The patient was a 58-year-old woman who presented with progressive low back pain for 3 months before admission. She had no history of hypertension, diabetes mellitus, systemic carcinoma, or congenital tissue abnormalities. On admission, she exhibited marked gait disturbance with low back pain and sciatic nerve pain, which was dominant on her right side. The strength of the right tibialis anterior and extensor hallucis longus muscles was Grade 3-4, and sensory disturbance, including pain as well as thermal and touch sensations, occurred on the bilateral lower thigh. Findings of deep tendon reflexes and pathological reflexes were normal. Blood examination results revealed a tartrate-resistant acid phosphatase (TRACP)5b level of 967 mU/dl and an alkaline phosphatase (ALP) level of 393 ml/dl (Table 1). Initial X-ray and computed tomography (CT) results revealed the presence of an osteolytic lesion involving the L4 vertebra with the abnormal alignment of anterior spondylolisthesis (Fig. 1a and b). Magnetic resonance imaging (MRI) revealed low signal intensity and intermediate-to-high signal intensity areas on T1- and T2-weighted images, respectively. Gadolinium-enhanced axial images revealed that the tumor mass expanded into the extravertebral and intraspinal canal spaces (Fig. 1c-e). Results of CT-guided percutaneous biopsy were consistent with the diagnosis of giant-cell tumor of the spine.
As per the protocol in a previous study, the patient was preoperatively administered 10 courses of denosumab (120 mg at a time) in monthly cycles with initial additional loading doses. Following denosumab therapy, her severe low back pain was resolved and no neurological deficits were noted. Follow-up pre-operative X-ray and CT revealed progression of anterior deviation and an increase in vertebral body mineralization (Fig. 1f and g). MRI revealed a decrease in tumor enhancement and a marked reduction in the tumor size in the retroperitoneum space and intraspinal canal region (Fig. 1h-j). The TRACP5b and ALP levels returned to normal after 3and 10courses of denosumab therapy, respectively (Table 1).
A combined anterior and posterior approach was used to perform the total spondylectomy of the L4 vertebra. First, we exposed the dura mater by en bloclaminectomy and detached the bilateral L4 pedicles using a threaded T-saw. The lamina and pedicles were rigid, and there was no adhesion between the dura mater and tumor section. The lateral aspect of the L4 vertebral body was exposed, and disc resection was performed using the posterior incision approach. Using the anterolateral approach, the vertebral body was resected piece by piece, and the bone in the regenerated cortical GCTB was treated with denosumab. Furthermore, corpectomy of L4 was performed; subsequently, titanium cage reconstruction was performed with posterior L3-L5 stabilization.
Postoperatively, the patient remains pain free without neurological symptoms, and there is no radiologic evidence of tumor recurrence for 1 year after surgery, i.e., following three courses of denosumab administered at 2-month intervals.
Light microscopy revealed numerous multinucleated giant cells in the background of neoplastic mononuclear stromal cells in pre-operative biopsy samples (Fig. 2a). Immunohistochemical staining revealed RANK-positive mononuclear cells and aggregations of strongly cyclooxygenase-2 (COX-2)-positive mononuclear stromal cells (Fig. 2b and c). The microscopic examination of tissues harvested after denosumab therapy revealed a fibrous matrix with no multinucleated giant cells (Fig. 2d). Immunohistochemistry detected RANK-positive cells around the woven bone, although almost all of the RANK and COX-2-positive cells disappeared (Fig. 2e and f).