• Campanacci
• Case report
• Excision
• Giant cell tumour
• Tenodesis

• Case report
• Cervical spine
• Corpectomy
• Denosumab
• Giant cell tumor

• Humans
• Male
• Giant Cell Tumor of Bone/diagnosis
• Giant Cell Tumor of Bone/genetics
• Giant Cell Tumor of Bone/pathology
• Female
• India
• Middle Aged
• Adult
• Adolescent
• Immunohistochemistry/methods
• Bone Neoplasms/diagnosis
• Bone Neoplasms/pathology
• Young Adult
• Tertiary Care Centers
• Aged
• Histones/genetics
• Child
• Biomarkers, Tumor/genetics
• Diagnosis, Differential

• Cranial fossa, posterior
• Denosumab
• Giant cell tumor of bone
• H3-3A protein, human

• 800-20220266 Seoul National University
• 0520200030 Seoul National University Hospital

• Denosumab
• Giant cell tumors
• Prognosis
• Spine
• Surgery
• Survival analysis

• PET
• denosumab
• giant cell tumor of bone
• metastasis
• unresectable

• Arthrodesis
• Arthrodèse
• Arthroplastie
• Arthroplasty
• Distal radius
• Fibular flap
• Giant-cell tumor
• Lambeau de fibula
• Radius distal
• Resection
• Résection
• Tumeur à cellules géantes

• Bone Neoplasms/pathology
• Bone Neoplasms/surgery
• Bone Transplantation/methods
• Giant Cell Tumor of Bone/surgery
• Humans
• Neoplasm Recurrence, Local/pathology
• Neoplasm Recurrence, Local/surgery
• Radius/pathology
• Radius/surgery
• Retrospective Studies
• Treatment Outcome

Background and objective

There is scarce data on demography and different surgical treatment modalities for giant cell tumor of bone (GCTB) from eastern India. In light of this, the present study aimed to examine the demographic characteristics, different surgical treatment modalities, and recurrence rate of GCTB at a tertiary care institute in Bihar.

Materials and methods

A retrospective audit of 52 GCTB patients who were treated at the center from January 2016 to December 2020 was conducted. The minimum follow-up period was one year. GCTB patients underwent surgical procedures ranging from extended intralesional curettage with bone graft or bone cement with or without fixation to wide local excision to resection with or without reconstruction or amputation depending on the stage and site of the tumors.

Results

The mean age of patients was 31.86 years (range: 13-67 years). The distal femur (20 patients, 38.46%) and proximal tibia (11 patients, 21.15%) were the most common sites of the tumor. Sixty-eight confirmed cases (male: 32, female: 36) of GCTB were operated on, with a male-to-female ratio of 1:1.125. Sixteen patients (four males and 12 females) were lost to follow-up. So, the final study consisted of 52 patients with a median age of 28 years (first quartile: 24 years, third quartile: 38 years). The majority of patients (32 patients, 61.53%) were in the third and fourth decades of life.

Conclusion

Based on this retrospective audit, it is concluded that the knee region is the most common site of GCTB. Surgery is the mainstay of management. Most of the patients came under Campanacci Grade 3 with low compliance with follow-up and adherence to the treatment. Hence, educational programs, the establishment of early detection centers, and timely referral to expert treatment are necessary.

En bloc resection is typically performed to treat giant cell tumors of bone (GCTB), particularly when curettage can be challenging owing to extensive bone cortex destruction with soft tissue extension. Few reports have addressed the clinical outcomes after reoperation for local recurrence in patients with GCTB who underwent en bloc resection. In this multicenter retrospective study, we investigated local recurrence, distant metastasis, malignant transformation, mortality, and limb function in patients treated for local recurrence following en bloc resection for GCTB. Among 205 patients who underwent en bloc resection for GCTB of the extremities between 1980 and 2021, we included 29 with local recurrence. En bloc resection was performed for large tumors with soft tissue extension, pathological fractures with joint invasion, complex fractures, and dispensable bones, such as the proximal fibula and distal ulna. Local re-recurrence, distant metastasis, malignant transformation, and mortality rates were 41.4% (12/29), 34.5% (10/29), 6.9% (2/29), and 6.9% (2/29), respectively. The median Musculoskeletal Tumor Society score was 26 (interquartile range, 23–28). The median follow-up period after surgery for local recurrence was 70.1 months (interquartile range, 40.5–123.8 months). Local recurrence following en bloc resection for GCTB could indicate an aggressive GCTB, necessitating careful follow-up.

