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Background: Scabies is one of the most common and, in terms of burden of disease, one of the most significant skin diseases worldwide. In Germany, an increase in cases is currently being discussed, for which reliable data have been lacking until now., Objectives: The goal is to clarify the prevalence and treatment of scabies in Germany., Materials and Methods: Multisource analyses of treatment data from a nationwide statutory health insurance company, the Federal Statistical Office and company skin screenings., Results: In Germany, the number of cases of scabies has been rising since 2009 and especially since 2014. In the outpatient setting, there was an increase of 52.8% to around 128,000 treatment cases between 2010 and 2015. Currently, more than 11,000 inpatient cases are documented annually in Germany with scabies as the main diagnosis (ICD-10 B86). The increase between 2010 and 2016 was about 306%. The main outpatient specialist groups providing care are dermatologists and general practitioners, while in the inpatient sector treatment is provided by departments of dermatology, paediatrics and internal medicine., Conclusion: Due to the aforementioned development of prevalence and incidence, the need for care will remain at a high level in the future, which suggests an increased need for education and early detection., (© 2021. The Author(s).)

Background: Psoriasis (Pso) and atopic dermatitis (AD) are chronic skin diseases that result in significant physical and psychological impairment, financial burden, and loss of quality of life. According to previous data, there are regional differences in healthcare., Objectives: The aim was to analyse the epidemiology as well as the treatment of insured people with Pso and AD in Germany in a regional comparison., Methods: Data of the insurance company Techniker Krankenkasse for the year 2019 regarding treatment prevalences as well as drug prescriptions on the regional level for all physicians were examined., Results: In 2019 the overall prevalence of Pso was 2.5% (about 2 million insured people in Germany) and AD was 4.2% (about 3.6 million insured people). In Pso, new guideline-compliant drugs were frequently utilised, yet systemic glucocorticosteroids (GCS) were still disproportionally prescribed. Regionally, there were pronounced disparities with higher prescription rates of the new drugs in the north and east. Insured people with AD most frequently received topical GCS (approx. 88%), of which most were class III (66%), and significantly less frequently calcineurin inhibitors (< 10%), which also conform to guidelines. Systemically, GCS were by far most commonly used (about 25% of all insured people with drug prescriptions). Dupilumab, the only long-term drug approved in 2019, was very rarely prescribed, accounting for less than 1%. Again, large regional differences similar to Pso were found., Conclusion: Pso and AD show relevant disparities and gaps in drug care in the regional comparison despite uniform national guidelines and patient needs. The barriers to appropriate modern pharmaceuticals need to be clarified and mitigated., (© 2021. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Hepatic immune-related adverse events (irAE) including elevated liver function tests (transaminases) occur in 1.4-22.3% of melanoma patients receiving immune checkpoint inhibitors (ICPI) and constitute a potentially serious toxicity that is challenging to treat. In contrast to the liver transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST), only little is known about the frequency and impact of gamma-glutamyl transferase (GGT) elevations., Methods: GGT determined prior to and during therapy of metastatic melanoma patients treated with ICPI were retrospectively assessed in two independent cohorts (PD-1: n = 218, Ipi + Nivo: n = 148). Overall survival (OS) and best objective response were analyzed according to baseline and immune-related GGT (irGGT) elevations during treatment., Results: In multivariate analysis, OS was reduced in patients with elevated baseline GGT (PD-1 group: hazard ratio [HR] 1.76, p = .0073; Ipi + Nivo group: HR 1.77, p = .032). Immune-related GGT elevation was recorded in 17% (PD-1 group) and 38.5% (Ipi + Nivo group). Of these patients, the majority (81 and 68%, respectively) had normal ALT and AST and showed no clinical signs of hepatotoxicity. Patients who experienced irGGT elevation had superior response (PD-1 group: odds ratio [OR] 3.57, p = .00072; Ipi + Nivo group: OR 1.74, p = .12) and OS (PD-1 group: HR 0.37, p = .0016; Ipi + Nivo group: HR 0.33, p = .00050)., Conclusions: The frequency of hepatic irAE is currently underestimated. The addition of the sensitive enzyme GGT to the laboratory panel before and during therapy with ICPI allows to detect two to three times more patients developing hepatic or hepatobiliary toxicity than known so far. Immune-related GGT elevations correlate with response and favorable survival. Precis for use in the Table of Contents The frequency of hepatotoxicity under immune checkpoint blockade is currently underestimated. We suggest the addition of gamma-glutamyl transferase to the laboratory panel in checkpoint inhibitor patients for the detection of hepatobiliary toxicity.

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers of the Caucasian population and accounts for 20% of all skin tumours. An S3 guideline of the German Guideline Program in Oncology has been available since 2019. The diagnosis is based on the clinical examination. Excision and histological confirmation is required for all clinically suspicious lesions to allow prognostic assessment and correct treatment. The therapy of first choice is complete excision with histological control of the surgical margin. In cSCC with risk factors such as tumor thickness >6 mm, sentinel lymph node biopsy may be discussed, but there is currently no clear evidence of its prognostic and therapeutic relevance. Adjuvant radiation therapy may be considered in cases of high risk of recurrence and should be tested in cases of inoperable tumors. The indication for electrochemotherapy should also be considered in the treatment of local or locoregional recurrence. The immune checkpoint inhibitor cemiplimab is approved for the treatment of inoperable or metastasized cSCC. In case of contraindications, chemotherapeutic agents, epidermal growth factor receptor (EGFR) inhibitors or palliative radiotherapy can be used. Since the evidence is low in these cases, a systemic therapy should be used preferentially within clinical studies. Follow-up care should be risk-adapted and includes a dermatological control, supplemented by ultrasound examinations in high-risk patients.

Engineered cytokine products represent promising agents for the treatment of immunogenic tumors, such as malignant melanoma, in addition to immune checkpoint inhibitors. Here we describe the results of a controlled, randomized phase II clinical trial, aimed at assessing the therapeutic potential of L19IL2, a fully human fusion protein consisting of the L19 antibody specific to the alternatively spliced extra-domain B of fibronectin, fused to human interleukin-2 in advanced metastatic melanoma. In one arm, patients received dacarbazine (DTIC; 1000 mg/m 2 of body surface on day 1 of 21-day cycles) as single agent, while in two other arms L19IL2 (22.5 million international units of IL2 equivalents) was added, based on two different schedules of administration. In total, 69 patients with stage IV melanoma were enrolled (24 in the dacarbazine arm, 23 and 22 in the other combination arms, respectively) and 67 received treatment. Analyses of efficacy results show a statistically significant benefit in terms of overall response rate and median progression-free survival for patients receiving L19IL2 in combination with DTIC, compared to DTIC as single agent. In light of these results, further clinical investigations with L19IL2 (alone or in combination with other agents) are warranted.

