Tumour pathology of the neuron-paraneuron system and its evolutionary background, with special attention to neuro-endocrine differentiation in prostate and mammary carcinomas.

Abstract
From results of phylogenetical investigations of the neuron-paraneuron or neuroendocrine system it is known that cells producing hormonal peptides appear first in the nervous system, then also as disseminated cells of an open or closed type in the mucosa of the alimentary tract, and, lastly, as the parenchyma of the classical endocrine glands. In all these three parts of the neuroendocrine system the parenchymal cells can undergo neoplastic transformation, expressing "eutopic" and/or "ectopic" peptide hormones and/or biogenic amines. The neuro-paraneuronal tumours arising in the central or peripheral nervous system in man are rare. In contrast, they are more common when they originate from the disseminated neuroendocrine cells in the gut mucosa, and when they arise in the endocrine glands. Here, a broad spectrum of histopathologically benign or malignant neoplasms, hyperplastic nodules, and other tumour-like lesions occur, some of which are associated with well-known clinicopathological entities. Typical examples are the gastrointestinal carcinoids, pancreatic insulomas, pituitary adenomas, medullary thyroid carcinomas, and phaeochromocytomas. The fact that neoplastically transformed cells of some traditionally non-endocrine tumours, e.g., mammary and prostatic carcinomas, can undergo neuroendocrine differentiation has recently become well established. The "malignancy potential" of neuroendocrine carcinomas and that of the paraneuronally differentiated cells of prostatic and mammary carcinomas have both been studied by means of cytochemical DNA assessments of the nuclei of the tumour cells, applying a recently developed deparaffinisation-disintegration procedure using archival material. So far, it seems as if about 1/4 of common gut carcinoids show a DNA distribution pattern of the "aneuploid" type, whereas the other 3/4 are "euploid" i.e., show a "diploid" or "diploid/tetraploid" DNA distribution pattern. The cell nuclei in areas in prostatic and mammary carcinomas with high amounts of paraneuronally differentiated cells displayed to a greater extent "euploid" DNA patterns than those in areas of the same carcinomas without such paraneuronal cells. Thus, the "malignancy potential" of the neoplasms of neuro-paraneuronal cells seems to be rather low.