Giant Cell Tumor Research Articles

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.

A case report on dilated engorged epidural vein causing sciatica

Sciatica is most of the time due to lumbar disc herniation. Some other pathologies such as aneurysmal bone cysts, proximal femur osteomyelitis, arachnoid cysts, facetal cysts, giant cell tumours, and pyriformis syndrome mimic sciatica are termed sciatica mimickers in literature. In this case report, we present a 66-year-old man with low back pain and left sciatica and neurogenic claudication who underwent transforaminal lumbar interbody fusion L4–5. In magnetic resonance imaging, the finding was degenerative changes with foraminal stenosis of L4–L5, but intraoperatively, we found an engorged epidural vein causing the compression of L4 exiting nerve root. The engorged epidural vein sometimes can cause sciatica which mimics the disc herniation.

Biological knee joint reconstruction using patella following giant cell tumor excision: a case report

A 20-year-old female patient presented to us with a large expansile swelling over right knee diagnosed clinically and confirmed histopathological and radiologically to be Giant Cell Tumor of upper end of Tibia involving both condyles with a breach in the posterior cortex. In this case report we tried to retain the joint function by biological reconstruction using the Patella after the wide excision of the tumor mass. A radical excision of the upper end of the Tibia was done. The Patella was used as an articular surface supported by ipsilateral Fibula and cortico-cancellous bone chips from the ipsilateral iliac crest as struts and complemented with synthetic bone graft pieces. Thus, the joint was reconstructed biologically. The case was followed for 1 year. The tumor was excised in toto, the knee joint was restored by the Patella and the bone graft struts. The results were discussed in detail.

Innovative approaches to cage reconstructions in orthopedic limb surgery: Advances and insights with two cases

BackgroundLimb tumors, though rare, pose significant challenges to surgical management due to their impact on limb function and quality of life. Effective treatment requires precise tumor resection alongside advanced reconstructive techniques to restore limb function, particularly in cases of compromised bone healing. Titanium cages, traditionally used in spinal surgeries, have recently gained attention for their potential in limb reconstruction within orthopedic oncology, offering a novel approach to managing complex bone defects. Case PresentationThis retrospective case series presents two patients treated with titanium cages for limb reconstruction following tumor resection.Case 1: A 53-year-old female with a solitary plasmacytoma of the femur experienced a pathological fracture and nonunion after initial treatment. A titanium cage was employed to bridge the resected bone segment, leading to successful callus formation at the six-month follow-up and restored limb function.Case 2: A 31-year-old female with a giant cell tumor and hemangioma of the foot underwent en bloc resection followed by reconstruction using a vertebral cage and iliac corticospongious graft. Six months postoperatively, the patient had resumed full weight-bearing with no complications. ConclusionTitanium cages offer a promising solution for limb reconstruction in patients with tumors, particularly for large bone defects where traditional methods may be inadequate. This case series demonstrates successful outcomes in limb preservation and functional recovery using titanium cages. Their use in the adult population shows potential for broader application in orthopedic oncology, warranting further clinical investigation.

Abstract B005: Denosumab Enhances Cytotoxic T Cell Infiltration by supressing SPP1 Expression in Giant Cell Tumour of Bone

Abstract Denosumab, a RANKL inhibitor, is primarily used to prevent osteoclastogenesis for the treatment of conditions like osteoporosis, bone metastasis, and giant cell tumor of bone (GCTB). RANKL is also key in immunity, activating NFκB and its target genes, including the osteopontin-coding gene SPP1, which is linked with CXCL9:SPP1 macrophage polarization and prognosis. Retrospective studies of bone metastasis have demonstrated improved clinical outcomes when immune checkpoint inhibitors (ICIs) are combined with denosumab. We undertook a study to explore denosumab's direct role in anti-tumor immunity. Single-cell RNA sequencing was performed on nine primary human GCTB samples, including three untreated and six treated solely with denosumab, to exclude confounding treatment factors linked with bone metastasis samples. Furthermore, we utilized immunohistochemistry staining from paired pre- and post-denosumab treated samples from a cohort of nine GCTB patients and conducted pan-cancer analysis on primary tumors, spanning 31 distinct types of cancers, sourced from the Genomic Data Commons Data Portal. Our single-cell analysis of GCTB resulted in a comprehensive cell atlas of this rare disease, revealing denosumab's role in inhibiting SPP1 expression and augmenting cytotoxic T cell infiltration. This was confirmed in nine pairs of pre- and post-denosumab treated GCTB samples using immunohistochemistry staining. The pan-cancer analysis indicated a negative correlation between SPP1 expression and CD8A levels across most tumor types, with the CD8A/SPP1 ratio correlating with clinical outcomes in 14 cancer types. Our research provides robust clinical evidence that denosumab improves anti-tumor immunity by inhibiting SPP1 expression, presenting a significant step towards patient selection for combined ICI and denosumab therapy. Citation Format: Zezhuo Su, Maximus Chun Fai Yeung, Jason Pui Yin CHEUNG, Kelvin Sin Chi Cheung. Denosumab Enhances Cytotoxic T Cell Infiltration by supressing SPP1 Expression in Giant Cell Tumour of Bone [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B005.