Background: Inhibition of the mitogen-activated protein kinase (MAPK) pathway as well as programmed death 1 receptor (PD-1) blockade was shown to prolong overall survival (OS) in patients with advanced B-Raf proto-oncogene (BRAF)-mutant melanoma. However, due to the lack of head-to-head trials, it remains unclear if one of these therapeutic approaches should be preferred in first-line therapy. Here, we present a retrospective analysis comparing anti-PD-1 monotherapy with BRAF/MAPK/ERK kinase (MEK) combined inhibition used as first-line agents in a real-world clinical setting., Patients and Methods: Clinical data, routine blood counts and lactate dehydrogenase (LDH) levels of 301 patients with unresectable or metastatic melanoma harboring an activating mutation in BRAF (V600E/K) were included. Of these, 106 received anti-PD-1 antibodies, while 195 patients were treated with a selective BRAF inhibitor combined with an MEK inhibitor as palliative first-line therapy. Patients were sub-grouped according to previously described predictive and prognostic markers., Results: OS was significantly longer in patients receiving anti-PD-1 monotherapy compared to patients receiving combined MAPK inhibitors. Subsequent therapies were comparable among these groups. The difference in OS was less pronounced in patients with high LDH levels and visceral metastatic spread., Conclusion: First-line treatment with a PD-1 blocking antibody might be associated with longer OS than first-line inhibition of the MAPK pathway in patients with advanced melanoma harboring mutant BRAF. These hypothesis-generating data need to be confirmed or rejected in prospective, randomized trials.

Increasing numbers of trials employing anti-PD-1 immunotherapy emphasize the requirement for predictive biomarkers of clinical response. Many studies examine the cell surface expression of PD-1 and other key regulators of T-cell activation and inhibition. Here, we compared common commercially available anti-PD-1 diagnostic antibodies and tested whether they can bind the PD-1 receptor in the presence of the therapeutic antagonists pembrolizumab and nivolumab. We observed that currently no antibodies are available that can reliably stain all PD-1 receptors on T-cells from patients treated with anti-PD-1 antibodies. Furthermore, none of the diagnostic antibodies detected the entire population of PD-1 + T-cells relative to indirect staining using the therapeutic antibodies themselves. To overcome this problem, here we present a reliable method for quantifying PD-1 expression on immune cells from treated patients which can be included in any conventional flow or mass cytometry antibody panel used for patient monitoring.

Background: Combined ipilimumab and nivolumab induces encouraging response rates in patients with unresectable or metastatic melanoma. However, the approved protocol for dual checkpoint inhibition (3 mg/kg ipilimumab over 90 min and 1 mg/kg nivolumab over 60 min) is time-intensive and several trials have shown that both single agents can be safely administered at faster infusion rates., Aim: To investigate whether combined checkpoint inhibition with 3 mg/kg ipilimumab and 1 mg/kg nivolumab can be safely administered over 30 min per agent., Patients and Methods: We reviewed the rate of infusion-related reactions (IRRs) in the first 12 months of our single-institution experience using shortened infusion times for combined checkpoint inhibition with ipilimumab and nivolumab., Results: Between May 24, 2016 and June 10, 2017, a total of 46 melanoma patients received 100 shortened cycles of combined 3 mg/kg ipilimumab and 1 mg/kg nivolumab. One patient (2.2%; 1/46) had a questionable reaction after administration of 1 mg/kg nivolumab over 30 min, but none of the other patients had a bona fide IRR., Conclusions: Shortened infusion times for combined ipilimumab and nivolumab treatment are safe, thereby facilitating a more efficient use of outpatient facilities and enhancing patient's convenience.

The activating BRAF mutation V600E and related mutations in this codon are most important for the activation of the RAS/RAF/MEK/ERK mitogen-activated protein kinase (MAPK) signalling pathway in melanoma. BRAF V600E mutations have been detected in ~40% of melanoma patients and BRAF V600K mutations in ~5% of melanoma patients. Activation of the MAPK pathway results in continuous stimulation of cell proliferation and inhibits programmed cell death. Vemurafenib (PLX4032) was developed as a low-molecular-weight molecule for the inhibition of the mutated serine-threonine kinase BRAF, and it selectively binds to the ATP-binding site of BRAF V600E kinase and inhibits its activity. The biochemical affinity of vemurafenib for mutated BRAF translates to potent inhibition of ERK phosphorylation and of cell proliferation exclusively in BRAF-mutant cell lines. In animal model experiments, it was demonstrated that vemurafenib achieved tumour regressions in cells harbouring the BRAF V600E mutation. The clinical trials with vemurafenib in unresectable metastatic melanoma in phases I, II and III for patients harbouring BRAF V600E mutations demonstrated all unexpected high objective response rates ranging between 50 and 80%. Median progression-free survival was prolonged from 2 months with dacarbazine to 7 months with vemurafenib, and median overall survival was, respectively, prolonged from 9 to 14 months. A major problem remains in the development of resistance to vemurafenib treatment after several months in the majority of patients, and multiple resistance mechanisms have already been described. Under vemurafenib treatment, about 25% of patients developed cutaneous squamous cell carcinomas of the keratoacanthoma type with low invasive potential and without the occurrence of metastasis. The overall tolerability of the drug was quite good, and many patients remained on treatment for long times. As other solid tumours like papillary thyroid cancer, colorectal cancer, non-small-cell lung cancer and ovarian cancer likewise harbour BRAF mutation, vemurafenib is also tested in these entities. In future, combinations of vemurafenib with other kinase inhibitors and with immunotherapies will improve its therapeutic potential.

