Search

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. Conclusion 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). [ABSTRACT FROM AUTHOR]

Zhuangzhi Zhou,1 Yao Chen,2 Na Tan,1 Li Hu3 1Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Nursing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Correspondence : Li Hu, Email 993602708@qq.comBackground: Extramammary Paget’s disease (EMPD) is a rare skin cancer with unclear pathogenesis, insidious progression, and high recurrence rate. The purpose of this study was to investigate the clinical features and postoperative recurrence factors of primary EMPD.Methods: We retrospectively analyzed the medical records of 40 patients with primary EMPD who underwent wide local excision surgery at a single medical center between 2009 and 2019. Risk factors for recurrence of primary EMPD were analyzed using multivariate binary logistic regression.Results: The study included 40 patients with primary EMPD, comprising 31 males (77.5%) and 9 females (22.5%), with a median age of 75.52 years (range 52– 99 years). The most common lesion location was the scrotum (22 cases, 55.0%), followed by the vulva, penis, scrotum, underarm and anus. Multivariable regression analysis revealed significant differences in the presence of ill-defined tumour borders, exudation and nodules in the primary lesion affecting the relapse of primary EMPD (p< 0.05).Conclusion: Our findings indicate that ill-defined tumour borders, exudation and nodules in the primary site should be considered as independent risk factors for disease recurrence, which may provide useful suggestions for the diagnosis, treatment and follow-up of primary EMPD.Keywords: extramammary paget’s disease, factors, recurrence, postoperative, retrospective

Introduction: Extramammary Paget’s disease (EMPD) is a rare skin cancer that tends to be multicentric, with quadruple EMPD cases being scarcely reported. Case Presentation: We report the case of an 81-year-old man with heterochronous quadruple EMPD. Twelve years after total resection of vulvar EMPD, the patient developed erythematous lesions on the resection margin in the lower abdomen, umbilical region, and both axillae. Histological examination revealed that all lesions were in situ EMPD. Discussion: We reviewed six reported cases of quadruple EMPD with respect to race, sex, site, recurrence, time to recurrence, serum carcinoembryonic antigen, and depth. All patients were elderly Japanese males. In all but one case, the lesions were located in the apocrine region, which is a common site in such as the genital and axillary areas. Our case was the only heterochronous quadruple EMPD. The lesions were limited to the epidermis; therefore, they were unlikely to cause metastasis. It has been reported that the therapeutic effects of imiquimod can be expected in in situ EMPD. Therefore, quadruple EMPD may be a good indication of treatment option. Conclusion: EMPD is a disease whose pathogenesis is not yet clear; however, it is hoped that the origin and aetiology of EMPD will be elucidated from the clinical features of multiple EMPD in the future.

Abstract Extramammary Paget's disease (EMPD) is a skin cancer that can metastasize to distant lymph nodes and organs. However, there are no reports showing histological evidence of metastasis to the ureter. Here we report a case of EMPD that metastasized to the ureter in an 80‐year‐old man. The primary EMPD was resected and the right inguinal lymph node metastasis was dissected. Radiation therapy was administered around the right inguinal lymph nodes postoperatively. Four years later, a thickening of the wall of the right ureter was found, and a total right nephroureterectomy was performed due to suspicion of primary ureteral cancer. Histological examination showed nests of atypical cells in the renal adventitia and the surrounding lymphatic vessels, muscular layer and mucosal layer, but not in the ureteral epithelium. Immunohistochemical staining of tumour cells was positive for carcinoembryonic antigen, cytokeratin 7 and gross cystic disease fluid protein‐15 and was negative for cytokeratin 20. These results are consistent with a primary skin lesion. Although EMPD is not a frequent source of ureteral metastasis, EMPD can metastasize to the ureter. This case implies the feasibility of an accurate preoperative diagnosis through immunostaining, offering the potential to circumvent nephroureterectomy and instead facilitate appropriate management using a ureteral stent.

Background Methods Results Conclusions Level of evidence Extramammary Paget's disease (EMPD) is a rare intra‐epidermal adenocarcinoma, and reconstruction of the penoscrotal region remains a clinical challenge. The superficial circumflex iliac artery perforator (SCIP) flap has been successfully used as a free flap, while its application as a propeller flap in the reconstruction of penoscrotal EMPD defect is rarely reported. The objective was to evaluate the safety and efficacy of the SCIP propeller flap in the reconstruction of penoscrotal defects in EMPD.Between September 2010 and August 2022, consecutive patients diagnosed with penoscrotal EMPD were enrolled. All patients underwent penoscrotal EMPD excision and reconstruction with SCIP propeller flap combined with other flaps or skin grafts on individual defects. Demographic information, surgical parameters, postoperative complications, patient satisfaction, and recurrence rates were analyzed.Twenty‐four patients (mean age, 73 ± 8.8 years; mean BMI, 23.98 ± 3.62 kg/m2) with 33 SCIP propeller flaps (mean size 120.1 cm2; range, 24–208 cm2) were included, and the mean defect size was 67.4 cm2 (range, 12–255 cm2). The mean operative duration was 385.4 ± 146.8 min. Fifteen patients received autologous full‐thickness skin grafts, and four received other flaps simultaneously. All flaps survived without total or partial loss, and all donor sites achieved primary closure, though local hematoma (one case) and limited skin graft necrosis (two cases) were observed. All patients experienced complete wound healing and maintained penoscrotal morphology and function without recurrent lesions over a mean follow‐up of 59 months.The SCIP propeller flap seems a safe and effective reconstructive method for penoscrotal EMPD.IV. [ABSTRACT FROM AUTHOR]

Background: Extramammary Paget's disease (EMPD) is a rare epithelial malignancy, and approximately 30%-40% of EMPD patients overexpress human epidermal growth factor receptor 2 (Her-2). Currently, there are no established standard treatments for advanced EMPD while anti-Her-2 therapy is recommended for Her-2-positive cases. Case presentation: Here, we report a 51-year-old male diagnosed with advanced Her-2-positive EMPD, presenting with numerous lymph node metastases. This patient received disitamab vedotin (an antibody-drug conjugate, targeting Her-2) combined with serplulimab as first-line treatment. After seven cycles of combination therapy, the patient tolerated the treatment well and the lymph node lesions continued to shrink. However, the patient developed immunotherapy-related pneumonia following the eighth treatment. Hormone therapy was administered while all the anti-tumor therapies were halted. After the pneumonia improved, the patient underwent positron emission tomography-computed tomography, revealing a complete response to his tumor. To consolidate the effect, he received another five cycles of disitamab vedotin monotherapy as maintenance therapy, without experiencing any adverse events. To date, the patient has remained in good health without any recurrence 10 months after drug discontinuance. Conclusion: Disitamab vedotin combined with immunotherapy demonstrated a long-term clinical benefit in advanced Her-2-positive EMPD. For rare solid tumors with Her-2 overexpression, disitamab vedotin combined with immunotherapy might offer a viable therapeutic choice. [ABSTRACT FROM AUTHOR]

