Divergent differentiation in endocrine and nonendocrine tumors of the skin

In the skin, endocrine tumors showing areas with nonendocrine features and nonendocrine tumors showing endocrine differentiation are present. (1) Neuroendocrine carcinomas with nonendocrine differentiation: Merkel cell carcinoma (MCC) of the skin has been frequently described in association with squamous cells carcinoma (SCC) which can arise separately (as synchronous or metachronous lesions) from MCC as well as closely intermixed. In the first event the possibility that the lesions are sustained by same causative factors (among which sun exposure is the most probable) is suggested. In cases of lesions closely intermixed the possibility of an origin from a common precursor is suggested. Furthermore, cases of MCC have been described to contain glandular, melanocytic, striated muscle, and lymphoepithelioma-like features. These latter findings further support the hypothesis of tumors showing divergent differentiations. (2) Nonendocrine tumors showing endocrine differentiation: Basal cell carcinoma (BCC) was the first cutaneous nonendocrine tumor described to contain neuroendocrine granules. Presence of endocrine features were subsequently confirmed with immunohistochemical studies. Endocrine features were then described in sweat gland apocrine and eccrine carcinomas. Endocrine elements present in BCC and in sweat gland carcinomas do not show morphological and immunohistochemical features of Merkel cells. Thus the possibility that these tumors develop an immature Merkel cell or a new type of endocrine cell of the skin is suggested. Tumors with follicular differentiation such as trichoblastomas and trichofolliculomas contain a high number of Merkel cells. As Merkel cells are numerous in hair follicles of human fetal skin, the possibility that these tumors recapitulate the human skin embryogenesis is suggested.