Pharmacoproteogenomic approach identifies on-target kinase inhibitors for cancer drug repositioning.

Drug repositioning of approved drugs offers advantages over de novo drug development for a rare type of cancer. To efficiently identify on-target drugs from clinically successful kinase inhibitors in cancer drug repositioning, drug screening and molecular profiling of cell lines are essential to exclude off-targets. We developed a pharmacoproteogenomic approach to identify on-target kinase inhibitors, combining molecular profiling of genomic features and kinase activity, and drug screening of patient-derived cell lines. This study examined eight patient-derived giant cell tumor of the bone (GCTB) cell lines, all of which harbored a signature mutation of H3-3A but otherwise without recurrent copy number variants and mutations. Kinase activity profiles of 100 tyrosine kinases with a three-dimensional substrate peptide array revealed that nine kinases were highly activated. Pharmacological screening of 60 clinically used kinase inhibitors found that nine drugs directed at 29 kinases strongly suppressed cell viability. We regarded ABL1, EGFR, and LCK as on-target kinases; among the two corresponding on-target kinase inhibitors, osimertinib and ponatinib emerged as on-target drugs whose target kinases were significantly activated. The remaining 26 kinases and seven kinase inhibitors were excluded as off-targets. Our pharmacoproteomic approach enabled the identification of on-target kinase inhibitors that are useful for drug repositioning.

Surgical Treatment of Primary Spinal Tumors

Primary spinal tumors appear to be much less common than metastatic lesions, but their surgical treatment comprises a complex and multifaceted task. Numerous factors influence indications and timing of surgical intervention, including neurological status of the patient, histological characteristics of the tumor, its localization, stability of the spinal column, and comorbidities. Significant spinal cord compression, rapid progression of neurologic deficits, or pronounced instability of the spinal column may require urgent surgical intervention. When the spinal canal is not affected, treatment should start with a biopsy to accurately determine the histology of the tumor. Some tumor types, such as giant cell tumors, osteoblastomas, chordomas, and chondrosarcomas, require complete removal of the tumor. However, performing a wide resection in a single block is often found difficult due to compression of vascular and nerve structures. Current approaches to surgical management of primary spinal tumors involve minimally invasive techniques that significantly improve postoperative recovery and reduce the risk of complications. These techniques were originally used to treat degenerative spinal diseases and trauma; however, they have also demonstrated their effectiveness in tumor surgery. Adapting surgical strategy based on histology and tumor location, as well as integrating minimally invasive techniques, can improve patient survival and quality of life. The present paper describes the latest advances in the surgical treatment of primary spinal tumors, discusses current techniques and strategies, and prospects for further research in this area.

Treatment Modalities for Refractory-Recurrent Tenosynovial Giant Cell Tumor (TGCT): An Update

Background and Objectives: Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive, benign neoplasm arising from the synovium of joints, tendon sheaths, and bursa. There are two main subtypes of TGCT: localized-type TGCT(L-TGCT) and diffuse-type TGCT (D-TGCT). While surgical excision is still considered the gold standard of treatment, the high recurrence rate, especially for D-TGCT, may suggest the need for other treatment modalities. Materials and Methods: This study reviews current literature on the current treatment modalities for refractory-relapsed TGCT disease. Results: The gold standard of treatment modality in TGCT remains surgical excision of the tumor nevertheless, the elevated recurrence rate and refractory disease, particularly in D-TGCT indicates and underscores the necessity for additional treatment alternatives. Conclusions: TGCT is a benign tumor with inflammatory features and a potential destructive and aggressive course that can lead to significant morbidity and functional impairment with a high impact on quality of life. Surgical resection remains the gold standard current treatment and the optimal surgical approach depends on the location and extent of the tumor. Systemic therapies have been recently used for relapsed mainly cases.

Targeting Bone Tumours with 45S5 Bioactive Glass.

