UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

UNASSIGNED: To evaluate the efficacy of Mohs micrographic surgery (MMS) combined with photodynamic therapy (PDT) in treating non-invasive extramammary Paget\'s disease (EMPD).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.

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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

Extramammary Paget\'s disease (EMPD) is a rare form of adenocarcinoma usually found in apocrine gland-containing cutaneous regions. EMPD affects the vulvar area most commonly, followed by the perianal area, scrotum, penis, and axillary region. In its initial form, EMPD presents as an erythematous plaque with well-defined edges, fine scaling, excoriations, exulcerations, and lichenification. Generally, a definitive diagnosis can be made through histopathological analysis. Importantly, associated malignancies should be investigated prior to treatment initiation. Photodynamic therapy (PDT) is a modern, noninvasive treatment strategy for non-oncological diseases as well as various cancers. In recent years, PDT has been widely used to treat EMPD. This present article presents a discussion of the diagnosis and treatment of EMPD as well as the usefulness of PDT in its management.

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。.

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.

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.
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.
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.
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.