Background: Paget's disease (PD) is a carcinoma, in which irregular atypical cells with abundant cytoplasm proliferate mainly within the epithelium and is classified into PD occurring in the breast and extramammary Paget's disease (EMPD) occurring outside the breast. Essentially, extramammary PD is reported as a tumor for which it is difficult for surgeons to properly determine the line of resection. Case presentation: An 83-year-old male was admitted to our hospital because of roughness of the esophageal epithelium during the follow-up examination for a gastric ulcer. A preoperative biopsy revealed squamous cell carcinoma; therefore, endoscopic submucosal dissection (ESD) was performed. Conclusions: The characteristic feature in this patient was the distribution of tumor cells and, accordingly, the difficulty in identifying the neoplastic distribution. In this patient, the odd distribution and growth pattern of the tumor cells made it difficult for the operator to identify the distribution of the lesion preoperatively. [ABSTRACT FROM AUTHOR]

Opinion statement: Skin tumors commonly seen in dermatology are involved in all layers of the skin and appendages. While biopsy of affected skin remains an essential method to confirm diagnosis and to predicate tumor prognosis, it has its limitations. Recently, photodynamic diagnosis (PDD) has demonstrated high sensitivity in detecting affected skin and mucosal tissues, providing valuable guidance for precision surgery to resect skin and mucosal tumors. In this review, we summarized the literatures concerning the applications of PDD in diagnostic process and treatment of skin and mucosal conditions such as actinic keratoses (AK), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Bowen's disease (BD) and extramammary Paget's disease (EMPD). The findings suggest that PDD holds substantial promise for expanding clinical applications and deserves further research exploration. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the efficacy of Mohs micrographic surgery (MMS) combined with photodynamic therapy (PDT) in treating non-invasive extramammary Paget’s disease (EMPD).Materials and methods A 77-year-old male patient with non-invasive EMPD was treated with MMS followed by PDT. Preoperative fluorescence localization using 5-aminolevulinic acid (ALA) was performed to determine the surgical scope. MMS was conducted under lumbar anesthesia with intraoperative frozen-section pathology. Postoperative PDT was administered weekly for three sessions.Results The patient achieved negative surgical margins after two rounds of intraoperative pathology. Postoperative follow-up over two years showed no recurrence, and the patient did not experience significant adverse reactions.Conclusion The combination of MMS and PDT was effective in treating non-invasive EMPD, demonstrating favorable clinical outcomes and no recurrence over the two-year follow-up period.

Introduction: Extramammary Paget's disease of the scrotum and penis is a relatively rare cutaneous malignant tumor. At present, its pathogenesis, and clinical and pathological characteristics are not very clear. This is controversial regarding surgical margin width to decrease the high recurrence rate. This paper aimed to report the case and review the literature of extramammary Paget's disease of scrotum and penis. Case Presentation: We presented the case of a 74-year-old male patient with the patchy erythema and pruritus in the perineum who was admitted to our department. Biopsy of the large plaque revealed Paget disease. Under the condition of ensuring negative surgical margins by rapid frozen pathology, a wide local excision of the lesion, bilateral orchiectomy, and adnexectomy were performed on the patient. Pathology revealed that many scattered vacuolated Paget cells were observed in the epidermal layer, and the diagnosis was Paget's disease of the scrotum and penis. The 2 cm outside the skin lesion was used as the initial surgical margin, and free skin flap transplantation was used to repair the surgical wound. The patient recovered well and was discharged 1 week after surgery. Conclusion: Currently, histopathologic biopsy is the most important diagnostic method for EMPD. Once confirmed, for patients eligible for surgical intervention, wide local excision of the lesion and rapid intraoperative frozen pathological examination should be performed as soon as possible. The skin flap transplantation is the first choice for the repair of large-scale wound after surgery. [ABSTRACT FROM AUTHOR]

Extramammary Paget disease (EMPD) is a rare skin cancer mainly found in areas rich in apocrine sweat glands. Since the effective treatments for advanced and/or metastasized EMPD are limited, there is an urgent need to develop novel therapeutic approaches. Nectin cell adhesion molecule 4 (NECTIN4) is highly expressed in cancers and considered to be a promising therapeutic target. NECTIN4 is also expressed in EMPD, but its role and the efficacy of NECTIN4‐targeted therapy in EMPD remain unclear. This study investigated the potential of NECTIN4 as a novel therapeutic target for EMPD. NECTIN4 expression was immunohistochemically analysed in EMPD patients' primary (118 samples) and metastatic (21 samples) lesions. Using an EMPD cell line, KS‐EMPD‐1, the effects of NECTIN4 inhibition on cell proliferation and migration were investigated. NECTIN4 was expressed in primary and metastatic EMPD lesions, and the H‐score of NECTIN4 staining was significantly higher in metastatic lesions than in primary ones. Knockdown of NECTIN4 significantly inhibited cell proliferation and affected cell migration. The cytotoxic effects of NECTIN4‐targeted antibody–drug conjugate (ADC) were further evaluated, revealing a significant decrease in EMPD cell viability. In conclusion, NECTIN4 is a potential therapeutic target and NECTIN4‐targeted ADC is promising as a therapeutic option for EMPD. [ABSTRACT FROM AUTHOR]

