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Inhibitors of the epidermal growth factor receptor (EGFR) are increasingly used in the treatment of various entities of malignant tumors. Patients treated with EGFR inhibitors very likely develop cutaneous side effects. The development of a papulopustular, follicular exanthema during the first weeks of therapy correlates with therapeutic benefit. However, this exanthema and other cutaneous side effects can impair the quality of life of the patient and might limit the therapy with the EGFR inhibitor. For an optimal therapeutic benefit and quality of life an adequate management of cutaneous side effects is necessary. A panel of German dermatologists developed on the basis of personal experience and current literature consensus recommendations for the management of cutaneous side effects of EGFR inhibitors., (© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.)

Background: Merkel cell carcinoma is a rare skin cancer of neuroendocrine origin, which is characterized by a high rate of recurrence, metastatic spread and mortality. Because of its rarity, evidence-based therapeutic regimens are difficult to establish. Merkel cell carcinoma is known to be both radio- and chemosensitive. Toxicity is a key factor in assessing any regimen, as the patients are usually elderly and likely to have other significant medical problems., Patients and Methods: We retrospectively evaluated five patients with metastatic Merkel cell carcinoma to see if liposomal doxorubicin (Caelyx) or Myocet) in combination with radiotherapy exhibited clinical anti-tumoral effects accompanied by acceptable side effects., Results: The outpatient chemotherapy regimen was tolerated without major side effects and produced good response rates. All patients achieved at least tumor stabilization; four of five had a partial remission. Effects of therapy were usually seen in the first cycle of therapy but the responses were of short duration with an average interval of two months until progression., Conclusions: As combined radiochemotherapy with liposomal doxorubicin is well tolerated even in older patients with other illnesses and can be given on an outpatient basis, it is an attractive option for metastatic Merkel cell carcinoma. Based on response rate or overall survival, it offers no advantages compared to polychemotherapy.

Background: It is unclear if differences between melanoma-associated hypopigmentation (MAH) and classical vitiligo exist., Patients and Methods: Hypopigmented areas and associated lesions (halo nevi, hypopigmented scars) in 15 melanoma patients and 31 patients with classical vitiligo were analyzed by digital photography. The activity of the respective lesions was assessed by the vitiligo disease activity (VIDA) score. Associated diseases were recorded by history and serological tests;genotyping of HLA class I antigens as well as histology/immunohistology were performed., Results: MAH were diagnosed in 12 of 15 melanoma patients; mean onset was 4.8 years after the primary diagnosis of the melanoma. Three melanoma patients reported hypopigmentation more than 15 years before diagnosis of melanoma. In the history and family history of vitiligo patients, autoimmune diseases were much more frequent and haplotype HLA-A2 was twice as common compared to MAH patients. MAH lesions were most often distributed in a bilateral symmetrical pattern, corresponding to vitiligo. MAH was less progressive compared to classical vitiligo; however, it was more often associated with other acquired leukodermas. In both groups hypopigmentation spread centripetally to the trunk. Histological and immunohistological differences were not found., Conclusions: Whereas differences exist concerning associated autoimmune diseases, MAH and vitiligo shared many common clinical and histological features. Further studies are needed to assess the clinical relevance of vitiligo-like alterations in melanoma patients.

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin. The incidence of this rare tumor is increasing rapidly; the American Cancer Society estimates for 2008 almost 1500 new cases in the U.S. Thus, the incidence of MCC will exceed the incidence of cutaneous T-cell lymphoma. Moreover, the mortality rate of MCC with 33% is considerably higher than that of cutaneous melanoma. These clinical observations are especially disturbing as we are only recently beginning to understand the pathogenesis of MCC. For the same reason, the therapeutic approach is often unclear; reliable data are only available for the therapy of locoregional disease.

