Clinical significance of immunocyte- and ferroptosis-related markers for the prognosis of patients with tenosynovial giant cell tumor: A cross-sectional study.

BACKGROUND

Tenosynovial giant cell tumor (TGCT) comprises localized (L-TGCT) and diffuse (D-TGCT) subtypes, but how ferroptosis regulators, tumor-associated immune-cell markers and proliferation indices jointly relate to subtype and recurrence is poorly defined. We explored ACSL4, GPX4, CD8, CD163, CSF1R and Ki-67 as candidate markers for subtype discrimination and recurrence prediction in TGCT.

METHODS

This single-center, retrospective cross-sectional study included 49 consecutive patients with histologically confirmed TGCT (25L-TGCT, 24 D-TGCT) treated between 2008 and 2022. Archival FFPE specimens were analyzed. Iron deposition and marker expression were quantified via Prussian blue staining and blinded, standardized immunohistochemistry, with integrated optical density (IOD) measured by digital image analysis. Group comparisons used appropriate statistical tests. Receiver-operating characteristic (ROC) analysis with bootstrap 95% CIs was performed to assess single and combined biomarkers for subtype discrimination and recurrence prediction.

RESULTS

D-TGCT specimens showed significantly higher iron deposition, ACSL4, CD163, CSF1R, and Ki-67 expression, along with lower GPX4 and CD8 levels than L-TGCT (all P < 0.05). Recurrent cases (11/49) exhibited similar molecular patterns, with elevated iron, CD163, CSF1R, Ki-67, and reduced GPX4/CD8 (all P < 0.05). The ACSL4+CD8 combination discriminated subtypes with an AUC of 0.992. The Ki-67+CSF1R+tumor diameter model predicted recurrence with an AUC of 0.988.

CONCLUSIONS

Ferroptosis, immune, and proliferation markers differ significantly between TGCT subtypes and recurrence status. The ACSL4+CD8 signature shows excellent potential for subtype differentiation, while the Ki-67+CSF1R+tumor diameter index is a strong recurrence predictor. These exploratory findings support targeted biomarker use in TGCT management, though external validation in larger, prospective cohorts is required.