Background: Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy, commonly affecting the external genitalia and perianal area of the elderly with unclear pathogenesis. Metabolomics provides a novel perspective for uncovering the metabolic mechanisms of a verity of cancers. Materials and methods: Here, we explored the metabolome of EMPD using an untargeted strategy. In order to further investigate the potential relationship between metabolites and gene expression, we re-analyzed the gene expression microarray data (GSE117285) using differential expression analysis and functional enrichment analyses. Results: Results showed that a total of 896 metabolites were identified and 87 metabolites including 37 upregulated and 50 downregulated significantly in EMPD were sought out. In the following feature selection analyses, four metabolites, namely, cyclopentyl fentanyl-d5, LPI 17:0, guanosine-3',5'-cyclic monophosphate, kynurenine (KYN, high in EMPD) were identified by both random forest and support vector machine analyses. We then identified 1,079 dysfunctional genes: 646 upregulated and 433 downregulated in EMPD. Specifically, the tryptophan-degrading enzyme including indoleamine-2,3- dioxygenase-1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2) were also increased. Generally, cancers exhibit a high expression of IDO1 and TDO2 to catabolize tryptophan, generating abundant KYN. Moreover, we also noticed the abnormal activation of sustaining proliferative signaling in EMPD. Conclusion: In conclusion, this study was the first to reveal the metabolome profile of EMPD. Our results demonstrate that IDO1/TDO2-initialized KYN metabolic pathway may play a vital role in the development and progression of EMPD, which may serve as a potential therapeutic target for treating EMPD. [ABSTRACT FROM AUTHOR]

Introduction This article describes an unusual case of perianal Paget's Disease in a 42-year-old man, highlighting distinct characteristics about more typical cases.

Introduction: Extramammary Paget's disease (EMPD) is a rare skin cancer that tends to be multicentric, with quadruple EMPD cases being scarcely reported. Case Presentation: We report the case of an 81-year-old man with heterochronous quadruple EMPD. Twelve years after total resection of vulvar EMPD, the patient developed erythematous lesions on the resection margin in the lower abdomen, umbilical region, and both axillae. Histological examination revealed that all lesions were in situ EMPD. Discussion: We reviewed six reported cases of quadruple EMPD with respect to race, sex, site, recurrence, time to recurrence, serum carcinoembryonic antigen, and depth. All patients were elderly Japanese males. In all but one case, the lesions were located in the apocrine region, which is a common site in such as the genital and axillary areas. Our case was the only heterochronous quadruple EMPD. The lesions were limited to the epidermis; therefore, they were unlikely to cause metastasis. It has been reported that the therapeutic effects of imiquimod can be expected in in situ EMPD. Therefore, quadruple EMPD may be a good indication of treatment option. Conclusion: EMPD is a disease whose pathogenesis is not yet clear; however, it is hoped that the origin and aetiology of EMPD will be elucidated from the clinical features of multiple EMPD in the future. [ABSTRACT FROM AUTHOR]

Evidence regarding long-term therapeutic outcomes and disease-specific survival (DSS) in Extramammary Paget's disease (EMPD) is limited. To assess the DSS and outcomes of surgical and nonsurgical therapeutic modalities in a large cohort of EMPD patients. Retrospective chart review of EMPD patients from 20 Spanish tertiary care hospitals. 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. Retrospective design. 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. [ABSTRACT FROM AUTHOR]

Electron beams represent an important treatment modality for providing an accurate dose of therapy to superficial cancers. This case reports important findings of dermal invasion in patients with extramammary Paget's disease (EMPD) using microscopic measurements and electron beam coverage. EMPD is a rare cutaneous adenocarcinoma generally arising in the anogenital region. Surgery is still a curable treatment option for patients with EMPD, whereas radiation therapy (RT) is an alternative for inoperable cases and is necessary in cases where surgery is not performed. This case report describes our experience and reviews the relevant literature on the feasibility of electron RT according to the dermal invasion length. An 80-year-old patient was diagnosed with EMPD and presented for definite radiation treatment. We observed no grade 3 toxicities during electron RT, and at the last follow-up visit, no signs of relapse were observed. There are no reports of electron irradiation as a feasible treatment option for EMPD considering the epidermal invasion length. [ABSTRACT FROM AUTHOR]

Simple Summary: The main treatment for extramammary Paget's disease (EMPD) is still surgery, but this neoplasm usually spreads beyond the clinical surroundings of the lesion, and achieving histopathologically free margins can be challenging and requires mutilating surgery. Moreover, the recurrence rate of the disease is high, reflecting its multifocal nature. Topical immunotherapy could be an alternative treatment for EMPD. The aim of this systematic review was to assess the effectiveness of topical imiquimod in the clinical response of EMPD patients and to describe the management of topical imiquimod in EMPD. Learning about non-surgical treatments such as topical imiquimod can help clinicians manage EMPD and find a balance between disease resolution and treatment morbidity. Extramammary Paget's disease (EMPD) is subclinical in extent and multifocal in nature. There is no global consensus for treatment, so its management represents a challenge in clinical practice. Therefore, we conducted a systematic review through the main electronic databases to assess the effectiveness of topical imiquimod in cutaneous EMPD and to discuss its management. Finally, 24 studies involving a total of 233 EMPD patients treated with topical imiquimod were selected. The topical imiquimod response rate was 67%, and the complete response (CR) rate was 48%. Patients were treated with a three–four times a week regimen in most cases, ranging between 2 to 52 weeks. In addition, imiquimod was applied as an adjunctive treatment in 21 patients, achieving a CR rate of 71%. Consequently, imiquimod therapy could achieve a good response ratio as a first-line treatment, as adjuvant and neo-adjuvant therapy, and as a treatment for recurrent disease. The heterogeneity between studies and the lack of a control arm made it impossible to conduct a meta-analysis. To improve the quality of evidence on EMPD, multicenter studies are essential to collect a larger number of patients and, consequently, obtain high-quality evidence to standardize treatment. The Prospero registration number is CRD42023447443. [ABSTRACT FROM AUTHOR]

Perianal Paget's disease (PPD) is a rare intraepidermal neoplastic disease, presenting with nonspecific symptoms, such as pruritis ani or eczema. Perianal Paget's disease may present as a primary lesion or as a paramalignant phenomenon. Uniform evidence-based treatment strategies have not been defined for this rare condition, and currently, different treatment methods are suggested. This case report presents three cases of perianal Paget's disease with three different treatments and outcomes. Pathogenesis, treatment, and the importance of a strict follow-up program are discussed. [ABSTRACT FROM AUTHOR]

