Disruption of the HIF-1 pathway in individuals with Ollier disease and Maffucci syndrome.

Ollier disease (OD) and Maffucci Syndrome (MS) are rare disorders characterized by multiple enchondromas, commonly causing bone deformities, limb length discrepancies, and pathological fractures. MS is distinguished from OD by the development of vascular anomalies. Both disorders are cancer predisposition syndromes with malignancies developing in ~50% of the individuals with OD or MS. Somatic gain-of-function variants in IDH1 and IDH2 have been described in the enchondromas, vascular anomalies and chondrosarcomas of approximately 80% of the individuals with OD and MS. To date, however, no investigation of germline causative variants for these diseases has been comprehensively performed. To search for germline causative variants, we performed whole exome sequencing or whole genome sequencing of blood or saliva DNA in 94 unrelated probands (68 trios). We found that 7 had rare germline missense variants in HIF1A, 6 had rare germline missense variants in VHL, and 3 had IDH1 variants including 2 with mosaic IDH1-p.Arg132His variant. A burden analysis using 94 probands assigned as cases and 2,054 unrelated individuals presenting no OD- or MS-related features as controls, found that variants in HIF1A, VHL, and IDH1 were all significantly enriched in cases compared to controls. To further investigate the role of HIF-1 pathway in the pathogenesis of OD and MS, we performed RNA sequencing of fibroblasts from 4 probands with OD or MS at normoxia and at hypoxia. When cultured in hypoxic conditions, both proband and control cells showed altered expression of a subset of HIF-1 regulated genes. However, the set of differentially expressed genes in proband fibroblasts included a significantly reduced number of HIF-1 regulated genes compared to controls. Our findings suggest that germline or early post-zygotic variants identified in HIF1A, VHL, and IDH1 in probands with OD and MS underlie the development of the phenotypic abnormalities in a subset of individuals with OD and MS, but extensive functional studies are needed to further confirm it.

NAMPT enhances LOX expression and promotes metastasis in human chondrosarcoma cells by inhibiting miR-26b-5p synthesis.

Chondrosarcoma is a malignant bone tumor that emerges from abnormalities in cartilaginous tissue and is related with lung metastases. Nicotinamide phosphoribosyltransferase (NAMPT) is an adipocytokine reported to enhance tumor metastasis. Our results from clinical samples and the Gene Expression Omnibus data set reveal that NAMPT levels are markedly higher in chondrosarcoma patients than in normal individuals. NAMPT stimulation significantly increased lysyl oxidase (LOX) production in chondrosarcoma cells. Additionally, NAMPT increased LOX-dependent cell migration and invasion in chondrosarcoma by suppressing miR-26b-5p generation through the c-Src and Akt signaling pathways. Overexpression of NAMPT promoted chondrosarcoma metastasis to the lung in vivo. Furthermore, knockdown of LOX counteracted NAMPT-facilitated metastasis. Thus, the NAMPT/LOX axis presents a novel target for treating the metastasis of chondrosarcoma.

MiR-29a-3p mediates phosphatase and tensin homolog and inhibits osteoarthritis progression.

Despite substantial progress in clinical trials of osteoarthritis (OA) gene therapy, the prevalence of OA is still on the rise. MiRNAs have a potential biomarker and therapeutic target for OA. OA cartilage and chondrosarcoma cells were studied to determine the role of miR-29a-3p and PTEN. OA cartilage and human chondrosarcoma cells (SW1353) were obtained. miR-29a-3p and PTEN signature expression was determined by RT-qPCR. The binding relationship between miR-29a-3p and PTEN was investigated by dual-luciferase reporter gene and western blot assay. TUNEL, immunohistochemistry, CCK-8, and flow cytometry were utilized to determine the proliferation and apoptosis of SW1353 cells. This study indicated downregulation of miR-29a-3p expression and upregulation of PTEN expression in human OA primary chondrocytes or OA tissue samples, compared with the normal cartilage cells or tissues. PTEN expression was negatively correlated with miR-29a-3p expression, and miR-29a-3p targeted PTEN mechanistically. miR-29a-3p reduced SW1353 cell activity and proliferation and promoted cell apoptosis. However, the aforementioned effects could be reversed by downregulating PTEN. miR-29a-3p can stimulate chondrocyte proliferation and inhibit apoptosis by inhibiting PTEN expression.

