Transcription factor lineage and surgical outcomes in nonfunctioning pituitary neuroendocrine tumors: a systematic review and meta-analysis

Abstract Background The 2022 WHO classification groups pituitary neuroendocrine tumors (PitNETs) by transcription factor lineage. Whether lineage predicts invasiveness, resection and recurrence independently of tumor size and invasion is uncertain. Methods We searched PubMed, Europe PMC, Scopus and Web of Science to 6 September 2026, with OpenAlex citation chasing, for surgical cohorts of PitNETs classified by PIT1, TPIT and SF1 immunohistochemistry. Risk ratios (RRs) were pooled by random effects with Hartung–Knapp–Sidik–Jonkman (HKSJ) intervals. Results Thirty-two reports from 23 independent cohorts were included. In nonfunctioning tumors, invasion was more frequent in TPIT- than SF1-lineage tumors (54% vs 31%; RR 1.66, 95% HKSJ CI 1.44–1.92; I² = 0%; six cohorts) and gross total resection less frequent (75% vs 83%; RR 0.92, 0.87–0.98; I² = 0%; seven cohorts). Each study’s own definition raised the invasion RR to 2.03 (1.35–3.06), with substantial heterogeneity (I² = 69%). Crude recurrence was higher in all six SF1-comparator cohorts but significant in none; pooling the three sharing an outcome definition gave RR 1.58 (HKSJ 0.63–3.96). Two adjusted hazard ratios against SF1 (2.04, 1.10–3.82; 1.29, 0.58–2.84) were not comparable. Female sex was more frequent in TPIT-lineage tumors (RR 2.83, 2.40–3.33; I² = 0%); evidence for PIT1-lineage and null cell tumors was inconsistent. Conclusions TPIT-lineage tumors were more often invasive and less completely resected than SF1-lineage tumors. Crude recurrence was consistently higher but imprecise; whether lineage predicts it independently of invasion and resection is unresolved. Future series should report surgical approach, GTR by Knosp grade, and adjusted lineage-specific estimates.