Improved survival of advanced melanoma patients receiving immunotherapy with concomitant antithrombotic therapy - A multicenter study on 2419 patients from the prospective skin cancer registry ADOReg.

Background: Cancer immunotherapy has revolutionized melanoma treatment, but the high number of non-responders still emphasizes the need for improvement of therapy. One potential avenue for enhancing anti-tumor treatment is through the modulation of coagulation and platelet activity. Both have been found to play an important role in the tumor microenvironment, tumor growth and metastasis.

A Retrospective Analysis of the Prognostic Factors and Adverse Events in the Treatment of Mucosal Melanoma in a Single Centre.

Despite the dramatic advances in the management of metastatic cutaneous melanoma, there remains no consensus-based, evidence-based strategy for the management of mucosal melanoma. The rare nature of the disease, its late clinical presentation, and distinct tumour biology all complicate efforts to optimise patient outcomes. To this end, we carried out a monocentric, retrospective analysis of all patients diagnosed with mucosal melanoma and treated between 2013 and 2021.

Shortened progression free and overall survival to immune-checkpoint inhibitors in BRAF-, RAS- and NF1- ("Triple") wild type melanomas.

Background: Melanomas lacking mutations in BRAF, NRAS and NF1 are frequently referred to as "triple wild-type" (tWT) melanomas. They constitute 5-10 % of all melanomas and remain poorly characterized regarding clinical characteristics and response to therapy. This study investigates the largest multicenter collection of tWT-melanomas to date.

[Complex cutaneous leishmaniasis with bone involvement].

We report an immunocompromised patient with a complex cutaneous leishmaniasis (CL) who suffered from singular bone involvement of the little left toe due to Leishmania (L.) infantum infection. The diagnosis was confirmed by positive polymerase chain reaction (PCR) testing in skin and bone tissue.

Stringent monitoring can decrease mortality of immune checkpoint inhibitor induced cardiotoxicity.

Background: Immune checkpoint inhibitor (ICI)-induced myocarditis is a rare immune-related adverse event (irAE) with a fatality rate of 40%-46%. However, irMyocarditis can be asymptomatic. Thus, improved monitoring, detection and therapy are needed.

Increased cardiovascular risks and mortality in prurigo nodularis: a global cohort study.

Background: Prurigo nodularis (PN) presents with intensely itchy hard nodules. Despite being limited to the skin, PN was noted to be associated with systemic diseases including diabetes and chronic renal failure. In previous smaller retrospective studies, several cardiac and vascular diseases were found more frequently in patients with PN.

Baseline metastatic growth rate is an independent prognostic marker in patients with advanced BRAF V600 mutated melanoma receiving targeted therapy.

Background: Targeted therapy (TT) of BRAF V600 mutated unresectable melanoma with inhibitors of the MAPK pathway achieves response rates of up to 76%, but most patients develop secondary resistance. Albeit TT is strikingly efficacious during the first days of treatment, even in advanced cases, long-term survival is highly unlikely, especially in patients with unfavorable baseline characteristics like elevated lactate dehydrogenase (LDH). In patients treated with anti-PD-1 immune checkpoint inhibitors, elevated baseline metastatic growth rate (MGR) was the most important prognostic factor.

Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany: the non-interventional study coveNIS.

Cobimetinib/vemurafenib combination therapy is approved for treatment of adults with unresectable or metastatic BRAF V600 mutated malignant melanoma (mM). The non-interventional post-authorisation safety study coveNIS collected real-world data on cobimetinib/vemurafenib treatment focussing on overall survival (OS), safety and utilization. MM patients with brain metastases are usually excluded from clinical studies.

Ring-shaped plaque on the face.

Granulomatosis Miescher is a very rare, chronic, granulomatous (non-necrobiotic) disease. Clinical characteristics are a slowly centrifugally growing brownish plaques with partly yellowish parts and telangiectasias. Histology shows perivascular epithelioid cell granulomas with few giant cells and only isolated necrobiosis lesions.

Treatment management for -mutant melanoma patients with tumor recurrence on adjuvant therapy: a multicenter study from the prospective skin cancer registry ADOREG.

