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Background: Hand-foot syndrome (HFS) and nail changes are frequent adverse events of anticancer therapies., Objectives: To provide a review of current evidence in HFS and nail disorders associated with medical tumor treatment., Materials and Methods: Basis is the current German S3 guideline "Supportive therapy in oncologic patients" and literature on this topic published since the guideline was finalized., Results: Two variants of HFS are distinguished: a chemotherapy-associated and a kinase-inhibitor-associated variant. In the first form, painful erythema, blisters and ulceration can occur, also in other areas with a high number of sweat glands such as axillary and inguinal regions. Thus, the secretion of toxic substances through sweat glands is a proposed pathogenetic mechanism. For the second form, which results in callus-like painful thickening of the horny layer on areas of mechanic pressure, a vascular mechanism is proposed. For prophylaxis of HFS, avoidance of mechanical stress, regular cleaning of predisposed areas, and also urea- and diclofenac-containing ointments are recommended; in case of infusions (taxanes, doxorubicine), cooling of hands and feet during infusion is recommended. In case of manifest HFS, dose reduction or prolongation of intervals of the associated treatment are recommended. Nail changes often develop under therapy with chemotherapeutic agents but also under treatment with agents such as checkpoint inhibitors or under targeted therapy. Different components of the nail unit may be involved such as the nail matrix, nail bed, nail plate, hyponychium, lunula and proximal and lateral nail folds., Conclusion: This work gives insight into the pathophysiology of HFS and nail disorders that develop under systemic oncologic treatments and gives recommendations for prophylaxis and treatment., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

We report a case of a 75-year-old man with facial edema that also affected the periorbital area who was admitted to the hospital with the suspected diagnosis of Quincke's edema. The diagnosis of cutaneous angiosarcoma was made by microscopic examination and immunohistochemical staining. Chemotherapy was initially initiated because the angiosarcoma was unresectable and the radiation situation was difficult. Therapy has to be switched to second and third line therapy due to disease progression. The case illustrates the complexity of diagnosis and therapy in patients with cutaneous angiosarcoma., (© 2021. The Author(s).)

Malignant melanoma is an aggressive skin cancer that originates from cells of the melanocytic lineage and is associated with an invasive growth pattern and early spread. Besides endogenous risk factors such as fair skin type or genetic disposition for the formation of multiple nevi, exposure to ultraviolet light is the most important exogenous risk factor. Treatment of patients with primary tumors includes the complete excision of the primary lesion with appropriate safety margins and in patients with an increased risk of metastasis sentinel lymph node excision. Prognostically significant parameters are the Breslow invasion depth, ulceration of the primary lesion, and sentinel lymph node status. Systemic therapy plays an important role in the adjuvant setting and for inoperable tumors. Depending on the indication and the molecular profile of the tumor tissue, immune checkpoint inhibitors or targeted kinase inhibitors can be used and may result in a significant prolongation of survival times.

Merkel cell carcinoma is a rare, highly aggressive skin tumor with neuroendocrine features found in older people. The pathogenesis is associated with immunosuppression, chronic UV light exposure and the Merkel cell polyomavirus. Clinically, Merkel cell carcinoma presents as a solitary, cutaneous or subcutaneous, red to bluish node. Due to early lymphogenic metastasis, locoregional metastases are already present in approximately 30% of cases at the time of diagnosis. The frequent local recurrences as well as the regional and distant metastases usually appear within the first 2-3 years after the initial diagnosis. The first treatment after diagnosis consists of complete surgical removal of the primary tumor with wide safety margins as well as a sentinel lymph node biopsy. Subsequently, adjuvant irradiation of the primary site should be performed. By additional radiotherapy of the regional lymph node stations, the rate of locoregional recurrence can be reduced. For systemic therapy of advanced Merkel cell carcinoma checkpoint inhibitors targeted against the PD-1/PD-L1 axis have proven to be highly and durably effective. In contrast the formerly frequently used chemotherapy shows moderate to good response rates but they are as a rule very short-lived.

