Anatomic Subtype Differences in Extramammary Paget Disease: A Meta-Analysis.

Importance: Extramammary Paget disease (EMPD) is a rare, highly recurrent cutaneous malignant neoplasm of unclear origin. EMPD arises most commonly on the vulvar and penoscrotal skin. It is not presently known how anatomic subtype of EMPD affects disease presentation and management. Objective: To compare demographic and tumor characteristics and treatment approaches for different EMPD subtypes. Recommendations for diagnosis and treatment are presented. Data Sources: MEDLINE, Embase, Web of Science Core Collection, and Cochrane Reviews CENTRAL from December 1, 1990, to October 24, 2022. Study Selection: Articles were excluded if they were not in English, reported fewer than 3 patients, did not specify information by anatomic subtype, or contained no case-level data. Metastatic cases on presentation were also excluded. Data Extraction and Synthesis: Abstracts of 1295 eligible articles were independently reviewed by 5 coauthors, and 135 articles retained. Reporting was in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The analysis was cunducted in August 2019 and updated in November 2022. Findings: Most vulvar EMPD cases were asymptomatic, and diagnosis was relatively delayed (mean, 25.1 months). Although most vulvar EMPD cases were intraepidermal (1247/1773 [70.3%]), radical surgeries were still performed in almost one-third of cases. Despite this aggressive surgical approach, 481 of 1423 (34%) recurred, commonly confined to the skin and mucosa (177/198 [89.4%]). By contrast, 152 of 1101 penoscrotal EMPD cases (14%) recurred, but more than one-third of these recurrences were regional or associated with distant metastases (54 of 152 [35.5%]). Perianal EMPD cases recurred in one-third of cases (74/218 [33.9%]), with one-third of these recurrences being regional or associated with distant metastasis (20 of 74 [27.0%]). Perianal EMPD also had the highest rate of invasive disease (50% of cases). Conclusions and Relevance: The diagnosis and treatment of EMPD should differ based on anatomic subtypes. Considerations for updated practice may include less morbid treatments for vulvar EMPD, which is primarily epidermal, and close surveillance for local recurrence in vulvar EMPD and metastatic recurrence in perianal EMPD. Recurrences in penoscrotal subtype were less common, and selective surveillance in this subtype may be considered. Limitations of this study include the lack of replication cohorts and the exclusion of studies that did not stratify outcomes by anatomic subtype.

Case report: A case of Paget disease outside the axillary breast.

BACKGROUND: Extramammary Paget disease is a relatively rare and less malignant intraepithelial adenocarcinoma. t is found in areas with abundant distribution of apocrine sweat glands such as the external genitalia, external genitalia, and perianal area, with fewer armpits. The disease progresses slowly and is prone to misdiagnosis in clinical practice. METHODS: We retrospectively analyzed a female patient. She had a left axillary mass for more than 2 years. Recently, the mass increased and the surface skin was ulcerated. Then she went to Jiangxi Provincial Dermatology Hospital for left axillary lesion resection, and the postoperative pathology showed Paget disease outside the breast. For further diagnosis and treatment, she came to our hospital. We diagnosed a tumor with uncertain or unknown dynamics in the left axillary breast. Under general anesthesia, left subaxillary mass resection, freezing and left breast cancer breast conserving surgery was performed. RESULTS: The postoperative pathology of the left axillary mass combined with morphological and immunohistochemical results was consistent with Paget disease. Postoperative immunohistochemistry showed estrogen receptor (+, 20%), progesterone receptor (-), human epidermal growth factor receptor-2 (3+), Ki-67 (30%), cytokine7 (+), and p63 (-). Following up for 22 months, there has been no local recurrence, no swelling of the right axillary lymph node, no distant metastasis found on follow-up, and no complications such as upper limb lymphedema, upper limb sensory abnormalities, or motor disorders have been observed. CONCLUSION: Paget disease outside the axillary breast is relatively rare, and surgical resection is the best choice. The prognosis is good, and the recurrence rate is low.

Therapeutic outcomes and survival analysis of Extramammary Paget's disease: A multicentre retrospective study of 249 patients.