Despite advances in treatment modalities, bone tumour therapies still face significant challenges. Severe side effects of conventional approaches, such as chemo- and radiation therapy, result in poor survival rates and high tumour recurrence rates, which are the most common issues that need to be improved upon. The aim of this study was to evaluate the therapeutic properties of 45S5 bioactive glass (BG) for targeting bone tumours. The viability of the cells derived from osteosarcoma, chondrosarcoma, and giant cell tumours was significantly reduced in the presence of 45S5-BG. In contrast, the viability of non-malignant osteoblast-like cells, chondrocytes, and bone marrow-derived stromal cells was not or only slightly affected. While alterations to the particle surface induced by heat treatment, acid etching, or incubation in a simulated body fluid had only minor effects on cytotoxicity, reducing the particle size or sintering the material significantly improved the cytotoxic effect of 45S5-BG. Further, using a chicken chorioallantoic membrane assay, the co-transplantation of 45S5-BG resulted in a significant reduction in tumour formation in vivo. Given the known positive effects of BGs on bone regeneration, our findings suggest that 45S5-BG holds great potential for the development of new and effective bone tumour therapies, with minimal side effects on non-malignant cells and simultaneous contribution to bone healing.

Giant Cell Tumour of the Spine

Giant Cell Tumour of the Spine

Vimseltinib versus a placebo in patients with tenosynovial giant cell tumor: a plain language summary of the MOTION phase 3 trial.

This article presents a patient-friendly summary of the MOTION phase 3 clinical trial results, which were published in The Lancet in June 2024.The primary goal of the MOTION trial was to understand if treatment with a drug called vimseltinib shrank tumors more than a placebo in participants with symptomatic tenosynovial giant cell tumor, also known as TGCT, for which surgery was unlikely to provide benefit. A placebo is something that looks like the treatment being studied but does not contain any medicine.The MOTION trial compared the effects of vimseltinib versus a placebo using several different outcomes associated with TGCT. These outcomes included tumor size, active range of motion of the affected joint, and several patient-reported quality-of-life measures including physical function, stiffness, overall health, and pain. The trial showed that more participants treated with vimseltinib experienced significant tumor shrinkage, as defined by a 30% or greater reduction in tumor size, compared with those receiving a placebo. Participants receiving vimseltinib had improved active range of motion, and they reported improved physical function, stiffness, overall health, and pain, regardless of the amount of tumor shrinkage, compared with participants receiving a placebo. Most side effects in participants treated with vimseltinib were not severe and were manageable. Vimseltinib was better at shrinking tumors and improving active range of motion, stiffness, pain, and other health measures than the placebo for participants with TGCT. Vimseltinib has the potential to become a new treatment option for patients with TGCT for whom surgery may not provide benefit.

Postoperative challenges addressed through nursing care of patients receiving lower extremity tumor prosthesis

BackgroundPatients with primary Bone Sarcoma and Giant Cell Tumors in the lower extremities often require major surgery involving tumor prostheses. The postoperative course for this patient group can be complex and influenced by various factors and challenges that demand careful nursing care. This study aims to identify challenges related to the nursing care of individuals with primary bone tumors following surgery for tumor prostheses in the lower extremities.MethodsA retrospective cohort study of 15 patients treated at Rigshospitalet, Copenhagen, Denmark, between November 5. 2016, and April 1. 2020 was conducted by medical record review, focusing on challenges related to postoperative nursing care. All patients with the surgery code “Bone Excision” were identified within the surgery booking system and screened for eligibility.ResultsPatients experienced postoperative challenges such as severe pain, prolonged time to mobilization (mean: 4 days), and defecation (mean: 5 days). The mean length of stay at the Rigshospitalet was 13 days. Furthermore, eleven patients (73%) reported disrupted sleep and nausea.ConclusionPatients undergoing tumor prosthesis surgery in the lower extremities face considerable postoperative challenges that contribute to a prolonged hospital stay. These challenges, including severe pain, delayed mobilization, and gastrointestinal issues, significantly impact recovery. The findings highlight the urgent need for targeted nursing interventions to address these issues effectively. Enhanced pain management protocols, early mobilization strategies, and comprehensive postoperative care plans are essential to improve patient outcomes and reduce the length of hospital stays. Addressing these challenges through dedicated nursing care is crucial for optimizing the recovery process for patients receiving lower extremity tumor prostheses.

Recurrence and Risk Factors of Giant Cell Tumors in Hand Bones: A Systematic Review.