Development of Injectable Thermosensitive Nanocomposite Hydrogel for Ratiometric Drug Delivery to Treat Drug Resistant Chondrosarcoma In Vivo.

Chondrosarcoma(CS), a prevalent primary malignant bone tumor, frequently exhibits chemotherapy resistance attributed to upregulated anti-apoptosis pathways such as the Bcl-2 family. In this manuscript, a new strategy is presented to augment chemosensitivity and mitigate systemic toxicity by harnessing a nano-enabled drug delivery hydrogel platform. The platform utilizes "PLGA-PEG-PLGA", an amphiphilic triblock copolymer combining hydrophilic polyethylene glycol (PEG) and hydrophobic polylactide glycolide (PLGA) blocks, renowned for its properties conducive to crafting a biodegradable, temperature-sensitive hydrogel. This platform is tailored to encapsulate a ratiometrically designed dual-loaded liposomes containing a first-line chemo option for CS, Doxorubicin (Dox), plus a calculated amount of small molecule inhibitor for anti-apoptotic Bcl-2 pathway, ABT-737. In vitro and in vivo evaluations demonstrate successful Bcl-2 suppression, resulting in the restoration of Dox sensitivity, evident through impeded tumor growth and amplified necrosis rates at the tumor site. This delivery system showcases remarkable thermal responsiveness, injectability, and biodegradability, all finely aligned with the clinical demands of CS treatment. Collectively, this study introduces a transformative avenue for tackling drug resistance in CS chemotherapy, offering significant clinical potential.

CHRNA6 RNA In Situ Hybridization Is a Useful Tool for the Diagnosis of Extraskeletal Myxoid Chondrosarcoma.

Extraskeletal myxoid chondrosarcoma (EMC) is an uncommon mesenchymal neoplasm characteristically composed of uniform-appearing round to spindle-shaped cells with eosinophilic cytoplasm and abundant myxoid extracellular matrix. Although the majority of cases harbor a pathognomonic t(9;22) translocation that fuses EWSR1 with the orphan nuclear receptor NR4A3, there are less common variants that partner NR4A3 with TAF15, TCF12, or TFG. By immunohistochemistry, EMC has features of both cartilaginous and neuroendocrine differentiation, as evidenced by inconsistent expression of S100 protein and synaptophysin or INSM1, respectively, in a subset of cases. Given the limitations of available immunohistochemical stains for the diagnosis of EMC, we analyzed genome-wide gene expression microarray data to identify candidate biomarkers based on differential expression in EMC in comparison with other mesenchymal neoplasms. This analysis pointed to CHRNA6 as the gene with the highest relative expression in EMC (96-fold; P = 8.2 × 10-26) and the only gene with >50-fold increased expression in EMC compared with other tumors. Using RNA chromogenic in situ hybridization, we observed strong and diffuse expression of CHRNA6 in 25 cases of EMC, including both EWSR1-rearranged and TAF15-rearranged variants. All examined cases of histologic mimics were negative for CHRNA6 overexpression; however, limited CHRNA6 expression, not reaching a threshold of >5 puncta or 1 aggregate of chromogen in >25% of cells, was observed in 69 of 685 mimics (10.1%), spanning an array of mesenchymal tumors. Taken together, these findings suggest that, with careful interpretation and the use of appropriate thresholds, CHRNA6 RNA chromogenic in situ hybridization is a potentially useful ancillary histologic tool for the diagnosis of EMC.

