The Role of T-box Transcription Factor in a Pituitary Adenoma Diagnostic Algorithm

Abstract

Context.— We previously examined pituitary adenomas with immunohistochemical (IHC) stains for steroidogenic factor 1, Pit-1, anterior pituitary hormones, cytokeratin CAM 5.2, and the α-subunit of human chorionic gonadotropin and found that a screening panel comprising stains for steroidogenic factor 1, Pit-1, and adrenocorticotropic hormone successfully classified most cases and reduced the overall number of stains required. Objectives.— To examine the potential role of IHC stain for T-box transcription factor (Tpit) in the classification of our series of pituitary adenomas and to update our screening panel as necessary. Design.— We collected 157 pituitary adenomas from 2 institutions and included these in tissue microarrays. Immunostains for Tpit were scored in a blinded fashion using the Allred system. Adenomas were assigned to a gold standard class based on IHC pattern followed by application of available clinical and serologic information. Test characteristics were calculated. Correlation analyses, cluster analyses, and classification tree analyses were used to see whether IHC staining patterns reliably reflected adenoma class. Results.— Of the cases collected, 147 (93.6%) had sufficient material for Tpit analysis. IHC stain for Tpit identified 8 null cell adenomas (all nonfunctioning clinically) as silent corticotrophs; Tpit stains showed better sensitivity, specificity, positive predictive value, and negative predictive value than IHC for adrenocorticotropic hormone and cytokeratin CAM 5.2. Correlation analyses continued to show the expected relationships among IHC stains. Cluster analyses showed grouping of adenomas into clinically consistent groups. Classification tree analysis underscored the central role of transcription factor IHC stains, including Tpit, in adenoma classification. Conclusions.— Substitution of Tpit stain for the adrenocorticotropic hormone stain improves our prior algorithm by reducing the number of false-negatives and false-positives. As a result, fewer adenomas are classified as null cell adenoma, and more adenomas are classified as silent corticotroph adenoma.

Development of a cost-effective diagnostic algorithm incorporating transcription factor immunohistochemistry in the evaluation of pituitary tumours

“…Several studies have proposed similar diagnostic algorithms [7,9], confirming comparable results with regards to excellent concordance. Other studies were performed on tissue microarrays rather than whole sections, which were utilised here and are routine clinical practice.…”

“…Other studies were performed on tissue microarrays rather than whole sections, which were utilised here and are routine clinical practice. All other studies were published prior to the release of the 2022 WHO classification, therefore did not include relevant and important changes [5,[7][8][9]. The EPPG proposed hormonal IHC in all cases, with subsequent transcription factor IHC in certain circumstances only such as plurihormonal tumours [8].…”

“…However, the expansion of diagnostic IHC is also associated with increased cost and burden of work for laboratory staff [2,6]. Clinical and economic feasibility pose the need for a tiered approach [6][7][8]. The European Pituitary Pathology Group (EPPG) proposed a diagnostic algorithm in 2017.…”

Classificazione e nomenclatura dei tumori neuroendocrini dell’ipofisi anteriore

“…Il gruppo europeo di patologia ipofisaria e altri gruppi hanno recentemente proposto una standardizzazione dei referti istologici [3,21]. Questo gruppo suggerisce una prima valutazione dell'espressione degli ormoni ipofisari, seguita dalla valutazione dei FT, in particolare per tumori che non esprimono ormoni, quelli che contengono solo isolate cellule positive per un ormone e i casi che dimostrano espressione di due o più ormoni.…”

An Update on Silent Corticotroph Adenomas: Diagnosis, Mechanisms, Clinical Features, and Management

“…Some studies on SCAs have been conducted following the 2017 WHO classification guidelines [ 9 , 15 , 16 , 17 , 18 , 19 ]. All have seen an increase of the proportion of SCAs among the NFPAs with the detection of T-PIT-positive ACTH-negative SCAs as T-PIT immunostaining reduces the number of false-negatives and false-positives.…”