Hidden Heterogeneity of Surgically Treated Prolactinomas: Implications of Who 2022 Classification

Background: Dopamine agonists remain the standard treatment for prolactinomas, but recent studies have suggested a potential role for surgical resection. The WHO 2022 classification highlights the heterogeneity of prolactin (PRL)-secreting tumors, identifying high-risk subtypes such as immature PIT1 lineage tumors. Characterizing the distribution of these subtypes in surgically treated prolactinomas may offer new insights into tumor biology and patient management. Methods: We retrospectively reviewed surgically treated pituitary adenomas at our institution between October 2019 and March 2025. Nine patients with PRL-secreting tumors were identified and reclassified according to the WHO 2022 classification with transcription factor-based immunohistochemistry. Clinical data including prior medical therapy, preoperative PRL levels, extent of resection, and postoperative endocrinologic remission (ER) were collected and summarized. Results: Among nine surgically treated prolactinomas, six patients (67%) had prior medical therapy. Preoperative PRL levels varied widely and were significantly higher in patients without treatment history. Gross total resection was achieved in eight patients (89%). ER was obtained in six patients (67%) with surgery alone, and the remaining three achieved ER after additional medical therapy. All tumors were reclassified as PIT1 lineage, with only three cases (33%) identified as lactotroph adenomas. Other subtypes included mammosomatotroph adenoma, acidophilic stem cell adenoma, and immature PIT1 lineage adenoma. Conclusion: These findings highlight the heterogeneous distribution of PIT1 lineage subtypes in surgically treated prolactinomas, with lactotroph adenomas representing only a minority. The presence of rare and often drug-resistant entities such as acidophilic stem cell adenomas and densely granulated lactotroph adenomas, along with high-risk immature PIT1 lineage tumors, suggest that surgical resection may be particularly valuable in selected patients. Publication History Article published online: 27 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany