Osteoclast formation is dependent on Receptor activator of nuclear factor kappa-Β ligand (RANKL) and the most compelling evidence for a role of the TME in GCT pathogenesis is the clinical observation that Denosumab, a humanised antibody to RANKL, which blocks osteoclast formation, controls tumour growth by reducing mutant osteoblast proliferation and increasing maturation resulting in more bone formation [41, 46]. This evidence concerns the gene TNFSF11 and granular cell tumor.