Giant Cell Tumor Research Articles

UK guidelines for the management of bone sarcomas.

This document is an update of the British Sarcoma Group guidelines (2016) and provides a reference standard for the clinical care of UK patients with primary malignant bone tumours (PMBT) and giant cell tumours (GCTB) of bone. The guidelines recommend treatments that are effective and should be available in the UK, and support decisions about management and service delivery. The document represents a consensus amongst British Sarcoma Group members in 2024. Key recommendations are that bone pain, or a palpable mass should always lead to further investigation and that patients with clinical or radiological findings suggestive of a primary bone tumour at any anatomic site should be referred to a specialist centre and managed by an accredited bone sarcoma multidisciplinary team. Treatment recommendations are provided for the major tumour types and for localised, metastatic and recurrent disease. Follow-up schedules are suggested.

Repurposing of PSMA-targeted diagnostic and therapeutic agents for the detection and treatment of giant cell tumors of bone

Giant cell tumor of bone (GCTB) is a rare bone tumor often necessitating surgical intervention, radiation therapy, or treatment with bisphosphonates or denosumab. 99mTc-MDP bone scintigraphy for GCTB has limited specificity, and the relatively high uptake of 18F-FDG in GCTB makes it challenging to differentiate it from other benign bone tumors. More specific detection and treatment modalities for GCTB are needed to enhance patient monitoring and outcomes. Prostate Specific Membrane Antigen (PSMA) is present in the neovasculature of various tumors, yet unexplored in GCTB. PSMA-targeted imaging and radiotherapeutic agents Locametz and Pluvicto are a powerful theranostic pair for detecting and treating PSMA-positive metastatic tumors, including those in bone, and thus have considerable potential to be repurposed for GCTB. This study aimed to determine if the vasculature of GCTB was PSMA-positive and whether targeting it with PSMA-specific agents was feasible. Using bone core samples from 28 GCTB patients and 9 negative controls, we present the first robust detection of PSMA on the tumor vasculature of GCTB. To demonstrate the potential repurposed use of PSMA-targeted agents in detecting and treating GCTB, we used a PSMA-specific fluorescent probe (FAM-C6-1298) as a model for these radiopharmaceutical agents. Incubation of fresh GCTB tissue samples with FAM-C6-1298 showed increased fluorescence intensity compared to controls, indicating successful targeting of PSMA in GCTB tissue. In conclusion, our data established that PSMA is not only present in the tumor vasculature of GCTB patient tissue but can be effectively targeted with repurposed PSMA-specific radiopharmaceuticals for diagnosis and therapy.

Cognitive Bias: Chromoblastomycosis misdiagnosed as a giant cell tumor of soft tissue in a kidney transplant recipient.

Cognitive Bias: Chromoblastomycosis misdiagnosed as a giant cell tumor of soft tissue in a kidney transplant recipient.

Pimicotinib Significantly Improves Outcomes for Patients with Tenosynovial Giant Cell Tumor

Results from the Phase 3 MANEUVER trial (NCT05804045) of pimicotinib (ABSK021), an investigational orally administered, highly selective, and potent small-molecule inhibitor of colony-stimulating factor-1 receptor (CSF-1R) being developed by Abbisko Therapeutics, met its primary endpoint, demonstrating significant improvement in objective response rate (ORR) in patients with tenosynovial giant cell tumor (TGCT). The ORR for pimicotinib at week 25 was 54.0% compared with 3.2% for placebo (p<0.0001).

A phase 4, multicenter, global clinical study to evaluate discontinuation and rechallenge of pexidartinib in patients with tenosynovial giant cell tumor previously treated with pexidartinib.

