Endocrine Abstracts

Background: In 2017, the World Health Organization (WHO) adjusted the histopathological classification of pituitary adenomas (PAs) by including pituitary cell lineage specific transcription factors (TFs), elucidating a continuous spectrum between true null cell (NCA), silent, clinically silent, and functioning adenomas. The definitions of non-functioning (silent) gonadotroph, corticotroph, somatolactotroph and thyrotroph adenomas were previously reserved for immunohistochemically hormone positive (IHC hormone+) PAs, but have been expanded to also include PAs with positive immunohistochemistry of the corresponding cell lineage specific TF (SF-1+, TPIT+ or Pit-1+) despite negative IHC of the anterior pituitary hormones (TF+/hormone- PAs). On the other hand, the definition of NCA has been narrowed to adenomas that are IHC negative both for anterior pituitary hormones and TFs. It is, however, not clear, if, and to what extent, the novel histopathological classification translates into differences in clinical behavior in clinically non-functioning pituitary adenomas.

Objectives: To systematically review potential cell lineage specific differences in the prevalence of cavernous sinus invasion in clinically non-functioning PAs.

Methods: The conduct and reporting of this systematic review and meta-analysis were in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-statement). A comprehensive literature search in Medline, Embase and CENTRAL was performed on July 11th 2023. Cohort and cross-sectional studies were only included if the WHO 2017 histopathological classification of at least one transcription factor was applied using immunohistochemistry, and at least one clinical outcome related to invasion was reported.

Results: A total of 26 articles were included for the outcome of invasion, including a total of 2253 participants. Invasion of the cavernous sinus occurred more often in NCAs and TPIT+ non-functioning PAs compared to SF-1+ (prevalence ratio (PR) 1.60 [95% CI 1.29 – 1.97], and 1.43 [95% CI 1.22 – 1.69]). Invasion of the cavernous sinus also occurred more often in NCAs compared to PIT-1+ (PR 1.44 [95% CI 1.03 – 2.02]). There were no differences in cavernous sinus invasion between PIT-1+ compared to SF-1+, NCA compared to TPIT+ and TPIT+ compared to PIT-1+, although a trend was observed for TPIT+ being more often invasive compared to PIT-1+ (PR 1.51 [95% CI 0.88 – 2.59]).

Conclusion: The 2017 WHO classification enables to identify histopathological subgroups of clinically non-functioning PAs with distinct clinical behavior in terms of cavernous sinus invasion, with NCAs and TPIT+ PAs being more often invasive in the cavernous sinus compared to SF-1+ non-functioning PAs.