Clinicopathologic and prognostic characteristics of tumor budding‐like in giant cell tumor of bone

Abstract Background Currently, tumor budding (TB) is defined as an important factor for a poor prognosis in various types of cancers. The authors identified a significant presence of TB‐like structures at the tumor invasive front in giant cell tumor of bone (GCTB), which may have the same biologic function as TB. The objective of this report was to describe the distribution of TB in GCTB and investigate its correlation with clinicopathologic characteristics, the immune microenvironment, survival prognosis, and response to denosumab treatment. Methods This multicenter cohort study included 426 patients with GCTB who received treatment between 2012 and 2021 at four centers. Two independent pathologists performed visual assessments of TBL structures in hematoxylin‐and‐eosin–stained tumor sections. Immunohistochemistry was used to evaluate tumor‐infiltrating lymphocyte subtypes (CD3‐positive, CD4‐positive, CD8‐positive, CD20‐positive, programmed cell death protein‐1–positive, programmed cell death‐ligand 1positive, and FoxP3‐positive) as well as Ki‐67 expression levels in 426 tissue samples. These parameters were then analyzed for associations with patient outcomes (local recurrence‐free survival [LRFS] and overall survival [OS]), clinicopathologic characteristics, and response to denosumab treatment. Results High‐grade TB was associated with poorer LRFS and OS in both patient groups. In addition, TB was correlated with various clinicopathologic features, tumor‐infiltrating lymphocyte expression, and response to denosumab treatment. TB outperformed the traditional Enneking and Campanacci staging systems in predicting patient LRFS and OS. Conclusions The current data support the assessment of TBL structures as a reliable prognostic tool in GCTB, potentially aiding in the development of personalized treatment strategies for patients.