Intralesional curettage and surgical adjuvants in the treatment of giant cell tumor of bone: meta-analysis and systematic review.

BACKGROUND: The ideal treatment for giant cell tumor of bone (GCTB) is still controversial. Various surgical adjuvants have been introduced following intralesional curettage to improve local control rates. However, findings from relevant studies are inconsistent, and no consensus has been reached. The purpose of this study is to determine what intraoperative adjuvant is effective in decreasing the recurrence of GCTB. METHODS: We performed a systematic review and meta-analysis of articles published in the PubMed and Embase electronic databases which assessed the recurrence rate of GCTB following intralesional curettage with or without various surgical adjuvants. Two authors independently evaluated all publications. Meta-analysis was performed with Stata/MP (Version 17.0, StataCorp LLC, TX, USA) and Review Manager (RevMan, Version 5.4.1, The Cochrane Collaboration, 2020). Pooled risk ratio (RR) was used for analysis, with P values less than 0.05 considered statistically significant. RESULTS: Twenty-four studies involving 2,579 patients were included in this analysis. The overall recurrence rates for patients treated with or without high-speed burring (HSB) are 11.9% (26/218) and 47.7% (92/193), respectively. The pooled RR for tumor recurrence is 0.33 (95% CI: 0.22 to 0.49, P<0.001). In the meanwhile, the overall recurrence rates for patients treated with or without chemical adjuvants are 23.5% (77/328) and 26.1% (73/280), respectively, with a pooled RR of 0.84 (95% CI: 0.63 to 1.10, P=0.89). Additionally, the overall recurrence rates for patients treated with or without polymethyl methacrylate (PMMA) are 20.4% (205/1,006) and 33.4% (314/939), respectively, with a pooled RR of 0.59 (95% CI: 0.50 to 0.69, P<0.001). CONCLUSIONS: Intraoperative application of HSB or PMMA has an additional antitumor effect, while the use of phenol or H2O2 fails to make any significant difference (PROSPERO: CRD42022344262).

Reconstruction of the extensor mechanism using polypropylene mesh in a displaced pathological fracture of the patella affected by giant cell tumour.

A man in his 30s came to our clinic with a year-long history of progressive pain and swelling in his knee. Diagnostic imaging revealed a displaced patellar fracture with an osteolytic, septated lesion and thinned expanded cortex in both fracture fragments. A core needle biopsy confirmed the diagnosis of giant cell tumour. Treatment involved wide excision of the tumour and the use of polypropylene mesh and a peroneal longus tendon autograft to reconstruct the extensor mechanism of the knee joint. One year postoperatively, the patient experienced no pain, demonstrated full range of motion and showed no signs of functional impairment or local tumour recurrence. This case highlights that reconstruction of the extensor mechanism of the knee after tumour excision with synthetic mesh is an affordable, user-friendly and widely accessible method. It can address large defects effectively while minimising the risks of disease transmission and graft lengthening, resulting in satisfactory outcomes.

The risk of neurological deterioration while using neoadjuvant denosumab on patients with giant cell tumor of the spine presenting with epidural disease: a meta-analysis of the literature.

