Clinical features of plurihormonal pituitary adenoma subtypes

Plurihormonal pituitary neuroendocrine tumors/pituitary adenomas (PitNET/PAs) express multiple hormones and/or transcription factors. The two most common subtypes within the plurihormonal category are immature PIT-1 (pituitary-specific POU-class homeodomain factor-1) lineage tumors and mature PIT-1 plurihormonal tumors, most of which show PIT-1/SF-1 (steroidogenic factor 1) co-expression. Our aim is to provide direct comparison between these two PIT-1 plurihormonal tumor types in terms of demographic, radiological, neurosurgical, and endocrinological features. A database search and chart review of patients with plurihormonal PitNET/PAs who underwent resection between 2018 and 2024 was performed. Twenty-six plurihormonal PitNET/PAs (12 immature PIT-1-lineage, 14 mature PIT-1/SF-1 co-expressors) were identified. Immature PIT-1 lineage tumors were larger than mature PIT-1/SF-1 co-expressors (median size 27.5 mm vs 16 mm, p=0.02). No significant differences were detected between the two groups in terms of gender (females 67% vs. 50%), median age (45 vs 50 years), hormonal activity (83% vs 79%), invasion of the cavernous sinuses (50% each), residual tumor after surgery (55% vs 43%) or rate of recurrence (9% vs 7%), respectively. Immature PIT-1 lineage tumors trended towards higher Ki-67 levels when compared to mature PIT-1/SF-1 co-expressors (30% vs 0%, p=0.21) as well as need for medical therapy after surgery for hormone excess (33% vs 7%, p=0.15) but this was not statistically significant. In conclusion, immature PIT-1 lineage tumors exhibit larger size and an increased requirement for postoperative medical therapy than mature PIT-1/SF-1 co-expressors, underscoring the usefulness of careful histologic analysis. In contrast, these two plurihormonal subtypes cannot be predicted pre-operatively by gender, age, or hormonal profile.