S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" - update 2023, part 2: epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Is there an overtreatment of melanoma patients at the end of their life? Results of a multicenter study on 193 melanoma patients.

BACKGROUND AND OBJECTIVES: There is a lack of data regarding the situation of melanoma patients receiving systemic therapies in their last months of life. PATIENTS AND METHODS: All melanoma patients who died in 2016 or 2017 and who had been treated by systemic therapies within the last three months of life were retrospectively analyzed. The study was conducted within the Committee "supportive therapy" of the Work Group Dermatological Oncology (ADO). RESULTS: 193 patients from four dermato-oncological centers were included. More than 60 % of the patients had ECOG ≥ 2 and most of them received immune checkpoint inhibitors (ICI) or targeted therapies (TT). 41 patients benefited from the last therapy in terms of radiological and laboratory findings or state of health. Although ECOG was worse in the TT cohort compared to the ICI group, the proportion of patients benefiting from the last therapy with TT was significantly higher and TT therapy could be carried out more often on an outpatient basis. CONCLUSIONS: This study indicates that there is a tendency towards an overtreatment at the end of life. Nevertheless, TT might be a reasonable therapeutic option for advanced BRAF mutant melanoma, even in highly palliative situations.

Update on dermatomyositis in adults.

Dermatomyositis (DM) in adults has a prevalence of 6-7 per 100,000 population per year. This dedicated compact overview was prepared due to an increasing incidence as well as an often underestimated systemic involvement and new developments in myositis-specific antibodies (MSA). The spectrum of clinical dermatological and systemic symptoms is described. Related diagnostic procedures are depicted, and therapeutic regimens based on the German S2k guidelines and the current literature are presented. The urgency of an early diagnosis is emphasized as about 30 % of patients with DM manifest a tumor. Etiopathology is often associated with pulmonary fibrosis, and inflammation of myositis can cause irreversible muscle damage. Clinical signs and correct interpretation of serological markers can deliver valuable information on the extent of DM, and provide an indication for further diagnostic procedures, prognosis and choice of therapy.

S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma - short version, part 1: diagnosis, interventions for actinic keratoses, care structures and quality-of-care indicators.

Actinic keratoses (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guideline is aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AK and cSCC. The guideline is also aimed at affected patients, their relatives, policy makers and insurance funds. In the first part, we will address aspects relating to diagnosis, interventions for AK, care structures and quality-of-care indicators.

S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma (cSCC) - short version, part 2: epidemiology, surgical and systemic treatment of cSCC, follow-up, prevention and occupational disease.

Actinic keratoses (AKs) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guidelines for actinic keratosis and cutaneous squamous cell carcinoma were developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guidelines are aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AKs and cSCC. The guidelines are also aimed at affected patients, their relatives, policy makers and insurance funds. In the second part, we will address aspects relating to epidemiology, etiology, surgical and systemic treatment of cSCC, follow-up and disease prevention, and discuss AKs and cSCC in the context of occupational disease regulations.

[Psycho-oncology in dermatological practice : Evaluation of need and care structures]. / Psychoonkologie in dermatologischen Praxen : Bedarfseinschätzung und Versorgungsstrukturen.

BACKGROUND: Psycho-oncological care is a main component of comprehensive oncological care as stated in the National Cancer Plan of the German Federal Government. Correspondingly this goal has been adopted in the strategy of the German Skin Cancer Council. In certified skin cancer centers structural requirements for psycho-oncological care are established. Nevertheless, a large proportion of skin cancer patients are treated in dermatological practices. Up to now data on psycho-oncological care in dermatological practices are missing. MATERIALS UND METHODS: We conducted a descriptive cross-sectional written survey on psycho-oncological care in dermatological practices from October 2016 to February 2017. RESULTS: In all, 171 practices completed the questionnaire; 19.4% of these practices have an oncological focus. The mean number of treated skin cancer patients was 554.3 ± 659.1 and 62.4 ± 73.6 for melanoma patients. Dermatologists estimated a low proportion (≤5%) of patients with need for psycho-oncological care; however, 21.9% of practices actively offer information on psycho-oncological programs and 26.1% cooperate with psycho-oncological care providers. Interest in psycho-oncological care concepts was stated by 29.3%. CONCLUSIONS: Psycho-oncological care is only occasionally and partly deficiently provided in dermatological practices including referral to psycho-oncological care professionals. The results emphasize the necessity to raise awareness regarding psycho-oncological needs of skin cancer patients and to integrate psycho-oncological counselling into clinical routine in dermatological practices.

Primary cutaneous diffuse large B-cell lymphoma, NOS and leg type: Clinical, morphologic and prognostic differences.

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.

A new ALK isoform transported by extracellular vesicles confers drug resistance to melanoma cells.