BACKGROUND CONTEXT: Giant cell tumor (GCT) of bone is most commonly a benign but locally aggressive primary bone tumor. Spinal GCTs account for 2.7% to 6.5% of all GCTs in bone. En bloc resection, which is the preferred treatment for GCT of the spine, may not always be feasible due to the location, extent of the tumor, and/or the patient's comorbidities. Neoadjuvant denosumab has recently been shown to be effective in downstaging GCT, decreasing the size and extent of GCTs. However, the risk of neurologic deterioration is of major concern for patients with epidural spinal cord compression due to spinal GCT. We experienced this concern when a patient presented to our institution with a midthoracic spinal GCT with progressive epidural disease. The patient was not a good surgical candidate due to severe cardiac disease and uncontrolled diabetes. In considering nonoperative management for this patient, we asked ourselves the following question: What is the risk that this patient will develop neurologic deterioration if we do not urgently operate and opt to treat him with denosumab instead? PURPOSE: The purpose of this study was to assess the literature to (1) determine the risk of neurological deterioration in patients receiving neoadjuvant denosumab for the treatment of spinal GCT and (2) to evaluate the secondary outcomes including radiographic features, surgical/technical complexity, and histological features after treatment. STUDY DESIGN/SETTING: Meta-analysis of the literature. PATIENT SAMPLE: Surgical cases of spinal GCT that (1) presented with type III Campanacci lesions, (2) had epidural disease classified as Bilsky type 1B or above and (3) received neoadjuvant denosumab therapy. OUTCOME MEASURES: The primary outcome measure of interest was neurologic status during denosumab treatment. Secondary outcome measures of interest included radiographic features, surgical/technical complexity, histological features, tumor recurrence, and metastasis. METHODS: Using predetermined inclusion and exclusion criteria, PubMed and Embase electronic databases were searched in August 2022 for articles reporting spinal GCTs treated with neoadjuvant denosumab and surgery. Keywords used were "Spine" AND "Giant Cell Tumor" AND "Denosumab." RESULTS: A total of 428 articles were identified and screened. A total of 22 patients from 12 studies were included for review. 17 patients were female (17/22, 77%), mean age was 32 years (18-62 years) and average follow-up was 21 months. Most GCTs occurred in the thoracic and thoracolumbar spine (11 patients, 50%), followed by 36% in the lumbar spine and 14% in the cervical spine. Almost half of the patients had neurological deficits at presentation (10/22 patients, 45%), and more than 60% had Bilsky 2 or 3 epidural spinal cord compression. None of the patients deteriorated neurologically, irrespective of their neurological status at presentation (p-value=.02, CI -2.58 to -0.18). There were no local recurrences reported. One patient was found to have lung nodules postoperatively. More than 90% of cases had decreased overall tumor size and increased bone formation. Surgical dissection was facilitated in more than 85% of those who had documented surgical procedures. Four patients (18%) underwent initial spinal stabilization followed by neoadjuvant denosumab and then surgical excision of the GCT. Regarding the histologic analyses, denosumab eradicated the giant cells in 95% of cases. However, residual Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL)-positive stromal cells were noted, in 27% (6 cases). CONCLUSIONS: Neoadjuvant denosumab was a safe and effective means of treating spinal GCTs prior to surgery. Neurologic status remained stable or improved in all cases included in our review, irrespective of the presenting neurologic status. The most appropriate dosage and duration of denosumab therapy is yet to be determined. We recommend future well-designed studies to further evaluate the use of neoadjuvant denosumab for patients with spinal GCT.

Malignant giant cell tumour of distal ulna.

Giant cell tumour (GCT) accounts for 5% of all primary bone tumours. GCT in the distal third of ulna is quite rare. We present a case of recurrent GCT in distal third of ulna with malignant features involving tenosynovium. The case was treated by wide resection of tumour and on follow up, patient recovered well with no evidence of further recurrence. Considering the features, according to the literature reviewed, is the first case of its type.

Non-vascularized toe phalangeal transfer for reconstruction of a giant cell tumour of the proximal phalanx.

This article describes a 50-year-old woman with a giant cell tumour involving the base of the proximal phalanx, which was resected and reconstructed with a non-vascularised toe phalanx graft. The toe phalanx graft united well, and there was no tumour recurrence at the 24-month follow-up.

Giant Cell Tumor of the Acromion: Case Report and Literature Review.

BACKGROUND/AIM: Giant cell tumor of bone (GCTB) is a locally aggressive neoplasm that typically occurs in the ends (epiphyses) of long bones of young adults. Flat bones are uncommon sites of involvement. Herein, we describe an unusual case of pathologically proven GCT of the acromion. CASE REPORT: The patient was a 39-year-old woman with no history of trauma who presented with a 3-month history of right posterior shoulder pain. Physical examination revealed mild swelling and tenderness in the posterior aspect of the right shoulder. Plain radiograph showed a purely lytic lesion, suggestive of a bone tumor. Computed tomography demonstrated an intraosseous lytic lesion with associated cortical thinning and lack of periosteal reaction. On magnetic resonance imaging, the lesion exhibited slightly higher signal intensity compared to skeletal muscle on T1-weighted sequences and heterogeneous high signal intensity on T2-weighted sequences. Strong enhancement was observed following gadolinium administration. The lesion was treated by extensive curettage with adjuvant therapy comprising ethanol and the remaining cavity was filled with polymethylmethacrylate bone cement. Histologically, the lesion was composed of round or spindle-shaped mononuclear cells admixed with numerous osteoclast-like giant cells. Immunohistochemically, the mononuclear neoplastic cells were diffusely positive for H3.3 G34W. The patient was asymptomatic and there was no evidence of local recurrence or distant metastasis 5 months after surgery. CONCLUSION: Although rare, acromial GCTB should be considered in the differential diagnosis of posterior shoulder pain, especially in young and early middle-aged adults.