Racial disparities in the management and outcomes of primary osseous neoplasms of the spine: a SEER analysis.

PURPOSE: Primary osseous neoplasms of the spine, including Ewing's sarcoma, osteosarcoma, chondrosarcoma, and chordoma, are rare tumors with significant morbidity and mortality. The present study aims to identify the prevalence and impact of racial disparities on management and outcomes of patients with these malignancies. METHODS: The 2000 to 2020 Surveillance, Epidemiology, and End Results (SEER) Registry, a cancer registry, was retrospectively reviewed to identify patients with Ewing's sarcoma, osteosarcoma, chondrosarcoma, or chordoma of the vertebral column or sacrum/pelvis. Study patients were divided into race-based cohorts: White, Black, Hispanic, and Other. Demographics, tumor characteristics, treatment variables, and mortality were assessed. RESULTS: 2,415 patients were identified, of which 69.8% were White, 5.8% Black, 16.1% Hispanic, and 8.4% classified as "Other". Tumor type varied significantly between cohorts, with osteosarcoma affecting a greater proportion of Black patients compared to the others (p < 0.001). A lower proportion of Black and Other race patients received surgery compared to White and Hispanic patients (p < 0.001). Utilization of chemotherapy was highest in the Hispanic cohort (p < 0.001), though use of radiotherapy was similar across cohorts (p = 0.123). Five-year survival (p < 0.001) and median survival were greatest in White patients (p < 0.001). Compared to non-Hispanic Whites, Hispanic (p < 0.001) and "Other" patients (p < 0.001) were associated with reduced survival. CONCLUSION: Race may be associated with tumor characteristics at diagnosis (including subtype, size, and site), treatment utilization, and mortality, with non-White patients having lower survival compared to White patients. Further studies are necessary to identify underlying causes of these disparities and solutions for eliminating them.

A retrospective external validation study of the Birmingham Atypical Cartilage Tumour Imaging Protocol (BACTIP) for the management of solitary central cartilage tumours of the proximal humerus and around the knee.

OBJECTIVES: This study aimed to externally validate the Birmingham Atypical Cartilage Tumour Imaging Protocol (BACTIP) recommendations for differentiation/follow-up of central cartilage tumours (CCTs) of the proximal humerus, distal femur, and proximal tibia and to propose BACTIP adaptations if the results provide new insights. METHODS: MRIs of 123 patients (45 ± 11 years, 37 men) with an untreated CCT with MRI follow-up (n = 62) or histopathological confirmation (n = 61) were retrospectively/consecutively included and categorised following the BACTIP (2003-2020 / Ghent University Hospital/Belgium). Tumour length and endosteal scalloping differences between enchondroma, atypical cartilaginous tumour (ACT), and high-grade chondrosarcoma (CS II/III/dedifferentiated) were evaluated. ROC-curve analysis for differentiating benign from malignant CCTs and for evaluating the BACTIP was performed. RESULTS: For lesion length and endosteal scalloping, ROC-AUCs were poor and fair-excellent, respectively, for differentiating different CCT groups (0.59-0.69 versus 0.73-0.91). The diagnostic performance of endosteal scalloping and the BACTIP was higher than that of lesion length. A 1° endosteal scalloping cut-off differentiated enchondroma from ACT + high-grade chondrosarcoma with a sensitivity of 90%, reducing the potential diagnostic delay. However, the specificity was 29%, inducing overmedicalisation (excessive follow-up). ROC-AUC of the BACTIP was poor for differentiating enchondroma from ACT (ROC-AUC = 0.69; 95%CI = 0.51-0.87; p = 0.041) and fair-good for differentiation between other CCT groups (ROC-AUC = 0.72-0.81). BACTIP recommendations were incorrect/unsafe in five ACTs and one CSII, potentially inducing diagnostic delay. Eleven enchondromas received unnecessary referrals/follow-up. CONCLUSION: Although promising as a useful tool for management/follow-up of CCTs of the proximal humerus, distal femur, and proximal tibia, five ACTs and one chondrosarcoma grade II were discharged, potentially inducing diagnostic delay, which could be reduced by adapting BACTIP cut-off values. CLINICAL RELEVANCE STATEMENT: Mostly, Birmingham Atypical Cartilage Tumour Imaging Protocol (BACTIP) assesses central cartilage tumours of the proximal humerus and the knee correctly. Both when using the BACTIP and when adapting cut-offs, caution should be taken for the trade-off between underdiagnosis/potential diagnostic delay in chondrosarcomas and overmedicalisation in enchondromas. KEY POINTS: • This retrospective external validation confirms the Birmingham Atypical Cartilage Tumour Imaging Protocol as a useful tool for initial assessment and follow-up recommendation of central cartilage tumours in the proximal humerus and around the knee in the majority of cases. • Using only the Birmingham Atypical Cartilage Tumour Imaging Protocol, both atypical cartilaginous tumours and high-grade chondrosarcomas (grade II, grade III, and dedifferentiated chondrosarcomas) can be misdiagnosed, excluding them from specialist referral and further follow-up, thus creating a potential risk of delayed diagnosis and worse prognosis. • Adapted cut-offs to maximise detection of atypical cartilaginous tumours and high-grade chondrosarcomas, minimise underdiagnosis and reduce potential diagnostic delay in malignant tumours but increase unnecessary referral and follow-up of benign tumours.