BACKGROUND: Evidence regarding long-term therapeutic outcomes and disease-specific survival (DSS) in Extramammary Paget's disease (EMPD) is limited. OBJECTIVES: To assess the DSS and outcomes of surgical and nonsurgical therapeutic modalities in a large cohort of EMPD patients. METHODS: Retrospective chart review of EMPD patients from 20 Spanish tertiary care hospitals. RESULTS: Data on 249 patients with a median follow-up of 60 months were analyzed. The estimated 5-, 10-, and 15-year DSS was 95.9%, 92.9%, and 88.5%, respectively. A significantly lower DSS was observed in patients showing deep dermal invasion (≥1 mm) or metastatic disease (P < .05). A ≥50% reduction in EMPD lesion size was achieved in 100% and 75.3% of patients treated with surgery and topical therapies, respectively. Tumor-free resection margins were obtained in 42.4% of the patients after wide local excision (WLE). The 5-year recurrence-free survival after Mohs micrographic surgery (MMS), WLE with tumor-free margins, WLE with positive margins, radiotherapy, and topical treatments was 63.0%, 51.4%, 20.4%, 30.1%, and 20.8%, respectively. LIMITATIONS: Retrospective design. CONCLUSIONS: EMPD is usually a chronic condition with favorable prognosis. MMS represents the therapeutic alternative with the greatest efficacy for the disease. Recurrence rates in patients with positive margins after WLE are similar to the ones observed in patients treated with topical agents.

Network meta-analysis of treatments for perineal extramammary paget's disease: Focusing on performance of recurrence prevention.

INTRODUCTION: Perineal extramammary paget's disease (EMPD) is characterized with high recurrence rate. Although numerous therapeutic measures for this disease have been reported so far, it is unknown whether there is significant difference in their recurrence-preventing efficiency. This study aims to compare the recurrence outcomes of reported perineal EMPD treatments. METHODS: We searched public databases of for published studies concerning perineal EMPD treatments. After screening by inclusion and exclusion criteria, we extracted the data relevant to recurrence rate, and conducted network meta-analysis (NMA) by using Bayesian random-effects approach. RESULTS: Our analysis included 29 previous studies (involving both male and female patients) and 11 treatment designs which are wide local excision (WLE), local excision (LE), Mohs micrographic surgery (MMS), radiotherapy (RT), radical vulvectomy (RV), photodynamic therapy (PDT), lasers (LS), imiquimod, and WLE+RT, WLE+PDT, WLE+LS. Comparing with WLE, the MMS showed significant advantage in reducing recurrence [OR: 0.18 (0.03-0.87)], while none of the rest treatments has statistically significant results. After removing outlier studies, MMS still has the significant advantages [OR: 0.35 (0.11-0.82)], and LE turned to be the treatment with worst performance [OR: 13 (2.50-110)]. Covariance analysis of follow-up length, gender differences, and lesion locations indicated only short follow-up time could affect the recurrence statistics, which tend to conceal the real differences. Funnel plot demonstrated there is no significant small study effect. CONCLUSION: MMS has the best performance on reducing perineal EMPD recurrence, while LE exhibits the worst capability in such regard. Recurrence-preventing abilities of other treatments have no significant difference between each other.

Prognostic Factors of Extramammary Paget's Disease: A Retrospective Study at a Medical Center in Taiwan.

