Neuroendocrine Carcinomas with Multiple Immunoreactive Peptides and Melanin Production

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Abstract
Two primary neuroendocrine skin carcinomas, one bronchial carcinoma, and one typical medullary thyroid carcinoma have been shown by immunohistochemistry and electron microscopy to contain two or more immunoreactive peptides as well as melanosomes and premelanosomes. Of the battery of antisera tested, somatostatin was the only material present in all four tumors; calcitonin and ACTH were present in three of the four neoplasms. Neurosecretory granules on the one hand and melanosomes on the other were more readily identifiable in separate cells. However, in at least 2 cases, individual cells were thought to contain both types of structures. Of the various explanations possible, we choose to interpret these tumors as complex neuroendocrine carcinomas comprising cellular populations capable of synchronous production of immunoreactive peptides and melanin. Since melanocytes are members of the dispersed neuroendocrine (APUD) system, these observations may not appear entirely surprising. Noteworthy, however, is that melanin synthesis seemingly remains a synchronously available option to neoplastic neuroendocrine cell populations of possibly diverse histogenesis that are actively engaged in the production of multiple hormonal peptides. We consider that these phenomena represent yet another facet of neoplastic multidirectional differentiation. It is possible that the determination of immunoreactive peptides as “markers” may play a future role in the diagnosis, therapy, and prognosis of these and similar tumors and in the study of the dysplasias that may precede them.