Merkel Cell Carcinoma: From Pathobiology to Clinical Management

SIMPLE SUMMARY: Merkel cell carcinoma (MCC) is an uncommon type of skin cancer that carries a poor prognosis. It is seen predominantly in old age in sun-exposed body parts. Racial and geographical differences are seen in its occurrence. Viral infection and radiation exposure are the two leading factors implicated in its causation. Small, firm to hard nodule (usually in sun-exposed areas), red with a history of a rapid increase in size is a common personation of the disease. Other body parts such as upper limbs, trunk, and even lower limbs may be also involved. The disease is diagnosed by taking a tissue sample (biopsy) for examination, and other radiological investigations are needed to reach a proper diagnosis with the staging of the disease. There are various treatment options including surgery, radiotherapy, and chemotherapy. Surgery is the primary treatment option though some patients may not be the candidates for operation where other treatment options come into play. ABSTRACT: Merkel cell carcinoma (MCC) is an infrequent, rapidly growing skin neoplasm that carries a greater probability of regional lymph node involvement, and a grim prognosis in advanced cases. While it is seen predominantly in old age in sun-exposed body parts, the prevalence varies among different races and geographical regions. Merkel cell polyomavirus and UV radiation-induced mutations contribute to its etiopathogenesis. The clinical presentation of MCC lacks pathognomonic features and is rarely considered highly at the time of presentation. Histopathological examination frequently reveals hyperchromatic nuclei with high mitotic activity, but immunohistochemistry is required to confirm the diagnosis. Sentinel lymph node biopsy (SLNB) and imaging are advised for effective staging of the disease. Multimodal management including surgery, radiation therapy, and/or immunotherapy are deployed. Traditional cytotoxic chemotherapies may result in an initial response, but do not result in a significant survival benefit. Checkpoint inhibitors have dramatically improved the prognosis of patients with metastatic MCC, and are recommended first-line in advanced cases. There is a need for well-tolerated agents with good safety profiles in patients who have failed immunotherapies.