BACKGROUND/AIM: Extramammary Paget's disease (EMPD) is a rare, slow growing intra-epidermal malignant neoplasm that arises in areas rich in apocrine glands. Several common sites of occurrence have been reported, including the vulva, perianal region, perineum, and scrotum. Most relevant studies rely on small data bases. Our objective was to evaluate prognostic factors of EMPD patients at a single medical center. PATIENTS AND METHODS: We retrospectively analyzed 19 patients (8 males, 11 females) diagnosed with genital EMPD who were treated at the Taichung Veterans General Hospital between 2006/04 and 2022/08. Collected information included tumor location, margin condition in the case of surgical resection, recurrence rate, recurrence management, accompanied gastrointestinal malignancy, treatment details and survival data. RESULTS: Among 19 cases, 4 with initial margin being positive, and 3 received second surgery (one refused surgery and another expired within a year). Tumor recurrence was found in 7 cases, with 6 of them later receiving second surgery, and the remaining one received radiation therapy. Median DFS was 7.57 years. During the 15-year follow-up, 2 patients expired. Overall survival rate was 87.5%. Among all factors we had analyzed, only those accompanied with GI tract malignancy had significantly worse survival rate (p=0.018). Frozen sections taken at surgical margin during surgery significantly reduced cancer recurrence rate (p=0.45). Permanent pathology margins appeared to affect the recurrence rate, but that was not significant when comparing with intraoperative frozen sections. CONCLUSION: Local wide excision with skin flap reconstruction remains the major treatment option for genital EMPD. Following the standard-of-care procedure, the overall patient outcome was excellent. Among factors potentially associated with recurrence rate, intraoperative frozen biopsy was the most significant one. Performing intraoperative frozen biopsy is essential for recurrence-free rate elevation.

Identification of Predictive Factors for Post-operative Recurrence and Clinical Outcomes of Primary Vulvar Extramammary Paget Disease.

BACKGROUND/AIM: Data regarding the clinicopathological factors predicting recurrence and prognosis in patients with vulvar extramammary Paget disease (VPD) are limited. Therefore, we aimed to identify predictive factors for recurrence and outcomes in patients with VPD. PATIENTS AND METHODS: Forty-five patients with VPD were included in this study. We reviewed electronic medical records and pathology slides to collect clinicopathological information. RESULTS: Eighteen cases (40.0%) had resection margin (RM) involvement. Twelve patients (26.7%) received adjuvant radiation therapy (RT). Ten patients (22.2%) experienced recurrence. The recurrence rate was higher in patients who underwent wide local excision or simple vulvectomy than in those who underwent radical vulvectomy. Positive RM involvement was a significant and independent predictive factor for worse recurrence-free survival (RFS). The overall survival rate of patients who received adjuvant RT was significantly higher than that of those who underwent surgery alone. CONCLUSION: A positive RM involvement independently predicted worse RFS. The recurrence rate was significantly associated with the type of surgical procedure performed. Additionally, adjuvant RT can improve the prognosis of patients with VPD.

Extramammary Paget's disease: Our 15-year experience in a Southeast Asian population.

The treatment of choice for Extramammary Paget's disease (EMPD) is wide excision. However, owing to the tendency of microscopic spread and multi-centricity of the disease, resection margins are hard to determine. Despite the use of adjunctive methods such as mapping biopsy and Moh's micrographic surgery, recurrence rates remain high. We aim to establish treatment guidelines by determining the variables associated with recurrence and the optimal resection margin size. We reviewed 52 patients who underwent wide excision in our institution between 2002 and 2017. A retrospective review of patient demographics, disease characteristics, and resection margins was performed. Most patients were Chinese (n = 39, 75%) male (n = 38, 73.1%). The mean tumor size was 6.73 cm (SD=4.10; range, 1.50-21.0 cm). The mean resection margin was 2.5 cm (SD=1.21; range, 0.20-5.50 cm). Eleven patients (21.2%) had disease recurrence. Nodal involvement significantly correlated with disease recurrence or mortality related to disease (HR=4.645; 95% CI=1.539,14.018; p = 0.0064). Subgroup analysis showed a significant correlation between resection margin size and recurrence rates (p = 0.047). We observed that a smaller resection margin (<2 cm) is acceptable for smaller tumor sizes (<6 cm) to achieve the lowest possible recurrence rates (20%), whereas a larger resection margin (>2 cm) is required for larger tumor sizes (>6 cm) (p = 0.012). Our results suggest that a resection margin recommendation can be made in correlation to the tumor size. This serves as a guideline for surgeons to predict the defect size and provide options for reconstructive surgery while achieving low recurrence rates.

Outcomes and prognostic factors of surgically treated extramammary Paget's disease of the vulva.

