Variations in Hormonal and Immunostaining Patterns of Pituitary Adenomas in Relation to Intraoperative Consistency

Introduction: Variation in pituitary adenoma (PA) consistency, or texture, remains an important area of investigation for neurosurgeons and neuropathologists given its relationship with surgical outcomes. In this study, we investigate associations between intraoperative tumor consistency and PA immunostaining subtypes in patients undergoing resection of PAs.

Methods: Tumor consistency was prospectively assigned at the time of surgery using a previously validated 5-point grading scale by the senior author between 2011-2024. Stains included luteinizing hormone, follicle-stimulating hormone, α-subunit, prolactin (PRL), growth hormone, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone, steroidogenic factor (SF-1), pituitary-specific transcription factor 1 (PIT-1), and t-box transcription factor (T-PIT). Univariable and multivariable comparisons were performed across three consistency groupings (1+2, soft adenoma; 3, intermediate PA consistency, 4+5, firm adenoma).

Results: A total of 621 patients were included (mean age 52.1±14.0 years, 338 (54.4%) females) of which 264 (42.5%) had soft PAs (grade 1+2), 239 (38.4%) had intermediate (grade 3), and 118 (19%) had firm PAs (grade 4+5). On univariable analysis, soft PAs (consistency grades 1+2) were more likely to stain positive for PRL (OR:1.931, 95CI:1.267-2.976, p=0.003) and PIT-1 (OR:3.426, 95CI:1.599-8.197, p=0.003) compared to intermediate tumors (grade 3). The likelihood of a positive ACTH stain were greater for intermediate tumors compared to firm tumors (grade 4+5) (OR:0.482, 95CI:0.228-0.944, p=0.042). In a multivariable analysis adjusting for age, sex, maximum tumor diameter, and Knosp score, positive immunostaining for ACTH (OR:0.453, 95CI:0.234-0.879, p=0.019) and PIT-1 (OR:0.209, 95CI:0.068-0.639, p=0.006) were significant predictors for soft tumor consistency.

Conclusion : PA consistency is associated with important transcription factor (PIT-1) and hormone (ACTH) staining, though not directly with T-PIT, which is reasonable given that ACTH production in corticotroph tumors is not strictly regulated by T-PIT alone. These findings suggest that the biochemical activity driving ACTH and PIT-1 PAs may contribute to the growth and development of tumors with varying physical properties.