[The Cutaneous Squamous Cell Carcinoma - An Update].

Background: The cutaneous squamous cell carcinoma (CSCC) is the second most common nonmelanoma skin cancer with an increasing incidence rate. Patients presenting with high-risk lesions associated with locally advanced or metastatic CSCC face high rates of recurrence and mortality.

Methods: Selective literature review based on PubMed and consideration of current guidelines "Aktinische Keratosen und Plattenepithelkarzinom der Haut" and "Prävention von Hautkrebs".

Computer-Assisted Differential Diagnosis of Pyoderma Gangrenosum and Venous Ulcers with Deep Neural Networks.

(1) Background: Pyoderma gangrenosum (PG) is often situated on the lower legs, and the differentiation from conventional leg ulcers (LU) is a challenging task due to the lack of clear clinical diagnostic criteria. Because of the different therapy concepts, misdiagnosis or delayed diagnosis bears a great risk for patients. (2) Objective: to develop a deep convolutional neural network (CNN) capable of analysing wound photographs to facilitate the PG diagnosis for health professionals.

Encorafenib, binimetinib plus pembrolizumab triplet therapy in patients with advanced BRAF mutant melanoma: safety and tolerability results from the phase I IMMU-TARGET trial.

Background: Combination of immune checkpoint inhibitors and mitogen-activated protein kinase (MAPK) pathway inhibitors (MAPKi) has been proposed to enhance the durability of anti-tumour responses induced by MAPKi. Here, we present phase I safety results from an open-label, phase I/II study of pembrolizumab (PEM), encorafenib (ENC) and binimetinib (BIN) triplet therapy in advanced, B-Raf proto-oncogene serine/threonine kinase (BRAF)-mutated melanoma (IMMU-TARGET, NCT02902042).

Methods: The dose finding phase I part used a 3 + 3 design, starting with the approved doses of PEM (200 mg every three weeks), ENC (450 mg once daily [QD]) and BIN (45 mg twice daily [BID]) as dose level (DL) 0.

A case of multiple familial trichoepitheliomas responding to treatment with the Hedgehog signaling pathway inhibitor vismodegib.

Multiple familial trichoepitheliomas (MFT) is an autosomal dominantly inherited disease characterized by multiple skin appendage tumors. We describe a patient showing a continuous spectrum of follicular differentiated neoplasms including classical trichoepitheliomas but also infiltrative growing and finally metastasizing malignant follicular differentiated tumors. Germline mutation analysis revealed a nonsense mutation in the cylindromatosis (CYLD) gene.

Immune checkpoint blockade with concurrent electrochemotherapy in advanced melanoma: a retrospective multicenter analysis.

Growing evidence suggests that concurrent loco-regional and systemic treatment modalities may lead to synergistic anti-tumor effects in advanced melanoma. In this retrospective multicenter study, we evaluate the use of electrochemotherapy (ECT) combined with ipilimumab or PD-1 inhibition. We investigated patients with unresectable or metastatic melanoma who received the combination of ECT and immune checkpoint blockade for distant or cutaneous metastases within 4 weeks.

Afatinib-associated Stevens-Johnson syndrome in an EGFR-mutated lung cancer patient.

Introduction: Afatinib is a tyrosine kinase inhibitor (TKI), that has been approved for treating patients with epidermal growth factor receptor (EGFR) mutated advanced non-small-cell lung cancer (NSCLC). Stevens-Johnson syndrome (SJS) related to EGFR directed TKIs is a rare adverse event.

Case Presentation: We report a case of a 79-year-old white female with EGFR-mutated, metastatic non-small-cell lung cancer treated with afatinib as first-line palliative treatment, who developed a SJS after two months of treatment.

Melanoma-associated chondroitin sulphate proteoglycan as a new target antigen for CD4+ T cells in melanoma patients.

Melanoma-associated chondroitin sulfate proteoglycan (MCSP) (also known as high molecular weight-melanoma-associated antigen) represents an interesting target antigen for cancer immunotherapy which is expressed on human melanomas and other tumors such as breast carcinomas, gliomas, neuroblastomas and acute leukemias. MCSP seems to play an important functional role in melanoma as it is involved in tumor cell migration, invasion and angiogenesis. In this study, we isolated CD4(+) T helper cells from the blood of a healthy donor, recognizing a peptide from the MCSP core protein presented by HLA-DBR1*1101 molecules.

Tumor-reactive CD4+ T cell responses to the melanoma-associated chondroitin sulphate proteoglycan in melanoma patients and healthy individuals in the absence of autoimmunity.

To avoid immune escape by down-regulation or loss of Ag by the tumor cells, target Ags are needed, which are important for the malignant phenotype and survival of the tumor. We could identify a CD4(+) T cell epitope derived from the human melanoma-associated chondroitin sulfate proteoglycan (MCSP) (also known as high m.w.

Late syphilis mimicking a pseudolymphoma of the skin.

After a period of declining incidence of syphilis in most of Western Europe until the late 1990s, reports about an increasing trend have been published recently. In contrast to the rising incidence of early syphilis, cases of late (tertiary) syphilis are rarely seen in developed countries. In this report, we describe a 54-year-old patient with infiltrated erythematous plaques on his forehead and neck that histologically revealed a dense lymphocytic cell infiltrate with numerous plasma cells.

Mycosis fungoides palmaris et plantaris--an unusual variant of cutaneous T-cell lymphoma.

Mycosis fungoides (MF) represents a low-risk, cutaneous, non-Hodgkin, T-cell lymphoma with a wide spectrum of clinicopathological manifestations and therefore may mimic a number of other dermatoses. Sometimes the clinical diversity makes the diagnosis of MF, and especially its atypical forms, challenging. We report on an 18-year old male patient, who had been previously diagnosed with palmoplantar eczema.