Denosumab for an inoperable giant cell tumour of the ischial bone.

Giant cell tumour of bone is a benign, locally aggressive osteolytic tumour that typically affects skeletally mature young individuals. It predominantly emerges within the metaphysis, extending towards the epiphysis of long bones, while occurrences in flat bones are exceptionally rare. We present a case of a woman in her late 20s who presented with a large right ischial mass. A biopsy confirmed the mass as a giant cell tumour. The tumour extended to the acetabulum, and due to the potential risk of significant bleeding and contamination during en bloc excision, a prudent approach involved initiating denosumab therapy, a monoclonal antibody targeting receptor activator of nuclear factor-κB ligand therapy, before proceeding with radical surgery. Denosumab therapy successfully rendered a previously inoperable tumour favourable for surgical intervention. We went on to perform a type 2 and 3 internal hemipelvectomy, followed by a reconstruction with a hip endoprosthesis replacement.

Conversion in a Resectable Tumor after Denosumab Neoadjuvant in a Large Dorsal Giant Cells Tumor: A Case Report and a Literature Review.

Giant cell tumors of bone are a rare entity, usually occurring in young patients and characteristically arising in the long bones. The spinal location is rare and usually presents with pain and/or neurological symptoms. The treatment of choice is surgery. Treatment with Denosumab, a bisphosphonate inhibitor of RANK-L, which is highly expressed in these tumors, has shown extensive activity in unresectable patients or those undergoing incomplete surgery. Preoperative treatment with this drug is gaining increasing interest, as its high potency in tumor reduction in this subtype of neoplasm has allowed resectability in selected patients. We present the case of a young patient with a large spinal tumor who, after neoadjuvant Denosumab, underwent complete en bloc surgery with clean margins and a great pathological response.

Heat treatment for giant cell tumors of bone: A systematic review.

This systematic review evaluates the effects of heat treatments in de novo, residual and recurrent giant cell tumors of bone (GCTB). Studies were eligible for inclusion if one of the following treatments was administered: radiofrequency ablation (RFA), microwave ablation, argon cauterization, electrocauterization and hot liquid treatment. The primary outcome was recurrence. Secondary outcomes were complications, pain, function, and quality of life. Recurrence rates for microwave ablation as an adjuvant to intralesional curettage were 0%, 4% and 10% (3 retrospective single-group studies); for argon cauterization 4%, 8% and 26% (3 cohort studies); electrocauterization 0% to 33% (8 cohort studies); and hot liquid 9.5% and 24% (2 cohort studies). Follow-up was generally ≥24 months. Data on pain, function and quality of life were scarce. Complications included infection and secondary osteoarthritis. Current evidence does not demonstrate or exclude an effect of heat treatments on recurrence in GCTB. Further research should objectify if (subgroups of) patients benefit from these treatments.

Treatment of pelvic giant cell tumor by wide resection with patient-specific bone-cutting guide and reconstruction with 3D-printed personalized implant.