• Adult
• Bone Neoplasms
• Female
• Giant Cell Tumor of Bone/pathology
• Giant Cell Tumor of Bone/radiotherapy
• Humans
• Male
• Neoplasm Recurrence, Local
• Neoplasms, Second Primary
• Prognosis
• Retrospective Studies
• Sarcoma

(1) Background: Giant Cell Tumor of the spine remains a difficult tumor to treat. Recent advances in adjuvant therapy such as denosumab and innovations in surgical technique in the last 5 years have given providers new options for treatment after a successful diagnosis of the tumor. (2) Methods: Articles published between 1927 and 2021 were selected from PubMed and Scopus searches using key words “Giant Cell Tumor” AND “Lumbar Spine” AND “Treatment”. Relevant articles were reviewed and selected by the authors. (3) Results: A total of 191 articles were discovered. Complete en bloc spondylectomy remains the most definitive treatment option; however, this surgery is challenging and carries a high rate of complication. New adjuvant therapies including denosumab offer a viable alternative to surgery. (4) En bloc spondylectomy remains the gold standard treatment for Giant Cell Tumor of the spine with the lowest published recurrence rate. The use of (neo)adjuvant denosumab improves recurrence rates. More data are needed to determine if denosumab alone is a viable standalone definitive treatment.

• Bone Density Conservation Agents
• Denosumab
• Giant Cell Tumor of Bone/surgery
• Humans
• Lung
• Lung Neoplasms/surgery
• Metastasectomy

Giant cell tumor of bone (GC), osteosarcoma (OS) and Ewing’s sarcoma (ES) are three different types of bone cancer with common and specific pathology features.

The purpose of the study was to examine the relationship and differences of the three bone tumors using clinical samples.

Through screening the profiles of clinical samples from GC, OS and ES patients using a humanoncology array, we found 26, 25 and 15 tumorigenesis factors significantly increased in GS, OS and ES tissues compared to normal individuals. eNOS, endostatin, HIF-1α, IL-6, CCL2/MCP-1, CCL8/MCP-2, CCL7/MCP-3, Tie and VEGF directly or indirectly involve in the metastasis Therefore, expression levels of the 6 factors were further determined by Western blot.

The results showed levels of MCP1, MCP2, MCP3 or IL-6 in the GS, OS and ES significantly increased, and the expression levels of angiogenesis and anti-angiogenesis factors containing eNOS, endostatin, HIF-1α, Tie or VEGF were enhanced.

Our results suggest that eNOS, endostatin, HIF-1α, IL-6, CCL2/MCP-1, CCL8/MCP-2, CCL7/MCP-3, Tie and VEGF may play important roles in tumorigenesis, reveal the expression differences of tumor-associated cytokines and angiogenesis related factors, and provide clinical evidence for studying the mechanisms on the metastasis in GC, OS and ES.

• Ewing’s sarcoma
• Giant cell tumor of bone
• metastasis
• osteosarcoma

According to the 2020 World Health Organization classification, a giant cell tumor of bone is an intermediate malignant bone tumor. Denosumab treatment before curettage should be avoided due to the increased risk of local recurrence. Administration of denosumab before en bloc resection of the giant cell tumors of the pelvis and spine facilitates en bloc resection. Nerve-sparing surgery after embolization is a possible treatment for giant cell tumors of the sacrum. Denosumab therapy with or without embolization is indicated for inoperable giant cell tumors of the pelvis, spine, and sacrum. A wait-and-see approach is recommended for lung metastases at first, then denosumab should be administered to the growing lesions. Radiotherapy is not recommended owing to the risk of malignant transformation. Local recurrence after 2 years or more should be indicative of malignant transformation. This review summarizes the treatment approaches for non-malignant and malignant giant cell tumors of bone.

