Neuroendocrine cells in non-endocrine tumors: what does it mean?

In many human neoplasms histochemical techniques will demonstrate the presence of neuroendocrine cells. Their occurrence also in metastases indicates clearly that they form an integral part of the tumor cell population. As to their origin, for most tissues in which neuroendocrine cells normally occur, such as the digestive tract, the currently held view is that one stem cell population provides a repertoire of differentiation corresponding to all cell types which normally occur in that epithelium. Transformation of such a stem cell will give rise to a tumor stem cell in which the same repertoire of differentiation, including neuroendocrine cells, can be found. The tumor neuroendocrine cells usually express neurohormonal peptides corresponding to their normal counterparts. These cells almost never lead to clinically manifest overproduction of neurohormonal peptides. In other tissues, such as the normal ovary, neuroendocrine cells do not occur and yet in tumors, e.g. ovarian mucinous cystadenomas and cystadenocarcinomas, they can be found. In the epithelial components of ovarian and testicular teratomas neuro-endocrine cells have also been detected. In spite of the biological interest of this phenomenon its clinical significance remains an open question. Several investigators have found that colorectal cancers with neuroendocrine differentiation behave more aggressively than tumors without these cells. Others dispute these observations. In the breast and in the prostate neuroendocrine differentiation has been very extensively investigated and there seems to be a reasonable consensus that their presence is associated with poorer prognosis.