Clinical Implications of Pituitary Adenomas Exhibiting Dual Transcription Factor Staining: A Case Series of 27 Patients

OBJECTIVE: According to the 2017 World Health Orgaization classification of neuro-endocrine tumors, pituitary adenomas (PAs) are classified according to immunoexpression of the pituitary -specific transcription factors (TFs). A small subset of PAs exhibit multiple TF staining on immunohistochemistry and we present a series of 27 pathologically -confirmed cases of dual TF staining PAs (dsTF-PAs), and report clinically relevant implications. METHODS: A retrospective chart review of a multiinstitutional database of patients with PAs surgically resected between 2008-2021 was performed. PAs expressing immunopositivity 2D TFs. Patient demographics, neuro-imaging characteristics, histopathologic findings, and clinical data were collected. RESULTS: Twenty-seven patients had pathologically verified dsTF-PAs, of whom 17 were female (63%), with ages ranging from 20-84 years. Twenty-three (85.2%) patients harbored functional PAs, with acromegaly being the most common functional subtype (86.4%). The most common combination of TFs within a single tumor was PIT -1/ SF -1 (85.2%). Six PAs exhibited Knosp cavernous sinus invasion grades of 3 or 4 and the Ki-67 labeling index was double dagger 3% in 6 patients (24.0%) and all stained for PIT-1/SF-1. Hormonal remission was achieved in 78% of functional dsTF-PAs. No PAs showed evidence of recurrence or progression over the mean follow-up period of 28.5 months. CONCLUSIONS: PAs exhibiting dsTF-PAs represent a small but clinically relevant diagnostic subset of PAs according to the 2021 World Health Organization criteria, as a majority are GH-producing. Precise classification using TF staining plays a key role in understanding the biology of these tumors. Favorable outcomes can be achieved in this subset of PAs with evolving TF classification.