Objectives: To determine the cost of two surgical treatment approaches for vulvar Paget’s disease and model the cost-effectiveness considering differences in recurrence and reoperation over time. Methods: We assessed cost-effectiveness between excision guided by Mohs micrographic surgery (MMS-E) and traditional wide local excision (WLE). We examined billing data from patients with vulvar Paget’s disease who underwent MMS-E (cases, n = 24, 2018–2022) or WLE (controls, n = 64, 1990–2020). We created typical treatment bundles incorporating physician-administered services and facility costs standardized to Medicare reimbursements in 2022 United States Dollars (USD). The primary measure of effectiveness was disease-free years of life. A secondary analysis estimated quality-adjusted life years (QALY). A Markov model simulated treatment pathways over a 10-year time horizon. Transition probabilities were based on institutional recurrence rates (3-year RR 6.7 % for MMS-E vs 34.1 % for WLE). We used a willingness-to-pay threshold of 100,000 USD per QALY. Results: The cost of a single surgical episode was 34,664 USD for MMS-E and 14,969 USD for WLE. In the setting of lower recurrence rates with MMS-E, the incremental cost was 12,789 USD per disease-free year gained. A secondary analysis incorporating QALY showed an incremental cost of 72,820 USD per QALY. Conclusions: MMS-E appears to be a cost-effective treatment for vulvar Paget’s disease compared to historic standard of care. Our ability to estimate quality of life gained by avoiding disease recurrence was limited by scant data for this rare condition; thus, future studies incorporating health utility values are needed to facilitate a more comprehensive analysis.

Objectives: Extramammary Paget’s disease (EMPD) is a neoplastic skin disease of unknown etiology. EMPD is frequently associated with forkhead box A1 (FOXA1) expression, which correlates with the expression of estrogen receptor alpha (ER). FOXA1 regulates the transcriptional activity of ER and may function cooperatively in the tumorigenesis of breast cancer. Methods: We performed immunohistochemical staining for FOXA1 and ER using tissue samples from 16 patients with EMPD. Results: The nuclei of Paget cells isolated from each of the 16 patients with EMPD (100%) were strongly FOXA1-positive, and the FOXA1 staining intensity was similar across all samples. ER staining was detected in the nuclei of Paget cells originating from seven patients with EMPD (44%), and the ER staining intensity varied between these patients. Conclusions: In the present study, we confirmed that EMPD was frequently associated with FOXA1 expression. However, ER expression varied between patients and did not always coincide with FOXA1 expression. No clear relationship was observed between ER expression, the intensity of ER staining, or EMPD metastasis and prognosis. However, the results indicate that hormone-dependent cancer therapy may be effective in patients with ER-positive EMPD.

Extramammary Paget's disease is a slow-growing cutaneous intraepithelial adenocarcinoma of the apocrine glands in the anogenital and axillary regions. The disease is extremely rare, affects predominantly postmenopausal women, and has nonspecific clinical caracteristics, so that it can take 210 years from the first clinical signs to diagnosis. The vulva and the perianal region are the most affected zones. Extramammary Pagets disease is clinically manifested as well-defined erythematous plaques with secondary changes, such as scaling, ulceration and even bleeding. Differential diagnosis is made between primary and secondary forms of Extramammary Pagets disease, candidiasis, contact dermatitis, Crohn's disease, eczema, erosive lichen planus, hydradenitis suppurativa, Langerhans cell histiocytosis, sclerosing lichen, psoriasis, squamous cell carcinoma in situ, amelanotic melanoma and mycosis fungoide. Treatment mainly includes the surgical component, as well as the use of photodynamic therapy, cytostatic agents, and, depending on the stage, systemic chemotherapy.

Electron beams represent an important treatment modality for providing an accurate dose of therapy to superficial cancers. This case reports important findings of dermal invasion in patients with extramammary Paget's disease (EMPD) using microscopic measurements and electron beam coverage. EMPD is a rare cutaneous adenocarcinoma generally arising in the anogenital region. Surgery is still a curable treatment option for patients with EMPD, whereas radiation therapy (RT) is an alternative for inoperable cases and is necessary in cases where surgery is not performed. This case report describes our experience and reviews the relevant literature on the feasibility of electron RT according to the dermal invasion length. An 80-year-old patient was diagnosed with EMPD and presented for definite radiation treatment. We observed no grade 3 toxicities during electron RT, and at the last follow-up visit, no signs of relapse were observed. There are no reports of electron irradiation as a feasible treatment option for EMPD considering the epidermal invasion length. [ABSTRACT FROM AUTHOR]

Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma that mainly affects the anogenital and axillary regions. Although its etiology has not been fully elucidated, there is evidence that androgen receptors (AR) are expressed in most cases of EMPD. However, the role of androgen signaling in the pathogenesis of EMPD remains unclear. To evaluate the role of androgen signaling in tumor growth of AR-positive EMPD. Patient-derived organoids were established and cultured from two AR-positive EMPD patients: one man and one woman. Cultured organoids were treated with androgen agonists and/or antagonists, then subjected to analysis of changes in organoid proliferation, as well as changes in androgen signaling pathway-specific genes. Organoid cultures were established from each EMPD sample. These organoids were immunohistologically and genetically identical to the original tumor. For each organoid sample, viable cell number increased in response to androgen exposure. The mRNA level of Fkbp5 , a known AR target gene, increased in a concentration-dependent manner in organoids exposed to the synthetic androgen R1881. Conversely, the AR inhibitor darolutamide suppressed the viable cell number in a concentration-dependent manner. The mRNA expression levels of MKI67 and Fkbp5 were also suppressed by darolutamide. Our results indicate that androgen signaling is a key pathway involved in the growth of AR-positive EMPD. Therefore, androgen signaling inhibition may be a novel treatment option for EMPD patients who require systemic therapy. • Androgen receptor (AR) has been shown to be expressed in vast majority of extramammary Paget's disease (EMPD). • Several tumor types, such as prostate cancer, are known to proliferate depending on the androgen signal. • EMPD organoids were established from two AR positive EMPD cases. • Proliferation of organoids was enhanced by androgens and inhibited by additional treatment with an androgen antagonist. • Inhibition of androgen signaling pathway will be a useful treatment option in metastatic EMPDs. [ABSTRACT FROM AUTHOR]

