2025 Proffered Presentations
S006: TRANSCRIPTION FACTOR CELL LINEAGE DETERMINES AGGRESSIVE GROWTH PATTERNS AMONG NONFUNCTIONAL PITUITARY ADENOMAS
Alexander S Himstead, MD; Gianna M Fote, MD, PhD; Nischal Acharya, BS; William H Yong, MD; Mari Perez-Rosendahl, MD; Edward C Kuan, MD; Aaron B Simon, MD, PhD; Frank P Hsu, MD, PhD; Ahmed Mohyeldin, MD, PhD; University of California, Irvine
Introduction: Pituitary neuroendocrine tumors (PitNETs) are the second most common intracranial neoplasm. Silent or non-functional PitNETs represent a common neurosurgical challenge due to their size and unpredictable patterns of parasellar invasion. This makes their complete surgical resection challenging and places patients at higher risk for recurrence.
Objective: We characterized differences in tumor volume, cavernous sinus invasion, and recurrence among silent corticotroph adenomas, silent gonadotrophs and silent plurihormonal tumors as defined by WHO 2017 criteria.
Methods: Out of 578 transsphenoidal surgeries for tumor resection performed at a single institution from 2012 to 2024, there were 375 PitNETs, of which 231 were nonfunctional. Based on new WHO criteria for transcription factor profiling (PIT-1, T-PIT, and SF-1), there were 123 silent gonadotroph adenomas (SGA), 40 silent corticotroph adenomas (SCA), 13 silent pleurihormonal tumors (PHT), and 2 null cell adenomas. Fifty-three tumors had negative hormonal staining but no transcription factor profiling and were excluded. Out of 144 functional PitNETs, there were 26 functional corticotrophs. Tumor volume was calculated using (AxBxC/2). Knosp grade was calculated. Cavernous sinus invasion was defined as Knosp ≥ 3. Residual disease at 3 months postoperative was recorded and surgical intervention for growing residual disease was captured.
Results: Average tumor volume of functional corticotroph adenomas was significantly smaller than SCA. Average tumor volume of SCA (10.49 cm3) was similar to SGA (8.46 cm3) and PHT (13.92 cm3; p=0.095). Percentage of tumors of with Knosp grade 3 or higher was significantly higher in SCA than SGA (p<0.0001), but not PHT (p=0.11). Similarly, percentage of cavernous sinus invasion was significantly different between SCA (50.00%) and SGA (13.82%, p<0.0001), but not PHT (23.08%; p=0.12). There was a significantly higher residual rate in SCA (57.50%) compared to SGA (18.70%, p<0.0001), but not PHT (30.77%; p=0.12). There were significantly more reoperations in the SCA group (10.00%) compared to SGA (1.63%; p=0.032).
Conclusion: SCAs demonstrated a higher predisposition for invasion into the sphenoid sinus and the clivus compared to other NFPA subtypes despite similar tumor volume. Future work may include replicating this analysis with a larger sample size, understanding why SCAs show predilection for increased local invasion, and how this affects patient outcomes including overall rate of complications, likelihood for cerebrospinal fluid leak, and gross-total resection.
Figure 1. Scatterplot demonstrating size distribution of silent versus functional corticotroph adenomas demonstrating significantly larger size in the silent cohort.
Figure 2. Barplots showing significantly higher (A) tumor volume, (B) Knosp grade, (C) residual tumor, (D) and reoperation rate in silent corticotroph adenomas compared to silent gonadotroph adenomas.
Figure 3. T1-weighted contrasted magnetic resonance imaging (MRI) of (A) silent corticotroph adenoma and (B) silent gonadotroph adenoma showing differences in invasion patterns despite overall similar tumor volume. Immunohistochemical staining patterns showing (C) ACTH-staining in SCA, (D) TPIT-staining in SCA, (E) LH staining in SGA, and (F) SF1 staining in SGA.