Innovations and controversies in the WHO classification of pituitary adenomas

Abstract

The 2004 edition of the World Heath Organization (WHO) entitled ‘‘Pathology and genetics tumors of endocrine organs,’’ presents a step forward in the classification of pituitary tumors. This classification is mainly based on immunohistochemistry, which has become the gold standard of modern diagnostic approach; electron microscopy remains an important tool in difficult cases. Immunohistochemistry can accurately identify the full spectrum of pituitary hormones produced by adenoma cells, enable more defined configuration of cell morphology and reveal several structural elements and cytoskeleton components, such as cytokeratin filaments and mitochondria. Recognition of these elements, which could previously only be identified by electron microscopy, and application to the current diagnostic approach has facilitated the classification of pituitary adenomas. Immunohistochemistry for b -a nda-subunits of glycoprotein hormones discloses the polar shape of adenoma cells and their attenuated cytoplasmic process, distinct morphological features of ‘‘glycoprotein differentiation’’ of TSH and gonadotroph adenomas [7] (Fig. 1). Antibodies against low molecular weight keratins, particularly keratin 8 reveal fibrous bodies that might be difficult to identify on hematoxylin and eosin sections alone [8]. These structures that are composed of cytokeratin filaments represent a diagnostic key feature, mostly for the sparsely granulated variant of somatotroph adenomas (Fig. 2). In contrast, keratin 8 shows diffuse cytoplasmic distribution in densely granulated somatotroph adenomas. Fibrous bodies in association with mitochondrial gigantism and misplaced exocytosis represent a diagnostic hallmark of the rare type of acidophil stem cell adenoma, whereas small fibrous bodies are also present in mammosomatotroph adeno