Treatment of advanced melanoma patients with ipilimumab results in improved survival. However, only about 20% of treated patients experience long-term benefit. Combining treatment of ipilimumab with other drugs may improve immune activation and potentially enhance clinical efficacy. The aims of the phase II clinical trial reported here were to investigate tolerability and efficacy of a combined immunotherapeutic strategy comprising standard systemic ipilimumab at 3 mg/kg four times at 3-week intervals and intratumorally injected IL-2 at 9 MIU daily twice weekly for four weeks in pretreated melanoma patients with distant metastasis. The primary endpoint was the disease control rate according to immune-related response criteria at week 12; tolerability according to Common Terminology Criteria for Adverse Events criteria was secondary endpoint. No objective responses were observed in the 15 enrolled patients. Three patients had stable disease 12 weeks after starting treatment, yielding a disease control rate of 20%. Tolerability of this combination treatment was acceptable. Observed adverse events were those expected from the respective monotherapies. Autoimmune colitis was observed in two patients. Grade III/IV adverse events were observed in 40% of patients, and no treatment-related deaths occurred. Thus, this combined immunotherapy is associated with adverse events similar to those associated with the respective monotherapies. However, this study does not provide any evidence of improved efficacy of the combination over ipilimumab alone.

Background: Prognostic factors of melanoma patients with distant metastases remain poorly established. This study aimed to compare the prognostic impact of putative serum biomarkers, namely S100B, YKL-40 or CCL17, in stage IV melanoma patients., Patients and Methods: Serum concentrations were analyzed by ELISA. Disease-specific survival of 80 patients according to S100B, YKL-40 or CCL17 and clinical factors were calculated by univariate Kaplan-Meier survival and multivariate analysis., Results: Low serum levels of S100B, high concentrations of CCL17 and female gender correlated with improved survival. A trend for favorable prognosis was observed for the M categories M1a/b versus M1c according to the AJCC classification. No correlation with survival was evident for YKL-40 serum levels and age. In multivariate analysis, S100B (HR 2.1; p = 0.005) and CCL17 (HR 1.8; p = 0.029) had independent prognostic impact. Patients with a combination of normal S100B and high CCL17 had a high chance for long-term survival, which was 43 % after 3 years., Conclusion: Serum levels of CCL17 and S100B represent independent prognostic markers for melanoma patients with distant metastases. These biomarkers were more powerful than the M category according to the AJCC classification to indicate overall survival. CCL17 represents a promising biomarker upon immune checkpoint blockade in melanoma.

Since the discovery of activating mutations in the BRAF oncogene and also stimulation of immune mediated antitumor response in melanoma, there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma. This article addresses the latest developments of BRAF/MEK/ERK pathway signaling. In addition, the development of drugs to attack alternative mutations in melanoma, such as NRAS and KIT is described. Strategies for the management of BRAF inhibitor resistance, such as with combination therapy, are outlined. Antitumor immune therapies with monoclonal antibodies such as ipilimumab which acts by promoting T-cell activation or antibody blockade of programmed death-1 (PD-1) led to a long term response in metastatic melanoma. Results of latest clinical studies including the toxicity profile are described. Due to selective kinase inhibitors and immune checkpoint blockade, the therapy of unresectable metastatic melanoma has greatly improved and long-term survival of patients with metastatic melanoma seems a real possibility.

The activating BRAF mutation V600E and related mutations in this codon are most important for the activation of the RAS/RAF/MEK/ERK mitogen-activated protein kinase (MAPK) signalling pathway in melanoma. BRAF V600E mutations have been detected in ~40% of melanoma patients and BRAF V600K mutations in ~5% of melanoma patients. Activation of the MAPK pathway results in continuous stimulation of cell proliferation and inhibits programmed cell death. Vemurafenib (PLX4032) was developed as a low molecular weight molecule for the inhibition of the mutated serine threonine kinase BRAF, and it selectively binds to the ATP-binding site of BRAF-V600E kinase and inhibits its activity. The biochemical affinity of vemurafenib for mutated BRAF translates to potent inhibition of ERK phosphorylation and of cell proliferation exclusively in BRAF-mutant cell lines. In animal model experiments, it was demonstrated that vemurafenib achieved tumour regressions in cells harbouring the BRAF V600E mutation. The clinical trials with vemurafenib in unresectable metastatic melanoma in phase I, II, and III for patients harbouring BRAF V600E mutations demonstrated all unexpected high objective response rates ranging between 50 and 80%. Median progression-free survival was prolonged from two months with dacarbazine to seven months with vemurafenib, and median overall survival was respectively prolonged from 9 to 14 months. A major problem that remains is the development of resistance to vemurafenib treatment after several months in the majority of patients, and multiple resistance mechanisms have already been described. Under vemurafenib treatment, about 25% of patients developed cutaneous squamous cell carcinomas of the keratoacanthoma type with low invasive potential and without occurrence of metastasis. The overall tolerability of the drug was quite good, and a number of patients remained on treatment for long times. As other solid tumours like papillary thyroid cancer, colorectal cancer, non-small-cell lung cancer, and ovarian cancer likewise harbour BRAF mutation, vemurafenib is also tested in these entities. In future, combinations of vemurafenib with other kinase inhibitors and with immunotherapies will improve its therapeutic potential.

Systemic high-dose interleukin-2 (IL-2) treatment achieves long-term survival in a subset of advanced patients with melanoma. As we reported previously, intratumoral IL-2 induced complete local responses in more than 60% of melanoma patients. This study aimed to analyze the long-term outcome of 72 patients treated in two prior trials. Melanoma patients (49 stage III, 23 stage IV) with injectable metastases received intratumoral IL-2 injections thrice weekly at individually escalated doses (median duration, 6.5 weeks; median total IL-2 dose, 72 MIU; median number of injected metastases, 10). The observed 2-year overall survival rates were 95.5% for stage III patients with cutaneous metastases only (stage IIIB), 72% for those with combined cutaneous and lymph node involvement (stage IIIC), 66.7% for stage IV patients with disease limited to distant soft-tissue metastases (stage IV M1a), and 9.1% for those with visceral metastases (stage IV M1b and stage IV M1c). Thirty patients who reported recurrence of unresectable distant metastases subsequently received chemotherapy in the further course of disease and showed an overall response rate of 36.7% (16.7% complete responses, 20% partial responses). A high total dose of IL-2 and a dacarbazine/temozolomide-based chemotherapy regimen were variables correlated with a clinical response. In conclusion, patients with cutaneous metastasis without lymph node involvement in stage III and with soft-tissue metastasis without visceral involvement in stage IV showed unexpected favorable survival rates after intratumoral treatment with IL-2. Furthermore, the intratumoral IL-2 treatment seemed to be associated with increased complete and partial responses in subsequent chemotherapies.

