Denosumab Therapy Obscures Histological Features of Giant Cell Tumor of Bone

Giant cell tumor (GCT) of bone is a locally aggressive tumor with low metastatic potential, usually originating in long bones. Numerous spinal examples have been reported and thus GCTs can be encountered by neuropathologists. We describe a 69-year-old man with more than a 10-year history of GCT primary to the femur that had recently metastasized to the occipital skull bone. The patient had been receiving denosumab, an adjuvant therapy for GCT, prior to the metastasis. Review of the histological features of the original primary tumor in the femur showed archetypal features of GCT, but the posttreatment occipital skull metastasis showed a predominantly low-to-medium cell density spindle cell tumor with complete depletion of osteoclastic giant cells. Although this effect of the drug is increasingly being recognized by soft tissue pathologists, the current case illustrates the potentially confusing histology of postdenosumab-treated GCT for neuropathologists. The absence of giant cells leads the posttherapy primary or metastatic lesion to show histologic similarity to a multitude of benign and malignant fibro-osseous lesions or spindle cell sarcoma and highlights the importance of eliciting appropriate clinical history.