OBJECTIVE: Extramammary Paget's disease (EMPD) of the vulva is a rare disease which predominantly presents in postmenopausal Caucasian women. As yet, no studies on Asian female patients with EMPD have been performed. This study aimed to identify the clinical features of patients with vulvar EMPD in Korea, and to evaluate the risk factors of recurrence and postoperative complications in surgically treated EMPD. METHODS: We retrospectively reviewed 47 patients with vulvar EMPD who underwent wide local excision or radical vulvectomy. The clinical data and surgical and oncological outcomes following surgery were extracted from medical records and analyzed. Univariate and multivariate analyses for predicting recurrence and postoperative complications were performed. RESULTS: 21.3% of patients had complications after surgery, and wound dehiscence was the most common. 14.9% of patients experienced recurrence, and the median interval to recurrence from initial treatment was 69 (range 33-169) months. Vulvar lesions larger than 40 mm was the independent risk factor of postoperative complications (odds ratio [OR]=7.259; 95% confidence interval [CI]=1.545-34.100; p=0.012). Surgical margin status was not associated with recurrence in surgically treated vulvar EMPD patients (OR=0.83; 95% CI=0.16-4.19; p=1.000). CONCLUSION: Positive surgical margin is a frequent finding in the patients with vulvar EMPD, but disease recurrence is not related with surgical margin status. Since EMPD is a slow growing tumor, a surveillance period longer than 5 years is required.

The role of sentinel lymph node biopsy in extramammary paget disease: a systematic review.

Sentinel lymph node biopsy is increasingly used to detect subclinical nodal metastases in extramammary Paget disease. We performed a comprehensive systematic review of the literature to further explore the role of sentinel lymph node biopsy in extramammary Paget disease. Five databases were searched for relevant terms. Articles were included if they were in English and presented primary data on at least one patient with extramammary Paget disease who underwent sentinel lymph node biopsy in the absence of lymphadenopathy or known metastatic disease. Twenty-eight articles were included, with 366 subjects. Seventy-seven sentinel node biopsies (21.2%) were positive, including 12 in which the primary tumor had microinvasion (15.6%) and 56 with deep invasion (72.7%). Of the positive cases, 11 (14.3%) had no further treatment, 54 (70.1%) underwent nodal dissection, 4 (5.2%) were treated with systemic agents, and 1 (1.3%) had radiation. After a mean follow up of 24 months, 9 subjects with a positive lymph node biopsy experienced nodal recurrence (11.7%), 15 had distant metastases (19.5%), and 13 died of the disease (16.9%). In conclusion, invasive extramammary Paget disease is strongly associated with poor outcomes including nodal metastasis, distant metastasis, and disease specific death. Sentinel lymph node biopsy is a useful tool to screen for subclinical nodal metastases in invasive disease, and can be used to help guide clinical management.

Prognostic Analysis of Patients With Extramammary Paget Disease Treated With Conservative Excision.

BACKGROUND: Extramammary Paget disease (EMPD) is a malignant skin tumor with a relatively good prognosis. The standard treatment is wide local resection or Mohs micrographic surgery. However, conservative excision may be a better option when radical wide local excision is difficult to perform due to the patients' mental or physical condition. There have been no studies on the prognosis of patients with EMPD who underwent conservative excision. OBJECTIVE: To compare the prognosis of conservative excision cases to wide excision cases of EMPD. MATERIALS AND METHODS: The authors retrospectively analyzed the clinical data of 69 cases of EMPD without metastases to lymph nodes or organs (11 cases treated with conservative excision, 58 cases treated with wide local excision) who underwent resection of the primary tumor from 2002 to 2022 in the Department of Dermatology at Hokkaido University Hospital. RESULTS: The log-rank test showed no significant differences in overall survival or metastasis-free survival between the wide excision group and the conservative excision group, although conservative surgery was often chosen in elderly patients or patients with lower performance status. CONCLUSION: This study suggests that conservative surgery should be considered as a treatment option for EMPD.

[A Case of Laparoscopic Abdominoperineal Resection with TpTME for Adenocarcinoma of Anal Canal with Pagetoid Spread].

