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Choosing the adequate systemic treatment for melanoma is driven by clinical parameters and personal preferences.Evaluation of the impact of disease and treatment on the daily life of patients receiving systemic therapy for melanoma.A German-wide, cross-sectional comparative study was conducted at 13 specialized skin cancer centres from 08/2020 to 03/2021. A questionnaire was distributed to assess patients' perception of disease and symptoms, the impact of their current treatment on quality of life (QOL) and activities, adverse events (AEs), therapeutic visits, as well as believe in and satisfaction with their current systemic melanoma treatment. Patient-reported outcomes (PROs) were rated on a continuous numerical rating scale or selected from a given list.Four hundred and fourteen patients with systemic melanoma therapy were included. 359 (87%) received immune checkpoint inhibition (ICI) and 55 (13%) targeted therapy (TT). About 1/3 of patients were adjuvantly treated, the remaining because of unresectable/metastatic melanoma. In subgroup analyses, only in the adjuvant setting, TT patients reported a significant decrease in their treatment associated QOL compared to patients with ICI (p = 0.02). Patients with TT were 1.9 times more likely to report AEs than patients with ICI, a difference being significant just for the adjuvant setting (p = 0.01). ICI treatment intervals differed significantly between adjuvant and unresectable/metastatic setting (p = 0.04), though all patients, regardless of their specific ICI drug, evaluated their treatment frequency as adequate. TT patients with dabrafenib/trametinib (n = 37) or encorafenib/binimetinib (n = 15) did not differ regarding the strain of daily pill intake. Patients older than 63 years rated various PROs better than younger patients.Patients evaluated their treatment mainly positively. ICI might be preferred over TT regarding QOL and patient-reported AEs in the adjuvant setting. Older melanoma patients appeared to be less impacted by their disease and more satisfied with their treatment.

Purpose Uveal melanoma (UM) is an orphan cancer of high unmet medical need. Current patterns of care and surveillance remain unclear as they are situated in an interdisciplinary setting. Methods A questionnaire addressing the patterns of care and surveillance in the management of patients with uveal melanoma was distributed to 70 skin cancer centers in Austria, Germany and Switzerland. Frequency distributions of responses for each item of the questionnaire were calculated. Results 44 of 70 (62.9%) skin cancer centers completed the questionnaire. Thirty-nine hospitals were located in Germany (88.6%), three in Switzerland (6.8%) and two in Austria (4.5%). The majority (68.2%) represented university hospitals. Most patients with metastatic disease were treated in certified skin cancer centers (70.7%, 29/41). Besides, the majority of patients with UM were referred to the respective skin cancer center by ophthalmologists (87.2%, 34/39). Treatment and organization of follow-up of patients varied across the different centers. 35.1% (14/37) of the centers stated to not perform any screening measures. Conclusion Treatment patterns of patients with uveal melanoma in Germany, Austria and Switzerland remain extremely heterogeneous. A guideline for the treatment and surveillance is urgently needed.

Das primär kutane diffus-großzellige B-Zell-Lymphom, NOS (PCLBCL/NOS) ist ein seltenes PCLBCL. Über diesen Tumor liegen nur wenige Daten vor. Ziel dieser Studie war es, klinische und/oder immunhistochemische Marker (neben Bcl-2) zu identifizieren, die das PCLBCL/NOS charakterisieren und helfen es vom PCLBCL/leg type (PCLBCL/LT) zu unterscheiden. Dabei sollten auch der klinische Verlauf und die Prognose des PCLBCL/NOS näher untersucht werden.Fälle von Bcl-2PCLBCL/NOS-Patienten waren jünger, vorwiegend männlich und wiesen eine bessere Überlebensrate auf als Patienten mit PCLBCL/LT. Patienten mit PCLBCL/NOS stellten sich häufiger mit größeren Plaques vor, die auf eine oder zwei zusammenhängende Körperregionen beschränkt waren, während sich PCLBCL/LT-Patienten oft mit disseminierten Hautläsionen präsentierten. PCLBCL/LT Tumorzellen wiesen eine höhere Proliferationsrate (Ki67) auf. Das Tumormikromilieu von PCLBCL/NOS Tumoren war charakterisiert durch ein höheres CD3+ Infiltrat. Daten zum Überleben konnten für 37 Patienten eruiert werden. Die Analysen der Gesamtüberlebensraten ergaben, dass weibliches Geschlecht und Bcl-2-Expression mit einer ungünstigeren Überlebensrate korrelierten. Bcl-6-Expression und zentroblastischer Subtyp korrelierten mit einem besseren Überleben. Keiner der sonstigen untersuchten Marker (z. B. GCB-/Non-GCB-Subtyp) korrelierte mit der Überlebensrate.PCLBCL/NOS und PCLBCL/LT unterscheiden sich in ihrem klinischen Verlauf und ihrer Prognose. Bcl-2 scheint immer noch der beste Marker zur Unterscheidung zwischen diesen beiden Subgruppen zu sein. Bcl-2, weibliches Geschlecht und Bcl-6 sind prognostische Marker für PCLBCL.

