Diagnostic pathology of gastrointestinal and pancreatic neuroendocrine tumours.

The increased knowledge of the pathobiology of gastrointestinal and pancreatic neuroendocrine tumours and the improved therapeutic possibilities have brought a demand for more precise diagnosis. Although the neuroendocrine tumours can often be tentatively recognized in routinely processed microscopic slides, their more accurate identification requires additional diagnostic procedures. General neuroendocrine markers, such as the argyrophil reaction of Grimelius and immunohistochemistry with application of antibodies against chromogranin A and of neuron-specific enolase are discriminatory staining methods which are used to reveal the neuroendocrine origin of almost all highly differentiated neuroendocrine tumours of the gastrointestinal tract (carcinoids) and pancreas (insulomas). Midgut carcinoids, which predominate among these tumours almost unexceptionally contain serotonin. This biogenic amine can be demonstrated by the argentaffin reaction of Masson, serotonin immunoreactivity or by formalin-induced fluorescence. The characteristic staining pattern of midgut carcinoids is almost invariably preserved in the metastases and can thus be used to reveal a primary midgut carcinoid. The enterochromaffin-like (ECL) cell carcinoids of the body and fundic area of the stomach are argyrophil with Sevier-Munger silver stain. Other neuroendocrine tumours, viz, antral, duodenal and rectal carcinoids and insulomas, should be studied by a battery of relevant peptide hormone antisera for adequate diagnosis. About 50% of all insulin-producing insulomas are endowed with stromal amyloid deposits, which chemically are composed of a peptide designated islet amyloid polypeptide. This molecule has been observed by electron microscopical immunocytochemistry to occur exclusively in the beta-cells and is co-stored with insulin in the beta-cell granules.