BACKGROUND: Drug resistance remains an unsolved clinical issue in oncology. Despite promising initial responses obtained with BRAF and MEK kinase inhibitors, resistance to treatment develops within months in virtually all melanoma patients. METHODS: Microarray analyses were performed in BRAF inhibitor-sensitive and resistant cell lines to identify changes in the transcriptome that might play a role in resistance. siRNA approaches and kinase inhibitors were used to assess the involvement of the identified Anaplastic Lymphoma Kinase (ALK) in drug resistance. The capability of extracellular vesicles (EVs) to transfer drug resistant properties was investigated in co-culture assays. RESULTS: Here, we report a new mechanism of acquired drug resistance involving the activation of a novel truncated form of ALK. Knock down or inhibition of ALK re-sensitised resistant cells to BRAF inhibition and induced apoptosis. Interestingly, truncated ALK was also secreted into EVs and we show that EVs were the vehicle for transferring drug resistance. CONCLUSIONS: To our knowledge, this is the first report demonstrating the functional involvement of EVs in melanoma drug resistance by transporting a truncated but functional form of ALK, able to activate the MAPK signalling pathway in target cells. Combined inhibition of ALK and BRAF dramatically reduced tumour growth in vivo. These findings make ALK a promising clinical target in melanoma patients.

Interdisciplinary and multiprofessional outpatient secondary individual prevention of work-related skin diseases in the metalworking industry: 1-year follow-up of a patient cohort.

BACKGROUND: In Germany, work-related skin diseases are predominant within the spectrum of reported occupational diseases. Metal workers are among the high-risk professions. Offering effective prevention programs to affected patients is of utmost importance to avoid deterioration of the disease and job loss. We conducted a 1-year follow-up in patients who participated in a multidisciplinary, complex outpatient prevention program representing a standard procedure of patient care by the respective statutory accident insurance. METHODS: The multi-component prevention program consists of multiprofessional individual patient counseling, a structured skin protection seminar in a group, as well as workplace visits and on-site counseling in terms of appropriate skin protection (e.g. gloves). An observational study with a 1-year follow-up and four measurements (T1-T4, longitudinal pre/post-test design) including dermatological examinations and standardized written questionnaires was conducted between 2013 and 2016 to assess changes over time regarding job loss and disease severity. RESULTS: Data from 94 patients (87 male, mean age: 45.4 years) were included in the analysis. One year after the skin protection seminar (T4), 83 patients (88.3%) remained in their original professional metalworking activity and four patients (4.3%) had given up their profession because of their skin disease. At baseline (T1), irritant contact dermatitis of the hands was the most frequent diagnosis (80.7%). Methods for self-reported disease severity showed good correlation with the clinical gold standard at T1 and T2 (dermatological examination with the Osnabrück Hand Eczema Severity Index / OHSI), and a significant decrease of the self-reported disease severity was found over time from T1 to T4 (p < 0.001). Further results indicate an improved self-perceived disease control and an overall satisfaction with the prevention program. CONCLUSIONS: The results of this observational study demonstrate that the comprehensive prevention program positively influences the course of work-related skin diseases, increases the possibility to continue working in a "high-risk" profession and improves the disease management of metal workers. In the long term, the prevention program may lead to cost savings by preventing high therapy costs or professional retraining.

Psycho-oncological care of melanoma patients in certified skin cancer centers.

BACKGROUND: The establishment und certification of skin cancer centers (SCCs) in compliance with requirements issued by the German Cancer Society play a key role for quality-assured treatment of skin cancer patients. These requirements also call for the implementation of a qualified psycho-oncology program. When planning the present study, we assumed site-specific differences in the way such programs were implemented at various SCCs. METHODS: In 2014, we conducted a cross-sectional survey of all SCCs certified at the time (n = 43), in which these institutions were asked to provide information on the structural and process quality of their psycho-oncology programs. RESULTS: Overall, 81.4 % of certified SCCs (n = 35) participated in the survey. Thirty-seven percent of SCCs directly employed personnel trained in psycho-oncology. Nearly all facilities offered information/counseling, crisis intervention, one-on-one discussions, and palliative/end-of-life care as part of their psycho-oncology program. Standardized screening tools were commonly used to evaluate patients' need for psycho-oncological support. Eighty-three percent of psycho-oncology programs primarily focused on inpatients. On average, 25.2 % of melanoma patients received psycho-oncological support. Ninety-seven percent of SCCs stated that the certification requirements had actually improved the psycho-oncological care of their patients. Seventy-one percent of SCCs reported to be satisfied with the implementation of the requirements. CONCLUSIONS: The certification of institutions as SCCs has led to the implementation of personnel, structural, and content requirements relating to psycho-oncological care. The majority of SCCs surveyed reported to be satisfied with the quality of care thus achieved.