CLINICS 2011;66(10):1817-1823 REVIEW A review of the epidemiology and treatment of Merkel cell carcinoma Joa˜ o Pedreira Duprat,I Gilles Landman,II,IV Joa˜ o Victor Salvajoli,III Eduard Rene Brechtbu¨ hlI I Hospital do Caˆ ncer AC Camargo, Department of Skin C aˆncer, S a˜o Paulo/SP, Brazil. II Hospital AC Camargo - Post Graduation, S a˜o Paulo/SP, Brazil. III Instituto do C aˆncer do Estado de Sa˜ o Paulo Octavio Frias de Oliveira (ICESP), Radio-Oncology, S a˜o Paulo, SP, Brazil. IV Federal University of S a˜o Paulo, Department of Pathology, S a˜o Paulo/SP, Brazil. Merkel cell carcinoma is a very rare and aggressive neoplasm. Due to its rarity, therapeutic guidelines are not well established, especially for regionally advanced disease. Articles in English, French, Italian, Portuguese, and Spanish from the last 20 years were identified in MEDLINE and reviewed. The key word ‘‘Merkel’’ was used for the search, relevant articles were selected, and their references were examined. The most important articles related to epidemiology, genesis and treatment were reviewed. The incidence of Merkel cell carcinoma is increasing due to the advancing age of the population, higher rates of sun exposure and an increasing number of immunocom- promised individuals. With regard to etiology, the recently described Merkel Cell polyomavirus is thought to play a role. Either local or regional surgical intervention remains the standard of care, but adjuvant radiotherapy or radiotherapy as a primary treatment have been discussed as reasonable therapeutic options. An update on this rare neoplasia is essential because of its increasing incidence and changing treatment options. KEYWORDS: Carcinoma, Merkel CELL; Literature review; Radiotherapy; Polyomavirus. Duprat JP, Landman G, Salvajoli JV, Brechtbu¨ hl ER. A review of the epidemiology and treatment of Merkel cell carcinoma. Clinics. 2011;66(10):1817- 1823. Received for publication on March 11, 2011; First review completed on April 18, 2011; Accepted for publication on May 30, 2011 E-mail: jduprat@uol.com.br Tel.: 55 11 2189-5135 DOI:10.1590/S1807-59322011001000023 INTRODUCTION Merkel Cell Carcinoma (MCC) is a very rare and aggressive neoplasm. Due to its rarity, therapeutic guidelines are not well established, especially for regionally advanced cases. METHOD The MEDLINE database was searched for articles written in English, French, Italian, Portuguese, and Spanish. The key word ‘‘Merkel’’ was used as the basis for these searches. Relevant articles were selected, and their references were also evaluated. DISCUSSION Epidemiology and Etiopathology Merkel Cell Carcinoma (MCC) is a rare and aggressive neoplasia that was first described in 1972 by Toker.1 This tumor likely originates from a cutaneous mechanoreceptor cell (Merkel cell) located in the basal layer of the epidermis. In the last decade, reports on Merkel cell carcinoma have increased significantly, primarily due to the advent of new and specific immunohistochemical staining methods. This Copyright 2011 CLINICS – This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non- commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. No potential conflict of interest was reported. 1817 unusual cutaneous neuroendocrine neoplasia has many synonyms including ‘‘cutaneous neuroendocrine carci- noma,’’ ‘‘cutaneous trabecular carcinoma,’’ and ‘‘small cell primary cutaneous carcinoma’’.1,2 Currently, 950 to 1,300 cases of MCC are diagnosed per year in the United States. This number appears to be increasing due to the advancing age of the population, the higher incidence of damaging sun exposure, and increasing numbers of immunocompromised individuals.3-7 Feng et al. recently described a polyomavirus isolated from MCC specimens, which may explain why MCC is more frequently observed in immunocompromised patients. These authors studied ten tumors and detected the virus in eight cases. In six of the eight positive tumors, the virus was integrated into the tumor genome. In non-MCC patients, integration was observed in 16% of cases.8 The estimated annual incidence of MCC is 0.23 per 100,000 individuals for Caucasians, whereas the incidence in those of African descent is 0.01 per 100,000 and appears to be even lower in Polynesians. Merkel cell carcinoma occurs predominantly in elderly persons, with a mean of 69 years- old at diagnosis.9-11 Males are affected more commonly than females (61% male vs. 39% female).12 Other tumors, such as squamous cell carcinoma and chronic lymphocytic leuke- mia, are also common in this population.11 Angiogenesis has been described by many authors in this rare tumor. Gaudin and Rosai described a vascular distribution pattern common to Merkel and other neural and neuroendocrine neoplasms characterized by tufts of vessels, similar to a glomeruloid pattern, or long cords of vessels.13 They proposed that this characteristic pattern may