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To assess the incidence, treatment, and outcomes in patients with invasive vulvar extramammary Paget's disease (EMPD) in a national cohort of patients.Patients from the Surveillance, Epidemiology and End Results (SEER) database with diagnoses of vulvar EMPD from 1992 to 2016 were included. Demographic, treatment, and outcome data were analyzed.A total of 1268 cases of invasive EMPD were identified. Of those, 69.6% had localized disease, 12.0% regional disease, 1.3% distant disease, and 17.1% were unstaged. The annual incidence of invasive vulvar EMPD was 0.36 per 100,000 person years: rates have increased2-fold since 1992 (1992: 0.19 per 100,000 person years to 0.50 per 100,000 person years in 2016). Most patients underwent primary surgery (n = 1034; 81.5%). Five-year cancer specific survival (CSS) was 95.5% and was associated with stage. Compared to patients with localized disease, patients with distant metastases had dramatically worse CSS (HR: 85.8 (31.8-248) p 0.0001). Synchronous cancers (diagnosed within one calendar year of EMPD diagnosis year) were observed in 35 cases (2.8%), and 195 patients (15.4%) developed a secondary malignancy (diagnosedone year from year of EMPD diagnosis year). The most common synchronous breast, gastrointestinal tract, melanoma and the most common secondary cancers were breast, gastrointestinal tract and genitourinary tract.The incidence of invasive vulvar EMPD has increased over time. CSS is excellent for localized disease, but those with metastatic disease are in need of novel therapies. Approximately 15% will develop a secondary malignancy, indicating that patients with invasive vulvar EMPD should undergo site specific preventative health screens during recurrence surveillance.

Objectives To determine surgical and pathologic variables associated with recurrence in extramammary Paget's disease (EMPD). Methods Medical records of patients seeking care for EMPD from 1/1992–9/2015 were reviewed. Follow-up was restricted to 5years following primary surgery. Recurrence-free survival (RFS) was estimated using the Kaplan-Meier method. Risk factors were evaluated for an association with recurrence and positive margins, respectively, using Cox proportional hazards regression and logistic regression. Results Of 154 patients, 90 (58.4%) were female and 65 (41.6%) were male. Treatment consisted of wide local excision (WLE, includes WLE or radical vulvectomy, 77.3%), Mohs micrographic surgery (MMS, 19.5%), and abdominoperineal resection (3.2%). RFS at 1, 3, and 5years was 84.5% (95% confidence interval (CI), 78.2–91.4%), 66.1% (95% CI, 57.5–75.9%), and 56.1% (95% CI, 46.9–67.1%), respectively. Positive surgical margins were univariately associated with higher risk of recurrence (HR 3.55, 95% CI 1.74, 7.24). Margin status significantly correlated with procedure type (33.3% vs. 3.4% had positive margins with WLE vs. MMS, p =0.01). Among patients with negative margins, there was a 2.5 fold increased risk of recurrence after WLE compared to MMS (95% CI, 0.57–10.9, p =n.s.). Conclusion Inclusion of males allowed us to examine the influence of a different surgical approach (MMS) on margin status and recurrence rates in EMPD. In contrast to prior studies including solely vulvar EMPD, we observed strong association between margin status and recurrence risk. Risk of positive margins was significantly higher after WLE compared to MMS. MMS should be explored to improve outcomes in gynecologic patients with EMPD.

Objectives: To explore the incidence, trends and survival outcomes of invasive extramammary vulvar Paget's disease compared to squamous and basal cell vulvar cancers. Methods: Incidence data were extrapolated from the United States Cancer Statistics (USCS) from 2001 to 2017 by SEER*Stat. Trends analysis was performed by Joinpoint regression program and presented by average annual percent change (AAPC). Clinical data on demographics, disease and treatment were recorded from the National Cancer Database from the same period. Chi-squared test, Kaplan-Meier survival estimates, and Cox proportional hazards model adjusted for covariates were used. Results: From 2001-2017, there were 3,715 cases of malignant extramammary Paget's disease of the vulva. Whites comprised 3,172 cases (85.4%), followed by Asian/Pacific Islanders with 227 cases (6.1%), Hispanics with 198 cases (5.3%), and Blacks with 44 cases (1.2%). Most cases had localized disease (73.1%), 10.4% had regional spread and 1.2% had distant disease. The overall incidence was 0.12/100,000 women per year in 2017. The incidence increased with an average percent increase of 0.4% per year from 2001 to 2017 (p Conclusions: Invasive extramammary Paget's disease of the vulva is uncommon though the incidence is increasing. Older age and advanced stage are associated with poorer survival. Patients with metastatic vulvar Paget's disease and squamous cell carcinoma have a poorer survival compared to metastatic vulvar basal cell carcinoma.