BACKGROUND: This study reports our experience in the treatment of aggressive pelvic GCT through wide resection assisted with patient-specific bone-cutting guides (PSBCGs) and subsequent reconstruction with 3D-printed personalized implants (3DPIs), aiming to present the operative technique of this method and evaluate its clinical efficacy. METHODS: We retrospectively analyzed seven patients who underwent wide resection of pelvic GCT followed by reconstruction with 3DPIs from August 2019 to February 2021. There were two males and five females, with a mean age of 43 years. PSBCGs and 3DPIs were prepared using 3D-printing technology. The operational outcomes, local recurrence, radiological results, and any associated complications of this technique were assessed. And the functional outcomes were assessed according to the Musculoskeletal Tumor Society (MSTS) 93 functional score. RESULTS: The mean follow-up time was 35.3 months (range 28-45 months). There was no intraoperative complication. Negative surgical margins were achieved in all patients. Postoperative pelvic radiographs showed that 3DPIs matched the shape and size of the bone defect. The anterior-posterior, inlet, and outlet pelvic radiograph demonstrated precise reconstruction consistent with the surgical planning. In addition, tomosynthesis-Shimadzu metal artifact reduction technology (T-SMART) showed good osseointegration at an average of three months after surgery (range 2-4 months). There was no local recurrence or tumor metastasis. The average MSTS score was 24.4 (range 23-27) at the last follow-up. Delayed wound healing was observed in one patient, and the wounds healed after debridement. Prosthesis-related complications were not detected during the follow-up, such as aseptic loosening or structure failure. CONCLUSIONS: The treatment of aggressive pelvic GCTs through wide resection assisted with PSBCGs and subsequent reconstruction with 3DPIs is a feasible method, which provides good clinical results and reasonable functional outcomes.

Recurrent Giant Cell Tumor of Bone with New Pulmonary Metastases 9 Years After En Bloc Distal Radius Resection: A Case Report.

CASE: A 31-year-old man with a history of giant cell tumor of bone (GCTB) in the distal radius presents to clinic 9 years after en bloc distal radius resection. He was found to have a new soft tissue mass consistent with GCTB and new pulmonary metastases. Ultimately, he underwent excision of his soft tissue recurrence and partial lobectomy for his lung metastases. CONCLUSION: This case highlights the importance of having a high level of suspicion for local recurrence or metastasis, even years after wide resection and negative margins.

Effect evaluation of denosumab combined with curettage and bone cement reconstruction in the treatment of recurrent giant cell tumor of bone around the knee joint.

OBJECTIVE: Giant cell tumor of bone (GCTB) is a common primary bone tumor with latent malignant tendency. GCTB is prone to occur around the knee joint, and surgery is the major treatment method. There are relatively few reports on denosumab in the treatment of recurrent GCTB around the knee joint and postoperative function evaluation of patients. This research aimed to explore the appropriate surgical options for the treatment of recurrent GCTB around the knee joint. PATIENTS AND METHODS: 19 patients with recurrent GCTB around the knee joint, who were admitted to Hospital for 3 months following denosumab treatment from January 2016 to December 2019, were included as the research subjects. The prognosis was compared between patients treated with curettage combined with polymethylmethacrylate (PMMA) and those with extensive-resection replacement of tumor prosthesis (RTP). A deep learning model of Inception-v3 combined with a Faster region-based convolutional neural network (Faster-RCNN) was constructed to classify and identify X-ray images of patients. The Musculoskeletal Tumor Society (MSTS) score, short form-36 (SF-36) score, recurrence, and the rate of complications were also analyzed during the follow-up period. RESULTS: The results showed that the Inception-v3 model trained on the low-rank sparse loss function was obviously the best for X-ray image classification, and the classification and identification effect of the Faster-RCNN model was significantly better than that of the convolutional neural network (CNN), U-Net, and Fast region-based convolutional neural network (Fast-RCNN) models. During the follow-up period, the MSTS score in the PMMA group was significantly higher than that in the RTP group (p<0.05), while there was no significant difference in the SF-36 score, recurrence, and the rate of complications (p>0.05). CONCLUSIONS: The deep learning model could improve the classification and identification of the lesion location in the X-ray images of GCTB patients. Denosumab was an effective adjuvant for recurrent GCTB, and widely extensive-resection RTP could reduce the risk of local recurrence after denosumab treatment for recurrent GCTB.

The efficacy and safety of short-course neoadjuvant denosumab for en bloc spondylectomy in spinal giant cell tumor of bone: a preliminary report.

