Gastrointestinal Carcinoid Tumours: Histogenetic, Histochemical, Immunohistochemical, Clinical and Therapeutic Aspects

Abstract

The increased knowledge of the pathobiology of gastrointestinal carcinoid (neuroendocrine) tumours and the improved therapeutic possibilities have brought a demand for more precise diagnosis. Although the carcinoid 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 carcinoid tumours of the gastrointestinal tract. Mid-gut carcinoids, which predominate among these tumours almost unexceptionally contain serotonin. This biogenic amine can be demonstrated by the argentaffin reaction of Masson, serotonin immunoreactively or by formalin-induced fluorescence. The characteristic staining pattern of mid-gut carcinoids is almost invariably preserved in the metastatic deposits and consequently the staining methods for identifying serotonin can also be used on metastases to reveal a primary mid-gut carcinoid. The enterochromaffin-like (ECL) cell carcinoids of the body and fundic area of the stomach often seen in association with pernicious anaemia are argyrophil with the Sevier-Munger silver stain. Other neuroendocrine tumours, viz. antral, duodenal and rectal carcinoids should be studied by a battery of relevant peptide hormone antisera for adequate diagnosis. During the last decade new peptide hormones have been found in circulation in patients with carcinoid tumours, but serotonin and urinary 5-HIAA are still the most important markers for carcinoids of the mid-gut origin. Other clinically useful tumour markers are chromogranin A + B, pancreatic polypeptide, human chorionic gonadotropin alpha and beta subunits. For localizing procedures, angiography is the most reliable investigative method for primary tumours in the gut, whereas CT-scan and ultrasound investigations are good for detection of liver metastases. During the last five years, the therapy for malignant carcinoid tumours has been considerably improved. Chemotherapy has only revealed objective response rates in about 10-30% of the patients giving median survivals from start of therapy of about 10 months. Recently treatment with alpha interferons and the new somatostatin analogue octreotide have given objective responses in 50-75% of patients with malignant mid-gut carcinoid tumours. These patients have now a median survival from start of therapy of 70 months when treated with alpha interferons. In the future new therapies will come into use such as monoclonal antibodies and perhaps also agents blocking different growth factors.