Background: Adjuvant therapy with immune-checkpoint inhibitors (CPI) or BRAF/MEK-directed targeted therapy (TT) improves recurrence-free survival (RFS) for patients with advanced, V600-mutant (mut) resected melanoma. However, 40% of these patients will develop distant metastases (DM) within 5 years, which require systemic therapy. Little data exist to guide the choice of upfront adjuvant therapy or treatment management upon DM.

Varicella Zoster Virus-Specific Hyperimmunoglobulin in the Adjuvant Treatment of Immunocompromised Herpes Zoster Patients: A Case Series.

Introduction: Immunocompromised patients are at increased risk for herpes zoster (HZ)-associated complications. Despite standard therapy with systemic antiviral drugs and analgesics, complications are frequently encountered, including generalization of lesions or persistent neuropathic pain, so-called post-herpetic neuralgia (PHN). Given the scarcity of literature and awareness of therapeutic options to improve patient outcomes, especially for vulnerable patient groups, here we describe a strategy based on early intensification of treatment with a varicella zoster virus-specific hyperimmunoglobulin (VZV-IgG), which is approved in the adjuvant treatment of HZ.

Early switch from run-in treatment with vemurafenib plus cobimetinib to atezolizumab after 3 months leads to rapid loss of tumour control in patients with advanced BRAFV600-positive melanoma: The ImmunoCobiVem phase 2 randomised trial.

Aim: ImmunoCobiVem investigated whether a planned switch to atezolizumab after achieving tumour control during run-in with vemurafenib + cobimetinib improves progression-free survival (PFS) and overall survival (OS) compared to continuous targeted therapy (TT) in patients with previously untreated advanced BRAF-mutated melanoma.

Methods: In this multicenter phase 2 study, patients received vemurafenib plus cobimetinib. After 3months, patients without progressive disease (PD) were randomly assigned (1:1) to continue vemurafenib + cobimetinib (Arm A) or switch to atezolizumab (Arm B) until first documented PD (PD1).

Early decrease of blood myeloid-derived suppressor cells during checkpoint inhibition is a favorable biomarker in metastatic melanoma.

Background: The need for reliable clinical biomarkers to predict which patients with melanoma will benefit from immune checkpoint blockade (ICB) remains unmet. Several different parameters have been considered in the past, including routine differential blood counts, T cell subset distribution patterns and quantification of peripheral myeloid-derived suppressor cells (MDSC), but none has yet achieved sufficient accuracy for clinical utility.

Methods: Here, we investigated potential cellular biomarkers from clinical routine blood counts as well as several myeloid and T cell subsets, using flow cytometry, in two independent cohorts of a total of 141 patients with stage IV M1c melanoma before and during ICB.

Cutaneous lupus erythematosus is associated with an increased risk of cardiac and vascular diseases: a large-scale, propensity-matched global retrospective cohort study.

Background: Autoimmune skin diseases can expedite various systemic sequelae involving other organs. Although limited to the skin, cutaneous lupus erythematosus (CLE) was noted to be associated with thromboembolic diseases. However, small cohort sizes, partially discrepant outcomes, missing data on CLE subtypes, and incomplete risk assessment limits these findings.

Immune checkpoint inhibition in patients with NRAS mutated and NRAS wild type melanoma: a multicenter Dermatologic Cooperative Oncology Group study on 637 patients from the prospective skin cancer registry ADOREG.

Background: Melanomas frequently harbour somatic mutations in BRAF (40%) or NRAS (20%). Impact of NRAS mutations on the therapeutic outcome of immune checkpoint inhibitors (ICI) remains controversial. Potential correlation of the NRAS mutational status and programmed cell death ligand-1 (PD-L1) expression in melanoma is unknown.

S2k Guideline - Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) - Update 2022.

Merkel cell carcinoma (MCC, ICD-O M8247/3) is a rare, malignant, primary skin tumor with epithelial and neuroendocrine differentiation. The tumor cells share many morphologic, immunohistochemical, and ultrastructural features with cutaneous Merkel cells. Nevertheless, the cell of origin of MCC is unclear.