Giant cell tumor of bone (GCTB) is a locally aggressive tumor that may affect the bones of the hand and rarely causes pulmonary metastasis. It exhibits a variable recurrence rate after surgical interventions, which presents challenges in its management. This systematic review aims to delineate recurrence rates and identify risk factors for GCTB in the hand. We conducted a systematic literature search in April 2024, following PRISMA guidelines, on PubMed and TDNet for studies reporting postsurgical recurrence of GCTB in the hand. Cohort and case-control studies provided recurrence rates, whereas case reports and series were utilized to identify risk factors, compensating for the sparse data in the primary studies. We used descriptive statistics, χ2 tests, and logistic regression to analyze demographics, lesion characteristics, treatments, and outcomes. We reviewed 13 cohort and case-control studies involving 244 patients, finding an overall recurrence rate of 19.57%. Curettage was associated with higher recurrence rates compared with other surgical methods. After additional review of case reports, a limited range of motion in patients emerged as a significant protective factor against recurrence, suggesting potential benefits in surgical management and outcome prediction. The significant recurrence rate associated with curettage highlights the need for alternative surgical strategies in GCTB management of the hand. The protective role of limited ROM underscores the importance of thorough preoperative assessments to optimize surgical approaches and enhance patient outcomes.

Overview and Management of Sacral Tumors

Sacral tumors can range from benign to malignant. The sacrum is a common site of metastases however surgical intervention is not common for sacral metastases unless there is neurological compromise. Benign aggressive tumors such giant cell tumors, osteoblastomas and aneurysmal bone cysts (ABC)can be found in the sacrum. Malignant primary tumors including chordoma, chondrosarcomas and osteosarcomas can affect the sacrum. Management depends on the tumor histology including debulking and stabilization for metastatic spine lesions. For benign tumors such as ABCs intralesional resection is an option. For primary spine tumors partial or total sacrectomies are an option and morbidity is dependent on the level sacral resection.

Endoscopic En Bloc Resection of Giant Cell Tumor of Tendon Sheath of Anterior Ankle

Giant cell tumor of the tendon sheath (GCTTS) originates from the synovial cells of the tendon sheath. It is one of the most common benign soft-tissue tumors of the foot and ankle affecting the joints, bursae, and tendon sheaths and can behave in a locally aggressive manner. Complete surgical resection with long-term follow-up is the preferred treatment. Because GCTTS is a benign condition, the equilibrium between the quality of the surgical margins and functional preservation should be considered. If more aggressive resection is applied, the outcome may negatively affect quality of life, whereas incomplete resection may lead to recurrence. The purpose of this technical note is to describe the details of endoscopic en bloc resection of GCTTS of the anterior ankle. This endoscopic approach can provide a magnified view of the operative site, allowing accurate surgical assessment to ensure complete resection of the lesion without damage to the adjacent normal structures.

Comparative Analysis of Extended Curettage with Plate Fixation and Extended Curettage with Intramedullary Nail Fixation for Campanacci Grade Ⅱ and International Society of Limb Salvage Zone H2 Giant Cell Tumors of the Proximal Femur: A Retrospective Study

Comparative Analysis of Extended Curettage with Plate Fixation and Extended Curettage with Intramedullary Nail Fixation for Campanacci Grade Ⅱ and International Society of Limb Salvage Zone H2 Giant Cell Tumors of the Proximal Femur: A Retrospective Study

Localized type tenosynovial giant cell tumor with metastases to lungs and pleura: a case report and literature review

BackgroundTenosynovial giant cell tumor is a rare soft tissue tumor of the synovium of joint, bursae, or tendon sheath. It is divided into localized or diffuse types on the basis of the growth pattern. Localized tenosynovial giant cell tumors are usually benign and treated successfully by excision. Diffuse tenosynovial giant cell tumors, in contrast to localized type, can destroy bone and cartilage and are associated with frequent local recurrences and distant metastasis. Localized type tenosynovial giant cell tumors rarely metastasize to distant organs. Here, we report a case of localized tenosynovial giant cell tumor presenting with lung metastases and systematically review literature.Case presentationA 55-year-old Asian male presented with a dry cough, right-sided chest pain and progressive dyspnea for 1 month. At 18 months before this presentation, he had undergone excision of a painless swelling on his right index finger. The swelling recurred within 3 months of excision, and a biopsy was then suggestive of a giant cell tumor. Given the suspicion of a giant cell tumor, a wide excision of the lesion was performed and the excisional biopsy was consistent with a diagnosis of tenosynovial giant cell tumor, localized type. At admission to our hospital, the patient had tachypnoea and absent breath sounds on the right side. A chest radiograph showed a right-sided pleural effusion with a homogenous opacity in the left mid-zone. A contrast-enhanced computed tomography of the chest and abdomen showed right massive pleural effusion and bilateral multiple lobulated heterogeneously enhancing pleural-based masses with areas of internal calcification. Pleural fluid analysis revealed an exudate with no malignant cells on cytology. A lung biopsy showed osteoclast-like giant cells and mononuclear spindle cells with areas of hemorrhage and necrosis, suggesting tenosynovial giant cell tumor metastasis. A final diagnosis of localized type tenosynovial giant cell tumor of the right index finger with metastases to the lungs and pleura was made. The patient passed away after receiving three cycles of denosumab injection owing to progressive disease.ConclusionLung metastasis is extremely rare in patients with localized tenosynovial giant cell tumor. The survival is usually poor in patients with lung metastasis. A close follow-up of patients with localized type tenosynovial giant cell tumor is necessary for early detection of pleuropulmonary complications.

