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Introduction: Cutaneous T-cell lymphomas (CTCLs) are rare diseases characterized by infiltration of malignant T-cells into the skin. We evaluated the prevalence, epidemiology, and therapy of CTCLs, focusing on its most well-known subtypes, namely mycosis fungoides (MF) and Sézary syndrome (SS)., Patients and Methods: We retrospectively analyzed the medical data of patients with a histologically confirmed diagnosis of CTCL presenting to our outpatient department during a 5-year period from January 2015 to December 2019., Results: We evaluated the files of 102 patients, of whom 67% were men and 33% women. The overall mean age was 59.1±14.1 (24-86) years. Ninety-two patients (90%) were diagnosed with MF and ten patients (10%) with SS. According to ISCL/EORTC, the majority of patients initially classified as stage IA (34%) and IB (45%). Disease frequency decreased at advanced stages (II: 4%; III: 7%; IV: 10%). Forty-five patients (44.1%) received only skin-directed therapy (SDT). Twenty patients (19.6%) progressed from SDT to systemic therapy (ST). Thirty-seven patients (36.3%) received ST combined with SDT (TS) from the start of treatment. Overall, fifty different therapeutic approaches of TS were initiated due to lack of response to therapy or disease progression., Conclusion: Management of CTCLs aims to maintain patient quality of life while minimizing side-effects. As CTCLs are usually incurable diseases, the focus of treatment is on symptom control and prevention of disease progression. Due to the large patient group and the long observation period, our study allows for a valid evaluation of the frequency and therapy of MF and SS in a university outpatient clinic in Germany. We favor topical therapies in early stages with more invasive therapies in advanced stages.

Introduction: In this survey, we analyzed data from patients suffering from the most common cutaneous T-cell lymphomas (CTCLs) subtypes mycosis fungoides (MF) and Sézary syndrome (SS), treated with the retinoid alitretinoin during a 7-year period at our outpatient department between 2015 and 2020., Materials and Methods: We analyzed patient medical records including TNMB stage, side effects under therapy with alitretinoin, time to next treatment (TTNT), and previous photo documentation., Results: A total of 35 patients with MF (n = 28) and SS (n = 7) were included in the study, of whom 69% were male and 31% were female. The mean age of onset was 56 ± 15 years in MF and 65.4 ± 10.8 years in SS with 51.4% having early stage (IA-IIA) and 48.6% having advanced stage (IIB-IVA) CTCL. Of these patients 37.2% responded to alitretinoin, 28.6% had a stable course, and 34.3% experienced progression. Alitretinoin was administered as a monotherapy (25.7%) or combined with five concomitant therapies (74.2%), most frequently with ECP (31.4%) and PUVA (11.4%). 63% did not report any side effects, most often hypertriglyceridemia (20%) was described., Conclusion: Considering that nearly two thirds of the CTCL patients treated with alitretinoin showed a response or stable disease, together with a low number of side effects and low cost compared to bexarotene, alitretinoin may be a potential alternative in the treatment of less advanced CTCLs. This survey represents the largest number of recorded therapies with the retinoid alitretinoin in CTCLs in a European patient collective., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Early detection of melanoma can be lifesaving but this remains a challenge. Recent diagnostic studies have revealed the superiority of artificial intelligence (AI) in classifying dermoscopic images of melanoma and nevi, concluding that these algorithms should assist a dermatologist's diagnoses., Objective: The aim of this study was to investigate whether AI support improves the accuracy and overall diagnostic performance of dermatologists in the dichotomous image-based discrimination between melanoma and nevus., Methods: Twelve board-certified dermatologists were presented disjoint sets of 100 unique dermoscopic images of melanomas and nevi (total of 1200 unique images), and they had to classify