As extramammary Paget's disease (EMPD) sometimes invades and metastasizes from the skin to the mucosa, radical surgical resection of these lesions is often difficult. The purpose of this study was to analyse the association between surgical margins and survival as well as the benefit of functional preservation over complete resection, in patients with EMPD. We retrospectively analysed 230 patients diagnosed with EMPD between 1969 and 2020. Patient and treatment characteristics were recorded. Since our centre is a specialized hospital and almost all patients were referred from other hospitals, we reviewed their referral letters. Prognostic factors and survival time were also analysed. Among 230 patients, 78 (33.9%) had positive margins. The presence of margin positive lesions increased the local recurrence rate but was not significantly correlated with survival. Of all the patients who had received a thorough explanation about the surgical procedure in the referring hospital, 43.8% were scheduled for surgeries that would result in functional impairment, and all of them had function‐preserving surgeries at our hospital with a 10‐year survival rate of 100%. Our result suggest that less invasive surgery preserves anogenital and urethral function may be an acceptable option for EMPD treatment. [ABSTRACT FROM AUTHOR]

It has been reported that nardilysin (NRDC), a metalloendopeptidase which regulates various growth factors and cytokines, is associated with malignancies in a conflicting manner, in which it promoted gastric, hepatocellular, and colorectal cancers and suppressed pancreatic ductal adenocarcinoma. However, it has not been investigated how NRDC is associated with cutaneous malignancies for now. Immunohistochemical staining has revealed that NRDC expression is observed in all extramammary Paget's disease (EMPD) cases. Notably, other cutaneous malignancies including basal cell carcinoma, squamous cell carcinoma, and eccrine porocarcinoma, did not show increased NRDC expression in immunohistochemistry. EMPD typically presents several types of lesions including nodules, and positive staining of NRDC on EMPD was observed regardless of the type of lesions. Examination using samples taken from nodular lesions showed that some cases showed heterogenous NRDC expression within each lesion. We also found that NRDC staining was weaker in the marginal parts of EMPD lesion than in the central parts in several cases, and tumor cells tend to be distributed beyond the macroscopic skin lesions in these cases. It was speculated that decreased NRDC expression in the marginal zones of the skin lesions may be associated with the ability of tumor cells to produce the cutaneous manifestation of EMPD. This study suggests that NRDC may be associated with EMPD like other malignancies reported previously. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Heat shock protein 90 (HSP90) facilitates diverse cellular processes by interacting process with more than 200 client proteins. Overexpression of HSP90 contributes to the pathogenesis of various malignant tumors, and HSP90 inhibitors attenuate the progression of malignant tumors in vitro/vivo. Numerous clinical trials have used HSP90 inhibitors to treat several cancers, and pimitespib (an HSP90 inhibitor) is covered by insurance for advanced gastrointestinal stromal tumor in Japan. In this study, we investigated the expression pattern of HSP90 and analyzed its clinical significance in extramammary Paget's disease (EMPD). All 77 EMPD tissues investigated were positive for HSP90 expression. The immunoreactivity of HSP90 in fetal cases due to EMPD tended to be highly stained. Although there was no significant difference in HSP90 mRNA levels between 24 paired lesional and nonlesional tissues, microRNA‐inhibiting HSP90 levels in tumor tissues were significantly decreased compared with those in normal tissues. Thus, HSP90 may play an important role in the pathogenesis of EMPD and may be a novel therapeutic target for EMPD. [ABSTRACT FROM AUTHOR]

Abstract is missing (Short communication)

Aim Methods Results Conclusion Practitioner points This study aimed to analyze extramammary Paget's disease (EMPD)‐specific survival, overall survival, and recurrence rate (RR) in patients with EMPD in South Korea, with a focus on wide local excision.We retrospectively reviewed the medical records of patients with EMPD from 1993 to 2020 at Kyungpook National University Hospital. We determined the survival and RRs after wide local excision.A total of 95 patients (66 males and 29 females; mean age 67.4 years) were included. The 5‐year disease‐specific survival and overall survival were 91.8% and 79.3%, respectively, whereas the 10‐year rates were 81.6% and 64.7%, respectively. No significant sex differences were observed. Seventy‐five patients (78.9%) underwent wide local excision. Mucosal involvement and lymphadenopathy were identified as the significant prognostic factors of disease‐specific survival in multivariate analysis. The RR was 14.7% in patients who underwent wide local excision: seven local, two regional, and two distant metastases, with a mean recurrence‐free interval of 42.3 months.Based on the survival and RRs obtained, surgical treatment of EMPD with wide local excision provides fair curative resection.Wide local excision can be a feasible treatment option for extramammary Paget's disease. [ABSTRACT FROM AUTHOR]

Abstract Background Perianal Paget’s disease (PPD) is an intraepithelial invasion of the perianal skin and is frequently associated with underlying anorectal carcinoma. The relatively rare nature of this disease has made it difficult to develop treatment recommendations. This study aims to analyze the clinical and pathological features of perianal Paget’s disease (PPD) and to explore rational treatment options and follow-up for this disease. Methods The National Cancer Center Hospital database was searched for all cases of perianal Paget’s disease diagnosed between 2006 and 2021. In the 14 patients identified, we reviewed the diagnosis, management, and outcomes of adenocarcinoma with pagetoid spread, including suspected or recurrent cases. Results All 14 cases met the inclusion criteria. The median follow-up period after diagnosis was 4.5 (range, 0.1–13.0) years. Pagetoid spread before initial treatment was suspected in 12 cases (85.7%). Underlying rectal cancer was identified in 6 cases, and no primary tumor was detected in the other 6 cases. Seven patients had recurrent disease, with the median time to recurrence of 34.6 (range, 19.2–81.7) months. The time to the first relapse was 3 months, and that to the second relapse was 6 months. The overall 5-year survival rate was 90.0%. Conclusions Endoscopic and radiologic evaluation, as well as immunohistologic examination, should be performed. is to differentiate PPD with and without underlying anorectal carcinoma. The time to first recurrence varies widely, and long-term and regular follow-up for more than 5 years is considered necessary for local recurrence and distant metastasis.