Transplant recipients are at significantly increased risk of cancer development as a long term complication. Skin cancer is the most common cancer, representing 40-50% of post transplant malignancies. In the first 10 years post transplantation, some 15%-40% of patients develop skin cancer, primarily squamous cell carcinoma and basal cell carcinoma, but also melanoma, Merkel cell carcinoma and virally-induced Kaposi sarcoma. The management of skin cancer includes secondary prophylaxis and address attention to areas of widespread actinic damage, usually with topical agents. In high risk skin cancer or metastatic disease a substantial reduction in immunosuppression to switching to mTOR inhibitors appears to substantially improve the prognosis. The management of the individual tumor types is discussed; in general it follows the current guidelines.

While the incidence of cutaneous melanoma (CM) continues to rise steadily, the mortality has stabilized. Risk factors for the development of CM are UV light exposure and individual characteristics relating to pigmentation, and especially the number of melanocytic nevi. The most important prognostic factor in CM is the vertical thickness of the primary tumor in the histological specimen. Excision of the primary tumor with adequate safety margins is the treatment of choice. In the case of a tumor 1.0 mm or more thick biopsy of the sentinel node is recommended. Interferon-alpha is currently the only adjuvant therapy shown to have significant benefit in prospective randomized trials. When distant metastases are present treatment is palliative and is aimed primarily at achieving tumor remission by operative, radiological, and pharmacological means. Dacarbazine is considered the standard drug for systemic treatment. Follow-up depends on the initial tumor parameters and the current stage of the disease.

The procedure of sentinel node biopsy (SNB) has emerged as an important advance especially with respect to staging of malignant melanoma. Elective (prophylactic) lymph node dissection that had been practiced in primary melanoma with a suspected increased risk of (clinically occult) lymphatic metastasis has been replaced by SNB. Patients with proven metastatic involvement of the sentinel node (12-25%) can be specifically selected for regional lymph node dissection. Metastatic involvement of the sentinel node (SN) is a significant independent prognostic factor. The value of detecting metastasis by highly sensitive diagnostic tools such as RT-PCR is just as uncertain as is the therapeutic benefit of operative or conservative therapies in sentinel node-positive patients with respect to improving prognosis and is currently under study.

Treatment of melanoma in the stage of distant metastasis aims on palliation and achievement of durable tumor remission with prolongation of survival. As long as metastasis is confined to one organ system and is removable, surgery remains the treatment of first choice. In limited metastasis radiotherapy may likewise be indicated, particularly in bone and brain metastasis. More extensive metastasis should be treated by chemotherapy or chemoimmunotherapy. Monochemotherapy with dacarbazine, temozolomide, fotemustine and vindesine or its combinations with interferon-alpha are currently preferred. Polychemotherapy or its combinations with interferon-alpha and interleukin-2 are suitable to produce higher response rates but failed to prolong survival. As these treatments are associated with substantially higher toxicity they have been widely abandoned. Combined treatment with dacarbazine and interferon-alpha obtain tumor responses or stable disease in 40-50% and objective tumor remissions in 15-20% of patients. Effective cancer vaccination strategies and blockade of melanoma specific target molecules are currently developed as new treatment options.

Dermoscopy (dermatoscopy, epiluminescence microscopy, surface microscopy) is a non-invasive method in dermatology. With this method pigmented and non-pigmented skin tumours can be diagnosed with a clear higher sensitivity and specificity compared to clinical examination. Malignant skin tumours are detected earlier and unnecessary excisions of benign skin tumours can be avoided. The knowledge about the correlation between dermoscopy and histopathology is hereby an essential condition. In this continuing medical education article the correlation of both examination techniques is presented for the dermoscopic differential diagnoses.

Unlabelled: The term epidermolysis bullosa (EB) encompasses a heterogeneous group of genodermatoses, characterised by fragility and blistering of the skin, often associated with extracutaneous manifestations. The clinical picture comprises severe subtypes with lethal outcome in the first years of life as well as milder subtypes with localised blistering or minimal symptoms confined exclusively to nail or teeth abnormalities. We present the case of a male infant, who was born with a few bullae and rapidly developed extensive blistering of the skin. The disease was complicated by painful erosions of the oral mucosa, refused ingestion, and recurrent infections. The child died at the age of 4 months because of cardiac failure due to severe sepsis. Antigen mapping of a skin biopsy showed a split within the lamina lucida of the epidermal basement membrane zone and junctional epidermolysis bullosa (JEB) was diagnosed within the first 3 weeks of life. Markedly reduced staining for laminin 5 indicated the Herlitz type of JEB (OMIM 226700), which could be confirmed by mutation analysis in the LAMB3 gene, showing homozygous nonsense mutations., Conclusion: early antigen mapping using antibodies against the proteins affected in epidermolysis bullosa, is a useful tool providing early mutation analysis and valuable prognostic information needed for adequate therapeutic strategies. The recently published literature on current diagnostic procedures and the revised classification system for inherited epidermolysis bullosa aim towards a better understanding of the disease.

There are no generally accepted guidelines for the follow-up of cutaneous melanoma (CM), and there is an ongoing debate about the value of follow-up examinations. Some authors doubt whether early detection has any beneficial effect on patient survival and suggest that it may only prolong the patient's period of suffering from the knowledge of having metastasis. A systematic review of the literature on early detection and resection of CM metastasis shows the following picture: (1) In in-transit metastasis and in regional node metastasis, the tumour volume of the metastatic nodules at the time of diagnosis is prognostically significant. Either the number of nodes involved in regional metastasis or the diameter of the largest node showed prognostic impact in different studies. Therefore, early detection seems to affect the cure rate in this stage of disease. (2) In distant metastasis, surgical resection of all recognisable metastases prolongs survival. This is true as long as only one organ system is involved and particularly if complete resection of all metastases can be achieved. Therefore, early detection contributes to prolongation of survival. We performed a follow-up study in 2008 prospectively documented consecutive patients with stage I-III cutaneous melanoma who presented for follow-up examination at the Department of Dermatology of the University of Tübingen from August 1996 to August 1998. Stage-appropriate follow-up examinations were carried out according to the German Society of Dermatology guidelines. A total of 3,800 clinical examinations and 12,398 imaging techniques were documented: 62 second primary melanomas were detected in 46 patients and 233 disease recurrences in 112 patients during this time. Physical examination was responsible for the discovery of 50% of all recurrences, with the patient initially detecting the metastasis on self-examination in 17% of these cases. Technical examinations were responsible for the detection of the remaining 50%. In the primary tumour stages, 21% of all recurrences were discovered by lymph node sonography, the majority being classified as early detection. Among the recurrences, 48% were classified as early detection, and these patients had a significantly more favourable probability of recurrence-free survival than those with recurrences classified as late detection. The results of our study suggest that a follow-up schedule elaborated for cutaneous melanoma is suitable for the early detection of second primary melanomas and of early recurrences in approximately 5% of patients during a 2-year follow-up period.

