Modern diagnostics and treatment of Merkel cell carcinoma

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with epithelial andneuroendocrine differentiation, the incidence of which has increased substan-tially during the last decades. Risk factors include advanced age, fair skin type,UV exposure, and immunosuppression. Pathogenetically, a type caused by theMerkel cell polyomavirus is distinguished from a UV-induced type with a hightumor mutational burden. Clinically, MCC presents as a mostly painless, rapidly growing, reddish-violet tumorwith a shiny surface, which is preferentially localized in the head-neck regionand at the distal extremities. A reliable diagnosis can only be made based onhistological and immunohistochemical features. At initial diagnosis, 2026% ofpatients show locoregional metastases and 814% distant metastases, makingstaging examinations indispensable. If there is no clinical evidence of metastases,a sentinel lymph node biopsy is recommended. Essential columns of therapy are surgery, adjuvant or palliative radiotherapyand, in advanced inoperable stages, medicamentous tumor therapy. The intro-duction of immune checkpoint inhibitors has led to a paradigm shift, as theyprovide a considerably longer duration of response and better survival ratesthan chemotherapy. The PD-L1 inhibitor avelumab is approved for treatmentof metastatic MCC in Germany, but the PD-1 antibodies pembrolizumab andnivolumab are also used with success. Adjuvant and neoadjuvant treatment con-cepts, immune combination therapies and targeted therapies as monotherapy orin combination with immune checkpoint inhibitors are in the clinical trial phase.