Increasing evidence suggests that cancer is a disease in which the persistence of the tumor relies on a small population of tumor-initiating cells, the so called tumor stem cells (TSC). Only these cells are capable of self-renewal and thereby possess the ability for unlimited proliferation. One reason for the inability of conventional tumor treatments to achieve long-term cures seems to be that TSC are resistant to many therapeutic approaches. A detailed characterization of TSC should have a substantial impact on the optimization of therapeutic protocols. While TSC in hematopoietic malignancies have been most intensively studied, subpopulations with stem cell properties have been identified in some solid tumors including breast carcinomas, gliomas and melanomas. In case of melanoma, however, a clear-cut molecular characterization is still pending. Considerable research is needed to establish standard procedures for the isolation of melanoma stem cells to facilitate determining how these cells, critical for tumor persistence and progression, can be effectively eliminated. A pressing question is if melanoma stem cells are in principle sensitive to immunotherapy.

In recent years the traditional treatment spectrum of tumors--chemotherapy or radiotherapy--has been extended with immune-modulating strategies. For some tumors, clinical responses have been observed but for numerous others no satisfactory approach has been established. Many new agents have been developed; the targeted or smart drugs modulate a constantly growing list of tumor-specific signal pathways and represent an enormous hope for cancer patients. The clinical evaluation of these targeted drugs alone or in combination also presents an enormous challenge. Since the number of possible combinations of targeted drugs seems almost limitless, an accurate strategy for determination of success-promising combination patterns for the individual cancer patient is of special importance.

Assessing pigmented lesions within or covered by tattoos is difficult, both at a clinical and dermatoscopic level. Patients with tattoos may provide a challenge in the early recognition and follow-up of melanoma.

Immunotherapy has assumed increasing importance in the therapy of malignant melanoma. The main reason is the high immunogenicity of the tumor itself, so that an immune response against the tumor often exists even without immune stimulation. The goal of modern immunotherapeutic approaches is to augment these anti-tumoral immune reactions to fight the tumor. Despite multiple successes, the ultimate breakthrough in the therapy of malignant melanoma has not yet been achieved. This overview summarizes the reasons for this lack of success and highlights future strategies for more successful therapy of malignant melanoma.

Recent results from basic and translational research on tumor genesis and progression establish the basis for future therapeutic approaches. Targeted therapeutics are tailored toward the molecular abnormalities that cause tumor progression and could potentially provide an effective, non-toxic therapeutic approach in a broad range of cancers including melanoma. Cancer is as much a (cyto)genetic disease as it is an epigenetic disease. Indeed, the fate of the cell depends on a delicate balance between expression and repression of genes. The notion that drastic changes in DNA methylation and histone modifications are present in a variety of human tumors has prompted the development and characterization of epigenetic drugs. Inhibitors of histone deacetylases and methyltransferases as well as of the proteasome are covered in this review.

Recent results from basic and translational research on the causes and mechanisms of melanoma genesis and progression will impact on future therapeutic approaches. The increasing understanding of the molecular pathology of malignant disease and the detailed analysis of the signal transduction pathways involved allows specific intervention with these oncogenic events. These interventions address the molecules associated with or responsible for the malignant transformation and have therefore been termed "targeted therapy". The present review focuses on the therapeutic options involving modulation of the Ras/MAPK- and PI3K/AKT-signal transduction pathways.

Background: According to guidelines of the German STD Association, appropriate treatment of extensive anogenital warts with comparable recurrence rates includes cryotherapy, surgical excision, electrosurgery, CO2- and Nd:YAG-laser vaporisation. All these procedures are associated with varying degrees of risk for bleeding, release of potentially infectious aerosol, deep thermal destruction, slow wound healing, and scarring., Methods: Using argon-plasma coagulation anogenital warts can be removed in layers in a controlled manner. High frequency current flows through the argon plasma to the tissue, allowing well-controlled, superficial tissue destruction., Results: From January 2001 to March 2003, 54 patients with extensive genital, anal or anogenital warts were treated. After one treatment, 66% of the pa- tients remained disease-free in the following 4 months. Thirteen patients (24%) showed early recurrence after 4 weeks, five patients (9%) at a later date. In these patients, further treatment, in 9 cases combined with topical imiquimod cream, were necessary for complete remission., Conclusion: Compared to other therapeutic procedures, argon-plasma coagulation is a better controlled, quick and low-risk option for the treatment of anogenital warts. Depending on the type of involvement and individual risk factors, postoperative treatment with topical imiquimod cream may be useful.