Recycled bone grafts treated with extracorporeal irradiation or liquid nitrogen freezing after malignant tumor resection.

INTRODUCTION: Recycled bone autografts prepared using extracorporeal irradiation (ECIR) or liquid nitrogen freezing (LNF) methods have been used for the reconstruction of skeletal elements after wide resection of sarcomas involving bone tissues. Few reports include long-term follow-up data for histological analyses of recycled autografts, particularly in the case of ECIR autografts. MATERIALS: A total of 34 malignant bone and soft tissue tumors were resected and reconstructed using 11 ECIR- and 23 LNF-recycled autografts; the mean postoperative follow-ups were 14 and 8 years, respectively. ECIR was used for either osteosarcomas or Ewing sarcomas, whereas in addition to these tumors LNF was used for chondrosarcomas and soft tissue sarcomas involving bone tissues. Recycled bone was implanted as total bone, osteoarticular, or intercalary grafts, with or without prosthesis or vascularized fibular grafts. RESULTS: The 10-year graft survival rate was similar between groups, 81.8% using ECIR and 70.2% using LNF. There were no autograft-related tumor recurrences in either group. Graft survival was unrelated to type of graft or additional procedures. Complication rates tended to be higher using ECIR (64%) compared with LNF (52%) and the infection rate was significantly higher with ECIR (27%) versus LNF (0%). At the final assessment, plain radiographs revealed original recycled bone was present in 7 of 11 ECIR cases and in zero cases treated with LNF autografts, indicating that recycled bone treated with LNF autografts was remodeled into new bone. Histological examination of ECIR-treated bones revealed a delayed and incomplete endochondral ossification process, necrosis and empty lacunae. Conversely, LNF autografts showed remodeled bones with normal trabecular structures. CONCLUSIONS: ECIR and LNF treatment of autografts provided adequate tumor control with acceptable clinical results as a reconstruction method.

The application of three-dimensional custom-made prostheses in chest wall reconstruction after oncologic sternal resection.

