Five-year Survival (%)* 79 60 58 49 47 45 30 18 CLINICS 2011;66(10):1817-1823 Table 2 - Staging System. Stage 0 IA IB IIA IIB IIC IIIA IIIB IV * (Lemos). Tis T1 T1 T2/T3 T2/T3 T4 Any T Any T Any T N0 pN0 cN0 pN0 cN0 N0 N1a N1b/N2 Any N M0 M0 M0 M0 M0 M0 M0 M0 M1 characterized by distant metastasis. Later, stage I disease was classified as IA (#2 cm) or IB (.2 cm) based on publications by Yiengpruksawan and Allen.25,27,28 However, that study was not able to show any statistical differences in the prognosis between tumor size groups. In a study of 251 patients, Allen et al. showed that the proposed stage system with the division of IA and IB resulted in a different prognosis; thus, they used a four-stage system defined as follows: Stage I T (tumor size) ,2 cm, Stage II T $2 cm with no evidence of regional or distant disease, Stage III with positive lymph nodes in the drainage basin, and Stage IV with distant metastasis. After a forty-month average follow- up, the survival rates were 81% for Stage I, 67% for Stage II, 52% for Stage III, and 11% for Stage IV.29 Pitale et al. did not observe any influence of the tumor size on the prognosis of 306 patients, but their meta-analysis was a summary of the literature and did not represent data from a single institu- tion.30 Lemos et al. evaluated 2,856 patients and were able to analyze the impact of tumor size with 1-cm increments. They found that the most important difference was between #2 cm and more than 2 cm (five-year survival rate of 66% vs. 51%, respectively; p,0.0001). Interestingly, tumors that are ,1 cm are associated with only minimal improvement in survival when compared with those that are 1 to 2 cm in diameter (69% vs. 61%, respectively).12 Nodal disease is an important negative prognostic factor for this type of tumor. Clinical versus pathological staging seems to be important in prognosis and treatment; patients with a clinically enlarged node had a worse prognosis than those whose nodes were evaluated histopathologically by sentinel lymph node biopsy, fine needle aspiration or elective lymphadenectomy.12 Even in the tumor (T) cate- gory, the authors categorized the tumors as pathologically negative or clinically negative nodes, with different prog- noses (Tables 1 and 2). It is noteworthy that approximately 50 to 70% of all patients will develop lymph node metastases, and of these patients, 33 to 70% will develop distant disease.1,2,30-35 The most frequent sites of metastasis are liver (13%), bone (10-15%), lung (10-23%), brain (18%), distant skin (9-30%) and distant lymph nodes (9%).29,36-38 In the largest patient cohort of patients from the American National Cancer Database, Lemos et al. evaluated the mortality of each clinical presentation and adjusted for age. For the overall population, the 5-year survival was 54%; for those with local, nodal and distant disease at presenta- tion, these values were 64, 39, and 18%, respectively.12 The Seventh Edition of AJCC39 integrates Lemos et al.’s findings, as summarized in Table 2 (excluded Tx and T0). 1819 Epidemiology and treatment of Merkel cell carcinoma Duprat JP et al. It was possible, with a greater cohort of patients, to show that in the nodal-negative group clinically evaluated, relative survival was worse when compared to pathologyi- cal proof, such as sentinel, fine-needle or elective lymph node biopsy (HR 1.80, 95% confidence interval 1.4-2.4, p,0.0001). For the positive nodal group, the survival was worse when a node was clinically detected (HR 1.48, 95% confidence interval 1.1-1.9, p = 0.004).12 Treatment Due to its rare incidence, there is currently a lack of standard therapeutic procedures ascribed for the treatment of MCC, especially when the disease is locally advanced. Surgical excision and radiotherapy remain the mainstays of therapy in the initial stages.2,10,25,27,31,32 Primary Lesion Following a confirmatory biopsy of a suspected lesion that confirms the diagnosis, surgery is the usual treatment choice.2,10,27,31,32,36 Depending on the physician’s and patient’s preference, a wide local excision made deep into the muscle fascia or Mohs micrographic surgery can be performed. Both are successful in achieving tumor-free margins and an acceptable level of disease-free survival. Of note, at our institution, the wide margin resection was preferred. If Mohs micrographic surgery (MMC) is per- formed, adjuvant radiotherapy seems to be essential. In support of this, Boyer et al. conducted a study among patients who underwent Mohs surgery. Twenty patients had radiotherapy as adjuvant treatment, and 25 did not receive any adjuvant radiotherapy. In the adjuvant radio- therapy group, there was no recurrence, but in the Mohs surgery-only group, recurrence was detected in four cases. Given the small study numbers, this difference was not statistically significant.40 Since adjuvant radiotherapy is typically performed regardless of a tumor’s margins, it is not reasonable to compare wide local excision and MMC. Wide local excision for MCC is often performed as it is performed for melanoma, with 2 cm margins, if feasible. Unfortunately, there are no prospective studies on the ideal margin. Allen et al., in a study of 251 patients from a single institution, found that obtaining a surgical margin of more than 1 cm was not associated with decreased local recur- rence (,1 cm 9% vs. $1 cm 10%, p = 0.8). Local recurrence occurred in 18% of patients with positive margins; if the margins were negative, recurrence occurred in 8%, and this difference was not statistically significant (p = 0.31). In addition, in their study, the use of radiotherapy as opposed to surgery did not decrease the local recurrence rate (radiotherapy 10% vs. no radiotherapy 8%, p = 0.76). Unfortunately, this was not a randomized study, so patients with tumors $2 cm received additional adjuvant radio- therapy (,2 cm 10% vs. $2 cm 23%, p = 0.02). It is also worth noting that radiotherapy was given only to 12% of patients, who generally represented the most severe cases; this could have influenced the outcome in patients with positive margins who received adjuvant treatment.29 Jabbour et al.41 reinforced previous evidence that, if adjuvant radiotherapy is associated, the margin does not interfere with recurrence or survival. Thus, those authors emphasized the benefit of adjuvant radiotherapy adminis- tered either locally or regionally. There are some authors who advocate the use of adjuvant radiotherapy based on histological features, such as thickness