UNASSIGNED: Extramammary Paget\'s disease (EMPD) is a rare skin cancer that tends to be multicentric, with quadruple EMPD cases being scarcely reported.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

BACKGROUND: 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.
METHODS: 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.
CONCLUSIONS: 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.

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.

Perianal Paget\'s disease (PPD) is a rare malignant cutaneous tumor. This paper reported a case of PPD complicated by lung adenocarcinoma and anal canal cancer. The patient, a 76-year-old female, had been experiencing recurrent lower abdominal pain and perianal pruritus for the past 5 years. Upon physical examination, a cauliflower-like neoplasm in size of 5 cm×6 cm was observed on the right perianal skin, with local skin ulceration and a small amount of fluid discharge. The left perianal skin was also involved. In thoracoknee position, a hard mass was palpable in the rectal submucosa at 5-6 points 2 cm from the anal verge. Chest CT revealed multiple lesions in both lungs, indication of metastatic tumors. Further evaluation with fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) indicated multiple hypermetabolic nodules in the lungs, hypermetabolic lymph nodes throughout the body, early FDG uptake in a small patch of skin on the left hip, and increased FDG uptake in the anorectal region. Histopathological examination confirmed the diagnosis of lung adenocarcinoma. This resulted in the patient being diagnosed with PPD, lung adenocarcinoma, anal canal cancer, and systemic multiple lymph node metastasis. The combination of PPD with gastrointestinal tumors and other metachronous malignant tumors is highly prevalent. Colonoscopy, FDG-PET/CT, histopathology, and immunohistochemistry play crucial roles in early identification of local lymph node and distant involvement, facilitating the evaluation of potential malignant tumors and differential diagnosis. Treating methods for PPD are currently diverse, including postoperative combined or single chemotherapy, radiotherapy, targeted therapy, and photodynamic therapy. As trerapeutical options continue to develop, the extent and efficacy of surgery need to be reassessed.
肛周Paget病(perianal Paget’s disease，PPD)是一种罕见皮肤恶性肿瘤。本文报道1例PPD合并肺腺癌和肛管癌的患者资料。患者为76岁女性，反复下腹部疼痛伴肛周瘙痒5年。体格检查示右侧肛周皮肤5 cm×6 cm大小菜花状新生物，局部皮肤破溃并有少量液体渗出，累及左侧肛周。胸膝位，距肛缘2 cm直肠5~6点直肠黏膜下触及质硬包块。胸部CT示双肺多发病变，考虑转移瘤。氟代脱氧葡萄糖-正电子发射断层显像(fluorodeoxyglucose-positron emission tomography and computed tomography，FDG-PET/CT)提示双肺多发代谢增高结节，全身多发代谢增高淋巴结，左侧臀部小片皮肤早期FDG摄取增高，直肠肛管区FDG摄取增高。支气管镜下右上叶前段开口新生物活检，组织病理学提示肺腺癌。最终诊断为PPD合并肺腺癌、肛管癌、全身多发淋巴结转移。PPD合并消化道肿瘤和其他恶性肿瘤的发生率高，完善结肠镜检查、FDG-PET/CT、组织病理学及免疫组织化学检查，能早期识别局部淋巴结和远处受累，鉴别诊断潜在恶性肿瘤。目前治疗手段多样化，可术后联合或单一化学治疗、放射治疗、靶向治疗及光动力学治疗等，且随着治疗的进展，需重新评估外科手术的范围和有效性。.

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.

Extramammary Paget\'s Disease (EMPD) is a rare cutaneous, slow growing, intraepithelial adenocarcinoma that can be either primary (intraepithelial arising within the epidermis) or secondary (intraepithelial spread of a visceral carcinoma). Here we present the case of a 63-year-old male with EMPD of the glans penis stemming from underlying urothelial carcinoma. Our treatment decision elected for management with chemotherapy and local treatment with radiation therapy. Subsequent, review of the literature demonstrated a rare disease with a variety of underlying malignancies causing this secondary pathology. Caregivers should be aware of the association of Paget\'s disease and urothelial cancer and should have a high index of suspicion that erythematous penile lesions may represent Paget\'s disease and that penile biopsies should be performed early in this setting.

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.

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.
METHODS: 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: Rare cutaneous cancers require early management given their aggressive nature; however, few therapeutic options exist for managing these rare cancers.
OBJECTIVE: To identify emerging therapies for extramammary Paget\'s disease, Merkel cell carcinoma, sebaceous gland carcinoma, microcystic adnexal carcinoma, Kaposi sarcoma and cutaneous angiosarcoma.
METHODS: A systematic review was conducted using PubMed database from October 2010 to October 2020. Published clinical trials and case reports/series were included if they involved primarily a targeted agent rather than classic cytotoxic chemotherapy or photosensitizing medication. Active clinical trials were evaluated using ClinicalTrials.gov, the Japanese University Hospitals Clinical Information Network, and the ISRCTN registry. Quality of evidence for each study was rated using the Oxford Centre for Evidence-Based Medicine Level of Evidence Rating Scale.
RESULTS: There are several emerging therapies for rare cutaneous cancers with many clinical trials actively recruiting. PD-1 receptor inhibitors were the most investigated treatment, targeting several cancers. Merkel cell carcinoma and Kaposi sarcoma had the most clinical trials while microcystic adnexal carcinoma and sebaceous gland carcinoma had the least. The main limitation was a lack of key findings from clinical trials still in progress.
CONCLUSIONS: Emerging therapies exist for rare cutaneous cancers; results of ongoing studies will provide more robust evidence in the future.

BACKGROUND: Extramammary Paget\'s disease (EMPD) is a rare malignant disease originating from the apocrine glands involving the perineum, vulva, axilla, scrotum, and penis.
OBJECTIVE: To study the clinical presentation, extent of disease, efficacy of treatment, and survival outcomes of the cases in a single institution.
METHODS: Retrospective observation data analysis of 19 EMPD cases was performed. Demographic information, clinical management records, and histopathologic data of individual cases were obtained from the inpatient hospital data registry.
RESULTS: The mean age (years) at time of diagnosis was 62.4 with equal gender distribution. Synchronous tumors were detected in 6 cases (31.5%). 18 out of 19 patients underwent definitive surgical management in the form of wide local excision (WLE) and reconstructive surgery. Positive margins were found in 11 (68.8%) cases and 7 out of these 11 cases underwent second look surgical intervention to achieve oncological clearance or adjuvant oncology treatment. Follow-up period for living patients varied depending on time of diagnosis and definitive treatment. 10 out 19 cases (52.7%) were alive at the time of the study. Among the 7 cases of mortality from cancer, 5 cases died from progression of underlying associated malignancy and only 2 cases died with advanced stage of EMPD.
CONCLUSIONS: EMPD can be quite aggressive, especially in the secondary form, and surgical management is challenging with a high rate of residual tumor at the surgical margin. EMPD can easily mislead the clinician and patient, leading to unnecessary delay prior to definitive effective management.