Update on the Biology and Clinical Management of Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine cutaneous malignancy, with a predilection for sun-exposed sites in elderly patients. Despite an incidence 30 times less than that of melanoma, its disease-specific mortality is three times higher. Management of MCC remains challenging because of a limited understanding of its molecular biology, lack of prospective clinical trials, and limitations associated with retrospective reviews of therapeutic options. With the recent discovery of an associated human polyomavirus, significant progress has been made in the understanding of the pathogenesis of this malignancy. With this progress, there has been increasing optimism regarding new tools in the therapeutic armamentarium to fight this deadly disease. Here we present an overview on MCC with an emphasis on the most recent biologic discoveries and the rationale for novel targeted and immunotherapies. Merkel cell carcinoma (MCC) is an aggressive neuroen-docrine skin cancer most commonly thought to orig-inate from theMerkel cells of the basal layer of the epidermis. This is supported by its shared cytoplasmic dense-core neu-roendocrine granules and keratin fılament (cytokeratin-20) expression characteristics,1,2 although some have argued that it may arise from an epidermal or dermal pluripotent stem cell.3 First described histologically in 1972 by Cyril Toker4 as “trabecular carcinoma of the skin, ” detection of MCCmark