BACKGROUND AND OBJECTIVES: As one of the cutting-edge advances in the field of reconstruction, three-dimensional (3D) printing technology has been constantly being attempted to assist in the reconstruction of complicated large chest wall defects. However, there is little literature assessing the treatment outcomes of 3D printed prostheses for chest wall reconstruction. This study aimed to analyze the surgical outcomes of 3D custom-made prostheses for the reconstruction of oncologic sternal defects and to share our experience in the surgical management of these rare and complex cases. METHODS: We summarized the clinical features of the sternal tumor in our center, described the surgical techniques of the application of 3D customized prosthesis for chest wall reconstruction, and analyzed the perioperative characteristics, complications, overall survival (OS), and recurrence-free survival of patients. RESULTS: Thirty-two patients with the sternal tumor who underwent chest wall resection were identified, among which 13 patients used 3D custom-made titanium implants and 13 patients used titanium mesh for sternal reconstruction. 22 cases were malignant, and chondrosarcoma is the most common type. The mean age was 46.9 years, and 53% (17/32) of the patients were male. The average size of tumor was 6.4 cm, and the mean defect area was 76.4 cm2. 97% (31/32) patients received R0 resection. Complications were observed in 29% (9/32) of patients, of which wound infection (22%, 7/32) was the most common. The OS of the patients was 72% at 5 years. CONCLUSION: We demonstrated that with careful preoperative assessment, 3D customized prostheses could be a viable alternative for complex sternal reconstruction.

Skull Base Chordoma and Chondrosarcoma: Neuroradiologist's Guide to Diagnosis, Surgical Management, and Proton Beam Therapy.

Skull base chordomas and chondrosarcomas are distinct types of rare, locally aggressive mesenchymal tumors that share key principles of imaging investigation and multidisciplinary care. Maximal safe surgical resection is the treatment choice for each, often via an expanded endoscopic endonasal approach, with or without multilayer skull base repair. Postoperative adjuvant radiation therapy is frequently administered, usually with particle therapy such as proton beam therapy (PBT). Compared with photon therapy, PBT enables dose escalation while limiting damage to dose-limiting neurologic structures, particularly the brainstem and optic apparatus, due to energy deposition being delivered at a high maximum with a rapid decrease at the end of the penetration range (Bragg peak phenomenon). Essential requirements for PBT following gross total or maximal safe resection are tissue diagnosis, minimal residual tumor after resection, and adequate clearance from PBT dose-limiting structures. The radiologist should understand surgical approaches and surgical techniques, including multilayer skull base repair, and be aware of evolution of postsurgical imaging appearances over time. Accurate radiologic review of all relevant preoperative imaging examinations and of intraoperative and postoperative MRI examinations plays a key role in management. The radiology report should reflect what the skull base surgeon and radiation oncologist need to know, including distance between the tumor and PBT dose-limiting structures, tumor sites that may be difficult to access via the endoscopic endonasal route, the relationship between intradural tumor and neurovascular structures, and tumor sites with implications for postresection stability. ©RSNA, 2024 Supplemental material is available for this article.

Diagnosis of chondrosarcoma in a noninvasive way using volatile organic compounds in exhaled breath: a pilot study.

Aim: Aim of this explorative pilot study was to evaluate the capability of an electronic nose (aeoNose, the eNose Company) to classify healthy individuals and patients with chondrosarcoma, based on their volatile organic compound profiles in exhaled breath.Materials & methods: Fifty-seven patients (25 healthy controls, 24 chondrosarcoma and 8 different benign lesions) were included in the study from 2018 to 2023. An artificial neural network was used as classifier.Results: The developed model had a sensitivity of 75%, and a specificity of 65% with an AUC of 0.66.Conclusion: Results show that there is not enough evidence to include the aeoNose as diagnostic biomarker for chondrosarcoma in daily practice. However, the aeoNose might play an additional role alongside MRI, in questionable chondrosarcoma cases.

Evaluation of cranial nerve involvement in chordomas and chondrosarcomas: a retrospective imaging study.

