Treatment-induced anogenital melanosis is a very frequent finding in patients with vulvar lichen sclerosus.

Background: Pigmented lesions such as melanosis have rarely been reported in patients with vulvar lichen sclerosus (VLS) that is typically characterized by hypopigmented lesions. Objective: We aimed to analyze systematically anogenital melanosis in a large cohort of VLS patients. Methods: We analyzed the clinical data of 198 female patients with VLS. The anogenital lesions of all patients were professionally photographed in a standardized position and illumination. Severity classification of architectural findings followed an easy-to-use clinical score. A modified Melasma Area and Severity Index and an image analysis software were used to evaluate the area and intensity of pigmentation. Results: According to the clinical score, 79 (198/39.9%) patients showed grade 1 disease, 78 (198/39.4%) grade 2, 37 (198/18.7%) grade 3, and 4 (198/2%) grade 4 disease. About 111 (56.1%) of the 198 patients had anogenital melanosis with a median modified Melasma Area and Severity Index of 3.6 (0.4-14). Univariate analysis revealed that anogenital melanosis was positively correlated with the use of topical estrogens (P = .0018) and negatively correlated with the use of pulsed high-dose corticosteroids plus low-dose methotrexate (PHDC-LDM, P = .021). On multivariable analysis, the use of topical hormone therapy turned out to be a strong independent predictor for the presence of anogenital melanosis (odds ratio: 4.57, 95% confidence interval: 1.66-12.57, P = .0033), whereas PHDC-LDM use was an independent predictor for the absence of anogenital melanosis (odds ratio: 0.35, 95% confidence interval: 0.15-0.84, P = .018). Limitations: The study includes the retrospective monocentric design. Conclusion: Anogenital melanosis is a very frequent and so far, under-reported clinical finding in VLS patients. It is likely caused by the use of topical estrogens employed for VLS treatment. In contrast, patients with more severe disease and PHDC-LDM treatment appear to develop less likely anogenital melanosis.

Preferences of physicians for treatment-related toxicity vs. recurrence in melanoma (GERMELATOX-A): the doctors' perspective.

INTRODUCTION: Adjuvant treatment with immune checkpoint inhibitors, such as PD1-antibodies (ICI) ± CTLA4-antibodies (cICI) or targeted therapy with BRAF/MEK inhibitors (TT), has shown a significant improvement in disease-free survival (DFS) for high-risk melanoma patients. However, due to specific side effects, the choice of treatment is often influenced by the risk of toxicity. Therefore, the role of physicians in treatment decisions of patients is crucial. This study investigated for the first time in a multicenter setting the attitudes and preferences of dermatooncologists in Germany and Switzerland regarding adjuvant treatment with (c)ICI and TT. METHODS: In the GERMELATOX-A study, 108 physicians (median age: 32 yrs, 67.6% female) from 11 skin cancer centers were surveyed to rate typical side effect scenarios of (c)ICI and TT treatments and then compared to patients' ratings evaluated in a previous analysis from the same centers. The scenarios described mild-to-moderate or severe toxicity and included melanoma relapse leading to death. The physicians were asked about the level of side effects they would tolerate in exchange for a reduction in melanoma relapse and an increase in survival at 5 years. RESULTS: The preferences of physicians and patients revealed significant differences regarding adjuvant melanoma treatment with (c)ICI and TT (p < 0.05). Compared to patients, physicians tend to value a melanoma relapse less severe, according to a visual analog scale. They were also less threatened by all scenarios of side effects during adjuvant treatment with (c)ICI or TT, compared to patients. Physicians required lower risk reductions for disease-free survival (DFS) and overall survival (OS) for both ICI and TT and their drug-related side effects to accept these treatments. In case of severe side effects, physicians required similar 5-year DFS rates for ICI and TT (60-65%), while patients needed a 15% improvement of 5-year DFS for ICI compared to TT (80%/65%). For survival, physicians expected an OS improvement of + 10% for all three treatment modalities, whereas patients required a higher increase: + 18-22% for ICI and + 15% for TT. CONCLUSION: Our study highlights the importance of understanding the patient's perspective and a potential difference to the doctor's view when making decisions about adjuvant melanoma treatment with (c)ICI and TT, especially as these treatments are increasingly being implemented in earlier stages.

Current Progress in Vaccines against Merkel Cell Carcinoma: A Narrative Review and Update.

Merkel cell carcinoma is a rare, aggressive skin cancer that mainly occurs in elderly and immunocompromised patients. Due to the success of immune checkpoint inhibition in MCC, the importance of immunotherapy and vaccines in MCC has increased in recent years. In this article, we aim to present the current progress and perspectives in the development of vaccines for this disease. Here, we summarize and discuss the current literature and ongoing clinical trials investigating vaccines against MCC. We identified 10 articles through a PubMed search investigating a vaccine against MCC. From the international clinical trial database Clinical.Trials.gov, we identified nine studies on vaccines for the management of MCC, of which seven are actively recruiting. Most of the identified studies investigating a vaccine against MCC are preclinical or phase 1/2 trials. The vaccine principles mainly included DNA- and (synthetic) peptide-based vaccines, but RNA-based vaccines, oncolytic viruses, and the combination of vaccines and immunotherapy are also under investigation for the treatment of MCC. Although the management of MCC is changing, when compared to times before the approval of immune checkpoint inhibitors, it will still take some time before the first MCC vaccine is ready for approval.