An ultrastructural cytochemical stain specific for neuroendocrine neoplasms

Previous work from our laboratory has indicated that the uranaffin reaction, when run under specific conditions, will stain neurosecretory granules. In this ultrastructural cytochemical study, we analyzed the granule-staining properties of 13 normal, 10 abnormal (non-neoplastic), and 138 neoplastic tissues in an attempt to evaluate the specificity of the uranaffin reaction for diagnostic purposes when compared with routinely processed specimens. For the uranaffin reaction, previously fixed tissue stored in buffer was rinsed with 0.9% NaCl and reacted with a 4% aqueous solution of uranyl acetate (pH 3.9) for 48 hours. After three NaCl rinses, the tissue was dehydrated and processed for electron microscopy. The granules of normal or non-neoplastic neuroendocrine cells that stained positively with the uranaffin reaction included pancreatic islet cells, thyroid C cells, adrenal medullary cells, parathyroid chief cells, and the neuroendocrine cells of the intestine. All 42 neuroendocrine neoplasms studied possessed abundant uranaffin-positive granules and included carcinoids, oat cell carcinomas, islet cell neoplasms, medullary carcinomas of the thyroid, pheochromocytomas, carotid body paragangliomas, a pituitary adenoma, Merkel cell carcinomas, parathyroid adenomas, and a neuroblastoma. All 96 control neoplasms that were not classified as neuroendocrine in nature were negative for neurosecretory granules when studied with the uranaffin reaction and included 13 neoplasms derived from endocrine glands, 57 neoplasms from secretory epithelium, 10 of hematopoietic origin, and 16 miscellaneous neoplasms. It was determined that the uranaffin reaction is a useful ultrastructural cytochemical marker for neuroendocrine granules and helped distinguish these cytoplasmic organelles from ultrastructurally similar granules derived from non-neuroendocrine cells.