Diagnostic Utility and Cost Analysis of Sequential TF Immunohistochemistry in Hormone-Immunonegative Pituitary Adenomas

OBJECTIVE: To identify the routine use of all pituitary transcription factor (TF) immunohistochemistry (IHC) for pituitary adenoma diagnosis in Australia and New Zealand. To evaluate the diagnostic utility and cost analysis of selective sequential TF IHC, with SF1, followed by TPIT only if SF1-negative, and PIT1 only if SF1-and-TPIT-negative, in hormone-immunonegative pituitary adenomas. DESIGN: Prospective telephone survey and retrospective cohort study. METHODS: The pathology laboratories of pituitary centres in Australia and New Zealand were surveyed regarding their routine use of TF IHC. At a high-volume pituitary centre in Melbourne, Australia, all three TF IHC were retrospectively applied to the latest 94 labelled null cell adenomas (NCA) diagnosed before routine TF IHC use. Diagnostic efficacy and cost analysis of the simulated selective sequential TF IHC were evaluated compared to universal TF IHC testing. A cohort of 397 hormone-immunonegative pituitary adenomas from Tübingen, Germany, served as an independent validation cohort. RESULTS: Only 57.1% of pituitary centres in Australia and New Zealand performed routine TF IHC. Of the 94 NCAs, TF IHC revised the diagnosis to SF1-lineage (68.1%), TPIT-lineage (18.1%), and PIT1-lineage adenomas (1.1%). There were no pituitary adenomas with multiple lineages. The simulated selective sequential TF IHC achieved >99% diagnostic accuracy in both Melbourne and Tübingen cohorts, reducing costs by 51.4% (Melbourne) and 63.6% (Tübingen) compared with universal TF IHC. CONCLUSIONS: Although misclassification of pituitary adenomas with multiple lineages is possible, our selective sequential TF IHC approach may offer pragmatic, economical hormone-immunonegative pituitary adenoma classification where TF IHC is not standard practice.