Merkel Cell Carcinoma of the Head and Neck: Epidemiology, Pathogenesis, Current State of Treatment and Future Directions

Simple Summary Merkel cell carcinoma of the head and neck is a relatively uncommon cutaneous malignancy with distinct treatment management from Merkel cell carcinoma occurring in other anatomic locations. The efficacy of immunotherapy has markedly changed prognosis for patients with locally advanced or metastatic Merkel cell carcinoma of the head and neck. However, patients with primary or acquired resistance to immunotherapy remain therapeutically challenging, with novel treatment being vital to improving outcomes. Given the novel therapeutic options available for these patients, as well as increasing characterization regarding the differing oncogenesis of Merkel cell polyoma virus-positive vs. -negative tumors, up to date information regarding epidemiology; oncogenesis; current standards of treatment; and future therapeutic avenues are important to improving outcomes for patients with Merkel cell carcinoma of the head and neck. Merkel cell carcinoma (MCC) is a rare, cutaneous neuroendocrine malignancy with increasing incidence. The skin of the head and neck is a common subsite for MCC with distinctions in management from other anatomic areas. Given the rapid pace of developments regarding MCC pathogenesis (Merkel cell polyoma virus (MCPyV)-positive or virus-negative, cell of origin), diagnosis, staging and treatment, and up to date recommendations are critical for optimizing outcomes. This review aims to summarize currently available literature for MCC of the head and neck. The authors reviewed current literature, including international guidelines regarding MCC pathogenesis, epidemiology, diagnosis, staging, and treatment. Subsequently recommendations were derived including the importance of baseline imaging, MCPyV serology testing, primary site surgery, nodal evaluation, radiotherapy, and the increasing role of immune modulating agents in MCC. MCPyV serology testing is increasingly important with potential distinctions in treatment response and surveillance between virus-positive and virus-negative MCC. Surgical management continues to balance optimizing local control with minimal morbidity. Similarly, radiotherapy continues to have importance in the adjuvant, definitive, and palliative setting for MCC of the head and neck. Immunotherapy has changed the paradigm for advanced MCC, with increasing work focusing on optimizing outcomes for non-responders and high-risk patients, including those with immunosuppression.