Background: Malignant fibrohistiocytic tumors are a heterogeneous group of mesenchymal neoplasms that may occur in the skin and subcutaneous tissues., Diagnosis: Diagnosis of these tumors may be difficult, as they are rare, and a wide morphological diversity of types and subtypes has been described. In this update, relevant aspects of selected entities like dermatofibrosarcoma protuberans, desmoid tumor, atypical fibroxanthoma, pleomorphic dermal sarcoma, and myxofibrosarcoma are discussed according to the WHO classification of 2013. The typical clinical feature of these tumors is their mostly asymptomatic appearance. For diagnosis, the histologic workup is therefore the key feature; herein immunohistochemistry as well as molecular diagnostics become increasingly important., Therapy: The primary treatment for locally resectable tumors is complete surgical removal; chemotherapy, radiation, and targeted therapies with kinase inhibitors are available for inoperable and metastatic disease.

Background: BRAF and MEK inhibitors are new targeted therapies which are used in the treatment of malignancies, in particular of malignant melanoma., Side Effects: Cutaneous side effects are common during the treatment with both types of inhibitors. These side effects include inflammatory reactions such as maculopapular and papulopustular exanthema, hand-foot syndrome, panniculitis, paronychia, photo- and radio-sensitization. As a class effect, BRAF-inhibitors induce proliferative disorders of keratinocytes and melanocytes, such as palmoplantar hyperkeratosis (as part of the hand-foot syndrome), verruciform and acanthoma-like lesions, follicular and Grover disease-like hyperkeratoses, keratoacanthomas, squamous cell carcinomas and atypical melanocytic nevi with transition to secondary melanomas. Furthermore, hair alterations and xerosis are possible., Conclusions: Treatment with BRAF and MEK inhibitors requires close dermatologic monitoring of the patient. This manuscript summarizes the most frequent cutaneous side effects and their management.

Cutaneous metastases from gastric cancer are uncommon with a frequency of 7 % but can rarely be the presenting sign. A 54-year-old man complained of multiple pea-sized scalp nodules which had been present for four months. Histology showed a metastatic adenocarcinoma. Initial evaluation revealed liver metastases and gastroscopy then identified a tumor involving the distal esophagus and gastric cardia that was diagnosed as a gastric tubular carcinoma. The patient had a good response to polychemotherapy. While gastric carcinoma generally metastasizes to the abdominal wall or lymph nodes, our patient showed an exceptional variant with distant cutaneous metastases as the first clinical sign.

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.

Changes in skin and its adnexa such as hair follicles and nails are among the most common side effects of antineoplastic treatments. They pose a challenge with regard to diagnostic and therapeutic aspects. This article reviews the various cutaneous reactions to chemotherapy and their most common causative agents, the adverse events of radiation therapy, as well as the characteristic skin changes under treatment with new molecular-driven targeted agents.

The use of molecular targeted therapies currently is on the rise in the treatment of severe diseases, particularly for malignant tumors. The targeted agents show a high specificity against one or more molecular target structures, hereby inhibiting or modifying signal transduction pathways connected to these targets, and thus strongly altering proliferation, activation and interaction of the targeted cells. These manipulations of highly specific signaling pathways are associated with again highly specific side effects, which often affect the skin. These cutaneous reactions present a new spectrum of adverse drug events to the dermatologist. We reviews the cutaneous reactions of molecular targeted agents used in the treatment of psoriasis (alefacept, efalizumab, etanercept, infliximab and adalimumab), as well as agents used in cancer therapy (imatinib, sorafenib, sunitinib, EGFR antagonists and CTLA-4-antagonists).

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.

Follow-up, rehabilitation and palliative/supportive care are essential parts of the care and treatment of skin cancer patients. This review provides an overview on the state of knowledge and recent developments in these three disciplines, hereby providing standard operating procedures for the dermatologist in the care of skin cancer patients. Especially in follow-up and supportive care, the results of recent clinical trials have led to significant changes in the standard of care. These new insights and their consequences are the special focus of this article.

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.

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.