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A 43-year-old female with a history left humeral giant cell tumor of bone resected one year ago and treated with denosumab presents with a 4-week history of worsening left upper arm and shoulder pain that is exacerbated with activity.

Imaging demonstrates increased bony production superimposed on the lytic appearance of the left proximal humeral head (the location of the previous tumor) and slight lateral angulation consistent with a pathologic fracture. 

The lesion was curetted and histologic sections revealed a benign a fibro-osseous proliferation with bland spindle cells, histocytes, fibrous stroma and osteoid formation, consistent with treatment effect. There was no residual giant cell tumor identified in the entirely submitted sample. Giant cell tumor of bone treated with denosumab is a diagnostic pitfall with morphologic overlap with numerous benign fibro-osseous and fibrohistiocytic neoplasms. Denosumab is a human monoclonal antibody against receptor activator of nuclear factor kappa-B ligand (expressed by giant cells).

The drug prevents the formation of giant cells that cause osteolysis. Denosumab treatment produces a distinct histologic pattern including the disappearance of the osteoclast-like giant cells and bland spindle cells organized in short fascicles with a storiform pattern (Figure A).

Collagen matrix production was seen in thin bands and as thicker connected trabecular structures with a honeycomb appearance along with osteoid matrix and new bone deposition (Figure B). Additionally, clusters of foamy histiocytes within fibrous areas were identified (Figure C). There were also densely collagenized areas, with rare spindled tumor cells.

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