PURPOSE: Cranial nerve involvement (CNI) influences the treatment strategies and prognosis of head and neck tumors. However, its incidence in skull base chordomas and chondrosarcomas remains to be investigated. This study evaluated the imaging features of chordoma and chondrosarcoma, with a focus on the differences in CNI. METHODS: Forty-two patients (26 and 16 patients with chordomas and chondrosarcomas, respectively) treated at our institution between January 2007 and January 2023 were included in this retrospective study. Imaging features, such as the maximum diameter, tumor location (midline or off-midline), calcification, signal intensity on T2-weighted image, mean apparent diffusion coefficient (ADC) values, contrast enhancement, and CNI, were evaluated and compared using Fisher's exact test or the Mann-Whitney U-test. The odds ratio (OR) was calculated to evaluate the association between the histological type and imaging features. RESULTS: The incidence of CNI in chondrosarcomas was significantly higher than that in chordomas (63% vs. 8%, P < 0.001). An off-midline location was more common in chondrosarcomas than in chordomas (86% vs. 13%; P < 0.001). The mean ADC values of chondrosarcomas were significantly higher than those of chordomas (P < 0.001). Significant associations were identified between chondrosarcomas and CNI (OR = 20.00; P < 0.001), location (OR = 53.70; P < 0.001), and mean ADC values (OR = 1.01; P = 0.002). CONCLUSION: The incidence of CNI and off-midline location in chondrosarcomas was significantly higher than that in chordomas. CNI, tumor location, and the mean ADC can help distinguish between these entities.

Intravoxel Incoherent Motion and Dynamic Contrast-Enhanced Magnetic Resonance Imaging Can Differentiate Between Atypical Cartilaginous Tumors and High-Grade Chondrosarcoma: Correlation With Histological Vessel Characteristics.

OBJECTIVE: To differentiate between atypical cartilaginous tumors and high-grade chondrosarcoma of the major long bones using intravoxel incoherent motion (IVIM) and Dynamic Contrast-Enhanced magnetic resonance imaging (DCE-MRI), and explore the correlation of quantitative parameters with hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and microvessel density (MVD). METHOD: Between September 2016 and March 2022, 35 patients (17 atypical cartilaginous tumors, 18 high-grade chondrosarcoma) underwent MRI examination and pathological confirmation at our hospital. First, IVIM-derived parameters ( D , D* , and f ), and DCE-MRI parameters ( Ktrans , Kep , and V e ) were measured, and intraclass correlation efficient (ICC) and Mann-Whitney U test were performed. Second, receiver-operating characteristic curve analysis was performed to evaluate the diagnostic performance. Finally, Spearman's correlation analysis was performed between the quantitative parameters of IVIM-DWI and DCE-MRI and the immunohistochemical factors HIF-1α, VEGF, and MVD in chondrosarcoma tissue. RESULTS: D in atypical cartilaginous tumors was significantly higher than that in high-grade chondrosarcoma ( P = 0.003), whereas D* , Ktrans , and K ep in atypical cartilaginous tumors were significantly lower than those in high-grade chondrosarcoma (all P < 0.001). Ktrans demonstrated the highest area under the curve (AUC) of 0.979. The D* , Ktrans , and K ep were positively correlated with HIF-1α, VEGF, and MVD (all P < 0.001), whereas D had no correlation with HIF-1α, VEGF, and MVD ( P = 0.113, 0.077, 0.058, respectively). CONCLUSION: The IVIM-DWI quantitative parameters ( D , D* ) and DCE-MRI quantitative parameters ( Ktrans , Kep ) are helpful to differentiate between atypical cartilaginous tumors and high-grade chondrosarcoma and could be imaging biomarkers to reflect the expressions of HIF-1α, VEGF, and angiogenesis of chondrosarcoma.

Preoperative prediction of histopathological grading in patients with chondrosarcoma using MRI-based radiomics with semantic features.