Pexidartinib is effective in patients with tenosynovial giant cell tumor (TGCT) for whom surgery is not feasible. Durability of response after discontinuation of pexidartinib and the safety and efficacy of restarting pexidartinib have not been previously recorded. This phase 4 study was designed to mimic the real-world experience with pexidartinib to evaluate the effects of discontinuation of and retreatment with pexidartinib in patients with TGCT who previously benefited from the drug. This was a global, multicenter, phase 4 study that enrolled patients with TGCT who were experiencing clinical benefit from pexidartinib in one of four prior phase 1 or phase 3 studies investigating pexidartinib in the disease. Patients could choose to continue pexidartinib at the same dose (the treatment-continuation cohort) or discontinue treatment with the option to restart pexidartinib (the treatment-free/retreatment cohort). Tumor progression determined by Response Evaluation Criteriain Solid Tumors (RECIST) version 1.1, patient-reported outcomes (the Patient-Reported Outcomes Measurement Information System-Physical Function [PROMIS-PF] questionnaire and the EuroQol 5-dimension, 5-level [EQ-5D-5L] visual analog scale), and safety were assessed every 3 months. The primary end point was the proportion of patients in the treatment-free/retreatment cohort who remained treatment-free at month 12 and 24; this did not depend on disease progression. Thirty-two patients were enrolled: 21 chose to enter the treatment-continuation cohort, and 11 entered the treatment-free/retreatment cohort. During the treatment-free period, six of 11 (54.5%) patients in the treatment-free/retreatment cohort had progressive disease (PD) according to RECIST, version 1.1, whereas no patient in the treatment-continuation cohort had disease progression. Over the 24-month study, three of 11 (27.3%) patients in the treatment-free/retreatment cohort restarted treatment because of RECIST version 1.1 PD, symptomatic progression, or both (n=1 each). The probability of remaining treatment-free in the treatment-free/retreatment cohort was 73% (95% confidence interval, 37%-90%). In the treatment-free/retreatment cohort, the median progression-free survival of the treatment-free period was 22.8 months (95% confidence interval, 1.6 months to not estimable). By 6 months of retreatment, all retreated patients achieved new disease stabilization with no new safety concerns; two patients had clinically significant improvements in PROMIS-PF and EQ-5D-5L visual analog scale scores. The mean PROMIS-PF and EQ-5D-5L scores remained stable throughout the study. There was no hepatotoxicity and no new safety signal in either cohort. In this small phase 4 study designed to evaluate outcomes in patients who stopped and restarted pexidartinib, 54.5% of patients who discontinued pexidartinib showed PD, with a median progression-free survival of 22.8 months. Each of the three patients who restarted pexidartinib stopped progressing, and some reported a new gain in physical function. No PD was detected in patients who remained on treatment, and the safety profile did not indicate long-term hepatotoxicity or any new safety concerns. Pexidartinib is a medication for people with tenosynovial giant cell tumor (TGCT) for whom surgery is not recommended. This study examined what happens when patients stop taking pexidartinib (after it has helped them) to see whether it is safe and effective to restart if needed. Thirty-two patients were followed for 2 years: 21 chose to continue pexidartinib and did not experience disease progression, while 11 chose to stop pexidartinib; 54.5% of them had disease progression within 2 years. Three patients who stopped pexidartinib restarted treatment after their tumor size increased or their symptoms worsened. Restarting pexidartinib was safe and effective in these patients.

Is intercalary frozen autograft augmented with intramedullary cement and bridging plates fixation a durable reconstruction?

AimsWe analysed the survival, complications, and function of frozen autograft augmented with intramedullary cement and bridging plates fixation for intercalary bone defect reconstruction in primary bone sarcomas.Patients and MethodsA retrospective cohort study was conducted on 72 patients with primary bone sarcomas (34 males, 38 females) between January 2016 and June 2023. The average age was 22.0 ± 13.6 years (6 to 61 years) and the pathological type included osteosarcoma (55), followed by adamantinoma (5), Ewing’s sarcoma (4), undifferentiated pleomorphic sarcoma (4), chondrosarcoma (3), and malignant tenosynovial giant cell tumor (1). The oncological outcomes included local control, metastasis, progression-free survival and overall survival. The functional outcomes were evaluated by the Musculoskeletal Tumor Society Score (MSTS-93), the Toronto Extremity Salvage Score (TESS), and the motion of the joint.ResultsThe mean follow-up time was 50.0 ± 27.4 months (12 to 99 months). 10 patients died of the disease, 9 patients were alive with disease and 53 patients were alive with no evidence of disease. The average 5-year overall survival of autograft was 85.8% (95% CI, 72.1-93.1%). The average MSTS-93 score was 96% ( 67–100%) and the average TESS score was 98% (74–100%). Twenty-four patients (33.3%) had at least one complication in the follow-up period. The most common complications were nonunion (9.7%, 7/72) and local recurrence (9.7%, 7/72), followed by leg length discrepancy (6.9%, 5/72), infection (5.6%, 4/72), implant failure (4.2%, 3/72), delayed union (2.8%, 2/72), and graft fractures (1.4%, 1/72). Tumor site was an independent risk factor for bone nonunion (OR, 22.23; p = 0.006).ConclusionsWe presented a large technique series for preventing autograft-related complications (especially for autograft fractures) of intercalary frozen autograft reconstruction. This method showed promising functional outcomes and provided durable reconstruction.Level of evidencelevel IV therapeutic study.