The 2020 World Health Organization classification defined giant cell tumors of bone (GCTBs) as intermediate malignant tumors. Since the mutated H3F3A was found to be a specific marker for GCTB, it has become very useful in diagnosing GCTB. Curettage is the most common treatment for GCTBs. Preoperative administration of denosumab makes curettage difficult and increases the risk of local recurrence. Curettage is recommended to achieve good functional outcomes, even for local recurrence. For pathological fractures, joints should be preserved as much as possible and curettage should be attempted. Preoperative administration of denosumab for pelvic and spinal GCTBs reduces extraosseous lesions, hardens the tumor, and facilitates en bloc resection. Nerve-sparing surgery after embolization is a possible treatment for sacral GCTBS. Denosumab therapy with or without embolization is indicated for inoperable pelvic, spinal, and sacral GCTBs. It is recommended to first observe lung metastases, then administer denosumab for growing lesions. Radiotherapy is associated with a risk of malignant transformation and should be limited to cases where surgery is impossible and denosumab, zoledronic acid, or embolization is not available. Local recurrence after 2 years or more should be indicative of malignant transformation. This review summarizes the treatment approaches for non-malignant and malignant GCTBs.

• bisphosphonate
• denosumab
• giant cell tumor of bone
• malignant transformation
• metastasis
• recurrence
• surgery

• Chest metastasis
• Curettage
• Giant cell tumor
• Recurrence
• Resection
• Risk factors
• Treatment

• chest wall reconstruction
• giant cell tumor
• osteoma
• sternal resection

• EMMT
• breast carcinoma metastasis
• epithelial-mesenchymal-myeloid transition
• giant cell tumor of bone
• metastasis
• osteoclast
• tumor biology

• Animals
• Epithelial-Mesenchymal Transition/physiology
• Humans
• Neoplasm Metastasis/pathology
• Neoplasms/pathology
• Osteoclasts/pathology

• Giant cell tumour
• Prognosis
• Pulmonary metastasis
• Risk factors

• Bone Neoplasms/epidemiology
• Bone Neoplasms/therapy
• Giant Cell Tumor of Bone/epidemiology
• Humans
• Neoplasm Recurrence, Local/epidemiology
• Prognosis
• Retrospective Studies

The WHO defines giant cell tumor as a benign locally aggressive neoplasm with metastasizing capacity and aggressive behavior. Very rarely, these tumors are seen fungating, mostly when neglected. But when they do, the treatment option commonly conferred is amputation of the limb which is disabling and traumatizing.

We report three cases of fungating limb masses (proximal tibia, distal fibula, and distal radius) diagnosed with giant cell tumor histologically, undergoing limb saving surgeries with various reconstruction techniques to endorse a good quality of life and functioning limb.

Our study is one of the earliest to report medium-term follow-up after such limb salvage procedure. We recommend that salvage procedures should be considered in giant cell tumors even in the presence of fungation if there is no neurovascular encasement.

• Giant cell tumor
• endoprosthesis
• fungation
• limb salvage surgery
• mesh reconstruction

In the treatment of giant cell tumor of bone (GCTB), the efficacy and safety of denosumab, a receptor activator nuclear factor κ-B ligand inhibitor, has previously been demonstrated, especially for unresectable tumors. One of the current issues in denosumab treatment for unresectable GCTB is whether it can be discontinued, or whether the dosage or the dosing interval can safely be adjusted, if discontinuation is not possible, to avoid the occurrence of side effects.

