Giant Cell Tumor Management and Treatment Strategies

Giant cell tumour of bone is a locally aggressive neoplasm characterised by osteoclast-like giant cells driven by stromal cell expression of RANK ligand (RANKL). Management balances complete tumour removal with preservation of function and minimisation of recurrence. Intralesional curettage with high-speed burring remains the most common surgical approach, often complemented by adjuvant techniques such as phenol application, cryotherapy or cementation. In more extensive or anatomically challenging lesions, en bloc resection followed by reconstruction may be required. The advent of RANKL inhibitors, most notably denosumab, has transformed neoadjuvant and adjuvant strategies by inducing sclerosis at the tumour margin, reducing surgical morbidity and enabling joint preservation. Bisphosphonates have also been explored to inhibit osteoclastic activity. Emerging work in molecular profiling has identified distinct driver mutations and signalling pathways, opening avenues for targeted therapies. Optimal care demands a multidisciplinary team to tailor surgery, systemic therapy and long-term surveillance, with particular attention to the risk of local recurrence, malignant transformation and skeletal integrity in young patients.

Research from Nature Portfolio

Recent studies have uncovered somatic gain-of-function mutations in TRPV4, KRAS and FGFR1 in central giant cell lesions of the jaw. These mutations activate the MAPK pathway and increase channel activity, suggesting that antagonists of TRPV4 or RAS/MAPK signalling may represent novel therapeutic options beyond RANKL inhibition.

Giant Cell Tumor Management and Treatment Strategies publication trend

The graph below shows the total number of articles in giant cell tumor management and treatment strategies across all publications each year (not limited to Nature Index journals).

Technical terms

RANK ligand (RANKL): A cytokine produced by stromal cells that binds RANK on osteoclast precursors to drive osteoclastogenesis and bone resorption.

Neoadjuvant therapy: Treatment given before the main surgical intervention to reduce tumour size or extent.

Curettage: Intralesional removal of tumour tissue using a curette, often combined with adjuvants to reduce recurrence.

Osteoclast-like giant cells: Multinucleated cells resembling osteoclasts, recruited by the neoplastic stromal cells to mediate bone destruction.

References

1. Surgical Downstaging in an Open-Label Phase II Trial of Denosumab in Patients with Giant Cell Tumor of Bone. Annals of Surgical Oncology (2015).
2. Risks and benefits of combining denosumab and surgery in giant cell tumor of bone—a case series. World Journal of Surgical Oncology (2016).
3. High‐Speed Burring with and without the Use of Surgical Adjuvants in the Intralesional Management of Giant Cell Tumor of Bone: A Systematic Review and Meta‐Analysis. Sarcoma (2010).
4. Bisphosphonate treatment of aggressive primary, recurrent and metastatic Giant Cell Tumour of Bone. BMC Cancer (2010).
5. En bloc excision and autogenous fibular reconstruction for aggressive giant cell tumor of distal radius: a report of 12 cases and review of literature. Journal of Orthopaedic Surgery and Research (2011).
6. TRPV4 and KRAS and FGFR1 gain-of-function mutations drive giant cell lesions of the jaw. Nature Communications (2018).
7. Denosumab in Giant Cell Tumor of Bone: Current Status and Pitfalls. Frontiers in Oncology (2020).