Pediatric giant cell tumor of bone: a clinicopathological analysis of 35 cases

Objective: To investigate the clinicopathological characteristics of giant cell tumor of bone (GCTB) in children. Methods: A total of 35 cases of GCTB diagnosed at Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School from 2016 to 2023 were collected, and a retrospective analysis of clinicopathological features and imaging findings was conducted. Results: Pediatric GCTB accounted for approximately 4.6% of total GCTB cases during the study period. There were 11 males and 24 females. The onset age ranged from 9 to 18 years (mean age 15 years, median age 16 years), with 8 cases (8/35, 22.9%) experiencing postoperative recurrence. Twenty-eight cases (28/35, 80%) primarily affected long bones, while 7 cases involved small or irregular bones. Imaging revealed osteolytic changes as the predominant feature, with 3 cases exhibited open physis, one of which had the tumor primarily at the diaphysis without crossing the physis. Histologically, pediatric GCTB resembled adult cases, characterized by mononuclear cells and osteoclast-like giant cells. Seven cases with denosumab treatment demonstrated degrees of giant cell disappearance, increased fibrous tissue and reactive bone proliferation in the stroma. One case was diagnosed as pediatric multicentric GCTB, and three cases as pediatric primary malignant GCTB, with malignant transformation into osteosarcoma. In all 35 cases, mutations in the H3F3A gene were identified, comprising 32 cases with H3.3 p.G34W mutations, one case with H3.3 p.G34V mutation, and 2 cases with H3.3 p.G34L mutations. Notably, the former two categories were successfully validated at the protein level through immunohistochemical staining, utilizing highly specific antibodies tailored for these mutation types: H3.3 p.G34W antibody and H3.3 p.G34V antibody. However, immunohistochemical staining was not available for the last category. Conclusions: Pediatric GCTB predominantly affects females and occurs primarily in long bones, mainly around the knee joint, the majority of tumors predominantly arise in the epiphysis and extend into the metaphysis; however, in cases where the epiphyseal plates are still unclosed, the tumors may be restricted to the metaphysis. Detection of H3F3A gene mutation is crucial for the diagnosis and differential diagnosis of pediatric GCTB.

024. Case Report: Giant Cell Tumor Intravertebra

Background: Giant cell tumor is a rare neoplasm that most frequently occurs at the end of long bones and accounts for approximately 5% of all primary bone tumors in adults. The prevalence of spinal giant cell tumors is estimated at 2%–15% of all spinal giant cell tumors. However, Giant cell tumor is a rare finding in the spine, especially in the pediatric population. Case: A 6-year-old male patient presented with back pain that had spread to both legs for 1.5 years and had worsened in the past 4 months. The pain is intermittent. The patient also felt tingling in the waist and legs, which then turned into a thickening feeling from the waist to the toes since the last 6 months. The patient also complained of weakness in both legs since 1 year ago. Currently the patient is only on bed rest. The patient cannot walk but can still stand with assistance. Defecation and urination remain within normal limits. History of previous trauma (-) Prolonged cough (-), bed wetting (-), headache (-), seizures (-), decreased consciousness (-), progressive weight loss (-), nausea (-) vomiting (-), history of contact with TB sufferers (-). Conclusion: Complete resection of tumor by laminectomy was performed successfully followed by spinal fusion with a pedicle screw. The screws were placed correctly at all four levels of Vertebrae. The decision was made to give stability for spine and it was scheduled to remove the pedicle screw one year follow-up after surgery. Histopathology results showed characteristic findings of giant cell tumor.