The aim of the present study was to evaluate the incidence of concomitant vulvar cancers or premalignant lesions in women surgically treated for extramammary Paget’s disease of the vulva (EMPDV) through a multicenter case series. The medical records of all women diagnosed with and treated for EMPDV from January 2010 to December 2020 were retrospectively analyzed. Women with EMPDV and synchronous vulvar cancer, vulvar intraepithelial neoplasia (VIN) and/or lichen sclerosus (LS) at the histology report were included in the study. A total of 69 women eligible for the present study were considered. Concomitant vulvar lesions occurred in 22 cases (31.9%). A total of 11 cases of synchronous VIN (50%) and 14 cases (63.6%) of concomitant LS were observed. One patient (4.5%) had synchronous vulvar SCC (FIGO stage 1B). Women with EMPDV and concomitant premalignant/malignant vulvar lesions had a significantly higher rate of invasive EMPDV and wider lesions with an extravulvar involvement. The specific meaning of the association between EMPDV, VIN, SCC and LS remains unclear. The potential overlapping features between different vulvar lesions highlight the importance of dedicated gynecologists and pathologists in referral centers.

Introduction Extramammary Paget's disease is an eczematous skin condition that affects the vulva and perineum. Extramammary Paget's disease secondary to urothelial carcinoma is a rare condition that is typically treated with invasive surgical resection of the lesion. Case presentation An 80‐year‐old woman with a 7‐year history of urothelial carcinoma presented with erythema of the labia majora. Immunostaining of skin biopsy specimens suggested extramammary Paget's disease secondary to urothelial carcinoma. The patient did not consent to resection of the lesion. Nine cycles of first‐line platinum‐based chemotherapy for metastatic urothelial carcinoma were administered. As tumor cells remained after systemic chemotherapy, pembrolizumab will be administered to the patient for treating residual extramammary Paget's disease. Conclusion Platinum‐based chemotherapy can control extramammary Paget's disease secondary to urothelial carcinoma.

Objective: Extramammary Paget's disease (EMPD) is a rare cutaneous malignant disease. Due to its rarity, there is a paucity of data regarding best treatment strategy. EMPD primarily affects apocrine gland-bearing skin areas such as the vulva, scrotum, and penis. Our objective was to provide a present-day rationale for diagnosis, pathogenesis, and treatment of EMPD with a focus on recent progress in workup and management of the disease. Methods: Literature on EMPD until February 2022 was assessed through PubMed, MEDLINE databases, and Google scholar. A narrative review of the most relevant articles was provided. Results: EMPD usually presents with indolent growth while usually being diagnosed primarily as carcinoma in situ. The foundation of EMPD treatment centers around prompt and accurate diagnosis, wide local or Mohs micrographic surgical excision with proper management towards the margin status, and careful consideration for lymphadenectomy in patients with regionally positive disease. Conventional chemotherapies are alternative treatments modality for patients with distant metastases; however, they sometimes have suboptimal efficacy. At present, there is no agreement regarding adjuvant or systemic therapies, although recent studies have shown several insights into the molecular pathogenesis, tumor biology, and genomics of the development and advancement of EMPD, which may lead to novel and targeted treatment approaches for metastatic EMPD in the future. Conclusion: Patients with EMPD should seek care from physicians with expertise in disease management and patient counseling. These patients should be surveilled with close follow-up to evaluate them for disease recurrence or progression. Global collaborations with groups such as the Global Society for Rare Genitourinary Tumors, and especially patient support groups are crucial in designing clinical trials to help elucidate more robust data in this orphan disease.

Objective: Vulvar extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma of the vulvar skin. This study evaluated the clinical characteristics, treatment modalities, and oncologic outcomes in patients with vulvar EMPD. Materials and Methods: Cases of patients who were treated for vulvar EMPD between 1994 and 2022 were identified. Patient demographics, associated malignancies, treatments, histopathologic features, need for re-operations, and long-term outcomes were documented. Results: The study involved 10 patients with vulvar noninvasive EMPD, with a median age of 57 (31–86) years. None of the patients had prior malignancies. The index operations performed were wide local excision with reconstructive surgery (5 patients) and vulvectomy with reconstructive surgery (3 patients). Seven patients were positive for margin involvement. Five patients developed recurrences. The mean time of the first recurrence was 32.6 (4–88) months. All recurrences were treated with reoperations. Only 1 associated malignancy was found: cervical cancer. There was no disease progression in any of the patients who were followed; of the 10 patients, 2 were lost to follow-up. Conclusions: EMPD is characterized by a high tendency to recur after surgical resection. Surgical management can be a challenge due to the high rate of residual tumors in the surgical margins. (J GYNECOL SURG 39:66) [ABSTRACT FROM AUTHOR]

Simple Summary: Vulvar Paget's disease (VPD) is an extremely rare malignancy of the vulva with a high local recurrence rate and low mortality. Due to its non-specific symptoms and lack of clinical knowledge, VPD is often misdiagnosed with eczematous skin lesions, and the definitive diagnosis is often delayed. Since currently there is no global consensus on the optimal management of VPD, we present here a systematic review aiming to give readers a concise overview of the state-of-the-art evidence and the emerging therapeutic opportunities. Vulvar Paget's disease (VPD) is a rare form of cutaneous adenocarcinoma of the vulva, which accounts for about 1–2% of all vulvar neoplasms and mainly affects post-menopausal women. The clinical presentation is usually non-specific and mimics chronic erythematous skin lesions; therefore, the diagnosis is often difficult and delayed. Although VPD is typically diagnosed at a locally advanced stage and has a high recurrence rate, the prognosis is overall favorable with a 5-year survival of nearly 90%. Due to the limited and poor-quality evidence, there is no global consensus on optimal management. Therefore, we performed a systematic review of the literature through the main electronic databases to deepen the current knowledge of this rare disease and discuss the available treatment strategies. Wide surgical excision is recommended as the standard-of-care treatment and should be tailored to the tumor position/extension and the patient's performance status. The goal is to completely remove the tumor and achieve clear margins, thus reducing the rate of local recurrences. Non-surgical treatments, such as radiotherapy, chemotherapy, and topical approaches, can be considered, especially in the case of unresectable and recurrent disease. In the absence of clear recommendations, the decision-making process should be individualized, also considering the new emerging molecular targets, such as HER2 and PD-L1, which might pave the way for future targeted therapies. The current review aims to raise awareness of this rare disease and encourage international collaboration to collect larger-scale, high-quality evidence and standardize treatment. [ABSTRACT FROM AUTHOR]

