Giant cell tumor (GCT) of bone is a benign but locally aggressive neoplasm representing about 5% of primary bone tumors, typically affecting the metaepiphyseal region of long bones in young adults. On 18F-FDG PET/CT, these lesions often show intense uptake due to the high glycolytic activity of stromal and multinucleated giant cells. This overlap with malignant sarcomas can complicate diagnosis and impact therapeutic decision-making.

To describe the metabolic and morphological features of a distal femoral GCT on 18F-FDG PET/CT and discuss diagnostic challenges related to its high glycolytic activity and differentiation from sarcomatous lesions.

A 25-year-old male presented with progressive left-knee pain and swelling for six months. MRI showed an expansile metaepiphyseal lesion with cortical thinning and septations. Bone scintigraphy revealed a “doughnut” uptake pattern suggesting an aggressive yet likely benign lesion. Whole-body 18F-FDG PET/CT was performed 60 minutes after intravenous tracer injection using a dedicated hybrid scanner (BLINDING). Images were visually and semi-quantitatively analyzed using SUVmax measurement.

PET/CT demonstrated intense FDG uptake (SUVmax 15.1) in the distal femoral lesion with cortical rupture and a soft-tissue component of 11 cm, without other hypermetabolic foci. The high SUV initially raised suspicion for osteosarcoma, but histopathology revealed spindle cells and multinucleated giant cells with low mitotic activity, confirming GCT with fibrohistiocytic features. The patient underwent tumor resection and endoprosthetic reconstruction, achieving satisfactory functional recovery.

GCTs may exhibit SUV values as high as those of malignant sarcomas. This finding reflects increased glycolysis in tumor stroma and osteoclast-like cells rather than true malignant transformation. Histopathologic confirmation remains essential, as FDG uptake alone cannot distinguish benign from malignant bone lesions. Recent studies demonstrate that FDG PET/CT may aid in monitoring response to denosumab therapy and detecting recurrence after surgery. Understanding this metabolic overlap is crucial for avoiding overtreatment and optimizing management in musculoskeletal oncology.