Over 400 cases of neuroendocrine (Merkel cell) carcinoma of the skin (NCS) have been reported. This tumor continues to pose problems in diagnosis and effective treatment for physicians unfamiliar with its biological characteristics. Reported here are five additional cases of NCS and the literature for this rare neoplasm is comprehensively reviewed. An early and accurate diagnosis is made possible by combining clinical presentation with results of histologic study, immunoperoxidase staining for neuron-specific enolase (NSE), epithelial membrane antigen (EMA), cytokeratins, and electron microscopy. NCS is an aggressive tumor. Depending on the length of follow-up, up to 40% of tumors locally recur, 55% develop regional nodal metastases, and 36% undergo distant metastasis. Survival is sex, but not age, dependent, with an overall 2-year survival rate of 72% (males 58% vs. females 79%). No standard procedure for initial and/or follow-up treatment for NCS exists. The authors recommend that NCS be treated, whenever possible, using the same rationale as applied for the treatment of squamous cell carcinoma of the skin.

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The myenteric plexus consists of several subpopulations of morphologically and chemically distinct neurons known to contain a variety of peptides and amines, one of which is serotonin (5-hydroxytryptamine). These neurons are considered essential for nerve-to-nerve transmission. In the present study, we investigated the effect of 5,6- and 5,7-dihydroxytryptamine (5,6-DHT; 5,7-DHT), indoleamine neurotoxins that selectively and irreversibly injure the serotonergic neurons of the myenteric plexus. Treatment with 5,6-, or 5,7-DHT caused marked disruption of the activity front of the migrating myoelectric complex (MMC), increased its duration, and decreased its propagation velocity. At higher doses, 5,7-DHT also reduced the slow-wave frequency. Immunohistochemical techniques showed that tissue from rats treated with 5,7-DHT was depleted of serotonin-like immunoreactivity within the myenteric plexus neurons. Reserpine also caused motility and immunohistochemical changes similar to those induced by the two neurotoxins. Therefore, destruction of enteric serotonergic neurons disrupts the MMC. These studies support the cellular concepts that serotonergic neurons function as interneurons in the myenteric plexus, modulating and processing the neural stimuli, and that serotonin is an important neurotransmitter in the small intestine.