(Related to Figure 2). Epithelial and myeloid cell contributions to gene expression and 13C labeling features.

(Related to Figure 1). Clinical and pathological data from patients recruited to this study.

Supplementary Figure 2. CEACAM1 isoforms also modulate surface expression of DNMA-1 ligands in an isoform specific mode of action.

Supplementary Figure 1. CEACAM1-3S modulates melanoma cell sensitivity against NK cell-mediated cytolysis.

Background PD-1-based immune checkpoint inhibition (ICI) is the major backbone of current melanoma therapy. Tumor PD-L1 expression represents one of few biomarkers predicting ICI therapy outcome. The objective of the present study was to systematically investigate whether the type of tumor tissue examined for PD-L1 expression has an impact on the correlation with ICI therapy outcome.Methods Pre-treatment tumor tissue was collected within the prospective DeCOG cohort study ADOREG/TRIM (CA209-578; NCT05750511) between February 2014 and May 2020 from 448 consecutive patients who received PD-1-based ICI for non-resectable metastatic melanoma. The primary study endpoint was best overall response (BOR), secondary endpoints were progression-free (PFS) and overall survival (OS). All endpoints were correlated with tumor PD-L1 expression (quantified with clone 28-8; cutoff >= 5%) and stratified by tissue type.Findings Tumor PD-L1 was determined in 95 primary tumors (PT; 36.8% positivity), 153 skin/subcutaneous (34.0% positivity), 115 lymph node (LN; 50.4% positivity), and 85 organ (40.8% positivity) metastases. Tumor PD-L1 correlated with BOR if determined in LN (OR = 0.319; 95% CI = 0.138-0.762; P = 0.010), but not in skin/ subcutaneous metastases (OR = 0.656; 95% CI = 0.311-1.341; P = 0.26). PD-L1 positivity determined on LN metastases was associated with favorable survival (PFS, HR = 0.490; 95% CI = 0.310-0.775; P = 0.002; OS, HR = 0.519; 95% CI = 0.307-0.880; P = 0.014). PD-L1 positivity determined in PT (PFS, HR = 0.757; 95% CI = 0.467-1.226; P = 0.27; OS; HR = 0.528; 95% CI = 0.305-0.913; P = 0.032) was correlated with survival to a lesser extent. No relevant survival differences were detected by PD-L1 determined in skin/subcutaneous metastases (PFS, HR = 0.825; 95% CI = 0.555-1.226; P = 0.35; OS, HR = 1.083; 95% CI = 0.698-1.681; P = 0.72). Interpretation For PD-1-based immunotherapy in melanoma, tumor PD-L1 determined in LN metastases was stronger correlated with therapy outcome than that assessed in PT or organ metastases. PD-L1 determined in skin/subcutaneous metastases showed no outcome correlation and therefore should be used with caution for clinical decision making.Funding Bristol-Myers Squibb (ADOREG/TRIM, NCT05750511); German Research Foundation (DFG; Clinician Scientist Program UMEA); Else Kroner-Fresenius-Stiftung (EKFS; Medical Scientist Academy UMESciA).Copyright (c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Worldwide mass vaccination for COVID‐19 started in late 2020. COVID‐19 vaccines cause benign hypermetabolic lymphadenopathies. Clinical stratification between vaccine‐associated benign lymphadenopathies and malignant lymphadenopathies through ultrasound, MRI or FDG PET‐CT is not feasible. This leads to unnecessary lymph node biopsies, excisions and even radical lymph node dissections. Therefore, to avoid unnecessary surgeries, we assessed whether noninvasive multispectral optoacoustic tomography (MSOT) enables a better differentiation between benign and malignant lymphadenopathies.

Introduction: Microangiopathy in people with diabetes (PwD) represents the major cause of complications. Detection of microangiopathy at an early stage preventing further damage is challenging. The present study investigated whether dermal differences detected by photoacoustic imaging (PAI) may identify diabetes-induced microangiopathy.Patients and methods: In a monocentric study at Department of Dermatology of the Essen University Hospital PAI was performed with and without occlusion of subcutaneous palmar and plantar vessels in PwD and healthy controls. Results: In PwD, measurement of palmar PAI showed higher signal at baseline and after occlusion (both P<0.001). Positive correlation between diabetes duration and palmar PAT measurement was observed at baseline (rho=0.245; P=0.023) and after occlusion (rho=0.269; P=0.012). Abnormal PAI pattern in healthy patients was associated with higher risk of deterioration of glycemic metabolism in the future (sensitivity=75.0%; specifity=67.3%; P=0.004).Conclusion: PAI may serve as a new non-invasive method to detect hyperglycemia-induced microangiopathy.