Melanoma incidence rates rise as people age, but the impact of aging on distant metastasis is unclear.To investigate how timing, pattern, and extent of distant metastasis is influenced by age.Analysis of a single-center cohort of 1457 patients of the German Central Malignant Melanoma Registry with prospectively documented follow-up. Findings were compared with those for 1682 patients from 5 different institutions. All patients presented initially with stage IA to IIC and developed distant metastasis in their further disease course.The number of metastatic sites decreased with increasing age at melanoma diagnosis (P .001). The rate of stage M1d disease decreased from 50.2% in patients aged 50 years or younger to 30.1% in patients older than 70 years, and the rate of stage M1b disease increased from 5.8% to 21.5%. The rate of lung metastases remained stable in all investigated age groups (P = .54). Distant metastases occurred earlier and were more synchronized in patients older than 70 years than in patients aged 50 years or younger. An age-dependent decrease in metastatic sites and stable rate of lung metastasis were found and confirmed by data on the multi-institutional cohort.The study was not population based.Pattern, timing, and extent of distant metastasis change as people age. These findings may be considered when treating patients with melanoma of different ages.

BACKGROUND AND OBJECTIVES Primary cutaneous diffuse large B-cell lymphoma, NOS (PCLBCL/NOS) is a rare PCLBCL. Only few data are available for this tumor. The aim of this study was to identify clinical and/or immunohistochemical markers (in addition to Bcl-2) that characterize PCLBCL/NOS, assist in differentiating it from PCLBCL, leg type (PCLBCL/LT) and help to assess the clinical course/prognosis. PATIENTS AND METHODS Bcl-2- PCLBCL/NOS) cases (n = 14 were compared with Bcl-2+ PCLBCL/LT cases (n = 29). RESULTS PCLBCL/NOS patients were younger, predominantly male and had better survival rates than patients with PCLBCL/LT. Patients with PCLBCL/NOS presented more often with larger plaques limited to one or two contiguous body regions, whereas PCLBCL/LT cases often presented with disseminated lesions. Neoplastic cells had a higher proliferation rate (Ki67) in PCLBCL/LT patients. The tumor microenvironment of PCLBCL/NOS had a more prominent CD3+ infiltrate. Overall survival data for the whole cohort (n = 37) revealed that female gender and Bcl-2 expression correlated with a worse survival rate. Bcl-6 expression and centroblastic subtype correlated with better outcomes. None of the other markers studied (e.g. GCB/non-GCB subtype) correlated with survival rate. CONCLUSIONS PCLBCL/NOS and PCLBCL/LT differ in their clinical behavior and outcomes. Bcl-2 still seems to be the best marker for discriminating between these two subgroups. Bcl-2, female gender and Bcl-6 represent prognostic markers for PCLBCL.

Zusammenfassung Hintergrund: Die allogene Stammzelltransplantation (alloSCT) stellt eine Therapieoption des primar kutanen T-Zell-Lymphoms dar, mit der anhaltende Vollremissionen erzielt werden konnen. Dennoch existieren fur diese Indikation nur wenige Daten bezuglich ihrer Sicherheit und Wirkung. Patienten und Methodik: In einer retrospektiven Analyse untersuchten wir die Daten von Patienten mit primar kutanen T-Zell-Lymphomen der Universitatshautkliniken Bochum, Mannheim und Koln, die zwischen 2005 und 2012 einer alloSCT zugefuhrt wurden. Ergebnisse: 9 Patienten mit aggressiven primar kutanen T-Zell-Lymphomen erhielten eine alloSCT. Mit einer Nachbeobachtungszeit von 14 bis 36 Monaten nach alloSCT leben aktuell 4 Patienten in kompletter Remission. Zwei Patienten erlitten ein Posttransplantationsrezidiv, das jeweils erfolgreich mit der Gabe von Donor-LymphozytenInfusionen behandelt werden konnte. Drei Patienten mit fortgeschrittener Erkrankung verstarben therapiebedingt im Zuge der alloSCT innerhalb von 6 Monaten nach Therapie, ein Patient verstarb 32 Monate nach alloSCT und nur partieller Remission am Krankheitsprogress, ein weiterer Patient verstarb nach 26 Monaten aus ungeklarter Ursache. Schlussfolgerungen: Unsere Beobachtung verdeutlicht die Wirksamkeit des bereits fur andere T-Zell-Malignitaten beschriebenen Graft-versus-Lymphoma-Effekts und die Notwendigkeit groserer Studien, insbesondere zur Wirksamkeit mortalitatsvermindernder, intensitatsreduzierter Konditionierungsverfahren.

