Divergent differentiation in neuroendocrine tumors of the adrenal gland.

Composite tumors of the adrenal medulla usually consist of pheochromocytoma admixed with ganglioneuroma or ganglioneuroblastoma. These neoplasms reflect phenotypic plasticity shown by primitive sympathetic cells and mature chromaffin cells in vitro. They may give rise to metastatic neuroblastoma in adults and may cause signs and symptoms attributable to both catecholamine and neuropeptide production. Schwann cells and sustentacular cells are typically numerous in these tumors but it is not known whether they are neoplastic. Immunohistochemical staining for catecholamine biosynthetic enzymes, secretory vesicle proteins and S-100 protein tends to recapitulate staining of the normal adrenal medulla or sympathetic ganglia. Sparsity of chromogranin A in the cell bodies of immature and mature neurons is a diagnostically useful characteristic.