Artesunate in the treatment of metastatic uveal melanoma--first experiences.

Artesunate (ART) is a derivative of artemisinin, the active principle of the Chinese herb Artemisia annua L. Artesunate is approved for the treatment of multidrug-resistant malaria and has an excellent safety profile. It has been shown that Artesunate, apart from its anti-malarial activity, has cytotoxic effects on a number of human cancer cell lines, including leukemia, colon cancer and melanoma.

Optimizing the exogenous antigen loading of monocyte-derived dendritic cells.

Dendritic cell (DC) vaccination, i.e. the adoptive transfer of antigen-loaded DC, is still at an early stage and requires standardization.

Generation of an optimized polyvalent monocyte-derived dendritic cell vaccine by transfecting defined RNAs after rather than before maturation.

Transfection with RNA is an attractive method of Ag delivery to dendritic cells (DCs), but has not yet been standardized. We describe in this study the methods to efficiently generate an optimized mature monocyte-derived DC vaccine at clinical scale based on the electroporation of several RNAs either into immature DC followed by maturation or, alternatively, directly into mature DCs, which has not been possible so far with such high efficiency. Electroporation of DCs resulted in high yield, high transfection efficiency (>90%), and high migration capacity.

Differences in phenotype and function between spontaneously occurring melan-A-, tyrosinase- and influenza matrix peptide-specific CTL in HLA-A*0201 melanoma patients.

Melanoma-specific T cells can occur spontaneously or in response to vaccination or other therapies, but the frequency is much lower than observed in viral infections. The presence of tumor-specific T cells does not necessarily translate into clinical regressions for a variety of reasons such as an insufficient frequency, activation state or homing capacity of the T cells or escape strategies of the tumor. Having screened melanoma patients prior to inclusion in vaccination trials for spontaneous tumor-specific T cells either by Elispot or tetramer-staining, we have identified 3 patients with sufficient numbers of tumor-reactive T cells to more than 1 TAA and at least 1 virus-antigen to perform phenotypic and functional analysis directly ex vivo.

Functional analysis of tumor-specific Th cell responses detected in melanoma patients after dendritic cell-based immunotherapy.

Recently, we have demonstrated that tumor-specific CD4+ Th cell responses can be rapidly induced in advanced melanoma patients by vaccination with peptide-loaded monocyte-derived dendritic cells. Most patients showed a T cell reactivity against a melanoma Ag 3 (MAGE-3) peptide (MAGE-3(243-258)), which has been previously found to be presented by HLA-DP4 molecules. To analyze the functional and specificity profile of this in vivo T cell response in detail, peptide-specific CD4+ T cell clones were established from postvaccination blood samples of two HLA-DP4 patients.

Antigen loading of dendritic cells with whole tumor cell preparations.

Dendritic cells (DC) based vaccinations have been widely used for the induction of anti-tumoral immunity in clinical studies. Antigen loading of DC with whole tumor cell preparations is an attractive method whenever tumor cell material is available. In order to determine parameters for the loading procedure, we performed dose finding and timing experiments.

Tumor-specific shared antigenic peptides recognized by human T cells.

The first tumor-specific shared antigens and the cancer-germline genes that code for these antigens were identified with antitumor cytolytic T lymphocytes obtained from cancer patients. A few HLA class I-restricted antigenic peptides were identified by this 'direct approach'. A large set of additional cancer-germline genes have now been identified by purely genetic approaches or by screening tumor cDNA expression libraries with the serum of cancer patients.

Segmental neurofibromatosis.

Segmental neurofibromatosis is characterised by a limited, segmental distribution of cutaneous neurofibromatosis type 1 (NF1) lesions. It has been suggested that segmental NF results from a postzygotic NF1 gene mutation, and, recently, this hypothesis has been proven in a patient with regionally distributed café-au-lait (CAL) spots and freckles by demonstrating an NF1 microdeletion restricted to fibroblasts cultured from CAL spots. We describe here a patient with segmental NF in which we could not demonstrate any NF1 gene mutation in fibroblasts cultured from neurofibromas by use of the protein truncation test, enzymatic mutation detection and fluorescence in situ hybridisation.

Rapid induction of tumor-specific type 1 T helper cells in metastatic melanoma patients by vaccination with mature, cryopreserved, peptide-loaded monocyte-derived dendritic cells.

There is consensus that an optimized cancer vaccine will have to induce not only CD8+ cytotoxic but also CD4+ T helper (Th) cells, particularly interferon (IFN)-gamma-producing, type 1 Th cells. The induction of strong, ex vivo detectable type 1 Th cell responses has not been reported to date. We demonstrate now that the subcutaneous injection of cryopreserved, mature, antigen-loaded, monocyte-derived dendritic cells (DCs) rapidly induces unequivocal Th1 responses (ex vivo detectable IFN-gamma-producing effectors as well as proliferating precursors) both to the control antigen KLH and to major histocompatibility complex (MHC) class II-restricted tumor peptides (melanoma-antigen [Mage]-3.

The production of a new MAGE-3 peptide presented to cytolytic T lymphocytes by HLA-B40 requires the immunoproteasome.

By stimulating human CD8(+) T lymphocytes with autologous dendritic cells infected with an adenovirus encoding MAGE-3, we obtained a cytotoxic T lymphocyte (CTL) clone that recognized a new MAGE-3 antigenic peptide, AELVHFLLL, which is presented by HLA-B40. This peptide is also encoded by MAGE-12. The CTL clone recognized MAGE-3--expressing tumor cells only when they were first treated with IFN-gamma.