CLINICS 2011;66(10):1817-1823 head and neck region. In both situations, higher numbers of false-negatives have been obtained during the sentinel node biopsy evaluation. MCC more frequently invades deep into the tissues, such as deep dermis and subcutaneous layers, affecting different sentinel nodes than those of the mela- noma patients.42 However, data from AJCC 201039 have shown that the value of the procedure is easily demon- strated. Patients with positive sentinel lymph nodes who received adjuvant therapy localized to the nodal positive basin (surgery, radio-, or chemotherapy) had 50% disease- free survival at three years, but this was decreased to 0% if adjuvant therapy was not administered.6 As adjuvant therapy, a dose of 40 to 50 Gy is administered in 2-Gy daily fractions to the primary or regional basin.34,41,43 A major discussion in the literature refers to management after a positive node is detected: is it better to perform a complete node dissection, radiotherapy only, or both?42 The answer remains unclear. Lymphadenectomy associated with radiotherapy in axillary and inguinal regions can lead to substantial lymphedema. In older patients with micro- metastases, isolated radiotherapy seems to be a good option. For good performance status, in patients with larger tumors, macrometastases, or extra-nodal invasion, combined ther- apy is a reasonable option. For patients with less-than- optimal margins, especially in the head-neck region where adjuvant radiotherapy is planned, it is reasonable to excise lymph nodes close to the positive node basin (if micro- metastasis has minimal disease) without performing a complete lymph node dissection. Extrapolating from studies of the primary lesion, there are enough data to support that radiotherapy only applied to the positive sentinel node basin can be a reasonable option,50,51 but the data for positive sentinel nodes remain limited. Bichakjian et al. suggested that with the limited available data, radical lymphadenectomy should be considered the first-line treatment for sentinel node positive patients. In cases where surgery is a high-risk procedure for the patient, radio- therapy without surgery should be considered.36 If an enlarged regional node is present, lymphadenectomy and adjuvant radiotherapy are often performed.30,32,33,35,41,44,45 As previously mentioned, in the head and neck region, Gillenwater et al. found that local and regional recurrence differed significantly when patients received radiotherapy, but they did not find differences in overall survival.47 Patients receiving radiotherapy had a regional recurrence rate of 27 vs. 85% compared to those who did not. Disease-free survival increased from eight to twenty-four months if any radio- therapy was applied.41 In summary, it seems that adjuvant radiotherapy is beneficial both locally and regionally. Distant disease occurs in 36% of patients, regardless of the adjuvant therapy applied.47 In addition, adjuvant che- motherapy failed to provide any benefit. Garneski et al. showed that the chemotherapeutic regimen is toxic, and the target population is elderly, leading to a treatment-related death rate of approximately 16% in patients older than 65 years. Morbidity is also high in these cases, and the chemotherapeutic regimen is adapted from that used for small-cell lung carcinoma. Without evidence of improved outcomes, it does not seem reasonable to take on the risk of such a toxic treatment.29,41,55,56 Distant metastasis Chemotherapy plays a role in the treatment of distant metastatic disease. The preferred therapeutic regimen 1821 Epidemiology and treatment of Merkel cell carcinoma Duprat JP et al. consists of platinum-based components, such as cisplatin or carboplatin, plus etoposide or doxorubicin. Response rates of up to 40% were observed in some studies; however, those who responded did so only for a short time.33,35,44 In recurrent disease, the choice of treatment becomes a matter of debate. Many investigators defend radiotherapy as an important part of the treatment for such patients,27,31,45,57,58 whereas others believe that chemotherapy should play a role in recurrent disease. However, the results obtained with this therapy have been disappointing.58,59 Treatment of in-transit metastasis In-transit disease is a common phenomenon in cutaneous melanoma, as well as in MCC patients.46,60 For selected patients with in-transit disease or for whom limb amputa- tion would be indicated, local control of the tumor and limb preservation have been achieved with the increased use of hyperthermic isolated limb perfusion with melphalan.60-64 Alternative treatment options, such as radiotherapy and chemotherapy, have been reported. For extensive but localized lesions, radiotherapy can be a good option. Mortier et al. treated nine cases of primary lesions that were not eligible for surgical treatment. After a median follow-up of three years, there was no recurrence.49 Selected cases with in-transit metastasis may be success- fully treated with isolated perfusion of chemotherapeutic agents as an alternative to radical surgery. We recently published a review of the literature on hyperthermic isolated limb perfusion in MCC, which covered a series of nine cases, including one case in which we performed the operation. Five patients were treated with melphalan alone, and four were treated with melphalan and TNF-a. All patients treated with melphalan alone had a complete response, whereas in the melphalan and TNF-a treatment groups there were two complete responses, one partial response, and one patient with no response.63 CONCLUSION The incidence of MCC is increasing due to the advancing age of the population, a higher incidence of damaging sun exposure, and an increase in the number of immunocom- promised individuals. Regarding its etiology of MCC, the recently described Merkel cell polyomavirus must be considered. While local or regional surgical treatment remains the standard of care, adjuvant radiotherapy or radiotherapy alone have been shown to be reasonable therapeutic options. REFERENCES 1. Toker C. Trabecular carcinoma of the skin. Arch Dermatol. 1972;105:107- 10, doi: 10.1001/archderm.105.1.107. 2. Haag ML, Glass LF, Fenske NA. Merkel cell carcinoma. Diagnosis and treatment. Dermatol Surg. 1995;21:669-83. 3. Eng TY, Boersma MG, Fuller CD, Goytia V, Jones WE, 3rd, Joyner M, et al. A comprehensive review of the treatment of Merkel cell carcinoma. Am J Clin Oncol. 2007;30:624-36, doi: 10.1097/COC.0b013e318142c882. 4. Agelli M, Clegg LX. Epidemiology of primary Merkel cell carcinoma in the United States. J Am Acad Dermatol. 2003;49:832-41, doi: 10.1016/ S0190-9622(03)02108-X. 5. Hodgson NC. Merkel cell carcinoma: changing incidence trends. J Surg Oncol. 2005;89:1-4, doi: 10.1002/jso.20167. 6. 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