A 15-year-old boy with diplopia was referred to our hospital after a space-occupying lesion in the sphenoid bone was found on head CT. Partial removal of the tumor was performed through an endoscopic endonasal approach, and pathological diagnosis was confirmed as GCTB. Thereafter, the patient received 120 mg subcutaneous injections of denosumab every 28 days for the first 2 years. Since bone formation was induced and sustained along with tumor reduction, the dosing interval was gradually extended, with 4 monthly dosing for the next 1 year, followed by 6 monthly dosing for the succeeding 2 years. With the extension of the dosing interval, the ossified tumor has regrown slightly, but within an acceptable range.

Discontinuation of denosumab treatment for unresectable GCTB was not thought to be possible for the current case due to the nature of the drug, as reported in the literature. Extending the dosing interval up to 6 monthly, as could be done safely in the current case, can be considered a useful and appropriate measure.

• Denosumab
• Dosing interval
• Giant cell tumor of bone
• Sphenoid bone

• Giant cell tumor of bone
• Metastasis in GCT
• Seeding of tumor cells in GCT
• Soft-tissue recurrence in GCT

• Giant cell tumor
• Immunotherapy
• Resection
• Spinal
• Surgery

• denosumab
• elderly
• giant cell tumor of bone
• histone 3.3 G34W
• unresectable

Bone lesions can present the multi-displinary team with a challenge by way of diagnosis as some lesions share many radiological and histological characteristics. Giant cell tumours of the bone (GCTB) are relatively common, benign bone tumours. Aneurysmal bone cysts (ABC) are less common benign osteolytic lesions that are histologically similar to GCTBs but produce blood filled cavities. Both GCTBs and ABCs are locally aggressive and are typically found on meta-epiphyseal regions of long bones with pelvic tumours being less common.

A 17-year old female presented with atraumatic right groin pain and was initially diagnosed with a GCTB on the right superior pubic ramus of the pelvis. The patient was treated successfully with a wide excision, curettage and bone graft and underwent open reduction and internal fixation of the right hemi-pelvis. Following further intra-operative histological investigations, the lesion was diagnosed as an ABC.

This patient has had an uncomplicated post-operative course, has returned to comfortable weight bearing and will be reviewed for minimum 5 yr in the out-patient setting to monitor for reoccurrence.

• Pelvic
• Tumour
• Aneurysmal bone cyst
• Giant cell tumour
• Open reduction internal fixation of pelvis
• Case report

• Denosumab
• Giant cell tumor of bone
• H3F3A
• Histone H3.3
• Immunohistochemistry
• Mutation

• Bone Density Conservation Agents/therapeutic use
• Bone Neoplasms/diagnosis
• Bone Neoplasms/drug therapy
• Bone Neoplasms/genetics
• Bone Neoplasms/pathology
• Denosumab/therapeutic use
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Giant Cell Tumor of Bone/diagnosis
• Giant Cell Tumor of Bone/drug therapy
• Giant Cell Tumor of Bone/genetics
• Giant Cell Tumor of Bone/pathology
• Histiocytes/metabolism
• Histiocytes/pathology
• Histones/genetics
• Histones/metabolism
• Humans
• Immunohistochemistry
• Mutation
• Neoplasm Grading
• Neoplasm Recurrence, Local/diagnosis
• Neoplasm Recurrence, Local/drug therapy
• Neoplasm Recurrence, Local/genetics
• Neoplasm Recurrence, Local/pathology
• Osteoblasts/metabolism
• Osteoblasts/pathology
• Osteoclasts/metabolism
• Osteoclasts/pathology
• RANK Ligand/genetics
• RANK Ligand/metabolism
• Receptor Activator of Nuclear Factor-kappa B/genetics
• Receptor Activator of Nuclear Factor-kappa B/metabolism
• Sarcoma/diagnosis
• Sarcoma/drug therapy
• Sarcoma/genetics
• Sarcoma/pathology

