Classical pathomorphology (as presented in the preceding chapters) relies on a basic principle: the nucleus reveals whether a cell is benign or malignant, whereas the cytoplasm and the cells architectural arrangements hold the clues to the cell's origin and the direction of its differentiation. However, even the combined power of pattern recognition and individual cell morphology may fall short of achieving these goals. Nuclear changes indicative of malignancy may be obvious in one case, but missing in another. Some malignant cells, for example those of mesothelioma, have deceptively bland nuclei and are best recognized by a combination of their associated clinical data, morphological phenotype, and immunoprofile. Poorly differentiated neoplasms may offer no phenotypical clue as to the cell type involved.
Ancillary studies may assist further in elevating the precise nature of the lesion in such cases. These have evolved over the past 50 years and now include molecular analyses. The exact identification of cell populations in cytological specimens can be accomplished through: (1) special stains, with various reagents used in histochemical methods; and (2) immunological reactions, with a variety of antibodies that detect diagnostically helpful antigens either by immunofluorescence (IF) or immunohistochemistry (IHC). By far, IHC is the most widely used ancillary technique in the practice of pathology. Its main advantage derives from the limitation of IF, since IF does not permit the simultaneous visualization of a positive reaction and the morphological features of the sample under study. With IF, the reaction may fade over time, requiring image documentation.
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