Merkel Cell Carcinoma is a challenging and rare cutaneous neoplasm, with an incidence of about 5 cases for 1 million population [4]. This carcinoma typically has immunophenotypic similarities to Merkel cells of the skin: they are localized in the basal layer of the skin, close to nervous terminals forming mechanoreceptors and they are epithelial derived cells. Nevertheless, MCC origin is unclear: lymphoid B-cell markers are noticed in several cases, while other authors proposed an origin by dermal mesenchymal stem cells. Merkel Cell Carcinoma generally occurs in elderly people, more frequently in male patients, with immunological system dysfunction due to cancer(s), HIV, HCV, other severe infections or immunosuppression posttransplantation [5]. Clinically this neoplasm has a cystic or nodular aspect, sometimes presenting as a bleeding lesion or a plaque. Tumor size ranges from 2 to 200 mm, but it is usually < 20 mm.

Histochemical aspects of this kind of tumor are CK-20 (low molecular weight cytokeratin), NSE (neuro specific enolase) and NFP (neurofilament protein) expression [6]. In 2008 Feng and coll. found a novel viral sequence in four Merkel cell carcinoma cases. These data led to a new targeted therapy of neoplasm. Indeed, the related Merkel cell carcinoma virus is a polyomavirus, defined MCPyV (Merkel Cell Carcinoma PolyomaVirus), and it especially encodes large T-antigens that bind to host protein, promoting viral and cellular replication by oncosuppressor gene p53 blockade. This polyomavirus is highly expressed (80% of MCC) in local and metastatic disease, consequently it represents an interesting target for novel biological therapy which can be useful in most severe cases [7].

At early stage, surgical excision is the primary treatment with sentinel lymph node biopsy (SLNB). Excision should be done with at least 1 cm margin in case of local disease. Tissue reconstruction depends on tumor size, tumor site and histological result; we can consider several options such as direct suture, local flap, microsurgery flap, dermal regeneration template followed by skin graft, NPWT. If a positive SLNB is obtained, a complete lymph node dissection (CLND) is required. MCC is also radiosensitive, consequently radiotherapy (RT) is a valid therapeutic tool, especially to treat locally advanced neoplasm and to reduce local recurrence. As concern as medical treatment, in case of metastatic disease, etoposide and carboplatin represent the most common chemotherapeutic agents. MCC is very sensitive to chemotherapy, but duration of response is un clear and tumors often recur within 4-15 months. Immunotherapy is the most recent and innovative treatment and its use can be also related to MCVyP [8]. These tumors exhibit viral peptides that can be destroyed by cellular immune responses. Several therapies are based on monoclonal antibodies targeting programmed cell death receptor 1 / programmed cell death ligand 1 (PD – 1 / PD – L1) interaction reveal promising results for metastatic MCC. The binding of PD - L1 to PD – 1 on cytotoxic T cells inhibits their tumor-killing activity. PD – L1 is frequently expressed on MCC tumor cells and peritumoral immune cells. Pembrolizumab is an anti PD-1 antibody approved for the treatment of melanoma and non - small cell lung cancer [9] and it was recently approved also for metastatic MCC treatment. Another therapeutic option can be a peptide receptor radionuclide therapy (PPRT): MCC expresses somatostatin receptors and then radiolabeled somatostatin analogue is taken up by tumor to be effective.

Our report can represent an interesting example of a rare neoplasm as a biomarker of immune system dysfunction. It is worthwhile to highlight that our patient has a clinical history characterized by four past tumors, all successfully treated.