• Giant cell bone tumor
• Lower limbs
• Lung metastases
• Meta-analysis
• Osteosarcoma
• Risk factors
• Tumor recurrence

• RANKL
• denosumab
• giant cell tumor of bone
• pulmonary metastasis
• recurrence

• chemotherapy
• radiotherapy

• Giant cell tumor of the bone
• Giant cell tumors
• Stage III
• lung metastasis
• metastasis
• receptor activator nuclear kappa-B ligand
• tumor recurrence
• tumor staging

• Denosumab
• Giant cell tumor of bone
• H3F3A
• Immunohistochemistry
• Mutation

• COA1 (cytochrome C oxidase assembly factor 1 homolog)
• Giant cell tumor of bone
• PDIA6 (protein disulfide isomerase family A, member 6)
• miR-127-3p
• miR-376a-3p
• microRNA

• Animals
• Bone Neoplasms/genetics
• Bone Neoplasms/metabolism
• Bone Neoplasms/pathology
• Cell Line, Tumor
• Cell Proliferation/genetics
• Chick Embryo
• Electron Transport Complex IV/genetics
• Electron Transport Complex IV/metabolism
• Genes, Tumor Suppressor
• Giant Cell Tumor of Bone/genetics
• Giant Cell Tumor of Bone/metabolism
• Giant Cell Tumor of Bone/pathology
• Heterografts
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Protein Disulfide-Isomerases/genetics
• Protein Disulfide-Isomerases/metabolism
• Transfection

Giant cell tumors of the distal radius are challenging for surgeons because they are associated with high recurrence rates and poor functional outcomes. Between June 2005 and October 2015, patients with primary giant cell tumors of the distal radius were recruited from seven orthopedic centers in China. The patients’ clinical features and demographic characteristics were obtained from medical records and reviewed retrospectively. Overall, 48 cases of giant cell tumors of the distal radius were assessed in this study. These patients were more likely to be between 20 and 40 years of age, to have a Campanacci grade of III, and to undergo a surgical style of resection. The prevalence of pathological fractures was 12.5% overall (20.0% in men and 4.3% in women). The prevalence of local recurrence was 30.0% overall (38.1% in men and 21.1% in women) during the average follow-up period of 62.5 months, with a pulmonary metastasis rate of 5.0%. Giant cell tumors of the distal radius were predominant in men and were more likely to recur locally than around the knee. These findings suggest that it is crucial to evaluate the optimal surgical approach for balancing local recurrence control and functional outcomes to reduce the disease burden.

• Epidemiology
• Primary osseous tumors
• Spine

• Giant cell tumor
• Osteoclasts
• miRNAs

Giant cell tumors of the bone (GCTBs) are commonly diagnosed in Asian populations, usually around the knee. Herein, we aimed to determine the clinical characteristics, local recurrence rates, and relevant risk factors of primary GCTB around the knee. Univariate and multivariate survival analyses were used to identify the risk factors for local recurrence. Four hundred ten patients with primary GCTB around the knee, treated between March 2000 and June 2014, were recruited from 7 institutions in China. The overall local recurrence rate was 23.4%, but was higher in patients aged 20–39 years (28.5%; P = 0.039). The local recurrence rate was the highest in patients treated with intralesional curettage (53.4%), and the lowest in those treated with resection (4.9%). We found a higher risk of tumor recurrence in the proximal fibula compared to the distal femur (hazard ratio: 28.52, 95% confidence interval: 5.88–138.39; P < 0.0001), and in patients treated with curettage compared to those treated with resection (hazard ratio: 12.07, 95% confidence interval: 4.99–29.18; P < 0.0001). Thus, the tumor location must be considered when selecting the optimal surgical treatment approach to reduce the risk of local recurrence and preserve joint function, especially in young patients.

