Classic and recent special stains used in differential diagnosis of endocrine tumors

During the twentieth century, stains for endocrine cells and tumors were developed from empiric cytologic procedures aimed at modern cytochemical methods. Before the 1970s, endocrine stains were mainly based on silver reaction, although other reactions were also proposed; however, the chemical basis of most of these reactions is still unclear. The development of fluorescence procedures for detecting biogenic amines at the cellular level provided information about endocrine cell function of normal cells and related tumors. However, the application of immunocytochemical reactions brought greater and more definitive insights. Several immunocytochemical markers are now available. Some are specific for a definite cell type, while others detect endocrine differentiation in general. Some of these "pan-endocrine" markers are highly specific, and others are highly sensitive but less specific. They all play a definite role in diagnostic pathology. The use of molecular procedures to detect specific mRNA or genetic mutations of diagnostic interest in endocrine pathology should complement immunophenotyping, especially in some problematic fields, such as that of "poorly differentiated" tumors.