Summary Background Allogeneic stem cell transplantation (alloSCT) is a treatment option for primary cutaneous T-cell lymphomas that may induce long-lasting complete remissions. Little information is available on safety and efficacy. Patients and methods We retrospectively reviewed the data from patients with primary cutaneous T-cell lymphoma treated in the Departments of Dermatology of the Universities of Bochum, Mannheim and Cologne who received subsequent alloSCT between 2005 and 2012. Results Nine patients with aggressive primary cutaneous T-cell-lymphoma received alloSCT. With a follow-up of 14 to 36 months after transplantation, 4 patients are alive and in complete remission. Two patients had recurrent disease post-transplantation, which was successfully treated with donor lymphocyte infusions. Non-relapse mortality was observed in three patients in advanced disease stages within six months after alloSCT. One patient showed only partial remission and died of disease after 32 months and one patient died 26 months after alloSCT with cause of death unknown. Conclusions This report documents the possible benefit of a graft-versus-lymphoma effect in primary cutaneous T-cell lymphoma, as has been observed for other T-cell malignancies and emphasizes that alloSCT warrants further studies in this setting.

Objective: The aim of our case series was to show the therapeutic effect andthe safety of the use of polidocanol foam in ultrasound-guided sclerotherapy treatment ofrelatively small postoperative seromas after varicose vein surgery. Methods: We treated six patients with postoperative seromas after varicose vein surgery that were refractory to conventional treatments including compression dressings, repeated needle aspirations and manual lymph drainage. Results: A complete regression of the fluid collections was seen after one and two ultrasound-guided injections of polidocanol foam into the seroma cavity in two cases, respectively. Up to five treatment sessions and up to four further needle aspirations were necessary for the remaining two patients until complete regression of the seromas. No side-effects were reported. Conclusion: This is the first case series to report of the regression of postoperative seromas after varicose vein surgery induced by polidocanol foam sclerotherapy.

Clear cell sarcoma (CCS) of tendons and aponeuroses is an aggressive neoplasm that is characterized by a pathognomonic translocation, t(12;22)(q13;q12), resulting in an EWSR1-ATF1 chimeric gene. We report for the first time a female patient with CCS exhibiting both EWSR1-ATF1 fusion transcripts and hereditary homozygous point mutations in introns 11 and 16 of the KIT gene. Her parents and two brothers each had heterozygous point mutations in intron 11 or intron 16 of the KIT gene. The functional significance of these germline deep intronic point mutations and their relationship to the pathogenesis of CCS are unclear. Future studies investigating KIT intron mutations in a larger cohort of CCS patients are warranted.

Primary cutaneous large B-cell lymphomas, leg type (PCLBCL/LT) are primary cutaneous B-cell lymphoma (PCBCL) with an intermediate prognosis. Therefore, antracycline-based polychemotherapy combined with rituximab has been recommended as first-line treatment. Yet, despite this regimen, the 5-year survival rate remains 50-66% only. Angiogenesis, the formation of a vascular network, is essential for the pathogenesis of nodal lymphomas. So far, no study has analysed angiogenesis and its key factors in PCLBCL/LT. The present study was aimed at characterizing angiogenesis in PCLBCL/LT to identify the angiogenic molecules as potential therapeutic targets. The intra-tumoral microvessel density (MVD) was assessed by immunohistochemical studies of CD20 and CD31. The MVD was higher in PCLBCL/LT compared with indolent PCBCL. Analyses of open-source microarray data showed correlation between the angiogenic molecule angiopoietin-2 (Ang-2) and pan-endothelial cell markers. ELISA studies determined a shift between Ang-2 and Ang-1 towards Ang-2 in the peripheral blood of PCLBCL/LT patients. Immunofluorescence costainings against the Ang receptor Tie2/angiogenic integrins/CD34 revealed that the vasculature in both aggressive and indolent PCBCL tumors harbours an endothelial cell subpopulation with reduced expression of Tie2. In contrast, the alternative Ang-2 binding partners, angiogenic integrins, are strongly expressed in PCBCL. In line with these findings, downstream targets of Ang-2-integrin signalling, that is phosphorylation of focal adhesion kinase at Tyr397, and sprouting angiogenesis are enhanced in PCLBCL/LT. Our data present Ang-2 as a promising therapeutic target and anti-angiogenic therapy as a new line in treatment of PCLBCL/LT as a hitherto intractable disease.

