Clinical Integration and Application of the 2022 WHO Pituitary Tumor Classification

Abstract

The pituitary is a complex endocrine organ that gives rise to adenohypophysial epithelial neuroendocrine tumors, to hypothalamic neuroendocrine neuronal neoplasms, to non-endocrine glial-related pituicytomas and to Rathke’s pouch-derived craniopharyngiomas and pituitary blastomas. The past 30 years have seen significant advances in the classification of these tumors based on cell lineages, molecular alterations and biomarker features that distinguish tumor types and their subtypes. Adenohypophysial cells give rise to pituitary neuroendocrine tumors (PitNETs) that usually follow one of three cell differentiation pathways. Pituicytomas have multiple morphologic variants and hypothalamic neuronal tumors can be gangliocytomas composed of magnocellular neurons or neurocytomas composed of small neurocytes. Craniopharyngiomas have two distinct families, papillary and adamantinomatous, with different alterations in signaling pathways. Pituitary blastomas are primitive tumors composed of an admixture of immature elements of Rathke’s pouch with immature but differentiated hormone-secreting adenohypophysial cells. These various tumors are associated with specific clinical manifestations, creating a complex clinico-radiologic-pathologic classification that has both important clinical distinctions but also predictive therapeutic value. Syndromic disease has allowed the identification of genes that may be implicated in the development of these tumors, but the majority are sporadic tumors that, with a few exceptions, have no recurrent genetic alterations. The structure-function correlations that have been elucidated are critical to allow subclassification of clinical disorders that will pave the way for further advances in understanding genetic predisposition and environmental factors that alter epigenetic profiles of pituitary cells.