The impact of the WHO 2017 classification of PitNETs on prediction of biological behavior of non-functioning PitNETs – A Systematic Review (project plan) - Nederlandse Vereniging voor Endocrinologie

Background: The World Health Organization 2017 histopathological classification of pituitary neuroendocrine tumors (PitNETs), including cellular lineage specific transcription factors (TFs), has resulted in a shift in histopathological diagnosis and newly identified subgroups, mainly within non-functioning PitNETs (NF-PitNETs).

Objectives: Primary objective: to assess potential cell lineage specific differences in clinical behavior within hormone immunohistochemistry (IHC) negative subtypes of NF-PitNETs and between TF+/hormone IHC- subtypes and the TF+/hormone IHC+ counterparts. Secondary objective: to evaluate clinical behavior of TF-specific cell lineages of NF-PitNETs.

Search methods: A literature search (in Medline, Embase and CENTRAL) was performed from inception up to July 11^th 2023. Eligibility assessment based on full text is in progress.

Selection criteria: Cohort studies reporting original data of at least three patients with NF-PitNETs of which the vast majority were adults at the time of diagnosis. Histopathological diagnosis should be classified according to the WHO 2017/2022 classification, or include at least one of the following TF’s: SF-1, PIT-1, T-PIT.

Data collection and analysis: The conduct and reporting of this systematic review will be in accordance with the PRISMA-statement and is registered in PROSPERO (ID: CRD42023435409). Outcomes in terms of clinical behavior, including aggressiveness, invasiveness and recurrence/progression will be collected.

Main results: 1985 articles were screened based on title an abstract. 162 full copies of relevant articles will be retrieved and assessed for eligibility.

Authors’ hypotheses: We hypothesize that there will be differences in clinical behavior between TF+/hormone IHC- subtypes and true null cell NF-PitNETs and between TF+/hormone IHC- subtypes and the TF+/hormone IHC+ counterparts. Secondary, we hypothesize that silent T-PIT+ and silent plurihormonal PIT1+ NF-PitNETs display a more aggressive behavior compared to the other cell lineage specific NF-PitNETs.