Primary neuroendocrine (Merkel cell) carcinoma of the skin: morphologic diversity and implications thereof

A significant proportion of primary neuroendocrine cell carcinomas of the skin (Merkel cell carcinomas [MCCs]) have been reported to occur in intimate association with malignant epithelial neoplasms, mainly squamous cell carcinomas. In addition, divergent differentiation within these tumors, particularly of squamous and eccrine types, is not infrequent. This expanded morphologic spectrum of MCC calls for evaluation of potential biologic implications of the phenotypic diversity and begs reconsideration of the histogenesis of the lesion. The current retrospective review of 29 cases of primary cutaneous neuroendocrine cell carcinoma aims to address these issues by integrating new information with that which is extant. Eleven tumors were associated with evolving or established cutaneous carcinomas: 2 actinic keratoses, 5 Bowen's disease, 3 superficial squamous cell carcinomas, and 1 basal cell carcinoma. Two combined squamous-neuroendocrine tumors occurred in recipients of solid organ transplants, and another developed in a Marjolin's ulcer at the site of a previous burn. Squamous and/or adnexal differentiation within the dermal component of the tumor was observed in 4 instances and was significantly associated with MCCs in intimate association with another cutaneous carcinoma. The outcome of the group as a whole is similar to that recorded in previous series of MCC, with local recurrence in 32% of cases and death caused by the neoplasm in 28%. Only 52% of the patients were alive with no history of metastasis at follow-up. No significant difference in outcome was observed between the patients with pure MCCs and those with MCCs in combination with another cutaneous carcinoma.