Importance Topical corticosteroids are the current first-line therapy for vulvar lichen sclerosus (VLS). UV-A1 phototherapy may be a promising alternative treatment option, but controlled studies are lacking. Objective To compare the efficacy of high-potent topical corticosteroids with UV-A1 phototherapy in the treatment of VLS. Design, Setting, and Participants A 2-arm randomized clinical trial was conducted at a university hospital dermatology department according to the intention-to-treat principle with last observation carried forward. The study population comprised 30 female patients with VLS. Interventions Treatment of VLS with clobetasol propionate, 0.05%, ointment applied once daily for 3 months or medium-dose UV-A1 (50 J/cm 2 ) home-based phototherapy, performed 4 times weekly for 3 months. Main Outcomes and Measures Mean relative reduction of the total clinician’s score (TCS) was considered the primary outcome measure. Secondary outcome measures included the reduction of pruritus and burning and/or pain according to a visual analog scale (VAS), a health-related quality of life score (Skindex-29), 20-MHz ultrasonography, and histopathological analysis before and after 3 months of therapy. Results Fifteen patients were randomized in each treatment arm, and 2 patients dropped out in both treatment arms. After therapy, both therapies resulted in a significant decrease in mean TCS (51.4% [95% CI, 39.7% to 63.0%] for clobetasol ointment [ P P = .006]). No significant difference was found between both treatments ( P > .05). The Skindex-29 (mean difference [MD], 29.6 [95% CI, 7.9 to 51.2] [ P = .009]) and the VAS score for pruritus (MD, 4.6 [95% CI, 1.5 to 7.7] [ P = .005]) and burning and/or pain (MD, 4.2 [95% CI, 1.9 to 6.6] [ P = .001]) significantly decreased after clobetasol treatment. After UV-A1 phototherapy, the VAS score for burning and/or pain (MD, 3.2 [95% CI, 0.7 to 5.7] [ P = .01]) was also significantly reduced; however, there was no significant reduction in pruritus (MD, 2.1 [95% CI, 0.5 to 3.7] [ P = .16]) and in the Skindex-29 score (MD, 4.9 [95% CI, −12.6 to 22.4] [ P > .99]). A significant reduction of the corium thickness and a significant increase in dermal density in 20-MHz ultrasonography as well as significant histopathological reduction of the inflammatory infiltrate was observed after clobetasol treatment but not after UV-A1 phototherapy. Conclusions and Relevance Although resulting in a significant clinical improvement, UV-A1 phototherapy was inferior to the current gold standard treatment with topical high-potent corticosteroids with respect to practicability, relief of itch, and improvement in quality of life. UV-A1 phototherapy may be considered a potential second-line treatment for VLS. Trial Registration clinicaltrials.gov Identifier:NCT01400022

Allogeneic stem cell transplantation (alloSCT) is a treatment option for primary cutaneous T-cell lymphomas that may induce long-lasting complete remissions. Little information is available on safety and efficacy.We retrospectively reviewed the data from patients with primary cutaneous T-cell lymphoma treated in the Departments of Dermatology of the Universities of Bochum, Mannheim and Cologne who received subsequent alloSCT between 2005 and 2012.Nine patients with aggressive primary cutaneous T-cell-lymphoma received alloSCT. With a follow-up of 14 to 36 months after transplantation, 4 patients are alive and in complete remission. Two patients had recurrent disease post-transplantation, which was successfully treated with donor lymphocyte infusions. Non-relapse mortality was observed in three patients in advanced disease stages within six months after alloSCT. One patient showed only partial remission and died of disease after 32 months and one patient died 26 months after alloSCT with cause of death unknown.This report documents the possible benefit of a graft-versus-lymphoma effect in primary cutaneous T-cell lymphoma, as has been observed for other T-cell malignancies and emphasizes that alloSCT warrants further studies in this setting.