PURPOSE: This study aimed to investigate whether short course of neoadjuvant denosumab treatment for spinal GCTB could (1) Induce radiological and histological response? (2) Facilitate en bloc resection? (3) Achieve satisfactory oncological and functional outcomes? METHODS: The clinical information of ten consecutive patients between 2018 and 2022 with spinal GCTB treated with short course of neoadjuvant denosumab (≤ 5 doses) and en bloc spondylectomy was retrospectively reviewed. The radiological and histological response, operative data, oncological and functional outcomes were analyzed. RESULTS: The mean doses of neoadjuvant denosumab were 4.2 (range 3-5 doses). After neoadjuvant denosumab, there were 9 cases showing new ossification and 5 cases with reappearance of cortical integrity. The values of Hounsfield units (HU) of the soft tissue component were increased by > 50% in 7 cases. The signal intensity (SI) ratios of tumor/muscle in T2WI of plain MRI were decreased by > 10% in 60% of the cases. Shrinkage of soft tissue mass by > 10% was observed in 4 cases. The mean duration of operation was 575 ± 174 min, and the mean estimated blood loss (EBL) was 2790 ± 1934 ml. No obvious adhesion to dura mater or major vessels was encounter intraoperatively. There is no tumor collapse or breakage during surgery. Multinucleated giant cells were decreased in 6 cases (60%) with the remaining 4 cases showing absence of multinucleated giant cells. Mononuclear stromal cells existed in most of the cases (8 cases, 80%). New bone formation was noticed in 8 cases (80%). No patient had a worsening of neurologic function after surgery. No tumor recurrence was noticed within the mean follow-up of 24 ± 20 months. CONCLUSION: Short-term neoadjuvant denosumab could yield radiological and histological responses and might facilitate en bloc spondylectomy by hardening the tumor and causing less adhesion to segmental vessels, major vessels and nerve roots, which was beneficial to achieve the optimal oncological and functional outcomes.

An improved total en bloc spondylectomy for L5 vertebral giant cell tumor through a single-stage posterior approach.

PURPOSE: Although total en bloc spondylectomy (TES) is strongly recommended for spinal giant cell tumor (GCT), it is extremely difficult to excise a L5 neoplasm intactly through the single-stage posterior approach. Given the risk of neurological and vascular injury, intralesional curettage (IC) is usually recommended for the treatment of L5 GCT. In this study, we presented our experience with the use of an improved TES to treat L5 GCT through the single-stage posterior approach. METHODS: This study included 20 patients with L5 GCT who received surgical treatment in our department between September 2010 and April 2021. Of them, seven patients received improved TES without iliac osteotomy, and the other 13 patients received IC (n = 8), sagittal en bloc resection (n = 1), TES with iliac osteotomy (n = 3), and TES with radicotomy (n = 1) as control. RESULTS: The mean operative time was 331.43 ± 92.95 min for improved TES group and 365.77 ± 85.17 min for the control group (p = 0.415), with the mean blood loss of 1142.86 ± 340.87 ml vs. 1969.23 ± 563.30 ml (p = 0.002). Postoperative treatment included bisphosphonates in nine patients and denosumab in 12 patients including one patient who changed from bisphosphonates to denosumab. Three patients who received IC experienced local recurrence, and no relapse was observed in improved TES group. CONCLUSION: Single-stage posterior TES for L5 GCT was previously considered impossible. In this study, we presented our experience with the use of an improved surgical technique for L5 TES through the single-stage posterior approach, which has proved to be superior to the conventional procedures in terms of blood loss control and complication and recurrence rates. LEVEL OF EVIDENCE: IV.

Giant Cell Tumor of the Temporal Bone and Skull Base.

Giant cell tumor (GCT) is a benign tumor that originates from undifferentiated mesenchymal cells of the bone marrow. The craniums as well as temporal bone are extremely rare locations for GCTs. Clinical, radiological, and anatomical diagnosis of this locally aggressive disease poses a major challenge in clinical practice. In this article, we present a clinical study for a 35-year-old female who was found to have left-sided temporal bone GCT with extension to middle cranial fossa and temporomandibular joint (TMJ) with its clinical features and management.

Multicentric Giant Cell Tumor of Bone.