Extramammary Paget's disease (EMPD) is a rare but lethal intraepithelial malignancy without standardized guidelines concerning diagnostic or therapeutic approaches. We report a case of EMPD of the scrotum treated with excellent results using high-dose brachytherapy. A 76-year-old male originally presented in 2015 with pruritus and erythema of the right scrotum, biopsy proved to represent extramammary Paget's disease. He was treated for a year with topical creams without sustained relief. In July 2016 he underwent a right hemiscrotectomy which revealed stage 1 EMPD of the right scrotum and the medial thigh with positive margins but no deep invasion. Brachytherapy was selected as the most appropriate treatment option and carried out in December 2016 using HDR with a H.A.M. applicator and CT treatment planning. On December 2021, at 5 years of clinical and pathological follow up, the patient remains NED with minimal skin toxicity. High-Dose-Rate Brachytherapy appears to be a feasible treatment alternative as adjuvant therapy in patients with EMPD with incomplete resection. [ABSTRACT FROM AUTHOR]

Surgery is the standard treatment for genital extramammary Paget disease (gEMPD). To determine if gEMPD treatments and outcomes differ by sex and US region. A systematic review was performed of all English-language studies on initial gEMPD treatment in Medline via PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov. At least 2 reviewers performed title and abstract review and data extraction. Surgical categories included total skinning procedures, partial skinning procedures, Mohs micrographic surgery (MMS), or unspecified surgery. Chi-squared tests of association were used for comparisons. A total of 60 studies comprising 302 (79.7%) female and 77 (20.3%) male patients met criteria. Women were most often initially recommended partial skinning procedures. In all, 74 (24.5%) women and 0 men underwent a total skinning procedure. Men were more likely to be offered MMS than women (40.3% vs 1.9%, P <.0001), despite men having a significantly greater extent of disease involving the perineum and perianal skin (21.1% vs 1.7%, P <.0001). Treatment recommendations varied by US region. Only 20 states were represented. Women are more frequently offered total skinning procedures for gEMPD while men are more frequently offered MMS. MMS offers less recurrence and morbidity than total skinning procedures and should be recommended equally to both female and male patients with gEMPD. [ABSTRACT FROM AUTHOR]

Perianal Paget's disease (PPD) is a rare intraepithelial adenocarcinoma. The clinical appearance of PPD may be confused with dermatitis and fungal infections of the skin, resulting in delayed diagnosis, sometimes for years. It may also be associated with secondary malignancies. Surgery and non-surgical methods such as radiotherapy, immunomodulating drugs, and chemotherapy are used in the treatment of PPD. In this case report, two patients with PPD are presented; the first was treated with surgical excision and radiotherapy and the second did not accept surgical or medical therapy. Although the lesion deepened and expanded towards adjacent structures, no secondary malignancy or metastasis was observed. [ABSTRACT FROM AUTHOR]

Paget's disease was originally a distinct form of breast cancer; however, some tumors can affect outside of the breast, called Extramammary Paget's Disease (EMPD). EMPD occurs mainly in the vulva, postmenopausal-white females and became a rare entity on vulvar malignancies with an incidence less than 1%. Magnetic resonance imaging (MRI) has the potential to facilitate the diagnosis of EMPD, as well as improve staging, management, and disease monitoring. However, few small studies examined MRI in EMPD due to its low incidence. We aimed to report a 47-year-old Indonesian female, premenopause, who came with complaints of erythematous lesions over her groin area. The lesions initially had been treated with topical antifungals and steroids for 2 years. MRI showed a skin thickness heterogeneously enhanced from the vulva measuring approximately 15.2×2.5×0.5 cm in size that was extensive to the perineum, vagina, urethra, and rectum with inguinal lymphadenopathy and subcentimeter iliac lymph node. The patient underwent chemotherapy with docetaxel and carboplatin. This case is exceedingly rare with irregular extension makes delineating tumor margins challenging. Invasive EMPD is usually treated systemically and confers a worse prognosis. MRI offers precise anatomical details of primary and distant infiltration and can be used to improve disease assessment and management. This case emphasizes the rare phenomenon of an EMPD. Approaches based on clinical, pathological, and radiographic imaging are mandatory for diagnosis. For imaging, MRI has an essential role in addition to facilitating diagnosis; it offers new approaches to managing patients with EMPD, particularly in assessing tumor margins and disease spread. [ABSTRACT FROM AUTHOR]

Background: Perianal Paget's disease (PPD) is an intraepithelial invasion of the perianal skin and is frequently associated with underlying anorectal carcinoma. The relatively rare nature of this disease has made it difficult to develop treatment recommendations. This study aims to analyze the clinical and pathological features of perianal Paget's disease (PPD) and to explore rational treatment options and follow-up for this disease. Methods: The National Cancer Center Hospital database was searched for all cases of perianal Paget's disease diagnosed between 2006 and 2021. In the 14 patients identified, we reviewed the diagnosis, management, and outcomes of adenocarcinoma with pagetoid spread, including suspected or recurrent cases. Results: All 14 cases met the inclusion criteria. The median follow-up period after diagnosis was 4.5 (range, 0.1–13.0) years. Pagetoid spread before initial treatment was suspected in 12 cases (85.7%). Underlying rectal cancer was identified in 6 cases, and no primary tumor was detected in the other 6 cases. Seven patients had recurrent disease, with the median time to recurrence of 34.6 (range, 19.2–81.7) months. The time to the first relapse was 3 months, and that to the second relapse was 6 months. The overall 5-year survival rate was 90.0%. Conclusions: Endoscopic and radiologic evaluation, as well as immunohistologic examination, should be performed. is to differentiate PPD with and without underlying anorectal carcinoma. The time to first recurrence varies widely, and long-term and regular follow-up for more than 5 years is considered necessary for local recurrence and distant metastasis. [ABSTRACT FROM AUTHOR]

