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Background: Previous studies have reported the mutational landscape in extramammary Paget disease (EMPD); however, the prognostic implications of genetic alterations remain unexplored. While CDKN2A loss is known to be associated with tumour progression or poor prognosis in some types of cancer, its significance in EMPD has not been investigated., Objectives: To examine the association between common genetic alterations and prognosis in EMPD., Methods: A retrospective cohort study was carried out to analyse the data of patients with EMPD registered up to January 2024 in the Center for Cancer Genomics and Advanced Therapeutics database, a nationwide database that records clinical data and comprehensive genomic profiling (CGP) test results in Japan., Results: A total of 167 patients with EMPD were recorded in the database, with CDKN2A loss being the most frequent genetic variant. Survival analysis was conducted on data from 127 patients. Survival from the initiation of chemotherapy was analysed, adjusting for length bias inherent in the database with the Kaplan-Meier estimator, an established method of adjustment. Patients with BRCA2-mutant tumours (n = 18) had a worse prognosis than those with BRCA2 wildtype (WT) tumours [n = 109; hazard ratio (HR) 2.97, 95% confidence interval (CI) 1.46-6.01 (P = 0.003)]. Additionally, patients in the CDKN2A mutant group (n = 72) had a significantly worse prognosis compared with those in the CDKN2A WT group [n = 55; HR 1.81, 95% CI 1.06-3.07 (P = 0.029)]. Most CDKN2A variants were pathogenic, primarily characterized by loss, while most BRCA2 variants were variants of uncertain significance. In the survival analysis of CGP enrolment based on Eastern Cooperative Oncology Group performance status (ECOG-PS), patients with an ECOG-PS of 1 at the time of CGP enrolment had a significantly poorer prognosis compared with those with an ECOG-PS of 0 (P = 0.034; median survival time 531 vs. 259 days)., Conclusions: A somatic CDKN2A variant, mainly exhibiting loss, may be associated with a poor prognosis in EMPD. Patients with EMPD with BRCA2-mutant disease might also have a worse prognosis. In addition, CGP testing before ECOG-PS deteriorates is preferable, considering that the observed median survival of individuals undergoing CGP tests in an ECOG-PS 1 condition was < 9 months., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Competing Interests: Conflicts of interest None disclosed.

Competing Interests: Conflicts of interest see Appendix S2.

Basal cell carcinoma is the most common type of skin cancer, and surgical excision with clear margins is the standard of care. Surgical margins are determined based on risk factors (high or low risk) for recurrence according to the National Comprehensive Cancer Network and Japanese basal cell carcinoma guidelines. The clarity of the clinical tumor border (well-defined or poorly defined) is considered a risk factor, and significant discrepancies in the judgment of clinical tumor borders among dermato-oncologists may occur. Therefore, we analyzed the dermato-oncologists' concordance in judging the clinical tumor border of basal cell carcinoma. Forty-seven dermato-oncologists (experts: 37; young trainees: 10) participated in this study. The datasets of clinical and dermoscopic photographs of 79 Japanese cases of head and neck basal cell carcinoma were used to determine the concordance in the judgment of clinical tumor border. The probability of the border that was selected more often was used to calculate the rater agreement rate for each dataset. Correct judgment was defined as a more frequently selected border, and the concordance rate of clarity of clinical tumor border for each dermato-oncologist was calculated based on the definition of the correct judgment. A median concordance rate of 85% or higher for all dermato-oncologists was predefined as an acceptable rate for clinical use. Of the 79 datasets, rater agreement rates were 80-100%, 60-79%, and 51-59% for 55, 19, and five datasets, respectively. The median concordance rate for all dermato-oncologists was 86% (interquartile range: 82-89%). There was no significant difference in the concordance rate between the experts and the trainees (median, 87% vs. 85.5%; p = 0.58). The concordance rates of dermato-oncologists for all datasets were relatively high and acceptable for clinical use., (© 2022 Japanese Dermatological Association.)

Extramammary Paget's disease (EMPD) is a rare cutaneous adenocarcinoma with unfavourable prognosis once it becomes invasive. A tumour marker that reflects disease progression is required for adequate management of EMPD. Cytokeratin 18 is highly expressed in many types of cancer and its soluble forms are detected by M30 (for caspase-cleaved form) and M65 (for both caspase-cleaved and intact forms) assays. We report here that tumour cells of EMPD in both lesional skin and lymph node metastasis are immunohistochemically positive for CK18, and the baseline serum M30 and M65 levels in patients with metastatic EMPD are significantly higher than those in non-metastatic patients. In addition, serial serum M30 and M65 levels might reflect recurrence of EMPD and response to chemotherapy. These results suggest that serum CK18 levels may be a useful tumour marker for advanced EMPD.