the images based on personal experience alone (part I) and with the support of a trained convolutional neural network (CNN, part II). Additionally, dermatologists were asked to rate their confidence in their final decision for each image., Results: While the mean specificity of the dermatologists based on personal experience alone remained almost unchanged (70.6% vs 72.4%; P=.54) with AI support, the mean sensitivity and mean accuracy increased significantly (59.4% vs 74.6%; P=.003 and 65.0% vs 73.6%; P=.002, respectively) with AI support. Out of the 10% (10/94; 95% CI 8.4%-11.8%) of cases where dermatologists were correct and AI was incorrect, dermatologists on average changed to the incorrect answer for 39% (4/10; 95% CI 23.2%-55.6%) of cases. When dermatologists were incorrect and AI was correct (25/94, 27%; 95% CI 24.0%-30.1%), dermatologists changed their answers to the correct answer for 46% (11/25; 95% CI 33.1%-58.4%) of cases. Additionally, the dermatologists' average confidence in their decisions increased when the CNN confirmed their decision and decreased when the CNN disagreed, even when the dermatologists were correct. Reported values are based on the mean of all participants. Whenever absolute values are shown, the denominator and numerator are approximations as every dermatologist ended up rating a varying number of images due to a quality control step., Conclusions: The findings of our study show that AI support can improve the overall accuracy of the dermatologists in the dichotomous image-based discrimination between melanoma and nevus. This supports the argument for AI-based tools to aid clinicians in skin lesion classification and provides a rationale for studies of such classifiers in real-life settings, wherein clinicians can integrate additional information such as patient age and medical history into their decisions., (©Roman C Maron, Jochen S Utikal, Achim Hekler, Axel Hauschild, Elke Sattler, Wiebke Sondermann, Sebastian Haferkamp, Bastian Schilling, Markus V Heppt, Philipp Jansen, Markus Reinholz, Cindy Franklin, Laurenz Schmitt, Daniela Hartmann, Eva Krieghoff-Henning, Max Schmitt, Michael Weichenthal, Christof von Kalle, Stefan Fröhling, Titus J Brinker. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 11.09.2020.)

Background: High-risk α-genus human papillomaviruses (α-HPVs) are linked to cervical and genital carcinomas; however, their correlation with cutaneous squamous cell carcinoma (cuSCC) or premalignant skin lesions remains controversial., Objective: We evaluated the contribution of high-risk α-HPV to the occurrence of cuSCC, Bowen's disease and actinic keratosis (AK), and the distribution of high-risk α-HPV genotypes in these cutaneous tumours., Methods: HPV genotypes were determined using a commercial PCR-based microarray on skin tissue samples collected from 76 [38 young (<60 years) and 38 elderly (>60 years)] cuSCC, 34 Bowen's disease, 48 AK patients and 10 young controls. Associations between α-HPV prevalence and relevant risk factors were analysed., Results: High-risk α-HPV was more frequently detected in cuSCC patients (57.9%) than in the patients with Bowen's disease (38.2%), AK (0.0%) and control patients (10.0%). The high-risk α-HPV prevalence was higher in young than in elderly cuSCC patients (65.8% vs. 50.0%, P = 0.031). The most common HPV type was 16, present in 90.9% of all HPV-carrying cuSCC patients. Multiple infections with different high-risk α-HPV types were found in 20.5% of HPV-related cuSCC, whereas only single infection with type 16 was found in Bowen's disease. Although sun exposure is known as a major risk factor for cuSCC, high-risk α-HPVs were more frequently found in non-exposed sites rather than in sun-exposed sites of cuSCC., Conclusion: Multiple infections, as well as single infection with high-risk α-HPV may link to cuSCC. In spite of the involvement of high-risk α-HPV at high levels in cuSCC and Bowen's disease, no high-risk α-HPV was detected in AK patients, suggesting that Bowen's disease rather than AK might be involved in the development of HPV-related cuSCC as a precursor., (© 2019 European Academy of Dermatology and Venereology.)

