Abstract: Objective To investigate the histological features, diagnosis and differential diagnosis of giant cell tumor of bone (GCTB) with pseudosarcomatous changes and high mitotic activity after Denosumab treatment. Methods The clinical data, radiologic and pathological features of a patient with GCTB treated with Denosumab for 3 weeks prior to surgery in the Second Affiliated Hospital of Guangzhou Medical University was retrospectively analyzed, and the relevant literature was reviewed. Results A 39⁃year⁃old male patient presented with swelling and pain right knee joint and walking limitation as the main clinical symptom. The X⁃ray result showed an expansive, osteolytic lesion in the subarticular medullary cavity of the right distal femur. Th initial biopsy before Denosumab treatment showed typical features of GCTB. After 3 weeks of Denosumab treatment, curettage was performed. Histological findings showed that giant cells almost completely disappeared, and the tumor was mainly composed of spindle mononuclear cells with moderate to high density, accompanied by high mitotic activity, focal necrosis and immature new bone formation, forming a osteosarcoma⁃like morphology. No recurrence was found in 9 months follow⁃up. Conclusions The pseudosarcomatous change with high mitotic activity is a rare histological phenotype of GCTB after Denosumab treatment, which is easily misdiagnosed as the true sarcoma or malignant transformation of GCTB. Paying attention to clinical treatment history and being familiar with the histological features are essential for accurate diagnosis and avoiding misdiagnosis.

Key words: Giant cell tumor of bone, Denosumab, Histological feature, Differential diagnosis