The technique of sentinel lymph node (SLN) biopsy has been demonstrated to be highly predictive for the detection of melanoma micrometastases in the regional lymph node basin. Therefore, the SLN was proposed to accurately reflect the lymph node status of patients with primary cutaneous melanoma. As the regional lymph node status is one of the most powerful predictors of survival in patients with primary melanoma, the histopathologic assessment is critically important for accurate staging. In approximately 20% (ranging from 9% to 42%) of patients with primary melanoma, the SLN was found to be tumor-positive by histopathology or immunohistochemistry. However, the true incidence of metastatic melanoma cells in (sentinel) lymph nodes is underestimated by histopathologic examination. Recently, the method of reverse transcription-polymerase chain reaction (RT-PCR) for tyrosinase mRNA has been used as a molecular marker for the presence of melanoma cells. Tyrosinase RT-PCR was demonstrated to significantly increase the detection of melanoma cells in SLNs as compared to histopathology. All lymph nodes positive by histopathology were shown to express tyrosinase by RT-PCR. Furthermore, tyrosinase transcripts were also detected in 36-52% of stage I and II melanoma patients with SLNs negative by histopathology. Importantly, the recurrence rate was significantly higher in patients with histologically negative SLNs who were found to be positive by RT-PCR than in patients with negative results by both techniques. These findings indicate that RT-PCR status of the SLN is more sensitive for detection of minimal melanoma disease than histopathology. Therefore, the RT-PCR status of the SLN may be suitable to improve melanoma staging and may serve as a prognostic factor in patients with primary cutaneous melanoma.

Conflicting results were obtained by various research groups using the tyrosinase reverse transcription polymerase chain reaction (RT-PCR) for detecting melanoma cells circulating in peripheral blood. Whereas 100% positivity was initially reported for stage IV patients, more recent investigations reported positive detection rates between 30% and 50% in patients with disseminated melanoma. While the high detection rate initially reported in metastatic melanoma may be explained by contamination problems, methodological differences in different steps of the technical procedure of RT-PCR may account for the differences reported in more recent examinations. Major differences may result from the kind of blood preparation, the RNA isolation method, the kind of RT enzyme used, and the gene targeted by PCR primers. In our experience, blood purification by a Ficoll gradient increased melanoma cell detection rates compared to RNA extraction from total blood or after erythrocyte lysis. Amplification of MelanA in addition to tyrosinase resulted in a 30% enhanced sensitivity of melanoma cell detection compared to amplification to tyrosinase alone, whereas gp100/pMel17 and MUC18 gene products were already detected in blood from nonmelanoma patients. These findings are in agreement with those of other groups. Currently, an increase in the sensitivity for detection of circulating tumour cells to more than 50% of patients with disseminated melanoma seems to be unlikely. It is interesting that between 15% and 30% positive results and sometimes more have already been obtained from patients with primary melanoma. So far, there is no data for judging the prognostic significance of the detection of circulating tumour cells in patients without clinically recognisable metastases. Our limited experience shows that staging examinations in these patients reveal no proof of macrometastasis. Therefore, it is presently unclear whether these positive findings are associated with long-term prognosis or if they merely reflect false positive findings in this highly sensitive RT-PCR technique.

Background and Objective: Shave excision of nevi is a technique still under debate. Speed, simplicity, and the fact that it provides excised material for histologic examination are contrasted with the lack of excision margins and a higher rate of nevus recurrences. In this study, the pros and cons of shave excision were evaluated., Patients and Methods: Conventional excisions (268 nevi with intracutaneous butterfly sutures) and shave excisions (403 nevi) were compared with the patients' subjective assessments and objective parameters as recurrence, color, depth, surface smoothness of the scars, and the healing process. The nevi, found on the entire integument, ranged in diameter from 2 to 15 mm, with an average of 5 mm. A second excision was performed only in cases in which an early malignant melanoma could not be excluded., Results: Shave excisions were evaluated subjectively as being better. Shave excisions resulted in fewer complications (7.9% versus 15%), but recurrences were more frequent (18.1% versus 6.0%). There was no close relationship between histopathologic finding of complete excision and recurrences., Conclusions: Small nevi without clinical suspicion of malignant melanoma can be removed with the shave excision technique with good results. Patients should be informed about the higher rate of recurrences. The appliance of the shave technique requires exact knowledge and experience, enabling good histopathologic examinations.

Dermatologists and physicians of other specialties, as well as other health professionals have made tremendous efforts to improve the public education (primary prevention) and early detection (secondary prevention) of cutaneous malignant melanoma (CMM) especially during the last decade. In Australia, the country with the highest incidence of CMM in the world, the first public and effective campaigns were already carried out in the sixties. Through the public campaigns, the knowledge increased about skin cancer, and the attitude and behavior toward sun exposure changed in the population. In the USA and Great Britain too, effective public campaigns were carried out in great numbers and extensive experience was acquired. In Germany, prevention campaigns were first run in regional areas. In 1989, the Commission of Early Detection and Prevention of Melanoma of the German Dermatological Society launched nation-wide campaigns. These activities were complemented by regional campaigns in the 1990s. The analysis of previous campaigns demonstrates that single activities are less effective and repeated campaigns are necessary to increase knowledge about skin and to change attitudes and behavior towards UV-exposure. In addition, the development of sun protective clothing and structural changes, e.g. creation of shady places around open-air swimming pools, should be aimed for. Physicians of other specialties and other health professionals should also be included in prevention campaigns.

The evaluation of melanocytic tumors represents one of the most intriguing and challenging aspects of the daily practice in dermatohistopathology. For the diagnosis of malignant melanoma and melanocytic nevi, standardized and reproducible criteria are required. In case of the diagnosis of melanoma, the histopathological report must include all important data relevant for the prognosis which may also influence the therapeutic procedure. The following paper summarizes the recommendations of the study group on malignant melanoma formed by the Deutsche Dermatologische Gesellschaft.

