Methods in neuroendocrine histopathology, a methodological overview

Light microscopy is still the main tool in diagnostic histopathology, though it does not always lead to a definitive diagnosis. It has therefore been a constant ambition to develop methods which can add further information to the diagnosis. In endocrine pathology, a major problem has been to distinguish between neuroendocrine and non-neuroendocrine tumours. The silver stains, such as the Bodian, Grimelius and Sevier-Munger methods, were the first useful "general neuroendocrine" markers. Electron microscopy can also be useful for identifying neuroendocrine tumours. A further step forward was the introduction of histochemical fluorescence methods, as these could identify biogenic amines. With the introduction of immunohistochemical techniques, tumours could be characterized in a more specific way regarding peptide hormones and biogenic amines content, proliferation factors, hormone receptors, etc. Another method, DNA cytometry, has been used mainly in predicting the prognosis. In situ hybridization can be a useful complement to the histopathological diagnosis when other methods have failed to demonstrate the neuroendocrine nature of the tumour. Some endocrine tumours, especially the well-differentiated ones, still cause diagnostic problems in predicting tumour behaviour, why further complementary methods would be of great value.