Giant Cell Tumor of Capitate with Secondary Aneurysmal Bone Cyst: A Case Report

Abstract Background Giant cell tumors (GCTs) of the carpal bones are rare. GCTs of the hand tend to be aggressive, could result in multifocal presentation, and have a high rate of recurrence. Case Description We report a rare case of GCT of the capitate with secondary aneurysmal bone cyst (ABC) in a 40-year-old man. The patient presented with complaints of pain and swelling over his right wrist since 6 months. Radiographs showed the presence of a lytic lesion in the capitate. Magnetic resonance imaging scanning revealed a well-defined, lobulated, multiseptate lytic lesion involving the entire capitate, extending into its subarticular regions. Fine-needle aspiration revealed findings suggestive of a GCT. He underwent en-bloc excision of the capitate, bone grafting of the defect using an appropriately sized bicortical iliac crest autograft, and third carpometacarpal and midcarpal fusion. Histopathological examination of the lesion confirmed the presence of a GCT, with a secondary ABC. At 3 years following surgery, he was asymptomatic with no signs of tumor recurrence, radiocarpal arthritis, or instability. He was able to perform 45 and 60 degrees of wrist extension and flexion, respectively. Literature Review To our knowledge, there are no prior reported cases of GCT of the capitate with a secondary ABC. Clinical Relevance GCTs of the hand in general have a high rate of recurrence. The presence of a super-added ABC could further increase this risk. In the authors' opinion, en-bloc excision of the affected bone, reconstruction of the defect, and appropriate fusion is the optimal mode of management of these cases.

Central giant cell granuloma of mandible: a case report

Central Giant Cell Granuloma(CGCG) and giant cell tumour of jawbone are grouped underneath same umbrella but with distinct clinical behavior. CGCG is a rare benign lesion of the jaws distinguish by the presence of multinucleated giant cells within a fibrous stroma. The pathogenicity of CGCG still remains an enigma, which demands the differentiation from other look-alike lesions in order to have proper diagnosis and treatment planning. In this article, a case of CGCG in a 30-year-old female patient who presented with complaints of gradually increasing swelling and discomfort in the mandible is described.

Efficacy and safety of JMT103 in patients with unresectable or surgically-challenging giant cell tumor of bone: a multicenter, phase Ib/II study.

This was a multicenter, single-arm, open-label, phase Ib/II study (NCT04255576), aimed to evaluate the efficacy and safety of JMT103 in patients with unresectable or surgically-challenging giant cell tumor of bone (GCTB). JMT103 (2 mg/kg) was administered subcutaneously every four weeks, with loading doses on days 8 and 15. The primary endpoint was the objective tumor response rate (OTR) based on best response, defined as the proportion of patients who achieved elimination of at least 90% of the giant cells or radiologic complete or partial response per the modified Inverse Choi density/size (mICDS) or modified European Organization for Research and Treatment of Cancer (mEORTC) within 12 weeks. Secondary endpoints included objective response rate (ORR) per mICDS and mEORTC, and safety. A total of 139 patients were enrolled, and 135 were analyzed for efficacy. OTR, determined by the independent review committee (IRC) was 93.3% (95% CI 87.7-96.9). Treatment-related adverse events occurred in 90 (64.7%) patients, with hypophosphatemia and hypocalcemia being the most common. No serious treatment-related adverse events were observed. Thus, JMT103 demonstrates potential as a therapeutic option for GCTB.