Objective The objective of this prospective pilot study was to assess the clinical and histologic effects of topical imiquimod therapy on recurrent extramammary Paget's disease of the vulva. Methods Patients with biopsy-proven recurrent extramammary Paget's disease presenting to the gynecology outpatient services at two participating institutions were recruited for conservative treatment with 5% imiquimod cream from 2007 to 2011. The topical cream was to be applied 3 times per week for 12weeks. Punch biopsy and photography were performed at baseline and at the 12-week time point. Results Eight patients from two institutions were enrolled. Complete clinical and histologic response was achieved in 6 (75%) patients by the 12-week follow-up appointment. Of the two remaining patients, one had a complete clinical response but no significant histologic response; the other patient was removed from the study protocol secondary to intolerable local irritation. Two patients continue to have no evidence of disease after a median follow-up of 35months. Five are alive with disease. No patients progressed to invasive cancer while receiving therapy. Conclusion Topical 5% imiquimod cream is a safe and feasible option for women suffering from recurrent extramammary Paget's disease of the vulva, and should be considered as a viable alternative to surgical management. Given the rare nature of this disease, additional multi-institutional prospective studies should be conducted to explore the efficacy of this treatment regime.

Introduction Extramammary Paget disease (EMPD) is a rare neoplasm of the skin that presents with erythematous or leukoplacic plaques causing pruritus and pain. Standard treatment is surgical but local failures and recurrences are frequent, leading to multiple mutilating surgeries. Aim of the study is to evaluate the effectiveness of photodynamic therapy (PDT) to obtain a clinical response and symptom control with a non surgical approach in these patients. Materials and methods After disease extension evaluation and symptoms assessment women with EMPD were prospectively treated with aminolevulinic-acid methyl-esther (M-ALA) PDT. Clinical and symptoms response were evaluated after 3cycles and after any further PDT. Results Thirty-two patients with vulvar EMPD underwent M-ALA PDT. In sixteen (50%) patients the lesion extended to the perineal and/or perianal area. After three courses of treatment, three patients (9.4%) had a complete resolution of the symptoms; 25 patients (78.1%) a partial resolution and a stable disease was recorded in four patients (12.5%). None of the patients had progression of disease. Both size of the lesion and EMPD associated symptoms decreased significantly after three courses of treatment. Eighteen patients (56.2%) recurred and 16 (88.9%) were treated with further PDT. Among the 26 patients who underwent a further PDT, 16 patients (61.5%) achieved at least a partial response. Conclusion M-ALA PDT even if not curative is a reliable strategy to control EMPD and its associated symptoms even in an outpatient setting. M-ALA PDT is able to control large and multiple lesions regardless of the area involved, preserving cosmetic and/or functional anatomy.

Objective The outcome of patients with invasive Extramammary Paget's disease (EMPD) is poorly studied. The goal of the current study was to analyze the incidence, treatment approaches and outcome of patients with invasive EMPD. Methods We searched the SEER program database for patients diagnosed with invasive EMPD between 1973 and 2007. Demographic data, outcome and therapeutic modalities were included in the analysis. Disease specific survival (DSS) was calculated from the time of original diagnosis. Results 1439 patients were diagnosed with invasive EMPD. Most patients (80.4%) had localized disease, while 17.1% had locoregional spread, and 2.5% had distant disease. 1230 (86.4%) patients underwent site directed surgery, and 92 (6.4%) patients radiotherapy. 139 (9.7%) patients did not undergo any surgery or radiation therapy. The 5-year DSS was 94.9% for localized disease, 84.9% for regional disease and 52.5% for distant disease. Multivariate analysis showed a significantly shorter DSS associated with older age and advanced stage treatment modality (HR for death 1.07 and 2.5). Site directed surgery was associated with a significantly improved outcome when compared to patients who underwent no intervention (HR 0.44). Patients who received radiation, alone or in combination with site directed surgery, did not fare any better than patients who underwent surgery alone. Conclusions The DSS of patients with invasive EMPD is generally favorable. A poor outcome was associated with older age, advanced stage and treatment modality. The association between a shortened DSS and the use of radiotherapy, alone or in combination with surgery, is surprising and warrants further investigation.

