[Molecular characterization of cutaneous neuroendocrine (Merkel cell) carcinoma. Review of the literature and presentation of a caseload].

Molecular characterization of neuroendocrine (Merkel cell) carcinoma of the skin. Review of the literature and report of three cases. Although neuroendocrine carcinoma of the skin (NECS) is comparatively a rare clinical-histological entity, numerous morphological and ultrastructural studies have been carried out since the tumor was identificated by Toker (1972). Recently immunocytochemistry has allowed a better molecular characterization (immunophenotype) of this tumor and a more exact diagnosis. The main problem for the pathologist is the differential diagnosis between NECS and skin neoplasms--both primitive and metastatic--which require a more aggressive treatment. Often the classical morphological criteria do not distinguish NECS from non-Hodgkin's lymphoma, amelanotic melanomas, cutaneous metastases of lung small cell carcinoma or of neuroblastoma. The co-expression of cytokeratins and neurofilaments constantly found in NECS, is surely the best differential criterion from non-neuroendocrine carcinomas. Furthermore, the typical paranuclear location of both the intermediate filaments in NECS is a distinctive peculiarity as opposed to lung microcytoma, where cytokeratins and neurofilaments, when present, show widespread perinuclear positivity. Chromogranin A is found only in a small percentage of tumor cells, whilst synthesis of calcitonin, somatostatin, gastrin, ACTH, is very rare. Finally, the lack of common leukocyte antigen (CLA), S-100 protein and vimentin in NECS rules out the diagnoses of lymphoma, melanoma and sarcoma respectively.