Lymph node ultrasound examinations are performed during the follow-up of cutaneous melanoma in order to early recognise regional metastases. The excision of regional metastases is the only way to inhibit disseminated metastasis in a certain percentage of cases. Lymph node ultrasound has a sensitivity of 95% in the diagnosis of pathological lymph node changes. Sonographic findings normally show typical features of malignancy; only in some doubtful cases are further control examinations warranted over a period of 4-6 weeks. In violation of this rule, two cases are presented with a delayed onset of metastases causing difficulties in the diagnosis of malignant transformation. Four years after the excision of a nodular melanoma with 0.8 mm tumor thickness at the right lower leg, a suspicious lymph node change in the right groin was sonographically detected which did not fulfill all criteria of malignancy. Control examinations over a period of 1 year found only a further growth of 3 mm. Excision after 1 1/2 years showed a lymph node metastasis. The second case presented 9 years after the excision of a superficial spreading melanoma with 0.76 mm tumor thickness with a suspicious lymph node in the right axilla which similarly grew very slowly. The subsequent excision showed likewise a melanoma metastasis. A protracted growth may occur in thin malignant melanomas with late development of ultrasound features of malignancy. In doubtful cases an early biopsy is recommended.

Mollusca contagiosa predominantly affect children; their occurrence in adults is rare. In recent years many descriptions of mollusca contagiosa in immunosuppressed patients, mostly in HIV-infected individuals, have appeared. We analysed the occurrence of mollusca contagiosa in a large group of HIV-patients and examined their relation to the immune status and their prognostic significance. 456 patients with HIV-associated skin disorders were documented in the HIV follow-up clinics at the Department of Dermatology, University Medical Center Benjamin Franklin, Berlin, during the years 1982-1992. Molluscum contagiosum was diagnosed in 39 patients (8.6%). 38 of the 39 patients were homosexual and/or bisexual men. The median age of the patients was 34 years. Large, papular and nodular lesions up to 1 cm in diameter were observed in some, individuals. Frequently, multiple lesions in atypical localizations such as the face were found. Significant immunosuppression was present in the majority of patients with mollusca contagiosa at the time of their first diagnosis; median CD(4+)-T-lymphocyte count was 122/microliter and the median CD4+/CD(8+)-ratio was 0.2. The median survival time was 12 months in patients with mollusca contagiosa. There was no significant difference between the prognosis of patients with mollusca contagiosa and other HIV-infected patients showing similar reduction of their immune status. Our study showed that mollusca contagiosa are a rather frequent infection in HIV-patients. Mainly localized to the face, they are easily diagnosed and may serve as an excellent clinical marker for recognizing advanced immunosuppression in HIV-infection. Survival prognosis of patients with molluscum contagiosum is unfavourable, corresponding to their reduced immune status. The presence of mollusca, however, is not an independent prognostic marker, if the immune status is considered.

Extracorporeal photophoresis (ECP), a therapeutic modality that has been under investigation for some years, is based on separation of a leucocyte/lymphocyte-enriched cell fraction from the peripheral blood, extracorporeal treatment of the cells with 8-MOP/UVA and subsequent reinfusion of the cells in the patient. Its main effects seem to consist in changes to the immunologic behaviour of the photoinactivated/modulated cells. The immune response of the host is obviously stimulated by this treatment. ECP is normally performed for 4 h per day on 2 consecutive days every 4 weeks. The treatment is well tolerated and causes few side effects. In our department, 1210 ECP treatments were administered to 41 patients between 1990 and 1994 and a preliminary evaluation was performed. These patients included 21 with cutaneous T-cell lymphoma (CTCL), 10 with progressive systemic scleroderma, 4 with chronic graft-versus-host disease and 1 each with pemphigus vulgaris, epidermolysis bullosa acquisita, lupus erythematosus and cutaneous mucinosis. Patients with erythroderma and preserved immunocompetence achieved the best responses of all patients with CTCL. A treatment combining ECP with rIFN-alpha, PUVA and/or radiation was also successful in patients with tumour-stage CTCL and lymph node involvement. Progressive systemic scleroderma responded in more than 50% of our cases. Treatment results were impressive in 4 patients with chronic graft-versus-host disease presenting with sclerodermatous and lichenoid changes of the skin and mucous membranes. A clear improvement was also observed in the patient with pemphigus vulgaris refractory to standard therapies and in another patient with scleromyxoedema (Arndt-Gottron syndrome). The effectiveness of ECP seems to be quite well established in CTCL, but remains to be examined in autoimmune dermatoses. ECP is an attractive addition to the dermatological therapies available but our experience is still preliminary.

The role of elective lymph node dissection (ELND) in primary malignant melanoma is controversial. Our purpose was to evaluate the benefit of ELND regarding survival and disease-free survival in malignant melanoma of the trunk and extremities. By matched-pair analysis, 375 patients treated by wide local excision (WLE) plus ELND were compared to 375 patients treated by WLE only. There was no difference in survival between the two treatment groups; however, the disease-free interval was significantly higher in the collective treated by WLE plus ELND (P < 0.05). Increased survival rates were noted for intermediate tumor thickness of 1.51-4.0 mm for the WLE+ELND group although the difference was not significant (P = 0.14), and disease-free survival was significantly improved in this group (P < 0.001). ELND elicited a higher benefit in male patients with intermediate thickness melanoma. Our results confirm the findings of several studies that ELND improves the outcome after primary treatment of malignant melanoma of intermediate tumor thickness.

The median survival time for patients with disseminated malignant melanoma is 5-7 months; it is still not really known whether therapeutic measures prolong survival. The aim of the present investigation was to identify patients with prolonged survival in stage IV disease and to analyse the possible impact of therapy on the course of the disease. In the Department of Dermatology, Benjamin Franklin University Medical Centre at the Free University of Berlin, 263 patients with were diagnosed as having stage IV melanoma and enrolled in a computer-based registry between 1970 and 1993. In 89 cases systemic medical mentous treatment was given and 111 patients underwent surgery and/or radiation therapy. There were 48 patients who received both systemic and local therapy. On the other hand, 111 patients received no treatment. Twenty two patients were identified survived longer than 24 months (median survival time 33 months). None of the patients who had received no treatment survived for 2 years or longer. The 22 patients with prolonged survival were treated by multimodality included 16 who had received both systemic treatment and surgery and/or radiation, while 3 had had only systemic drug therapy and another 3, only local treatment. Twelve of the 22 patients became tumour free after their initial surgery or radiation. Active therapy in disseminated melanoma with reduction of tumour mass by surgery and radiation and with systemic medical treatment may lead to prolonged survival in a considerable percentage of patients.