The typical presentation of giant cell tumor of bone is a solitary lesion involving the meta-epiphyseal region of the long bones. The presence of more than one distinct giant cell tumor in the same patient is rare. This study reports on 7 patients with multicentric giant cell tumor of bone. Clinical and radiologic features were reviewed to evaluate the behavior of multicentric giant cell tumor of bone. Immunohistochemistry and genetic analysis for the H3F3A gene were performed to confirm the diagnosis. The knee was most frequently involved, and most of the lesions were in an ipsilateral extremity. All of the patients received surgical management with curettage or resection. The overall median follow-up was 194 months (interquartile range, 41-336 months). Five of 7 patients had local recurrence (71%), but considering the number of surgically treated lesions, the risk of local recurrence was 33% (5 local recurrences among 15 treated lesions). No lung metastases occurred. Multicentric giant cell tumor of bone tends to exhibit the same aggressive clinical behavior as solitary giant cell tumor of bone. Patients should be monitored for the occurrence of other lesions, especially in the ipsilateral extremity. [Orthopedics. 2023;46(6):e376-e380.].

Preoperative denosumab treatment in patients with giant cell bone tumors in limbs: A retrospective study using propensity score matching.

BACKGROUND AND OBJECTIVES: Denosumab is recommended for advanced giant cell tumor of bone (GCTB) that is unresectable or resectable with unacceptable morbidity. But the effect of preoperative denosumab treatment on the local control GCTB remains controversial. METHODS: We conducted a study of 49 patients with GCTB in the limbs treated with denosumab before surgery and 125 patients without in our hospital from 2010 to 2017. Propensity-score matching (PSM) at a 1:1 ratio between the denosumab and control groups was performed to minimize possible selection bias, and compared the recurrence rate, limb function, and surgical degradation between the two groups. RESULTS: The 3-year recurrence rates in the denosumab group and the control group were 20.4% and 22.9% after PSM, respectively (p = 0.702). In the denosumab group, 75.5% (n = 37/49) of patients experienced surgical downgrading. Limb joint preservation rates were 92.1% (35) for 38 patients treated with denosumab and 60.2% (71) for 118 control subjects. (p ≺ 0.001). Postoperative MSTS were higher in patients in the denosumab group than in the control group (24.1 vs. 22.6, p = 0.034). CONCLUSIONS: Preoperative denosumab treatment did not result in an increased risk of local recurrence of GCTB. Patients with advanced GCTB may benefit from preoperative denosumab treatment for surgical downgrading and the preservation of the joint.

An Arthroscopic Approach for the Intralesional Curettage of Giant Cell Tumor of the Distal Femur: A Case Report.

As a locally aggressive primary benign tumor, giant cell tumor of bone (GCTB) presents a challenge to surgeons, as it often recurs regardless of surgical resection. This report describes a case of GCTB of the distal femur in a man, aged 39 years, treated with intralesional curettage through an arthroscopic approach. A 360° view of the tumor cavity can be achieved with the help of an arthroscope, which can help complete intralesional curettage and minimize possible larger approach-related complications. The result is favorable in terms of functional outcome and recurrence after 1-year follow-up.

Association between preoperative denosumab and the risk of local recurrence in patients with giant cell tumor of bone: A meta-analysis and systematic review.

Objectives: This meta-analysis aimed at determining the association between preoperative denosumab and the risk of local recurrence in patients with giant cell tumors of the bone. Methods and Materials: Web of Science, EMBASE, Cochrane Library, and PubMed were comprehensively searched on April 20th, 2022. Data from the included articles were analyzed using meta-analysis. The bias of all included studies was evaluated according to ROBINS-I. Also, subgroup and sensitivity analyses were performed. Results: Eight studies with 1270 cases (195 in the denosumab group and 1075 in the control group) were eventually included. Patients receiving denosumab before curettage had a higher risk of local recurrence than those who underwent curettage alone (odds ratio: 2.29, 95% confidence intervals: 1.44-3.64, P = 0.0005). The denosumab group showed a significantly higher risk of local recurrence in most subgroup analyses, except for those with preoperative denosumab duration ≤six months/doses (P = 0.66) and sample size ranging from 100 to 180 (P = 0.69). Conclusion: Denosumab before curettage may increase the risk of local recurrence in patients with giant cell tumor of the bone. Preoperative denosumab should be used with caution after weighing an increased risk of local recurrence against the clinical benefits and a duration time of less than six months before surgery is recommended.