Background. There have been no reports of the efficacy of primary radiotherapy with concurrent chemotherapy for vulvar adenocarcinoma associated with extramammary Paget's disease. In this report we discuss the differential diagnosis and efficacy of treatment for this rare tumor. Case. The patient was diagnosed as having vulvar carcinoma stage IVb. A dose of 40 Gy in 20 fractions was administered to the vulva, including the tumor mass, and the inguinal–femoral lymph nodes with concurrent systemic chemotherapy. Outside the radiated field, bone scintigraphy showed an increase in abnormal uptake images. However, in the radiated field, the tumors disappeared macroscopically, and bone scintigraphy also showed a disappearance of the abnormal uptake images. Conclusion. Within the radiated field, the efficacy was brought about by either radiotherapy only or by radiotherapy together with the sensitizing effects of chemotherapy. As for the chemotherapy itself, it was not effective in this case.

Clinical data were retrieved from the hospital records of 34 patients with Paget's disease of the vulva treated from 1972 to 1990. Flow-cytometric (FCM) DNA measurements and p53 and c-erbB-2 immunostaining were performed on paraffin-embedded samples. Five patients had an underlying adenocarcinoma and 29 intraepithelial disease (IEP). Twenty-seven patients with IEP underwent surgery. The surgical margins were positive in 15 patients, negative in 10, and not evaluable in 2. The tumor was diploid in 15 patients, nondiploid in 11, and not evaluable in 1. Eight patients recurred, 6/15 (40%) with positive and 2/10 (20%) with negative margins. One patient with positive margins was never disease-free. Recurrence was seen in 6/11 (55%) patients with nondiploid tumors, 4 with positive and 2 with negative margins. Two of 15 (13%) patients with diploid tumors recurred/persisted, both with positive margins. None of the 6 patients with diploid tumors and negative margins recurred. p53 and c-erbB-2 were found negative in all but 4 patients. Tumor nondiploidy was associated with an increased risk of recurrence irrespective of surgical radicality. p53 and c-erbB-2 seemed to play no role in the pathogenesis or prognosis.

Objective To characterize the clinicopathological features and evaluate the treatment outcomes for cases of primary extramammary Paget's disease of the vulva (EMPDV). Methods The medical records and pathology slides were reviewed and analyzed for 43 patients with primary EMPDV. Results The mean age of the patients was 68.6years (range, 52–85). Intraepithelial EMPDV, invasive EMPDV and EMPDV with adnexal adenocarcinoma were observed in 33 (76.7%), 7 (16.3%) and 3 (7.0%) cases, respectively. Varied surgical procedures were initially performed in 35 (81.4%) cases. A positive incision margin was observed in 16 cases (47.0%). Definitive radiotherapy at a median dose of 60Gy was performed in 8 (18.6%) patients. Six patients received postoperative radiotherapy due to a positive margin or lymph node metastasis after surgical excision. During a follow-up period of 6–169months (median, 54), recurrence was observed in 12 (34.3%) patients. Nine (75.0%) patients underwent repeated surgery and 3 (25.0%) patients received radiotherapy. Long-term overall survival was observed in patients with intraepithelial EMPDV. The median overall survival was 124.5months in intraepithelial cases, 70.8months in invasive cases and 21.3months in cases with adnexal adenocarcinoma (log rank, P =0.032). Conclusions Intraepithelial EMPDV accounted for the majority of primary cases and had a better prognosis. Surgical excision was the standard curative treatment for EMPDV. Radiotherapy was an alternative choice for patients with medical contradiction or surgical difficulties. Postoperative radiotherapy could be considered in cases with positive surgical margin or lymph node metastasis. Recurrence was common and repeated excision was often necessary.