Measurable Progression of Giant Cell Tumour of Bone Associated with Pregnancy - A Tertiary Sarcoma Centre Analysis

Measurable Progression of Giant Cell Tumour of Bone Associated with Pregnancy - A Tertiary Sarcoma Centre Analysis

Operative and non-operative options for benign primary spine tumors

Benign primary spinal tumors (BPST) are rare entities with significant diagnostic and therapeutic challenges. These tumors can originate from the various mesenchymal tissues that compose the spinal column. They are typically classified using the Enneking or Weinstein-Boriani-Biagini (WBB) classifications, which guide surgical planning and intervention. The most frequent benign spinal tumors include osteoblastoma, osteoid osteoma, osteochondroma, giant cell tumors, aneurysmal bone cysts, hemangiomas, and Langerhans cell histiocytosis. Treatment options vary from nonoperative therapies such as analgesics, radiotherapy, and tumor ablation, to surgical interventions ranging from intralesional curettage to en bloc resection. The choice of treatment depends on factors such as tumor type, location, and potential for recurrence. A multidisciplinary approach, involving orthopedic surgeons, oncologists, and radiologists, is crucial for optimizing patient care. This review aims to provide concise information for the operative and nonoperative treatments of the most common extramedullary primary benign spinal tumors.

Subchondral curettage cement packing in the distal radius causes wrist joint degeneration: long-term evaluation of distal radius giant-cell bone tumour.

This study investigated wrist joint degeneration after curettage and PMMA treatment for giant cell bone tumours (GCBT) at the distal radius. We performed a retrospective single-centre study, which included 23 patients with GCBT at distal radius treated with curettage and PMMA between 2001 and 2021. The progression of wrist joint degeneration was assessed through radiographic evidence, comparing the postoperative grade with both the preoperative grade and the grade of the contralateral wrist at the latest follow-up. We also analyzed the influence of age, sex, tumour distance of the joint, subchondral bone involvement, tumour size and body mass index. The study included 23 patients with a mean age of 32.1 ± 13.3 years. The average duration of follow-up was 96.4 ± 69 months (range, 24-265 months). The mean tumour-cartilage distance was 1.79 ± 2.4 mm (range, 0-10 mm) and the mean BMI was 23.5 ± 3.8 kg/m2. Degeneration of the wrist joint was evident in 16 patients (69.6%) at the final assessment, however, 10 patients (43.4%) were identified as having a progression of joint degeneration secondary to the surgical procedure among the 16 patients with wrist joint degeneration at the final control view. Age, gender, dominance, tumour-cartilage distance, subchondral bone involvement, tumour size, patient height, weight, and BMI were not associated with secondary joint degeneration. Ten of 23 patients developed wrist joint degeneration over an average follow-up period of 8 years, and no particular factors associated with the degeneration were identified.

Pulmonary metastasis of giant cell tumour of tibia.

Giant cell tumour of the tibia with pulmonary metastasis is very rare and the malignancy usually appears several years after the initial lesion. Imaging at the earliest instance is highly beneficial since surgical resection to remove the metastases raises survival rates; therefore, relentless follow-up in GCT is vital.

Effects of Neoadjuvant Denosumab on Radiological and Histological Responses in Patients Undergoing En Bloc Resection for Giant Cell Tumor of Bone: A Systematic Review

Background: Giant cell tumor of bone (GCTB) is a rare primary bone tumor. The standard treatment is en bloc resection, which can be challenging due to tumor size or location. Denosumab, a monoclonal antibody, has emerged as a promising neoadjuvant therapy for GCTB, potentially facilitating surgical resection. However, its optimal use remains unclear, with debate surrounding its impact on local recurrence. This systematic review aims to synthesize evidence on the histological and radiological changes induced by neoadjuvant denosumab and its impact on surgical outcomes. Methods: This review followed PRISMA guidelines. The medical term "denosumab", "neoadjuvant", "GCTB", "radiological", and "histological" were used in PubMed (423 articles) and Google Scholar (18,100 articles), totaling 18,523 articles to discover studies of the effect of neoadjuvant denosumab on radiological and histological response up to July 2023. Six remaining studies were reviewed and screened for inclusion criteria based on their relevance to the study subject and clinical outcomes. Results: Based on six studies in this review, five showed histological response by decreasing the multinucleated giant cells and osteoclasts after neoadjuvant DT. Six studies showed increased significant bone reconstitution as a radiological response in the GCTB locale, replaced the extending tumor into soft tissue by abundant bone production with peripheral shell, and increased ease of en bloc resection. Conclusions: Neoadjuvant denosumab therapy shows promise in managing giant cell tumors of bone (GCTB) by reducing osteoclasts, shrinking tumor volume, and promoting cortical bone formation, thus facilitating en bloc resection. However, further research is needed to confirm these findings.

