== Microscopically, the Merkel cell carcinoma is usually characterized by intradermal proliferation of clusters of small cells (a, b) that are noticeable by keratin 20 (c, d), epithelial membrane antigen (e), the neuroendocrine markers (f-i), CD99 (j), and bcl-2 (k) (Chr=chromogranin; EMA=epithelial membrane antigen; NSE=neuron specific enolase; Syn=synaptophysin) == Table 1 . having finely dispersed chromatin and well-defined nucleoli. Immunohistochemically, the tumor cells displayed positivity for keratin 20 and neuroendocrine markers, being bad for keratin 7 and S100 protein. Maspin immunoreactivity was seen in cases 1 and three or more. Not one of the cases expressed DOG-1 or even TTF-1. Furthermore, this is actually the first report in books about maspin positivity in MCC that might be related to sun exposure. Keywords: Skin, Merkel cell carcinoma, Neuroendocrine, Maspin, DOG-1, TTF-1, bcl-2 == Background == Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine tumor firstly explained by Toker Cyril in 1972 as trabecular carcinoma of sweat glands Nazartinib mesylate [1]. It primarily occurs on sun-exposed skin, especially in the head and neck area, followed by the extremities and trunk [2]. MCC Il17a is recognized as a rare but highly malignant tumor, becoming 40 occasions less common than malignant melanoma, with a 3-year mortality rate of 30 % and 27-61. five % at 5-years, respectively, which is much lower compared to melanomas [25]. In a review published in June 2001, it was pointed out that only 836 cases of MCC have been reported in literature [6]. However , the incidence of MCC is significantly increasing, coming from 0. 15 cases per 100, 000 in 1986 to 0. 44 in 2001 and to 0. 6 cases per 100, 000 in 2010 [7, 8]. The estimated total annual percentage of change is about 8 % [7], with a tripling in the price every 15 years [3]. MCC incidence in whites is usually 8 occasions higher than in blacks and almost double the incidence in other ethnic organizations. MCC commonly affects men in all ethnic groups; the male: female percentage being about 1 . 52: 1 [4, 9]. In the 9thperiod of age, the incidence raises till 4. 28 cases per 100, 000 [7]. In contrast to healthy people, the overall risk of MCC raises 523. 8 times after solid organ transplantation [10] and 11 times in patients with AIDS, respectively [11]. However , even in the large diagnostic centers, only 35 cases of MCCs per year are diagnosed, and most of those cases are published because case reviews. Early diagnosis is important, a routine skin screening becoming recently proposed for non-melanoma skin cancers [12]. Although ultraviolet radiation, immunosuppression, and Merkel cell polyomavirus (MCV) contamination are considered the main factors responsible for Nazartinib mesylate carcinogenesis of MCC [5, 13], the molecular mechanism is usually poorly comprehended, and the neuroendocrine arhitecture makes the differential diagnosis very difficult. In this paper, we report the pathologic findings, criteria to get differential diagnosis, and the particularities of Nazartinib mesylate the immunoprofile of MCCs, based on three cases and a comprehensive books review. A hypothesis about the possible role of maspin in carcinogenesis of MCC was also postulated first time in literature. The disease stage was evaluated based on the 2010 AJCC TNM classification [14]. In all of the cases, a signed informed consent of the individuals was obtained for carrying out surgery and publication from the case-related data. == Case presentation == Nazartinib mesylate To select the cases, a database of 3, 410 consecutive cutaneous tumors was evaluated. From these, 1, 196 were malignant tumors, and the other 2, 214 becoming benign tumors or pseudotumors. Only three or more out of 1, 196 cutaneous malignant tumors were diagnosed as MCCs (0. 25 %). == Case 1 == A 67-year-old previously healthy white male was hospitalized with a slowly growing 17178 mm nodular ulcerated tumor located Nazartinib mesylate on the frontal region that was surgically removed, with totally free resection margins. Microscopically, the tumor consisted of nests of small round cells with scanty cytoplasm and round-oval nuclei with finely dispersed chromatin and well defined nucleoli (Fig. 1). Nuclear pleomorphism was moderate with a high mitotic rate (> 10/10 HPF). The tumor cells infiltrated the whole dermis and subcutaneous adipose cells, and the maximum thickness was of 8 mm. Based on the tumor size, histological aspect, immunoprofile (Table1), and absence of lymph node metastases,.