Daptomycin has proven efficacy in patients with Gram-positive complicated skin and soft tissue infections (cSSTIs), including those caused by Staphylococcus aureus, regardless of methicillin susceptibility. This study was undertaken to evaluate the efficacy and safety of daptomycin in elderly patients. This was an open-label, multicentre, randomized phase IIIb study conducted in hospitalized patients Patients aged ≥65 years with a diagnosis of Gram-positive cSSTIs with or without bacteraemia were included. In addition, infections were required to be of sufficient severity to require inpatient hospitalization and treatment with parenteral antibiotics for at least 96 h. The main exclusion criterion was the presence of a non-complicated SSTI that could heal by itself or be cured by surgical removal of the site of infection. Patients were randomized (2:1) to intravenous daptomycin or pooled intravenous standard therapies (semi-synthetic penicillin or vancomycin, referred to as the ‘comparator’). Duration of treatment was between 5 and 14 days for cSSTIs without bacteraemia and between 10 and 28 days for cSSTIs with bacteraemia. The primary objective was descriptive comparison of clinical success in clinically evaluable patients at test of cure, 7–14 days post treatment. Secondary objectives were microbiological outcome, duration of treatment and safety. In total, 120 patients were randomized (81 to daptomycin; 39 to the comparator) and 102 patients completed the study. Baseline characteristics were similar between the two groups. Common infections included cellulitis, ulcers and abscesses; six patients had bacteraemia [five documented (daptomycin, n = 3; comparator, n = 2); and one suspected (daptomycin, n = 1)]. Test-of-cure clinical success rates were numerically higher for daptomycin than for the comparator [89.0 % (65/73) vs. 83.3 % (25/30); odds ratio 1.65 (95 % confidence interval 0.49–5.54)]. For patients with S. aureus infections, cure rates were 89.7 % (35/39) versus 69.2 % (9/13), respectively; percentage points difference, 20.5 (95 % confidence interval −12.2 to 50.9)]. Rates of adverse events (AEs) and serious AEs were similar in both treatment arms; however, discontinuation rates for AEs/serious AEs were lower for daptomycin than for the comparator (3.8 % vs. 10.0 %). Three serious AEs were considered to be related to the study drug: one case each of pancytopenia (semi-synthetic penicillin), renal failure (vancomycin) and asymptomatic increase in creatine phosphokinase concentrations (daptomycin). In elderly patients, for whom data were previously limited, the efficacy and safety of daptomycin have been confirmed, including for infections caused by S. aureus, regardless of methicillin susceptibility.

Background : Regulatory T cells (Tregs) play an important role in autoimmune diseases. In skin, the presence of Tregs is thought to be mandatory for suppression of autoreactive T cells. Here, we assess the number of Tregs in skin of healthy subjects and patients with an autoimmune dermatosis. Methods : Immunohistochemical stainings for CD3 and FOXP3 on skin biopsies of healthy subjects and subjects with psoriasis, vitiligo, pemphigus vulgaris, bullous pemphigoid, and halo nevus to assess the number of T and regulatory T cells, respectively. Results : Low numbers of CD3+ and FOXP3+ cells were seen in the skin of healthy controls (median=0.5%). A significantly higher frequency of Tregs was seen in lesional skin of patients with psoriasis (median=12.4%) and patients with bullous pemphigoid (median=10.1%) as compared to controls. In vitiligo (median=0.0%), pemphigus vulgaris (median=5.2%), and halo nevi (median=5.4%), no significant difference in number of FOXP3+ cells was observed when compared to controls. Conclusions : As confirmed in the literature, few Tregs were seen in healthy skin. A high number of Tregs were present in lesional skin from patients with psoriasis and bullous pemphigoid. These results support the hypothesis that not a decrease in number but rather a decrease in function of Tregs would be at the basis of autoimmune skin diseases, which could result in unrestrained activation autoreactive T cells in skin of patients with autoimmune dermatoses.

Interleukin 33 (IL-33) belongs to the IL-1 family and was found in smooth muscle cells, epithelial cells, fibroblasts, keratinocytes, endothelial cells, dendritic cells and activated macrophages.1 IL-33 binds the orphan receptor ST2 and induces gene expression of Th2-associated cytokines. Treatment of wild-type mice with IL-33 led to changes in vessels, digestive tract and lungs.2 Manetti et al 3 recently investigated serum IL-33 levels by means of an ELISA in 58 patients with systemic sclerosis (SSc) and 30 healthy individuals. They observed that serum IL-33 was significantly increased in patients with SSc as compared with healthy controls. They also found that serum IL-33 levels were associated with early disease stage and microvascular involvement as determined by capillaroscopy. The study of Manetti et al 3 prompted us to investigate serum IL-33 …