Neuroendocrine neoplasms in unusual primary sites.

Primary neoplasms arising in the liver (3 cases), skin (3 cases) and larynx (2 cases) were studied with a combination of light microscopy, immunohistochemical and electron microscopic techniques. Clinically, only one case exhibited a hormonal syndrome (Zollinger-Ellison) while another had elevated levels of calcitonin in the serum. By light microscopy only one tumour appeared characteristically neuroendocrine ('carcinoid'). The other cases showed variable patterns of small to intermediate size cell carcinomas at times admixed with exocrine appearing areas. Immunoperoxidase studies showed reactivity for various peptides including gastrin, calcitonin, somatostatin and ACTH. Several tumours were positive for more than one peptide. Electron microscopy revealed variable populations of neurosecretory type granules either in the main cytoplasmic mass or in cytoplasmic processes. We conclude that some 'undifferentiated' neoplasms from the aforementioned sites may prove to have neuroendocrine differentiation if the proper techniques are applied to their study. Clinical hormonal syndromes appear to be rare in these tumours;s however, determination of various amine and/or peptide materials, or possibly their metabolites, may be valid aids for their recognition and monitoring. The structural patterns of these tumours are very variable and may include cells with squamous features as well as exocrine differentiation with occasionally prominent production of mucosubstances.