Clinical and Pathological Features of Pit1/SF1 Multilineage Pituitary Neuroendocrine Tumor

BACKGROUND AND OBJECTIVES: Lineage-based classification has critical clinical implications in pituitary neuroendocrine tumor (PitNET). As the most prevalent subtype of multilineage PitNET, PitNET originating from both pituitary-specific positive transcription factor 1 (Pit1) and steroidogenic factor-1 (SF1) lineages (Pit1/SF1-adenoma) is expected to exhibit rich and varied clinical behaviors. A comprehensive understanding of the clinical and pathological characteristics of Pit1/SF1-adenoma will provide mechanistic insight and influence the prognosis and treatment of PitNET. METHODS: A retrospective study was conducted by reviewing 57 cases of Pit1/SF1-adenoma between 2018 and 2022. We also included 88 cases of PitNET arising from Pit1 cell lineage (Pit1-adenoma) and 70 cases of PitNET arising from SF1 cell lineage (SF1-adenoma) as controls. Comprehensive data, including demographic, symptom, endocrinal, radiological, surgical, pathological, and prognostic information, were systematically collected. All specimens were immunostained for pituitary transcription factors (PTFs) and pituitary hormones. RESULTS: The detection rate was 8.0% for Pit1/SF1-adenoma within PitNET surgical specimens. Pit1/SF1-adenoma displayed a male predominance, with the mean diagnosis age falling between Pit1-adenoma and SF1-adenoma. The endocrine activity of Pit1/SF1-adenoma was lower than Pit1-adenoma but higher than SF1-adenoma. Pit1/SF1-adenoma had a higher incidence of cavernous sinus invasion (56.1%) than both Pit1-adenoma (38.6%, P = .039) and SF1-adenoma (27.1%, P = .001). Furthermore, Pit1/SF1-adenoma showed more postoperative complications than Pit1-adenoma (29.8% vs 8.0%, P = .001). Nonfunctional Pit1/SF1-adenoma had a higher radiological tumor recurrence rate than nonfunctional SF1-adenoma (34.8% vs 10.9%, P = .021). Notably, the immunostaining pattern was diverse in Pit1/SF1-adenoma, with various combinations of staining intensity for PTFs and 15 combinations for 6 pituitary hormones. Intriguingly, various PTFs combinations had no different impact on the outcome of Pit1/SF1-adenoma. CONCLUSION: Pit1/SF1-adenoma represents a unique pathological subtype of PitNET, characterized by distinctive clinical behaviors. Identifying Pit1/SF1-adenoma can facilitate more precise management of PitNET by the practical use of Pit1/SF1 immunostaining.