Lesions of the Palm – Mimickers of Dupuytren’s Disease

Background and Aims: Dupuytren’s contracture is a prevalent, hereditary fibroproliferative disorder affecting the palmar aponeurosis, which can resemble various neoplastic and non-neoplastic disorders of the hand. This resemblance poses a diagnostic challenge for healthcare professionals. This observational study aims to evaluate the range of conditions that can be mistaken for Dupuytren’s contracture over a 12-year period (2008–2020) at a specialised orthopaedic oncology centre. Materials and Methods: A retrospective analysis of palmar lesions referred to our tertiary orthopaedic oncology hospital was conducted. Data were gathered from oncology, radiology and histopathology databases. We specifically examined lesions located solely on the palmar aponeurosis, excluding the thenar and hypothenar regions. Patient demographics, clinical features, imaging results and clinical management outcomes were documented for descriptive analysis. Results: A total of 21 palmar lesions meeting the inclusion criteria were identified. The average age of the participants was 48 years (ranging from 3 to 69 years). There was no significant difference in gender distribution, with 11 females and 10 males represented in the cohort. The majority of the identified lesions were benign tumours (16), with one case of malignant rhabdomyosarcoma. Among the benign tumours, lipomas were the most common ( n = 5). Other benign tumours included three neurofibromas, a schwannoma, a granuloma, a ganglion cyst, a giant cell tumour (GCT), an angiomyxoma, a myofibroma, a cavernous haemangioma, a non-specific fibrovascular lesion and four additional non-neoplastic lesions. Conclusion: A variety of benign, malignant or neoplastic conditions of the hand can closely resemble Dupuytren’s contracture, particularly in the initial stages of their development. A thorough clinical examination, combined with a high level of suspicion, along with supplementary investigations and histopathological analysis, is essential for accurate diagnosis and effective management of patients.

Giant cell tumor of bone with late-onset lung metastasis and secondary osteosarcomatous transformation

Giant cell tumor of bone with late-onset lung metastasis and secondary osteosarcomatous transformation

Symmetric, Bilateral Auricular Calcifications in Twins With Noonan Syndrome.

Noonan syndrome (NS) is a rare, genetic multisystem disorder often presenting with associated craniofacial abnormalities. The authors report an identical twin pair with classical features of NS including short stature, mild ptosis, hypertelorism, down-slanting palpebral fissures, low-set angulated ears, and giant cell tumors in the craniofacial skeleton. Interestingly, these patients also presented with bilateral, symmetric, dystrophic auricular calcifications. Genome sequencing revealed identical germline son of sevenless homolog 1 mutations and inversion of chromosome 2 (p11.2q13). Awareness of the association of auricular calcifications and NS may help guide clinical management for these patients, particularly if auricular procedures are indicated.

Features of Magnetic Resonance Diagnostics of Tenosynovial Giant Cell Tumor (Pigmented Villonodular Synovitis)

Aim. Demonstrate the features of magnetic resonance diagnostics of tenosynovial giant cell tumor.Materials and Methods. Using magnetic resonance imaging, we identified patients with tenosynovial giant cell tumor of the knee joint, describing the diagnostic features and clinical course of diffuse and local forms of the tumor.Results. Specific MRI patterns of tenosynovial giant cell tumor are hemosiderin deposits, villous and nodular growths of the synovium of the knee joint, joint effusion and bone erosion.Conclusion. Тenosynovial giant cell tumor is a rare mesenchymal neoplasm arising from the synovium of joints and tendon sheaths, disabling young able-bodied people. Magnetic resonance imaging, being the “gold” standard for radiological diagnostics, helps to identify specific patterns.