Refining pituitary adenoma classification: the role of transcription factors in diagnosis and risk assessment

Abstract

JOINT1942

Introduction: The new classification of pituitary tumors (WHO 2022) is based on transcription factors (TF) detected through immunohistochemistry (IHC) to determine tumor lineage. The aim of our study was to evaluate the usefulness of incorporating the WHO 2022 classification into the pathological study of pituitary adenomas (PA).

Materials and Methods: We retrospectively analyzed records of adults with PA who underwent surgery between January 2023 and December 2024. Clinical, radiological (tumor size, cavernous sinus invasion), and histopathological data were reviewed, including IHC for hormones and TF: SF1, Tpit, Pit1, GATA3, and Ki-67%. High-risk PAs were identified according to WHO 2022 criteria. Tumors were classified as invasive if they had Knosp grade III or IV.

Results: A total of 112 tumor samples were included. The majority belonged to the SF1 lineage (50%), followed by Pit1 (29%), TPIT (21%). With the incorporation of TF analysis, the diagnosis was modified in 19 patients:.

• 11 clinically non-functioning adenomas (CNFA) with negative hormonal IHC were reclassified as gonadotropinomas (SF1+; n = 7), 1 corticotropinoma (TPIT+) and 1 null cell.

• Only 2 CNFA were triple-negative but GATA3+.

• 5 patients with acromegaly were reclassified as: 1 immature, 1 mature Pit1 lineage tumor, 2 acidophil stem cell tumors, and 1 plurihormonal (Pit1 and SF1).

• 2 patients with thyrotropinoma were reclassified as immature and mature Pit1 lineage tumors.

• 1 CNFA with IHC for PRL and GH was re3.

• classified as plurihormonal (Pit1 and SF1).

• 43 gonadotropinomas, 2 corticotropinomas, 1 acidophil stem cell, 3 Pit-1, and a plurihormonal tumor were GATA3+.

• 31 patients with high-risk histological subtype tumors (7 reclassified with TF). These tumors were associated with invasiveness in 48% and Ki-67 ≥ 3% in 6.4%.

• 81 patients with low-risk histology: 38% were invasive, and 3.7% had Ki-67 ≥ 3%.

Conclusions: The addition of IHC for TF to routine diagnostics allows a more accurate classification of pituitary adenomas, particularly in cases with absent or low hormonal expression. IHC for GATA3 could be a useful marker for diagnosing gonadotropinomas and certain immature tumors. Diagnosing Pit1 adenomas presents challenges due to variability in hormonal expression, coexpression of transcription factors, and distinction between mature and immature types. The classification of tumors into high- and low-risk groups provides an additional parameter for individualized risk assessment, which should be considered along with clinical, radiological, and histopathological factors. These findings reinforce the need for molecular techniques to refine PitNET classification and enhance diagnostic precision.

Keywords: pituitary neoplasms, tumor classification, WHO 2022.