Supplementary Table legend. Supplementary Table legends S1, S2

Supplementary Table 2. Quantitative expression analyses of CEACAM1 splice variants in melanoma biopsies.

Supplementary Information. Detailed material information, methods and supplemental figure legends

Developments within the field of image-guided surgery are ever expanding, driven by collective involvement of clinicians, researchers, and industry. While the general conception of the potential of image-guided surgery is to improve surgical outcome, the specific motives and goals that drive can differ between the different expert groups. To establish the current and future role of intra-operative image guidance within the field of image-guided surgery a Delphi consensus survey was conducted during the 2nd European Congress on Image-guided surgery. This multidisciplinary survey included questions on the conceptual potential and clinical value of image-guided surgery and was aimed at defining specific areas of research and development in the field in order to stimulate further advances towards precision surgery. Obtained results based on questionnaires filled in by 56 panel experts (clinicians: N=30, researchers: N=20 and industry: N=6) were discussed during a dedicated expert discussion session during the conference. The outcome of this Delphi consensus is indicative of the potential improvements offered by image-guided surgery and of the need for further research in this emerging field, that can be enriched by the identification of reliable molecular targets.

Telomere length, a hallmark of cellular senescence, decreases with age and is associated with age-related diseases. Environmental factors, including dietary and lifestyle factors, can affect the rate at which telomeres shorten, and telomere protection prevents this from happening. The protection of telomeres by natural molecules has been proposed as an antiaging strategy that may play a role in treating age-related diseases. This study investigated the effect of a cycloartane-type triterpene glycoside (astragaloside IV). Astragaloside IV is one of the primary compounds from the aqueous extract of Astragalus membranaceus, and it provides telomere protection both in vitro and in vivo. In a study cohort with 13 participants, telomere length in human skin samples was analyzed after daily treatment for 4 weeks. A comparison of the average median telomere length between the treatment and control groups (5342 bp vs. 4616 bp p = 0.0168) showed significant results. In the second clinical cohort with 20 participants, skin parameters at baseline and after 4 and 8 weeks were measured in vivo. The results show that the product improved hydration by 95%, the skin appeared brighter by 90%, and wrinkle visibility was reduced by 70%. The combination of biologically active compounds in the cream possesses telomere-protecting properties and notable antioxidant activity in vitro and in vivo.

Cutaneous squamous cell carcinoma (cSCC) numbers among the most common types of skin cancer and is known as one of the cancer entities with the highest mutational burden among all solid tumours. Due to the positive correlation between mutational burden and response rate to inhibitors of the programmed cell death 1 (PD-1), those inhibitors are considered promising candidates for the systemic therapy of cSCC. Recently, the PD-1 inhibitors pembrolizumab, nivolumab and cemiplimab demonstrated efficacy in the systemic treatment of locally advanced or metastatic cSCC leading to the approval of cemiplimab by the FDA (U.S. Food and Drug Administration) in 2018 and the EMA (European Medicines Agency) in 2019. Patients with haematological malignancies tend to develop skin cancers of high aggressiveness, enhanced cumulative recurrence rate and higher rates of metastases with subsequent death. Chronic lymphocytic leukaemia (CLL) is the most frequent type of leukaemia in the United States and Europe with the majority of patients older than 50 years of age. This neoplasm predominantly originates from B -cells leading to an impaired immune system of the patient. Although CLL is a B-cell malignancy, studies have also described the involvement of T cells in the pathogenesis and progression of the disease with contradictory findings on the effects of PD-1 inhibitors in CLL. Due to their underlying hematologic malignancy, these patients have commonly no access to PD-1 inhibitor trials for treatment of advanced cSCC. We report on two patients with locally advanced or metastatic cSCC. Both patients had been suffering from a CLL for many years without indication for treatment. Despite a potential immunosuppressive state of the patients due to their CLL, both were treated with the PD-1 inhibitor pembrolizumab resulting in different therapy outcomes.