During the past decade more than 90% of all melanoma patients in the German-speaking countries have been diagnosed with a primary tumour alone. Therefore, surgical intervention has been the most important element in the management of these patients. The present investigation was performed to analyse the different surgical procedures used in the treatment of primary melanoma during the years 1983-1993. The primary treatment of 15,054 patients with malignant melanoma and without recognizable metastasis has been examined. During the time period under investigation the percentage of cases treated with two-step surgical management increased from 30% to 60%. Primary excision was performed in local anaesthesia in 40% of all patients in 1983, whereas in 1993 surgical intervention under local anaesthesia had increased up to 80%. Over the same time, the average safety margin decreased from 33 mm to 21 mm for the final excision of primary melanomas, and this decrease was paralleled by marked decrease in the average thickness of the tumours excised from 2.1 to 1.5 mm. Elective node dissection was performed in 5% of all patients in 1983, whereas 9% of patients underwent elective node dissection in 1993. The different centres participating were found to differ noticeably in the therapeutic procedures applied for similar indications. In conclusion, the management of primary malignant melanoma has changed considerably during the years 1983-1993 in the German speaking area in favour of a two-step surgical procedure, local anaesthesia for the excision of the primary tumour and smaller safety margins. It seems that earlier diagnosis of the tumour and also ideas about treatment design may be responsible for these changes.

The Central Malignant Melanoma Registry of the German Dermatological Society was founded in 1983 and has meanwhile developed into a major continuously updated multicentre project. Up to June 1994, 19,250 reports of cutaneous melanoma had been received, from 41 departments of dermatology in the former Federal Republic of Germany, from 14 departments in the former German Democratic Republic, from 2 departments in Austria, and from 1 department in Switzerland. Analysis of the data revealed some epidemiological trends over time during the years 1983 to 1993. (1) During the last 10 years the percentage of male patients has steadily increased, from an average of 38% in the year 1983 to 46% in 1993. (2) Early diagnosis of malignant melanoma improved during the period of time investigated. The percentage of diagnoses of primary tumour alone increased between 1983 and 1993. The mean tumour thickness (Breslow) decreased in the West Germany from 1.8 mm to 1.3 mm and in East Germany from 2.5 mm to 1.7 mm. The proportion of nodular melanoma decreased correspondingly from 29% to 14% in the former Federal Republic of Germany and from 40.6% to 22.6% in the former Germany Democratic Republic. During the years 1990 and 1993, 64% of melanoma patients with the primary tumour alone were operated on in two consecutive sessions in the former Federal Republic of Germany and 34.2% of those in the former Germany Democratic Republic. During this period 73.7% of all melanoma patients were operated on under local anaesthesia. In recent years surgical operations were more often performed in two consecutive sessions, mostly under local anaesthesia and with decreasing safety margins, in keeping with the decrease in tumour thickness. The present analysis shows that the Central Malignant Melanoma Registry is an important instrument for investigating trends in clinical epidemiology and treatment of malignant melanoma in the German-speaking countries.

Risk factors for development of malignant melanoma have been investigated in several case control studies during the last decade, with some variation in results, partly with geographical region. Four studies have been conducted under the auspices of the Central Malignant Melanoma Registry of the German Dermatological Society; these have yielded consistent results allowing the identification of risk factors for melanoma development. The numbers of common melanocytic naevi, of atypical melanocytic naevi and the frequency of actinic lentigines were found by multivariate regression analysis to be the most important independent risk factors for melanoma development. Additional factors were hair colour, skin type and a history of naevus growth. A classification of relative risks was established by considering the first three risk factors mentioned, without any clear improvement of classification when further additional significant factors were taken into account. For example, in individuals with more than 50 common melanocytic naevi, 5 or more atypical melanocytic naevi and simultaneous presence of actinic lentigines the risk of developing melanoma was found to be 100-fold that in persons with 10 common melanocytic naevi or fewer and without atypical melanocytic naevi or actinic lentigines. Early recognition of melanomas may be substantially improved if these risk factors are considered. Furthermore, intermittent intensive sun exposure (sunburns as indicator) before the age of 20 induces the development of actinic lentigines; both factors are associated with an increased risk of melanoma development.

Kaposi's sarcoma (KS) is a multicentric neoplasia of microvascular origin arising during development of immunodeficiency in human immunodeficiency virus (HIV)-infected individuals. More than 130 patients with HIV-associated KS (98% male homosexuals; median age, 35 years) have been diagnosed at the Department of Dermatology, University Medical Center Steglitz, Berlin, during the years 1982-1992. Mucocutaneous and visceral involvement was a common finding in patients with HIV-associated KS, increasing from 39% at the first visit to 65% at the last observation. In 90% of the patients significant immunosuppression was found (75% had a CD4+ count < 200/mm3) at the time of first diagnosis. However, immunosuppression was not a prerequisite for the development of KS, since the tumor had been diagnosed before severe immunosuppression was present in about 10% of the patients. Significant prognostic predictors for the final outcome were: (a) the degree of immunosuppression, (b) the presence of mucosal and visceral manifestation, and (c) the past history of opportunistic infections. The median survival time was 28 months in KS patients with more than 300 CD4+ lymphocytes (n = 18), but only 14 months in immunosuppressed (less than 300 CD4+ lymphocytes) individuals with KS (n = 70). The median survival time in the entire group evaluated (n = 89 patients) was 17 months after first diagnosis. In 71 HIV-infected individuals who died at the Berlin Department during the last 8 years, disseminated KS was the major direct or indirect cause of death (49% of cases). Therapeutic benefit for KS patients was observed after long-term administration of recombinant interferon alpha (rIFN-alpha; 9-18 million IU s.c. every 2 days) alone or combined with antiretroviral drugs such as zidovudine over several months. Prolongation of survival was found after such treatment modalities in 30%-40% of treated patients. Bleomycin and vincristine and other systemically used cytostatics have also been applied with moderate results. The etiology of HIV-associated KS is still unknown and coinfection with herpes simplex virus (HSV), cytomegalovirus (CMV), or human papillomavirus (HPV) as well as certain growth-stimulating cytokines (transforming growth factors, TGF; tumor necrosis factor alpha, TNF-alpha; interleukin-6, IL-6; tat; vascular endothelial growth factors, VEGF; oncostatin M) produced by HIV-infected cells may be cofactors. Overall, KS was found to be a tumor with high malignant potential, and the median survival times were short.(ABSTRACT TRUNCATED AT 400 WORDS)

