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This study aims to characterize the clinicopathological features and treatment outcomes of immature PIT-1 lineage tumors classified as high-risk under the WHO 2022 guidelines.

May 15, 2026Open Access

Clinicopathological features and outcomes of immature PIT-1 lineage tumors: A high-risk pituitary neuroendocrine tumor/pituitary adenoma subtype per WHO 2022

Key Points

This study aims to characterize the clinicopathological features and treatment outcomes of immature PIT-1 lineage tumors classified as high-risk under the WHO 2022 guidelines.
Retrospective analysis of 13 patients with immature PIT-1 lineage tumors had surgery at a tertiary center from January 2022 to December 2024.
Diagnosis established using WHO 2022 criteria with transcription factor immunohistochemistry.
Evaluation included clinical, radiological, histopathological data, and follow-up outcomes.
Immature PIT-1 lineage tumors represented 4% of treated pituitary adenomas, with 61.5% presenting hormonal hypersecretion.
46% had residual disease post-surgery; 31% required reoperation within a median follow-up of 16 months.
Median Ki-67 proliferation index was 4%, with all cases showing cytologic atypia.

Abstract

PURPOSE: Immature PIT-1 lineage tumors are classified as high-risk pituitary adenomas/pituitary neuroendocrine tumors (PitNETs) under the 2022 WHO Classification, yet clinical outcome data remain scarce. This study aimed to characterize clinicopathological features and treatment outcomes of this rare entity. METHODS: We retrospectively analyzed 13 patients with pathologically confirmed immature PIT-1 lineage tumors who underwent surgery at our tertiary center between January 2022 and December 2024. Diagnoses were established according to WHO 2022 criteria using comprehensive transcription factor (TF) immunohistochemistry. Clinical, radiological, histopathological, treatment, and follow-up data were evaluated. RESULTS: Immature PIT-1 lineage tumors accounted for 4% (21/525) of surgically treated pituitary adenomas, of whom 13 with complete follow-up data constituted the primary analysis cohort. Median age was 37 years (range: 25-73), with female predominance (61.5%). Notably, 61.5% presented with hormonal hypersecretion: acromegaly (38.5%), TSH-secreting tumors (15.4%), and GH-PRL co-secretion (7.7%). All patients had macroadenomas (median diameter 28 mm (range: 15-59 mm)); 38.5% demonstrated cavernous sinus invasion (Knosp grades 3-4). Immunohistochemically defined plurihormonal phenotype was present in 77% of cases; cytologic atypia was identified in all cases. Despite maximal surgical resection, residual disease persisted in 46% and 31% required reoperation at 16-month follow-up (range: 4-51 months). The median Ki-67 proliferation index was 4% (IQR: 2-10%; range: 1-35%), and the median mitotic count was 4 per 2 mm² (IQR: 1-8; range: 1-20). CONCLUSION: Immature PIT-1 lineage tumors exhibit aggressive behavior with high residual disease rates, with 31% of patients requiring reoperation, 23% receiving adjuvant radiotherapy, and somatostatin analogue resistance observed in two patients. Routine TF immunohistochemistry is essential for accurate diagnosis; management requires maximal safe surgical resection and intensive long-term surveillance.

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Cite This Study

Ozkahraman et al. (Wed,) studied this question.

synapsesocial.com/papers/6a06b83de7dec685947aac8a https://doi.org/https://doi.org/10.1007/s11102-026-01691-9

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