specimen revealed a tumour mass with histologic features of pronounced osteogenesis and no more evidence of gctb. This case demonstrated a major tumour response to denosumab in the neoadjuvant setting, with a complete pathologic response.Is denosumab a breakthrough in the treatment of gctb? We reviewed the literature focusing on denosumab and gctb, and here we discuss the biggest questions related to the future management of gctb.
GIANT CELL TUMOUR OF BONEAs one type of giant-cell-rich lesion of bone, gctb is characterized by the presence of numerous multinucleated osteoclast-type giant cells, and in this mesenchymal tumour, the mononuclear stromal cells are the neoplastic cell type 2 . The giant cells have been confirmed to express rankl and are responsible for the aggressive osteolytic nature of the tumour 3 . Although generally benign, atypical gctb may be associated with multiple local recurrences, multicentricity, pulmonary metastases, or lesions that cannot be removed surgically without causing substantial morbidity 4 . The World Health Organization therefore classifies gctb as "an aggressive, potentially malignant lesion" 5 .In the United States, gctb accounts for approximately 5% of all primary bone tumours and 20% of all benign bone tumours in adults 6 . About 50−60 new cases of gctb are managed by specialist health care services each year in the United Kingdom 7 . The disease is more common in China and India, where it constitutes approximately 20% of all primary bone tumours 5 . Giant cell tumour of bone occurs most commonly during the second to fourth decades of life (60%-75%) and has a maleto-female ratio in the range 1:1.2 to 1:1.5 2,5 . Most lesions develop in the long bones (75%-90%), with most cases (50%-65%) occurring near the knee 1,2,8 . Other frequent sites are the distal radius, proximal humerus, fibula, sacrum, and vertebral body (fewer than 3% of cases) 2,8 . In no reported case has gctb ABSTRACT Giant cell tumour of bone (gctb) is one type of giantcell-rich bone lesion characterized by the presence of numerous multinucleated osteoclast-type giant cells. Giant cells are known to express rankl (receptor activator of nuclear factor κB ligand) and are responsible for the aggressive osteolytic nature of the tumour. No available treatment option is definitively effective in curing this disease, especially in surgically unsalvageable cases. In recent years, several studies of denosumab in patients with advanced or unresectable gctb have shown objective changes in tumour composition, reduced bony destruction, and clinical benefit.Denosumab is a fully human monoclonal antibody that targets and binds with high affinity and specificity to rankl. Several large phase iii studies have shown that denosumab is more effective than bisphosphonates in reducing skeletal morbidity arising from a wide range of tumours and that it can delay bone metastasis. The relevant articles are reviewed here. The controversies related to the future use of denosumab in the treatment of gctb are discussed.
KEY WORDSDenosuma...