• Bone tumor
• Denosumab
• Giant cell tumor of bone
• Targeted therapy

• Adolescent
• Adult
• Bone Neoplasms/drug therapy
• Bone Neoplasms/pathology
• Bone and Bones/drug effects
• Bone and Bones/pathology
• Denosumab/therapeutic use
• Female
• Giant Cell Tumor of Bone/drug therapy
• Giant Cell Tumor of Bone/pathology
• Humans
• India
• Male
• Middle Aged
• Neoplasm Recurrence, Local/pathology
• Referral and Consultation
• Young Adult

• Adult
• Aged
• Bone Neoplasms/mortality
• Bone Neoplasms/pathology
• Bone Neoplasms/therapy
• Female
• Giant Cell Tumors/mortality
• Giant Cell Tumors/pathology
• Giant Cell Tumors/therapy
• Humans
• Lung Neoplasms/mortality
• Lung Neoplasms/secondary
• Lung Neoplasms/therapy
• Male
• Middle Aged
• Prognosis
• Retrospective Studies
• Survival Rate
• Taiwan/epidemiology
• Young Adult

• giant cell tumor of bone
• neoplasm recurrence, local

We aimed to determine the demographic characteristics of giant cell tumor around the knee in China.

Between March 2000 and June 2014, patients with primary giant cell tumor around the knee were recruited from 6 institutions located in different regions of China, and were reviewed retrospectively the clinical features according to gender and age.

334 qualified patients were included in this study. The sex ratio was 1.14:1 (178/156), with mean ages of 36.9 years in men and 33.1 years in women, constituting a significant difference (P=0.007). The prevalence of pathological fracture was 32.9% overall (28.7% in men and 37.8% in women). The prevalence of simple fracture was significantly higher in women (26.3%) than in men (15.2%), P=0.042. Tumor location and staging did not differ significantly according to sex (P>0.05). However, comparing with >40 years old, those patients aged ≤40 were more likely to have a right knee tumor (56.7% vs. 44.7%, P=0.042), less likely to have Enneking stage 3 disease (18.6% vs. 35.0%, P=0.005), and less likely to have both soft-tissue extension and a mass (18.6% vs. 34.0%, P=0.009).

Giant cell tumor around the knee was more common in men than in women, although female patients were younger on average. Further, cases among patients ≤40 years old were observed to be milder than cases among older patients. The results suggest that efficient treatment and preservation of function should both be valued for young patients with giant cell tumor around the knee.

•

This is the first report of primary GCT around the knee in China.

• Clinical
• Epidemiology
• Giant cell tumor
• Knee
• Retrospective study

Giant cell tumor of bone (GCTB) is a very rare tumor entity, which is little examined owing to the lack of established cell lines and mouse models and the restriction of available primary cell lines. The stromal cells of GCTB have been made responsible for the aggressive growth and metastasis, emphasizing the presence of a cancer stem cell population. To identify and target such tumor-initiating cells, stromal cells were isolated from eight freshly resected GCTB tissues. Tumorigenic properties were examined by colony and spheroid formation, differentiation, migration, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, immunohistochemistry, antibody protein array, Alu in situ hybridization, FACS analysis and xenotransplantation into fertilized chicken eggs and mice. A sub-population of the neoplastic stromal cells formed spheroids and colonies, differentiated to osteoblasts, migrated to wounded regions and expressed the metastasis marker CXC-chemokine receptor type 4, indicating self-renewal, invasion and differentiation potential. Compared with adherent-growing cells, markers for pluripotency, stemness and cancer progression, including the CSC surface marker c-Met, were enhanced in spheroidal cells. This c-Met-enriched sub-population formed xenograft tumors in fertilized chicken eggs and mice. Cabozantinib, an inhibitor of c-Met in phase II trials, eliminated CSC features with a higher therapeutic effect than standard chemotherapy. This study identifies a c-Met⁺ tumorigenic sub-population within stromal GCTB cells and suggests the c-Met inhibitor cabozantinib as a new therapeutic option for targeted elimination of unresectable or recurrent GCTB.