CONTEXT: Immunohistochemistry (IHC) of cell lineage-specific transcription factors (TFs) has been added to the histopathological classification of pituitary adenomas since 2017, resulting in new histopathological subtypes of TF+/hormone- non-functioning pituitary adenomas (NFPAs) and a reduction in the prevalence of null cell adenomas (NCAs). OBJECTIVE: To evaluate associations between expression of cell lineage-specific TFs by IHC and radiological invasion and prognosis of NFPAs. DATA SOURCES: A literature search in Medline, Embase, and CENTRAL was performed from inception up to July 11th 2023. STUDY SELECTION: Eligible studies were cohort studies reporting on radiological invasion, recurrence and/or radiotherapy in patients with NFPAs who tested positive for one cell lineage-specific TF or negative for all three. Finally, 27 out of 1985 studies were included. DATA EXTRACTION: Two authors independently extracted data and critically appraised risk of bias using the QUIPS tool. DATA SYNTHESIS: Random-effects inverse variance models were used to pool effect sizes. Prevalence rate ratios (PRR) were calculated using the Mantel-Haenszel method. Cavernous sinus invasion was more prevalent in NCAs and TPIT+ NFPAs compared with SF1+ NFPAs (PRR 1.60, 95% confidence interval (CI) 1.22-2.08, I2 10%, 95% prediction interval (PrI) 1.23-2.06, p=0.0036, and PRR 1.43, 95% CI 1.21-1.70, I2 0%, 95% PrI 1.17-1.76, p=0.0017, respectively), and in NCAs compared with PIT1+ (PRR 1.44, 95% CI 1.01-2.06, I2 0%, 95% PrI 0.83-2.50, p=0.0454). Limited number of studies precluded data syntheses of recurrence and radiotherapy. CONCLUSIONS: The use of cell lineage-specific TFs by IHC enables to detect histopathological subtypes of NFPAs with distinct clinical behaviour.