A man in his 80s was referred to our hospital with the chief complaint of perianal erosion. Colonoscopy revealed a peripheral flat lesion in the anal canal. Since immunohistological examination showed positive for CK20 and negative for GCDFP15, we made a preoperative diagnosis of anal canal cancer with Pagetoid spread. It was diagnosed as cT1bN0M0, cStage Ⅰ by TNM classification, and laparoscopic abdominoperineal resection with TpTME was performed. Negative biopsy of the perianal skin was confirmed both preoperation and during the operation. The postoperative course was uneventful, and no urinary dysfunction was observed. The patient was discharged 15 days after the operation. The histopathological diagnosis was negative margin. The patient is alive without recurrence 1 year after the operation. Adenocarcinoma of anal canal with Pagetoid spread is rare, and differentiation from Paget's disease is important for determining treatment policy. By conducting a detailed examination of the extent of tumor progression and using TpTME together, it was possible to perform surgery that both secured the CRM and preserved urinary function.

Extra-mammary Paget's disease of the penis.

Paget's disease was first described in 1874 as an eczematoid changes of the nipple associated with underlying breast carcinoma. Extra-mammary Paget's disease (EMPD) is rare with involvement of the male genitalia described in small case series and management options varying according to location and extent. The diagnosis of EMPD requires a high index of clinical suspicion and close liaison with the multidisciplinary team, particularly histopathology. We present two cases of EMPD affecting the male external genitalia that highlight important learnings in the presentation, diagnosis, and management of EMPD.

Fluorescein Mapping in Vulvar Paget Disease.

BACKGROUND: Vulvar Paget disease often requires extensive and, in some cases, multiple resections to treat. A fluorescein-mapping procedure followed by a staged vulvectomy may be an effective technique to tailor resection and identify clinically occult lesions. TECHNIQUE: We describe a two-step procedure; first, intravenous fluorescein sodium is injected, and the vulva is illuminated with a Wood's lamp. Representative biopsies are obtained and correlated on final pathology with the extent of disease to develop a final plan for excision. Second, using fluorescein to identify the confirmed areas of disease, the appropriate excisional procedure is performed once mapping biopsy pathology is known. EXPERIENCE: We describe our experience with eight patients with vulvar Paget disease undergoing fluorescein mapping biopsies and staged vulvectomy. Using intravenous fluorescein sodium, all patients were found to have Paget disease beyond the visible margins of their gross lesions. No patients experienced a recurrence of Paget disease within a median follow-up time of 32 months, comparable with other directed methods of surgical resection. CONCLUSION: We report a technique for the injection of fluorescein sodium for the visualization of vulvar Paget disease capable of providing accurate surgical margins and identification of occult satellite lesions with a high degree of safety and a favorable cost profile. This staged approach to vulvectomy could offer improved accuracy of resection for vulvar Paget disease with few drawbacks.

The clinical effect of modified slow Mohs circular skin biopsy on penoscrotal extramammary Paget's disease.

OBJECTIVE: Determining the tumor margin is the main problem in penoscrotal extramammary Paget's disease (PEMPD) surgery. This study aimed to explore the role of modified slow Mohs circular skin biopsy in determining the tumor margin in patients with PEMPD before operation. METHODS: Thirty-six PEMPD patients were divided into the control group and the observation group according to the simple randomization method. The control group, which consisted of 16 patients, underwent wide local excision, and the observation group, which consisted of 20 patients, underwent a modified slow Mohs circular skin biopsy to determine the tumor margin before surgery. The duration of surgery, number of frozen sections, satisfaction with the appearance of the skin, tumor recurrence rate, and incidence of functional sequelae were statistically analyzed. RESULTS: The number of frozen sections, duration of surgery, incidence of functional sequelae, and tumor recurrence rate in the observation group were lower than in the control group. The satisfaction with the appearance of the skin was higher in the observation group than in the control group, and the difference was statistically significant (P < 0.05). CONCLUSION: Modified slow Mohs circular skin biopsy can determine the tumor margin before surgery and reduce the number of frozen sections, tumor recurrence rate, and the incidence of functional sequelae. It also increases the postoperative satisfaction of patients.