GCT was first described by Cooper and Travers in 1818, and it mainly occurs in the femur, tibia, and radius, accounting for 55% of the lesions, but rarely originates from the vertebra above the sacrum [8, 14]. Spinal GCT is usually located in the vertebral body as opposed to the posterior elements; however, it is rarely confined to the vertebral body, and it continues to grow and may extend to involve the laminae, spinous process, and even the paravertebral area [2, 8, 14, 15]. As an invasive bone tumour, the postoperative recurrence rate of GCT is higher, and distant metastasis might occur. Approximately 1–4% of patients have lung metastasis [12, 16]; however, there was no pulmonary metastasis in the present case.
GCTs of the spine are reported to be expansile lytic lesions, with pain caused by a stretched periosteum being the most common manifestation, followed by pathological fracture (41%) and neurologic symptoms (32%) [15,16,17]. Diagnosis may be delayed, because back pain is a very common symptom and can be easily misdiagnosed [3].
However, most of these tumours are benign, and only a small number of GCTs (1–2%) may undergo malignant transformation, leading to a poor prognosis. According to the previous reports, GCTs can transform into fibrosarcoma, osteosarcoma, malignant fibrous histiocytoma, undifferentiated high-grade pleomorphic sarcoma, and undifferentiated sarcoma [4, 18, 19]. GCTs of the bone appear as expansive lytic lesions with non-sclerosing, well-defined edges on radiography, whereas CT and MRI provide information on the extent of the bone, bone marrow, and surrounding soft tissue involvement. MRI differentiates the lytic lesions from infectious spondylitis or postoperative complications, such as infections [20]. However, aspiration biopsy guided by CT is still needed to make a definite diagnosis of GCT of the bone [2, 15]. Histologically, GCT of the bone shows osteoclast-like giant cells [21]. Ewing’s sarcoma is another invasive bone lesion, with typical histopathological features of uniform round cells and irregularly shaped chromatic nuclei surrounded by a scanty cytoplasm [22].
Owing to the complexity of the spinal anatomy, the treatment of GCT of the spine has become a huge challenge. Intralesional curettage and en bloc resection are the most commonly used surgical methods; the former causes minor trauma with a high recurrence rate (27–65%), while the latter causes major trauma, often resulting in permanent nerve injury, with a low recurrence rate (0–12%) [3, 7, 12]. Although the Spine Oncology Study Group has conducted a systematic review of the literature in 2009 and strongly recommended that total en bloc resection of GCT of the spine was technically feasible, this recommendation was based on some very low-quality evidence and consensus among some experts [17]. The method of resolving local recurrence after surgery is still key to the treatment of GCT of the spine. This problem was addressed with the emergence of denosumab.
Histologically, GCT of the bone contains osteoclast-like giant cells that express RANK and stromal cells that express RANKL, a key mediator of osteoclast formation, activation, function, and survival. Excessive secretion of RANKL causes an imbalance in bone remodelling in favour of bone breakdown [21]. Denosumab is a fully human monoclonal antibody that inhibits RANKL; through its high affinity and specific binding to RANK, denosumab prevents the interaction between RANKL and RANK in a manner similar to that of OPG, thereby inhibiting bone absorption [21]. Branstetter et al. reported a phase II clinical study of 17 patients with GCT, showing that denosumab significantly reduced or eliminated RANK-activated GCTs, reduced the proportion of proliferative stromal cells in lesions, and increased the proportion of non-proliferative well-differentiated new bone tissue [8]. Other studies have also showed that denosumab could provide an objective tumour response rate of 72–86%, promoting tumour shrinkage and calcification [3, 18]. These reports suggest that denosumab might be helpful in the treatment of GCT of the bone. In the present case, the recurrent GCT appeared to have a similar response to denosumab, which could facilitate the performance of three-level TES.
In conclusion, the present report highlights a rare case of a large recurrent GCT in the thoracic spine, which was managed using three-level TES and denosumab therapy. Denosumab therapy contributes to tumour regression. TES may be an effective and feasible strategy for managing huge recurrent GCTs of the spine after denosumab therapy.