H3F3A-mutated Giant Cell Tumour of Bone without Giant Cells - Clinical Presentation, Radiology, and Histology of Three Cases.

AIMS Giant cell tumour of bone (GCTB) is histologically defined as a lesion containing reactive giant cells and a neoplastic mononuclear cell population; in up to 92% GCTB is characterized by a specific mutation of the histone gene H3F3A. The cellular composition ranges from giant cell-rich to giant cell-poor tumours. The diagnosis of GCTB can be challenging and several other lesions need to be excluded, e.g., aneurysmal bone cysts, non-ossifying fibromas, chondroblastomas, brown tumours, and giant-cell-rich osteosarcomas. Our aim was to analyse the clinical history, imaging, molecular pathology, and histology of three H3F3A-mutated bone tumours without detectable giant cells. None of the patients received denosumab therapy. METHODS AND RESULTS Diagnostic material was obtained by curettage or resection and/or biopsy. Common histomorphologic features of all three reported lesions were fibrocytic, oval cells in a background of osteoid while multinuclear giant cells were not detected as confirmed by CD68-immunohistochemistry. We used immunohistochemistry and Sanger-sequencing to demonstrate positivity for H3.3 p.G34W mutation. Differential diagnoses were systematically excluded based on histomorphology, immunohistochemistry and FISH. The imaging (radiograph, CT, MRI) for all three cases is presented and discussed. CONCLUSIONS Therefore, we believe that these GCTB without giant cells expand one end of the heterogeneous range of GCTB. Due to the lack of giant cells the correct diagnosis of GCTB is challenging or even impossible based on pure histological grounds. In these cases, detection of the characteristic H3F3A gene mutation (G34W-specific antibody RM263 or sequencing) is extremely helpful to diagnose those lesions without giant cells as a giant cell tumour of bone.