Overview of the 2022 WHO Classification of Pituitary Adenomas/Pituitary Neuroendocrine Tumors: Clinical Practices, Controversies, and Perspectives

Abstract

The latest edition of the WHO classification of the central nervous system was published in 2021. This review summarizes the major revisions to the classification of anterior pituitary tumors. The most important revision involves preferring the terminology of pituitary neuroendocrine tumor (PitNET), even though the terminology of pituitary adenoma (PA) still can be used according to this WHO classification compared to the previous one. Moreover, immunohistochemistry (IHC) examination of pituitary-specific transcription factors (TFs), including PIT1, TPIT, SF-1, GATA2/3, and ERα, is endorsed to determine the tumor cell lineage and to facilitate the classification of PitNET/PA subgroups. However, TF-negative IHC staining indicates PitNET/PA with no distinct cell lineages, which includes unclassified plurihormonal (PH) tumors and null cell (NC) tumors in this edition. The new WHO classification of PitNET/PA has incorporated tremendous advances in the understanding of the cytogenesis and pathogenesis of pituitary tumors. However, due to the shortcomings of the technology used in the diagnosis of PitNET/PA and the limited understanding of the tumorigenesis of PitNET/PA, the application of this new classification system in practice should be further evaluated and validated. Besides providing information for deciding the follow-up plans and adjunctive treatment after surgery, this classification system offers no additional help for neurosurgeons in clinical practice, especially in determining the treatment strategies. Therefore, it is necessary for neurosurgeons to establish a comprehensive pituitary classification system for PitNET/PA that incorporates neuroimaging grading data or direct observation of invasiveness during operation or the predictor of prognosis, as well as pathological diagnosis, thereby distinguishing the invasiveness of the tumor and facilitating neurosurgeons to decide on the treatment strategies and follow-up plans as well as adjunctive treatment after surgery.

Keywords: PitNET; WHO pathological classification; pituitary adenoma; tumor classification.