This paper proposes a contact-less non-invasive diagnostic technique for skin cancer detection and screening based on millimeter-wave (mmW) to terahertz (THz) photonic near-field imaging. Key photonic technologies required for developing multi-spectral sensors are fabricated and reported. This includes broadband photodiodes and wideband near-field antennas, both offering an operational frequency tuning range in excess of 0.2 THz and a maximum operational frequency beyond 0.3 THz. Furthermore, a compact photonic K-a-band mmW imaging sensor has been developed. The sensor head consists of a broadband photodiode for mmW signal generation and a Schottky barrier diode for incoherent power detection within the K-a-band. Calibration of the integrated sensor head is performed using a manufactured gelatin-based skin phantom. Calibration results reveal that the expected refractive index difference of 1 between healthy skin tissue and malignant squamous cell carcinoma (SCC) tumor in the mmW range can be easily detected. Finally, the principal function of the developed photonic imaging sensor is proven in the first in-vivo experiments using human skin tissue and skin tumor tissue (SCC). Experimental results indicate that the tumor can be clearly distinguished from healthy skin.

For patients with Merkel cell carcinoma (MCC) who are refractory to immune checkpoint inhibition (ICI), treatment options are limited. Few cases of MCCs have been reported to show responses to peptide receptor radionuclide therapy (PRRT). A combination of PRRT and ICI has not been reported in MCC to date. A patient with metastatic MCC, who was resistant to first-line avelumab and acquired resistance to ipilimumab/nivolumab (IPI/NIVO) with additional radiotherapy, presented with multiple distant metastases. After confirmation of SSTR expression, treatment was continued with an additional 4 doses of IPI/NIVO combined with 2 cycles of PRRT. Treatment was well tolerated, with transient hemotoxicity and mild nausea. Restaging after 3 mo demonstrated an exceptional response. This case demonstrates the feasibility of combined treatment with IPI/NIVO and PRRT as an option for MCC patients progressing under ICI. Prospective evidence confirming the additive value of combining ICI and radionuclide therapy in a larger cohort is needed.

BACKGROUND:Radiological imaging such as computed tomography (CT) is used frequently for disease staging and therapy monitoring in advanced skin cancer patients. Detected lesions of unclear dignity are a common challenge for treating physicians. The aim of this study was to assess the frequency and outcome of CT-guided biopsy (CTGB) of radiologically unclear, suspicious lesions and to depict its usefulness in different clinical settings.METHODS:This retrospective monocentric study included advanced skin cancer patients (melanoma, Merkel cell carcinoma, squamous cell carcinoma, angiosarcoma, cutaneous lymphoma) with radiologically unclear lesions who underwent CTGB between 2010 and 2018.RESULTS:Of 59 skin cancer patients who received CTGB, 47 received CTGB to clarify radiologically suspicious lesions of unclear dignity. 32 patients had no systemic therapy (cohort A), while 15 patients received systemic treatment at CTGB (cohort B). In both cohorts, CTGB revealed skin cancer metastasis in a large proportion of patients (37.5%, 40.0%, respectively), but benign tissue showing inflammation, fibrosis or infection in an equally large percentage (37.5%, 46.7%, respectively). Additionally, a significant number of other cancer entities was found (25.0%, 13.3%, respectively). In patients receiving BRAF/MEK inhibitors, CTGB confirmed suspicious lesions as skin cancer metastasis in 83.3%, leading to treatment change. In immune checkpoint inhibitor-treated patients, skin cancer metastasis was confirmed in 11.1% of patients only, whereas benign tissue changes (inflammation/fibrosis) were found in 77.8%.CONCLUSIONS:Our results highlight the relevance of clarifying radiologically unclear lesions by CTGB before start or change of an anti-tumour therapy to exclude benign alterations and secondary malignancies.

JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 19, Issue 8 p. 1217-1219 Clinical LetterOpen Access Metastatic pigmented epithelioid melanocytoma in a 7-year-old female Carl Maximilian Thielmann, Corresponding Author Carl Maximilian Thielmann carlmaximilian.thielmann@uk-essen.de Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, Germany Correspondence to Carl Maximilian Thielmann, MD Department of Dermatology, Venereology and Allergology University Hospital Essen Hufelandstrasse 55 45147 Essen, Germany E-mail: carlmaximilian.thielmann@uk-essen.deSearch for more papers by this authorSelma Ugurel, Selma Ugurel Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, GermanySearch for more papers by this authorElisabeth Livingstone, Elisabeth Livingstone Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, GermanySearch for more papers by this authorLisa Zimmer, Lisa Zimmer Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, GermanySearch for more papers by this authorBruno E. Paredes, Bruno E. Paredes Dermatopathologie Friedrichshafen, Friedrichshafen, GermanySearch for more papers by this authorThomas Brinkmeier, Thomas Brinkmeier Hautärzte am Markt, Dortmund, GermanySearch for more papers by this authorKlaus Griewank, Klaus Griewank Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, GermanySearch for more papers by this authorDirk Schadendorf, Dirk Schadendorf Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, GermanySearch for more papers by this authorJoachim Klode, Joachim Klode Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, GermanySearch for more papers by this authorIngo Stoffels, Ingo Stoffels Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, GermanySearch for more papers by this authorEva Hadaschik, Eva Hadaschik Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, GermanySearch for more papers by this author Carl Maximilian Thielmann, Corresponding Author Carl Maximilian Thielmann carlmaximilian.thielmann@uk-essen.de Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, Germany Correspondence to Carl Maximilian Thielmann, MD Department of Dermatology, Venereology and Allergology University Hospital Essen Hufelandstrasse 55 45147 Essen, Germany E-mail: carlmaximilian.thielmann@uk-essen.deSearch for more papers by this authorSelma Ugurel, Selma Ugurel Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, GermanySearch for more papers by this authorElisabeth Livingstone, Elisabeth Livingstone Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, GermanySearch for more papers by this authorLisa Zimmer, Lisa Zimmer Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, GermanySearch for more papers by this authorBruno E. Paredes, Bruno E. Paredes Dermatopathologie Friedrichshafen, Friedrichshafen, GermanySearch for more papers by this authorThomas Brinkmeier, Thomas Brinkmeier Hautärzte am Markt, Dortmund, GermanySearch for more papers by this authorKlaus Griewank, Klaus Griewank Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, GermanySearch for more papers by this authorDirk Schadendorf, Dirk Schadendorf Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, GermanySearch for more papers by this authorJoachim Klode, Joachim Klode Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, GermanySearch for more papers by this authorIngo Stoffels, Ingo Stoffels Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, GermanySearch for more papers by this authorEva Hadaschik, Eva Hadaschik Department of Dermatology, Venereology and Allergology, University Hospital Essen, University School of Medicine Duisburg-Essen, Essen, GermanySearch for more papers by this author First published: 24 May 2021 https://doi.org/10.1111/ddg.14523AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume19, Issue8August 2021Pages 1217-1219 RelatedInformation

das pigmentierte epitheloide Melanozytom (PEM) gilt als eine niedriggradige Variante des malignen Melanoms, welche häufig mit Lymphknotenmetastasen einhergeht [1]. Es wurden fünf PEM-Fälle mit Fernmetastasen und zwei letale Fälle berichtet. Pigmentierte epitheloide Melanozytome treten häufiger bei Kindern und jungen Erwachsenen auf, sind aber in allen Altersgruppen berichtet worden [1]. Die Läsionen treten an Rumpf, Extremitäten, Kopf und Hals sowie an der Bindehaut auf [2]. Dermatoskopische Merkmale sind homogenes schwarzes, blaues und braunes Pigment, komedoartige Öffnungen, kristalline Strukturen und eine Pigmentierung, welche sich in Satellitenläsionen und Lymphgefäße ausdehnt. Die Histopathologie zeigt eine dermale Proliferation von pigmentierten dendritischen und epitheloiden Melanozyten mit größeren, weniger pigmentierten epitheloiden Zellen [3].

Introduction The Covid-19 pandemic has changed the lives of people around the world. Fortunately, sufficient vaccines are now available. Local reactions with ipsilateral lymphadenopathy are among the most common side effects. We investigated the impact of lymphadenopathy after Covid-19 vaccination on the value of ultrasound in tumor patients. Patients and methods Patients with melanoma or merkel cell carcinoma were included who underwent lymph node excision and received Covid-19 vaccination within 6 weeks before surgery. The consistency of the preoperative ultrasound findings with the histopathologic findings was investigated. Results Eight patients were included (two Merkel cell carcinoma and six melanoma patients) who underwent lymph node excision between April 16, 2021, and May 19, 2021, and had previously received Covid-19 vaccination. In three of the eight patients (one Merkel cell carcinoma and two melanoma patients), lymph node metastases were erroneously diagnosed preoperatively during tumor follow-up with physical examination, ultrasound, and or FDG PET/CT. In these three patients, the suspected lymph node metastases were located in the left axilla after Covid19 vaccination in the left upper arm, which resulted in selective lymph node removal in two patients and complete lymphadenectomy in one patient. Conclusion Covid-19 vaccine-associated lymphadenopathy is expected to be observed much more frequently in the near future due to increasing vaccination rates. This cause of lymphadenopathy, which may in ultrasound as well as in FDG PET/CT resemble lymph node metastases, must be considered, especially in oncologic patients undergoing tumor follow-up. In addition, Covid-19 vaccination should be given as far away as possible from an underlying primary on the contralateral side to avoid oncologic misdiagnosis followed by malpractice.