Merkel cell carcinoma

Merkel cell carcinoma (MCC, cutaneous neuroendocrine carcinoma) is a rare form of tumor of unclear histogenesis which predominantly occurs in elderly patients on areas exposed to the sun. A higher incidence and occurrence in younger people is predominantly found in immunosuppressed persons which is why a pathogenetic role is also attributed to immunosuppression in addition to ultraviolet (UV) radiation. Additionally, in 80% of cases clonally integrated polyomavirus (Merkel cell polyomavirus, MCPyV) could be detected. Clinically MCC represents an uncharacteristic tumor. Histopathologically, monomorphic dermal and/or subcutaneous nodes are found consisting of round or oval medium sized cells with a vesicular nucleus and sparse cytoplasm. The neoplastic cells of MCC express cytokeratin (CK) 20 with a dot-like perinuclear accentuation. In addition, pan-CK, neuroendocrine markers (e.g. chromogranin A and synaptophysin), neurofilament proteins, CD56, CD57, Bcl-2, TdT and PAX-5 are immunohistochemically positive. In most cases CM2B4, an antibody against MCPyV is also positive. Expression of p63 has been observed in some of the cases and in some studies was associated with a favorable prognosis. The markers thyroid transcription factor 1, mammalian achaete scute complex like 1, vimentin, S-100 and CK7 are not normally expressed by MCC. The prognosis is primarily dependent on tumor size and the lymph node status. The presence of intralymphatic tumor complexes is associated with a higher rate of local recurrence and lymph node metastasis. A larger number of intratumoral cytotoxic T-lymphocytes is accompanied by a favorable prognosis and the presence of > 50 % of K-67+ neoplastic cells with an unfavorable prognosis. Further morphological, phenotypical and genetic factors have not yet been validated in larger cohorts with respect to the prognostic relevance.