BACKGROUND: Distinguishing high-grade from low-grade chondrosarcoma is extremely vital not only for guiding the development of personalized surgical treatment but also for predicting the prognosis of patients. We aimed to establish and validate a magnetic resonance imaging (MRI)-based nomogram for predicting preoperative grading in patients with chondrosarcoma. METHODS: Approximately 114 patients (60 and 54 cases with high-grade and low-grade chondrosarcoma, respectively) were recruited for this retrospective study. All patients were treated via surgery and histopathologically proven, and they were randomly divided into training (n = 80) and validation (n = 34) sets at a ratio of 7:3. Next, radiomics features were extracted from two sequences using the least absolute shrinkage and selection operator (LASSO) algorithms. The rad-scores were calculated and then subjected to logistic regression to develop a radiomics model. A nomogram combining independent predictive semantic features with radiomic by using multivariate logistic regression was established. The performance of each model was assessed by the receiver operating characteristic (ROC) curve analysis and the area under the curve, while clinical efficacy was evaluated via decision curve analysis (DCA). RESULTS: Ultimately, six optimal radiomics signatures were extracted from T1-weighted imaging (T1WI) and T2-weighted imaging with fat suppression (T2WI-FS) sequences to develop the radiomics model. Tumour cartilage abundance, which emerged as an independent predictor, was significantly related to chondrosarcoma grading (p < 0.05). The AUC values of the radiomics model were 0.85 (95% CI, 0.76 to 0.95) in the training sets, and the corresponding AUC values in the validation sets were 0.82 (95% CI, 0.65 to 0.98), which were far superior to the clinical model AUC values of 0.68 (95% CI, 0.58 to 0.79) in the training sets and 0.72 (95% CI, 0.57 to 0.87) in the validation sets. The nomogram demonstrated good performance in the preoperative distinction of chondrosarcoma. The DCA analysis revealed that the nomogram model had a markedly higher clinical usefulness in predicting chondrosarcoma grading preoperatively than either the rad-score or clinical model alone. CONCLUSION: The nomogram based on MRI radiomics combined with optimal independent factors had better performance for the preoperative differentiation between low-grade and high-grade chondrosarcoma and has potential as a noninvasive preoperative tool for personalizing clinical plans.

Can the Cartilaginous Thickness Determine the Risk of Malignancy in Pelvic Cartilaginous Tumors, and How Accurate is the Preoperative Biopsy of These Tumors?