With consideration of the ongoing developments in treatment options for cutaneous melanoma, the Japanese Skin Cancer Society published the first guidelines for cutaneous melanoma in 2007 and later revised them in 2015. Here, we report on an English version of the 2019 Japanese Melanoma Guidelines. In this latest edition, all processes were carried out according to the Grading of Recommendations, Assessment, Development and Evaluation system. A comprehensive published work search, systematic review and determination of recommendations in each clinical question were performed by a multidisciplinary expert panel consisting of dermatologists, a plastic and reconstructive surgeon, and a radiation oncologist. The advent of novel agents, such as immune checkpoint inhibitors and molecular-targeted agents, has drastically changed the nature of treatment for adjuvant and advanced-stage diseases among melanoma patients worldwide. Additionally, recent reports of clinical trials regarding surgical procedures and a better understanding of molecular biology and tumor immunology in clinical types of melanoma have had an impact on clinical practise. Based on these viewpoints, eight relevant clinical questions were raised in this report that aim to help clinicians select the appropriate therapeutic approach., (© 2019 Japanese Dermatological Association.)

Background: The prognosis of cutaneous angiosarcoma (CAS), especially for patients with tumours > 5 cm has been reported to be dismal, even after conventional surgery and radiotherapy (S + RT)., Objectives: To demonstrate the efficacy of chemoradiotherapy with taxane (T + RT) and maintenance chemotherapy., Methods: We retrospectively reviewed 16 patients with CAS treated with T + RT and 12 patients treated with S + RT. None had distant metastasis. Tumour sites included the scalp (n = 25) and limbs (n = 3). The chemotherapy regimens used in T + RT were monthly docetaxel (n = 10), biweekly docetaxel (n = 1), weekly docetaxel (n = 5) and weekly paclitaxel (n = 1). The median radiation dose was 70 Gy. Nine patients receiving T + RT continued chemotherapy as maintenance therapy (monthly docetaxel in nine patients and monthly paclitaxel in two patients) and four patients receiving S + RT received adjuvant chemotherapy (weekly docetaxel)., Results: The response ratio of T + RT was 94% (14 complete remission and one partial remission). The 5-year overall survival (OS) rate of patients receiving T + RT was statistically higher than those receiving conventional S + RT (56% and 8%, respectively; P < 0·01). Moreover, patients who received T + RT with maintenance chemotherapy showed a significant improvement in OS than those receiving T + RT alone (P < 0·01). There was a strong trend for relapse-free survival, but it was not significant (P = 0·07). These data indicate that maintenance chemotherapy is crucial for long-term survival after T + RT., Conclusions: From these results, we suggest that T + RT followed by maintenance chemotherapy is a plausible method for managing CAS, especially large tumours that are difficult to manage with S + RT alone., (© 2014 British Association of Dermatologists.)

Unlabelled: Propranolol hydrochloride is a nonselective β-blocker that is used for the treatment of hypertension, arrhythmia, and angina pectoris. In Japan, it was recently approved for the treatment of childhood arrhythmia. It has been observed to produce drastic involution of infantile hemangiomas. The aim of this prospective study was to examine propranolol's superiority to classical therapy with pulsed dye laser and/or cryosurgery in treating proliferating infantile hemangiomas. Fifteen patients between the ages of 1 and 4 months with proliferating infantile hemangiomas received grinded propranolol tablets 2 mg/kg per day divided in three doses. Twelve patients with proliferating infantile hemangiomas receiving pulsed dye laser and/or cryosurgery were enrolled as controls. Baseline electrocardiogram, echocardiogram, and chest x-ray were performed. Monitoring of heart rate, blood pressure, and blood glucose was performed every 2 weeks. Efficacy was assessed by performing blinded volume measurements and taking photographs at every visit. Propranolol induced significantly earlier involution and redness reduction of infantile hemangiomas, compared to pulsed dye laser and cryosurgery. Adverse effects such as hypoglycemia, hypotension, or bradycardia did not occur., Conclusion: The dramatic response of infantile hemangiomas to propranolol and few side effects suggest that early treatment of infantile hemangiomas could result in decreased disfigurement. Propranolol should be considered as a first-line treatment of infantile hemangiomas.

A 54-year-old woman underwent resection of malignant melanoma of the left leg and inguinal lymph node metastases and subsequent radiation therapy (60 Gy) following three courses of dacarbazine, nimustine, vincristine and interferon-beta chemotherapy in January 2010. In September 2011, she was referred to our department with the chief complaint of asymptomatic gross hematuria. A non-papillary bladder tumor was detected on cystoscopy and fluorodeoxyglucose (FDG) positron emission fomography-computed tomography revealed increased uptake of FDG only in the area of the bladder tumor. Melanoma cells were also found on urinary cytology. Our diagnosis was metastatic malignant melanoma of the bladder. Complete transurethral resection of the bladder tumor was performed, and pathological examination confirmed metastatic malignant melanoma. Metastatic bladder tumors constitute less than 5% of all bladder tumors. There are metastases in other organs at the time of diagnosis in almost all cases. In Japan, metastatic malignant melanoma of the urinary bladder is rare in clinical practice, there having been about a dozen reported cases. Solitary metastasis as in our case is even rarer.