Background: Immune checkpoint blockade (ICB) has been a breakthrough in the treatment of metastatic melanoma. But with only about 20-40% long-term responders and severe side-effects in about 12-17%, finding predictive markers for treatment response is of great interest., Methods: We prospectively assessed clinical data, haematologic parameters and freshly isolated peripheral blood mononuclear cells of 30 patients treated with ipilimumab (n = 21) and pembrolizumab (n = 9) prior to the first 4 cycles with ICB and before the first tumour assessment., Results: We discovered that the baseline levels of CD45RO + CD8 + T cells significantly differed among the patients. Thirteen (43%) of our patients had normal baseline levels of CD45RO + CD8 + T cells, whereas 17 (57%) patients were low on CD45RO + CD8 + T cells. The baseline levels of CD45RO + CD8 + T cells correlated significantly with the response to ipilimumab but not pembrolizumab. Patients with baseline levels of lower/equal 25% of CD45RO + CD8 + T cells did not respond to treatment with ipilimumab. Phenotyping the CD8 + T cells in patients treated with ipilimumab revealed an activated HLA-DR + CD25 - phenotype, implying antigen non-specific stimulation. The levels of the HLA-DR + CD25 - CD8 + T cells were significantly higher in patients with a normal baseline of CD45RO + CD8 + T cells and even increased significantly during treatment. Furthermore, proliferation of melanoma antigen recognized by T cells 1 (MART-1)-specific CD8 + T cells was not observed. Patients with normal baseline levels of CD45RO + CD8 + T cells showed a significant longer overall survival when treated with ipilimumab but not pembrolizumab., Conclusion: Patients with normal baseline levels of CD45RO + CD8 + T cells respond significantly more frequently to treatment with ipilimumab and the CD8 + T cells appear to be antigen non-specifically activated. The baseline level of CD45RO + CD8 + T cells represents a promising factor as biomarker for the prediction of the response to ipilimumab., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Melanoma of unknown primary (MUP) is a type of metastatic melanoma with no evidence of a primary tumor. Recent evidence suggested better survival in MUP as compared to melanoma with a known primary site (MKP). However, prognostic markers that reliably predict overall survival in MUP are lacking. The primary objective of this study was to analyze the mutational status of the BRAF, NRAS, and KIT oncogenes and to investigate if the genotype or other clinical parameters were associated with overall survival. We retrospectively analyzed the genotype and the clinical course of 40 patients with MUP. Mutations of BRAF and NRAS were determined with pyrosequencing. Mutations of KIT were investigated with a nested PCR approach followed by Sanger sequencing. Survival fractions were calculated applying the Kaplan-Meier model. Mutations in the BRAF (50.0%), NRAS (17.5%), and KIT genes (5.0%) were found frequently, but had no major impact on overall survival (p=0.62). The AJCC stage was a strong prognostic factor with a hazard ratio for death of 0.17 (stage III vs. IV; p=0.04). All patients diagnosed with stage III disease survived the median follow-up period of 23 months (p=0.03). The survival rates of patients with stage IV were significantly associated with rapid disease progression but not with metastatic tumor load at primary diagnosis (p=0.01). Altogether, AJCC stage and time to disease progression were important prognostic parameters. We propose that the kinetics of the disease but not the initial metastatic burden nor the mutational status is relevant for survival in advanced MUP.

Background: Melanoma is a common type of skin cancer with poor survival in advanced stages. Screening efforts aim to detect and tackle tumors at an early stage. However, regional population-based data at the time of initial diagnosis are sparse., Objectives: To analyse clinical and pathologic tumor characteristics in a Swiss population., Materials and Methods: Melanoma samples diagnosed at a large Swiss academic department were evaluated for demographic, clinical and histopathologic data., Results: We analysed a total of 254 melanoma samples. In situ tumors were more common in females than in males (70.6% vs. 29.4%; p = 0.0032). The acro-lentiginous subtype was more common in in situ compared to invasive tumors (14.7% vs. 5.5%; p = 0.0011). Invasive tumors showed a preference for male gender in patients beyond 60 years of age (p = 0.0080). The most frequent anatomic sites were the trunk in males and the legs in females. Regression was more common in males than in females (35.2% vs. 11.7%; p = 0.0001). Breslow's thickness correlated significantly with age but not with gender. Ulceration was common in tumors thicker than 2.01 mm (48.4%; p = 0.0001). Regression was frequently detected in melanomas thinner than 1.00 mm (29.3%; p = 0.0263)., Conclusion: Screening efforts should target elderly patients. Skin examinations should include acral localisations and focus on the trunk in males and the lower extremities in females. Population-based analyses can help to fine-tune melanoma screening in defined regional populations.