Transcription-Factor Dependent Cytodifferentiation Drives Cavernoinvasive Behavior of Pituitary Tumors

Background: Pituitary tumors (PT) continue to offer unique challenges given their proximity to the cavernous sinus, whereby invasive behavior can limit extent of resection and surgical outcome, especially in functional tumors.

Objective: The aim of this study is to elucidate patterns of cavernoinvasive behavior by PT subtype.

Methods: A total of 169 consecutive first-time surgeries for PT were analyzed, 45% were functional. There were 64 PIT-1, 62 SF-1, 38 TPIT, and 5 none-staining PT. The gold standard for cavernous sinus invasion (CSI) was based on histopathological examination of the cavernous sinus medial wall and intraoperative exploration.

Results: Cavernous sinus disease was present 33% of the time. PIT-1 tumors had a significantly higher predilection for CSI, 53% versus 24% and 18% for TPIT and SF-1 tumors, respectively (OR: 6.08, 95% CI: 2.86–13.55; p < 0.001). Microscopic CSI was present in 44% of PIT-1 tumors compared with 7% and 13% for TPIT and SF-1 tumors, respectively (OR: 11.72, 95% CI: 4.35–35.50; p < 0.001). Utilizing the transcavernous approach to excise cavernous sinus disease, surgical biochemical remission rates for patients with acromegaly, prolactinoma, and Cushing disease were 88, 87, and 100%, respectively. Granule density of PIT-1 tumors and corticotroph functional status did not influence CSI.

Conclusion: Likelihood of CSI differed by transcription factor expression; PIT-1 expressing tumors had a higher predilection for invading the cavernous sinus, particularly microscopically, compared with other tumor subtypes. This elucidates a unique cavernoinvasive behavior absent in cells from other lineages. Innovative surgical techniques, however, can mitigate tumor behavior and achieve robust, reproducible biochemical remission and gross total resection rates. These findings can have considerable implications on the surgical management and study of PT biology and behavior.

Publication History

Article published online:
01 February 2023