Modern diagnostics and treatment of Merkel cell carcinoma

Abstract

SummaryMerkel cell carcinoma (MCC) is a rare, aggressive skin cancer with epithelial and neuroendocrine differentiation, the incidence of which has increased substantially during the most recent decades. Risk factors include advanced age, fair skin type, UV exposure, and immunosuppression. Pathogenetically, a type caused by the Merkel cell polyomavirus is distinguished from a UV‐induced type with a high tumor mutational burden.Clinically, MCC presents as a mostly painless, rapidly growing, reddish‐violet tumor with a shiny surface, which is preferentially localized in the head‐neck region and at the distal extremities. A reliable diagnosis can only be made based on histological and immunohistochemical features. At initial diagnosis, 20–26% of patients show locoregional metastases and 8–14% distant metastases, making staging 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 radiotherapy and, in advanced inoperable stages, medicamentous tumor therapy. The introduction of immune checkpoint inhibitors has led to a paradigm shift, as they provide a considerably longer duration of response and better survival rates than chemotherapy. The PD‐L1 inhibitor avelumab is approved for treatment of metastatic MCC in Germany, but the PD‐1 antibodies pembrolizumab and nivolumab are also used with success. Adjuvant and neoadjuvant treatment concepts, immune combination therapies and targeted therapies as monotherapy or in combination with immune checkpoint inhibitors are in the clinical trial phase.

Genetic predisposition to milder forms of COVID-19 may provide some resilience to head and neck cancers

“…The effects of immunosuppression are nonspecific; they do not depend on its etiology. For example, prolonged immunosuppression in inflammatory bowel disease also increases the risk of developing HNC ( 29 , 30 ). In the case of asymptomatic disease, which is expected to be common in adult COVID-19 controls according to recent epidemiological evaluations ( 31 , 32 ), the state of immunosuppression may be present at the time of infection and is due to various genetic or environmental causes.…”