In the present study the action of various cytokines as regulators of human melanocyte growth and differentiation was examined in vitro. Primary melanocyte cultures were obtained in complete medium free of 12-O-tetradecanoylphorbol-13-acetate or serum. First passage melanocytes were treated with various concentrations of recombinant tumour necrosis factor alpha and beta (rTNF-alpha, rTNF-beta), as well as with various recombinant interleukins (rIL-1a, rIL-1b, rIL-2, rIL-3, rIL-4 and rIL-6) for 6 days in complete medium and for 6 and 12 days in a mitogen-reduced medium variant. The 4-methylumbelliferyl heptanoate fluorometric microassay and Ki-67 staining were used for assessing cell proliferation, and the immunophenotype was evaluated using various monoclonal antibodies. Melanocyte proliferation in complete medium was inhibited by rTNF-alpha (-24%), rTNF-beta (-17%), rIL-1a (-21%), rIL-1b (-18%) and rIL-6 (-29%); in contrast, rIL-2, rIL-3 and rIL-4 had no antiproliferative effect. Measurements of Ki-67-positive nuclei confirmed these results. In the reduced medium variant, none of the above cytokines inhibited melanocyte proliferation. Recombinant TNF-alpha and rTNF-beta markedly reduced the expression of the pigment cell-associated antigens HMB-45 and K.1.2, and they enhanced the expression of VLA-2, ICAM-1 and HLA class I antigens and strongly induced HLA-DR. Similar changes were induced by rIL-1a, rIL-b and rIL-6, and rIL-2 decreased the expression of HLA class I antigens and of ICAM-1. In conclusion, several cytokines inhibited the growth and modulated the phenotype of melanocytes in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytokines have been tested in the treatment of different skin cancers during the last decade, and treatment schedules have been established or proposed for several malignant skin tumors. Preferentially, the interferons and interleukin-2 were found to be effective in treating skin cancers. Interferons alpha and beta have been approved for the treatment of human immunodeficiency virus (HIV)-associated Kaposi's sarcoma, cutaneous T cell lymphoma, and malignant melanoma in several countries. Interferon alpha was found to be most effective in cutaneous T cell lymphoma with 40%-60% overall responses. When combining interferon alpha with psoralens and ultraviolet A (PUVA) or with retinoids, even higher response rates up to 60%-90% were reported, and long-term remissions have been described. A considerable activity of interferon alpha was found in HIV-associated Kaposi's sarcoma with response rates of 30%-50%. The effectiveness of Kaposi's sarcoma's treatment was further improved by combining interferon alpha and zidovudine. Responses to interferon alpha in metastatic malignant melanoma are rather seldom (10%-15%), but a stabilization of the disease with prolonged survival was reported after interferon alpha treatment. Additionally, interleukin-2 was found to be active in metastatic melanoma, with overall response rates of about 20%, and both biological agents were found to have an additive efficacy in combination. Several combined regimens of interferon alpha, interleukin-2, and polychemotherapy have been described in metastatic melanoma, and overall response rates higher than 50% were found with these combined treatment modalities. Interferon alpha and beta were also intralesionally injected into basal cell carcinomas and other epithelial skin cancers, and complete responses were found in more than 80% of tumors treated. Local applications of interferons and interleukin-2 were likewise found to be effective in the treatment of cutaneous melanoma metastases and cutaneous manifestations of Kaposi's sarcoma. Cytokines and their combination with other treatment modalities has greatly enriched the treatment facilities in malignant skin tumors during recent years, and additional new cytokines will be introduced in skin cancer treatment in near future.

In order to improve the characterization of human malignant melanoma cells and their variant gene expression in vitro, a search for specifically regulated genes was performed. Four melanoma cell lines (M5, MEWO, IGR39, SKMEL13) and newly cultured normal human melanocytes were included in a comparative hybridization (differential screening) of a human melanoma cDNA-library. Six cDNAs were isolated showing a stronger expression (four genes) or a weaker expression (two genes) in melanoma cells than in normal human melanocytes. Quantification of the expression patterns of the two repressed genes in Northern blots revealed general expression in all melanocyte cultures examined, no expression in three cell lines (M5, IGR39, SKMEL13) and weak expression in MEWO. The four induced genes were found to be only weakly expressed in normal human melanocytes, but showed an elevated expression in all of the four melanoma cell lines tested. Thus, using the technique of differential screening, consistent gene regulation at the messenger RNA level was identified, which distinguishes the four melanoma cell lines tested from normal melanocytes. We conclude from the expression patterns that specific gene regulation in melanoma cells in vitro is characterized both by strong repression of some melanocyte genes, as well as by the induction of other genes, but there was no indication of new expression of genes specific for melanoma cells. Because of the uniform induction or repression in different melanoma cell lines, it is conceivable that the cloned genes may be involved in the malignant transformation of melanocytic cells.

The role of elective lymph node dissection (ELND) in clinical stage I malignant melanoma continues to be controversial. We present a matched pair analysis of 375 patients treated in the Department of Dermatology in Kassel between 1979 and 1991 by wide local excision (WLE) plus ELND. Multivariate analysis revealed tumor thickness, level of invasion, age, sex, and localization as independent prognostic factors, and 375 patients treated by WLE alone were matched as controls to the patients treated by ELND and WLE. There was no significant benefit from WLE plus ELND compared to WLE alone in the total group as shown by the 5-year survival rates (87.3% versus 86.4%) and 10-year survival rates (80.1% versus 77.82%). Increased survival rates were noted for tumor thicknesses 1.51-4.0 mm for the WLE plus ELND group, as shown by the 10-year survival rates of 73.1% versus 60.3%. However, these data were not significant (p = 0.14). Disease-free survival rates were significantly higher in the group treated by additional ELND for all tumor thicknesses (p < 0.05) and even more in intermediate tumor thicknesses of 1.51-4.0 mm (p < 0.001). A significant benefit of elective lymph node dissection was detected for malignant melanoma of the trunk (all tumor thicknesses), as shown by the 5-year survival rates of 92.0% versus 79.7% and 10-year survival rates of 80.4% versus 45.16% (p < 0.05). Malignant melanoma of the extremities revealed no significant differences in survival rates. We conclude that there is a certain benefit from ELND in clinical stage I malignant melanoma for tumor thicknesses of 1.51-4.00 mm. Especially in malignant melanoma of the trunk, WLE plus ELND was more beneficious than WLE alone.