A contemporary, multiinstitutional analysis of transcription factor lineage in pituitary adenomas: comparative study of neuroimaging, histopathology, and clinical outcomes

OBJECTIVE Pituitary adenomas (PAs) are common lesions that often present with endocrinopathy and/or visual symptoms. Classification of PAs has historically been based on functional status and histopathological staining of anterior pituitary hormones. In 2017, the WHO revised the classification of PAs, establishing cell lineages identified by the transcription factors (TFs) PIT1, TPIT, and SF1. The clinical behavior of PA subtypes based on TF typing, including growth patterns, response to treatment, and recurrence rates, is unknown. The authors aimed to assess clinical presentation and outcomes according to TF lineage in a contemporary series of PAs. METHODS A retrospective multicenter clinical study of patients undergoing resection of PAs between June 2017 and August 2021 was performed. Included tumors underwent immunohistochemical staining for WHO-defined TFs (TPIT, PIT1, and SF1). Clinical data including demographics, tumor characteristics, extent of resection, and clinical outcomes pertaining to tumor control and hormonal remission were assessed. RESULTS A total of 238 patients were included in the analysis, with the following clinical breakdown of PA subtypes: nonfunctional PAs (n = 150, 63.0%); growth hormone–secreting PAs causing acromegaly (n = 53, 22.3%); adrenocorticotropic hormone–secreting PAs causing Cushing’s disease (n = 30, 12.6%); and prolactinomas (n = 2, 0.8%). The most common TFs identifying cell lineages were SF1 (n = 104 samples, 43.7%), TPIT (n = 53, 22.3%), and PIT1 (n = 46, 19.3%). Thirty-five samples (14.7%) were positive for two TFs. Prevalence of suprasellar extension was highest in SF1 tumors (91.3%) and lowest in PIT1 tumors (54.3%), and varied significantly across groups (p < 0.001). Cavernous sinus and clival/sphenoid invasion also varied among TF subtypes, with the highest rates seen in PIT1 PAs (p = 0.002). Although no significant differences in progression-free survival (PFS) were noted across TF subtypes, among nonfunctional PAs the median PFS for SF1, PIT1, and TPIT TFs were 83 months, 26 months, and 45 months, respectively (p = 0.002). Nonfunctional PIT1 PAs had a significantly shorter PFS/recurrence-free survival compared to functional PIT1 tumors (HR 59.45, 95% CI 2.54–1394, p = 0.01). CONCLUSIONS The modern WHO diagnosis of PAs incorporates pituitary TF staining to standardize classification according to PA cell lineage. TF designation is associated with major clinical and endocrine variables including PA extension, extrasellar growth patterns, Ki-67 labeling index, and PFS among patients with PA subtypes.