Background: Vulvar Paget's disease (VPD) is defined as a neoplasm of epithelial origin, mostly in postmenopausal women. Due to the extreme rarity of VPD, limited data about recommended treatment options are available. Surgical excision has been the treatment of choice although in the recent decade medical treatments have been proposed. Methods: A systematic computerized search of the literature was performed in the main electronic databases (MEDLINE, EMBASE, Web of Science, PubMed, and Cochrane Library), from 2003 to September 2022, in order to analyze all medical and surgical strategies used for the treatment of VPD. Results: Thirty-four articles were included in this review with findings as follows: 390 patients were treated with medical or other conservative treatment while 2802 patients were treated surgically; 235/434 (54%) patients had a complete response, 67/434 (15%) a partial response, 10/434 (2.3%) a stable disease, 3/434 (0.7%) disease progress, 3/434 (0.7%) died of the disease, 55/434 (13%) died of other causes during follow up while 7/434 (1.6%) had to stop topical treatments with 5% imiquimod cream because of side effects; 239/434 patients (55%) had a recurrence and 11/434 (2.5%) were lost to follow-up. The length of follow-up was variable, according to the different studies analyzed. Conclusion: VPD is a chronic disease with a high recurrence rate and low mortality. There are no significant differences in recurrence rates in patients who undergo surgery and those who do not and the margin status at the time of primary surgery and recurrence. Several surgical and medical approaches providing both local control of the disease and minimal tissue damage have been developed. Clock mapping, a recent preoperative vulvo-vaginal workup tool, can predict the invasiveness and the extension of VPD. However, to date, due to the different treatment options available and in the absence of a global consensus, it is critical to tailor treatments to individual patient characteristics and biopsy histopathologic findings, to ensure the best type of therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Extramammary Paget's disease of the vulva (EMPDV) is a rare disease. However, an association between EMPDV and other premalignant/malignant vulvar lesions is not uncommon. Due to its potential clinical implication, such an association should be carefully evaluated in all women diagnosed with and treated for EMPDV. The aim of the present study was to evaluate the incidence of concomitant vulvar cancers or premalignant lesions in women surgically treated for extramammary Paget's disease of the vulva (EMPDV) through a multicenter case series. The medical records of all women diagnosed with and treated for EMPDV from January 2010 to December 2020 were retrospectively analyzed. Women with EMPDV and synchronous vulvar cancer, vulvar intraepithelial neoplasia (VIN) and/or lichen sclerosus (LS) at the histology report were included in the study. A total of 69 women eligible for the present study were considered. Concomitant vulvar lesions occurred in 22 cases (31.9%). A total of 11 cases of synchronous VIN (50%) and 14 cases (63.6%) of concomitant LS were observed. One patient (4.5%) had synchronous vulvar SCC (FIGO stage 1B). Women with EMPDV and concomitant premalignant/malignant vulvar lesions had a significantly higher rate of invasive EMPDV and wider lesions with an extravulvar involvement. The specific meaning of the association between EMPDV, VIN, SCC and LS remains unclear. The potential overlapping features between different vulvar lesions highlight the importance of dedicated gynecologists and pathologists in referral centers. [ABSTRACT FROM AUTHOR]

Abstract Background Male cases of accessory breast carcinoma and sweat gland carcinoma associated with extramammary Paget’s disease of the axilla are uncommon. In clinical diagnosis and treatment, it is necessary to determine the disease carefully and make a reasonable treatment strategy according to the patient’s situation. Case presentation We described two male cases of the special tumor with an axillary mass as the first clinical symptom, one of which was diagnosed as accessory breast cancer and the other as sweat gland cancer associated with extramammary Paget’s disease. We treated the two diseases individually in the hopes of providing a reference for the diagnosis and management of diseases with axillary nodules as the initial symptom. Conclusions The reports of these two cases can provide reference and corresponding thinking for clinical differentiation of axillary lymphadenopathy caused by different causes and subsequent treatment. These two cases may further enrich the database of rare cases and provide some ideas for the treatment of axillary lymphadenopathy caused by different causes.

Background: Extramammary Paget's disease (EMPD) is a rare malignancy occurring on apocrine sweat gland-bearing skin with occasional association with internal cancers. Its epidemiological characteristics are different between populations in Asian and Western countries. Objectives: The aim of this study was to report the clinical experience of EMPD in a single medical center in Taiwan, compare our results with previous literature, and provide strategies for diagnostic workup. Methods: Medical records and biopsies of 34 Taiwanese patients with EMPD, treated in a single medical center in Kaohsiung, Taiwan, from January 2000 to December 2019, were reviewed. The clinicopathological features, biological behavior, management, and follow-up courses of these patients were analyzed. Results: We found a male predominance in our 34 patients with EMPD, and most patients were diagnosed in their 70s. Only four patients (11.8%) had an associated malignancy while the rest had a primary cutaneous lesion. Most patients (22, 64.7%) underwent wide excision (22, 64.7%), with the rest adopting other various therapeutic modalities. The 5-year overall survival rate was 76.5%, and the statistically significant prognostic factors for survival were lymph node involvement (P < 0.001) and dermal invasion (P = 0.022). Conclusion: In summary, this single-center study described the clinical and histopathologic features of patients with EMPD in Taiwan with a review of literature. We also proposed a complete systemic workup when the diagnosis was made and an extended follow-up period as long as 5 years after the initial treatment.

Abstract Background Extramammary Paget’s disease (EMPD) is a rare malignant intraepidermal adenocarcinoma that is poorly understood. Regulatory long noncoding RNAs (lncRNAs) are characterized in many species and shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in different diseases, especially in cancer studies. In the present study, we used high-throughput sequencing to reveal the lncRNA–mRNA interaction network in extramammary Paget’s disease. Methods High-throughput sequencing was used to identify differentially expressed lncRNA and mRNA profiles between EMPD patients and healthy controls. Then, a series of bioinformatics analyses were conducted to construct the lncRNA–mRNA interaction network, which was finally confirmed in vitro. Results Six pairs of EMPD tumor and normal skin samples were collected and sequenced to identify the differentially expressed lncRNA and mRNA profiles between EMPD and healthy controls. A total of 997 differentially expressed mRNAs and 785 differentially expressed lncRNAs were identified. The GO and KEGG analyses show that epidermal development and cell adhesion play important roles in EMPD. The results of the lncRNA–mRNA interaction network analysis suggested that NEAT1, PGAP1, FKBP5 and CDON were the pivotal nodes of the network and that lncRNA NEAT1 might regulate mRNA PGAP1, FKBP5 and CDON. The results of the quantitative real-time RT–PCR performed in ten other patients for NEAT1, PGAP1, FKBP5 and CDON were consistent with those of the sequencing analysis. Moreover, an in vitro experiment confirmed the interactions between NEAT1 and PGAP1, FKBP5 and CDON in human immortalized keratinocytes. Conclusion These findings suggest that the lncRNA–mRNA interaction network based on four pivotal nodes, NEAT1, PGAP1 FKBP5 and CDON, may play an important role in EMPD, which will contribute to a deeper understanding of the pathogenesis of EMPD.