Primary Neuroendocrine Carcinomas of the Skin (Merkel Cell Tumors): A Clinical, Histologic, and Ultrastructural Study of Thirteen Cases

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Abstract
Neuroendocrine carcinomas of the skin have recently been recognized, and clinicopathologic information on these tumors is accumulating rapidly. We studied 13 such lesions by light and electron microscopy, and eight were subjected to immunohistochemical analysis. The ages of the patients (five women and eight men) ranged from 24 to 84 years. Nine patients had neoplasms occurring in sun-exposed areas; one patient had metachronous symmetric lesions on the arms, and another had antecedent hypohidrotic ectodermal dysplasia. Eight tumors metastasized, and six spread to regional or distant lymph nodes. Three patients died with visceral metastases to the liver, bones, and brain. All patients had their primary tumor confined to the corium and subcutaneous tissue without involvement of overlying epidermis. Tumor cells were round and uniform in size, with delicate nuclear chromatin and a high mitotic rate. An organoid growth pattern was seen in all tumors, with focal trabeculation and rare rosette formation. Ultrastructurally, peripheral cytoplasmic dense-core granules were evident, and perinuclear filament whorls could be seen in all 13 tumors. The latter feature was stable, even in specimens taken from paraffin blocks for electron microscopy. Immunoperoxidase studies failed to reveal serotonin, calcitonin, or adrenocorticotrophin within tumor cells.