adverse events were neutropenia (100%), hypoalbuminemia (84.6%), and mucocutaneous infection (84.6%), all of which were well tolerated.
CONCLUSIONS: The combination of docetaxel and trastuzumab demonstrated a favorable clinical effect and acceptable tolerability, which makes it a good treatment option for HER2-positive metastatic EMPD (ClinicalTrials.gov Identifier: UMIN000021311, jRCTs031180073).

Extramammary Paget\'s disease recurs often after traditional surgical excision. Margin-controlled surgery improves the recurrence rate for male genital disease but is less studied for female anatomy.
This study aimed to compare surgical and oncologic outcomes of margin-controlled surgery vs traditional surgical excision for female genital Paget\'s disease.
We conducted a prospective observational trial of patients with vulvar or perianal Paget\'s disease treated with surgical excision guided by Mohs micrographic surgery between 2018 and 2022. The multidisciplinary protocol consisted of office-based scouting biopsies and modified Mohs surgery followed by surgical excision with wound closure under general anesthesia. Modified Mohs surgery cleared peripheral disease margins using a moat technique with cytokeratin 7 staining. Medial disease margins (the clitoris, urethra, vagina, and anus) were assessed using a hybrid of Mohs surgery and intraoperative frozen sections. Surgical and oncologic outcomes were compared with the outcomes of a retrospective cohort of patients who underwent traditional surgical excision. The primary outcome was 3-year recurrence-free survival.
Three-year recurrence-free survival was 93.3% for Mohs-guided excision (n=24; 95% confidence interval, 81.5%-100.0%) compared to 65.9% for traditional excision (n=63; 95% confidence interval, 54.2%-80.0%) (P=.04). The maximum diameter of the excisional specimen was similar between groups (median, 11.3 vs 9.5 cm; P=.17), but complex reconstructive procedures were more common with the Mohs-guided approach (66.7% vs 30.2%; P<.01). Peripheral margin clearance was universally achieved with modified Mohs surgery, but positive medial margins were noted in 9 patients. Reasons included intentional organ sparing and poor performance of intraoperative hematoxylin and eosin frozen sections without cytokeratin 7. Grade 3 or higher postoperative complications were rare (0.0% for Mohs-guided excision vs 2.4% for traditional excision; P=.99).
Margin control with modified Mohs surgery significantly improved short-term recurrence-free survival after surgical excision for female genital Paget\'s disease. Use on medial anatomic structures (the clitoris, urethra, vagina, and anus) is challenging, and further optimization is needed for margin control in these areas. Mohs-guided surgical excision requires specialized, collaborative care and may be best accomplished at designated referral centers.

Extramammary Paget\'s disease (EMPD) is an intraepithelial adenocarcinoma. The chronic relapsing clinical course and unbearable clinical symptoms of extramammary Paget\'s disease usually result in a markedly diminished quality of life. No national data are available on descriptive epidemiology of EMPD in China, the most populous country over the world. This population-based study aimed to estimate the prevalence and associated sex and age patterns of EMPD in China.
This study was conducted using data from China\'s Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance, covering approximately 0.43 billion Chinese urban residents in 2016. Patients with EMPD were identified based on the diagnostic names and codes in claim data.
A total of 53 males and 31 females with EMPD were found. The crude prevalence in 2016 was 0.04 per 100,000 population [95% confidence interval (CI) 0.02-0.06], ranging from 0.01 (95% CI 0.00-0.02) in North or Northeast China to 0.08 (95% CI 0.03-0.16) in Southwest China. The rate was higher in males (0.05, 95% CI 0.03-0.08) compared with females (0.03, 95% CI 0.02-0.05). The mean age of patients was 65.87 (standard deviation: 14.21) years, with the peak prevalence appeared in patients aged 70-79 (0.28, 95% CI 0.16-0.42).
The prevalence of EMPD was markedly lower than those in the United States and Europe, and varied across regions in China. Chinese patients were much younger, with significant male predominance. Further studies are warranted to examine potential pathophysiologic mechanism.

Extramammary Paget\'s disease (EMPD) often invades the dermis and metastasizes to the lymph nodes. Patients with EMPD associated with lymph node metastases have poor prognosis; to date, effective treatment has not yet been established. Lymph node dissection, aiming to control the local disease, is a standard form of management for EMPD patients with lymph node metastases (LNM). We investigated the clinical and pathological features, treatment strategies and prognostic factors of patients with metastatic EMPD who underwent lymph node dissection. We retrospectively evaluated 38 cases of extramammary Paget\'s disease with lymph node metastasis over 10 years. All patients underwent wide resection of the primary lesion and lymph node dissection. Univariate analysis revealed the number of metastatic nodes and lymphadenopathy as prognostic factors. In multivariate analysis, the number of metastatic lymph nodes retained statistical significance (hazard ratio, 35.3; 95% confidence interval, 3.23-387.0; P = 0.003). The 5-year survival rate was 100% and 19.1% in patients with two or less LNM and with three or more LNM, respectively. In patients with three or more LNM, the 5-year survival rate after adjuvant radiation therapy was better than that after surgery alone (75% vs 0%). In conclusion, patients with two or less LNM can be expected to have long-term survival with lymph node dissection only, while patients with three or more LNM may require adjuvant radiation therapy to improve prognosis. These results suggest that lymph node dissection may be a strategy to treat EMPD with regional LNM.

To analyze the clinical and histopathological manifestations, immunohistochemistry, treatment, and prognostic factors of primary, extramammary Paget\'s disease (EMPD), we systematically reviewed the clinical presentations, histopathology and follow-up courses of 28 patients with primary EMPD. Clinically, their symptoms and morphology mimicked various types of dermatoses, such as seborrheic dermatitis, eczema, candidiasis, tinea cruris and erythrasma, so the initial diagnosis of EMPD was often delayed or missed. Histopathology showed invasive EMPD, and the tumor cells were mostly solid nests or had a glandular structure. The cellular atypia was obvious and signet ring Paget\'s cells could usually be observed. The acantholysis phenomenon in the epidermis could be seen. The condition was associated with stromal invasion, lymphatic metastasis, and even vascular invasion. Adnexal involvement in primary EMPD was a very common feature. The immunohistochemical markers CK7, GCDFP-15, CEA and HER-2 positive can identify other tumors similar to Paget\'s disease. We concluded that invasive EMPD is a rare malignant skin neoplasm with morphological diversity. Poorly differentiated cell morphology, extensive adnexal involvement, and an invasive pattern of solid sheets are significantly associated with lymph node metastasis and a worse prognosis. Pathologists should be alert to invasive lesions and make the correct diagnosis.