An Analysis of The Pattern and Frequency of Primary Malignant Bone Tumors in Nassyriah

Bone tumors are uncommon lesions and account for only 0.2% of all malignant tumors. Primary malignant bone tumors develop from bony tissue and are categorized according to their location of origin and the cell type that makes up the tumor. This research aims to report on the prevalence, geographic distribution, and comparison of malignant bone tumors in Nassyriha province. Malignant bone tumors were studied in 182 people (119 men and 63 females) between February 2021 and February 2023. Their ages varied widely (from 5 to 70), with the second decade being the most prevalent. The most common cancer was osteosarcoma, which accounted for 34.62 percent, followed by Ewing's sarcoma (24.73), chondrosarcoma (13.74), multiple myeloma (11.53), malignant giant cell tumors (8.14%), fibrosarcoma (2.74%), and 2 instances of chordoma (1.10%). None of the six instances (3.30%) could be definitively diagnosed. Primary malignant bone tumors are rising, with men being disproportionately impacted. Information gleaned from this study will be useful for both researchers and clinicians.

Denosumab combined with en bloc resection and arthrodesis for recurrent grade 3 giant cell tumor of bone in distal radius

PurposeThis study aimed to analyse the clinical outcomes of preoperative adjuvant denosumab therapy (PADT) combined with resection and arthrodesis for recurrent grade 3 giant cell tumor of bone (GCTB) in the distal radius.MethodsA retrospective study was conducted on twenty-three patients (8 males, 15 females) who were treated with the adjuvant denosumab combined with en bloc resection (EBR) and arthrodesis for biopsy confirmed recurrent Campanacci III giant cell tumor of bone in the distal radius between January 2015 and December 2022. All 23 patients were treated with wrist arthrodesis reconstruction using autogenous free iliac crest bone graft (ICBG), bridging plate and screws. The local control, metastasis and overall survival were evaluated during the follow-up period. Functional outcomes were evaluated using the Disabilities of the Arm, Shoulder and Hand (DASH) score, Musculoskeletal Tumor Society Score (MSTS-87 and MSTS-93), and grip strength in the follow-up period. Additionally, all surgical or denosumab-related complications that occurred were recorded in this study.ResultsTwenty-three patients were included in this retrospective study and no patients were lost in the follow-up period. The average patient age was 32.5 ± 10.2 years (range, 19–53 years) and the mean follow-up time was 35.5 ± 18.4 months (range, 13–72 months). The average tumor length was 71.7 ± 8.7 mm (range, 50 to 85 mm) and bone reconstruction length was 78.5 ± 8.5 mm (range, 60 to 90 mm). Four patients (17.4%) had secondary local recurrence after reoperation and two patients had (8.7%) multiple recurrences. One patient (4.3%) was deceased in the last follow-up due to multiple metastases. The estimated 5-year recurrence-free survival rate was 81.3% and 5-year metastasis-free survival rate was 95.7%. The mean union time was 8.5 ± 1.9 (6–12) months and the overall survivorship of the allograft was 82.7% (21/23) at an average 35 month follow-up. The average MSTS-87 and MSTS-93 scores were 27.8 ± 1.6 (range, from 23 to 30) and 91.5 ± 5.0 (range, from 76 to 100), and the average DASH score was 8.9 ± 3.2 (range, from 3 to 15), respectively. The average grip strength was 64.6 ± 15.7% (range, from 30 to 95%) of the uninvolved side. Eight patients (34.7%) had at least one complication in the follow-up time. Two autografts (8.7%) were removed due to local recurrence and bone nonunion, and the average autograft survival time was 32.8 ± 18.5 months (range, 12 to 72 months).ConclusionsPreoperative adjuvant denosumab therapy (PADT) combined with en bloc resection and arthrodesis is a promising method for the treatment of recurrent Campanacci III GCTB in distal radius with acceptable short-term local control and functional satisfaction.Level of evidence: level IV Therapeutic.