Fourteen patients with extramammary Paget's disease of the vulva treated at Yale-New Haven Medical Center from 1982 through 1993 were reviewed to evaluate the accuracy of methods used to delineate surgical margins and to determine if radical operations or surgical margin status was associated with likelihood of recurrence. These 14 patients underwent at total of 25 operations for extramammary Paget's disease. In 8 operations, a total of 44 separate frozen-section biopsies were performed to determine extent of disease with a mean of 5.5 biopsies per patient. Visual judgment alone was used to determine margin status in 17 operations. The ability to delineate free surgical margins on permanent sections was not different, whether judged visually or by frozen-section analysis. Frozen-section analysis was misleading in 3/8 (37.5%) cases, while visual judgment was in error in 6/17 (35%) cases. Moreover, permanent margin status was not found to be predictive of disease recurrence. Two of 5 (40%) patients with positive margins recurred after initial surgery compared with 3 of 9 (33%) patients with negative margins. Of the 14 primary operations, there were 8 wide local excisions, 3 simple vulvectomies, and 3 modified radical vulvectomies. The radicality of the operation as initial treatment did not statistically correlate with disease recurrence.

Background. Primaryadenocarcinoma of the vulva is a rare entity, and for widely metastatic vulvar adenocarcinoma, no effective treatment has been established. Case. A 65-year-old woman was diagnosed with regionally advanced vulvar adenocarcinoma, with bulky involvement of bilateral groin lymph nodes, and associated extramammary Paget's disease. Initial therapy consisted of multiagent chemotherapy and vulvar and groin irradiation, followed by radical vulvectomy with groin and pelvic lymph node dissection. She subsequently developed widely metastatic disease including brain, pulmonary, hepatic, osseus, and subcutaneous lesions. Treatment with liposomal doxorubicin (Doxil) resulted in dramatic regression of metastatic lesions and marked improvement in quality-of-life. She remains clinically well, greater than 1 year since initiating Doxil treatment for widely metastatic vulvar adenocarcinoma, and has surpassed 5 years of survival since her initial diagnosis. Conclusions. We report the first case of Doxil used for the treatment of metastatic chemorefractory vulvar adenocarcinoma. We observed that Doxil was a well-tolerated and effective agent for this gynecologic malignancy, and warrants further investigation.

A case of Paget's disease of the vulva is presented which, over a period of 6 years, was characterized by local recurrences and metastases to the bone marrow. Detailed examination of multiple sections of the primary tumor and of the bone marrow biopsy specimen failed to demonstrate an underlying adenocarcinoma in any of the sites. The routine histologic staining and immunohistochemical staining demonstrated that the metastatic cells strongly correlated with cells from the vulvar lesion. Specifically, immunohistochemical staining of the specimens from the primary and metastatic sites was positive for the gross cystic disease fluid protein-15, which has been associated with extramammary Paget's disease uncomplicated by underlying malignancies. Finally, during several years of close follow-up, no other primary site of Paget's disease declared itself clinically or was found by radiographic studies or analysis of serum tumor markers.

Extramammary Paget's disease of the vulva is an uncommon vulvar neoplasm with a high rate of recurrence. A 64-year-old white female with a history of extramammary Paget's disease of the vulva, excised in 1987 by skinning vulvectomy and treated again in 1993 by skinning vulvectomy with split-thickness skin grafting, presented in 1994 with recurrent Paget's disease in the area of the skin graft. Extramammary Paget's disease of the vulva may recur in an area previously totally excised and transplanted with autologous skin. Therefore, close follow-up is necessary in all patients with this pathologic entity.

Patients with extramammary Paget's disease of the vulva at the University of California--Irvine Medical Center and the Memorial Medical Center of Long Beach Women's Hospital between 1976 and 1986 were treated with nonradical surgery. These 14 patients were analyzed in a retrospective fashion to determine if conservative management was successful in eradicating the disease process while preserving appearance and sexual function. All patients were treated with nonradical surgery: skinning vulvectomy with split-thickness skin graft (86%), hemivulvectomy (7%), and simple vulvectomy (7%). In all cases intraoperative frozen-section analysis of surgical margins was performed to determine the extent of disease and outline the margins of resection. No patients had Paget's disease associated with an underlying adenocarcinoma. Three patients developed recurrent Paget's disease. Two of these patients recurred at the site of a positive margin and thus represent persistent disease. Only one patient (7%) had recurrent disease in the face of negative margins. The median duration of follow-up was 50 months. All patients are presently free of disease. The rationale for this conservative management is discussed.