BACKGROUND: Peripheral osteochondral tumors are common, and the management of tumors presenting in the pelvis is challenging and a controversial topic. Some have suggested that cartilage cap thickness may indicate malignant potential, but this supposition is not well validated. QUESTIONS/PURPOSES: (1) How accurate is preoperative biopsy in determining whether a peripheral cartilage tumor of the pelvis is benign or malignant? (2) Is the thickness of the cartilage cap as determined by MRI associated with the likelihood that a given peripheral cartilage tumor is malignant? (3) What is local recurrence-free survival (LRFS), metastasis-free survival (MFS), and disease-specific survival (DSS) in peripheral chondrosarcoma of the pelvis and is it associated with surgical margin? METHODS: Between 2005 and 2022, 289 patients had diagnoses of peripheral cartilage tumors of the pelvis (either pedunculated or sessile) and were treated at one tertiary sarcoma center (the Royal Orthopaedic Hospital, Birmingham, UK). These patients were identified retrospectively from a longitudinally maintained institutional database. Those whose tumors were asymptomatic and discovered incidentally and had cartilage caps ≤ 1.5 cm were discharged (95 patients), leaving 194 patients with tumors that were either symptomatic or had cartilage caps > 1.5 cm. Tumors that were asymptomatic and had a cartilage cap > 1.5 cm were followed with MRIs for 2 years and discharged without biopsy if the tumors did not grow or change in appearance (15 patients). Patients with symptomatic tumors that had cartilage caps ≤ 1.5 cm underwent removal without biopsy (63 patients). A total of 82 patients (63 with caps ≤ 1.5 cm and 19 with caps > 1.5 cm, whose treatment deviated from the routine at the time) had their tumors removed without biopsy. This left 97 patients who underwent biopsy before removal of peripheral cartilage tumors of the pelvis, and this was the group we used to answer research question 1. The thickness of the cartilage cap was recorded from MRI and measuring to the nearest millimeter, with measurements taken perpendicular in the plane that best allowed the greatest measurement. Patient survival rates were assessed using the Kaplan-Meier method with 95% confidence intervals as median observation times to estimate MFS, LRFS, and DSS. RESULTS: Of malignant tumors biopsied, in 49% (40 of 82), the biopsy result was recorded as benign (or was considered uncertain regarding malignancy). A malignant diagnosis was correctly reported in biopsy reports in 51% (42 of 82) of patients, and if biopsy samples with uncertainty regarding malignancy were excluded, the biopsy identified a lesion as being malignant in 84% (42 of 50) of patients. The biopsy results correlated with the final histologic grade as recorded from the resected specimen in only 33% (27 of 82) of patients. Among these 82 patients, 15 biopsies underestimated the final histologic grade. The median cartilage cap thickness for all benign osteochondromas was 0.5 cm (range 0.1 to 4.0 cm), and the median cartilage cap thickness for malignant peripheral chondrosarcomas was 8.0 cm (range 3.0 to 19 cm, difference of medians 7.5 cm; p < 0.01). LRFS was 49% (95% CI 35% to 63%) at 3 years for patients with malignant peripheral tumors with < 1-mm margins, and LRFS was 97% (95% CI 92% to 100%) for patients with malignant peripheral tumors with ≥ 1-mm margins (p < 0.01). DSS was 100% at 3 years for Grade 1 chondrosarcomas, 94% (95% CI 86% to 100%) at 3 years for Grade 2 chondrosarcomas, 73% (95% CI 47% to 99%) at 3 and 5 years for Grade 3 chondrosarcomas, and 20% (95% CI 0% to 55%) at 3 and 5 years for dedifferentiated chondrosarcomas (p < 0.01). DSS was 87% (95% CI 78% to 96%) at 3 years for patients with malignant peripheral tumors with < 1-mm margin, and DSS was 100% at 3 years for patients with malignant peripheral tumors with ≥ 1-mm margins (p = 0.01). CONCLUSION: A thin cartilage cap (< 3 cm) is characteristic of benign osteochondroma. The likelihood of a cartilage tumor being malignant increases after the cartilage cap thickness exceeds 3 cm. In our experience, preoperative biopsy results were not reliably associated with the final histologic grade or malignancy, being accurate in only 33% of patients. We therefore recommend observation for 2 years for patients with pelvic osteochondromas in which the cap thickness is < 1.5 cm and there is no associated pain. For patients with tumors in which the cap thickness is 1.5 to 3 cm, we recommend either close observation for 2 years or resection, depending on the treating physician's decision. We recommend excision in patients whose pelvic osteochondromas show an increase in thickness or pain, preferably before the cartilage cap thickness is 3 cm. We propose that surgical resection of peripheral cartilage tumors in which the cartilage cap exceeds 3 cm (aiming for clear margins) is reasonable without preoperative biopsy; the role of preoperative biopsy is less helpful because radiologic measurement of the cartilage cap thickness appears to be accurately associated with malignancy. Biopsy might be helpful in patients in whom there is diagnostic uncertainty or when confirming the necessity of extensive surgical procedures. Future studies should evaluate other preoperative tumor qualities in differentiating malignant peripheral cartilage tumors from benign tumors. LEVEL OF EVIDENCE: Level III, diagnostic study.

Application of microwave ablation assisted degradation therapy in surgical treatment of intramedullary chondrosarcoma of extremities.

AIM: Clinical diagnosis and surgical treatment of chondrosarcoma (CS) are continuously improving. The purpose of our study is to evaluate the effectiveness of microwave ablation (MWA) assisted degradation therapy in the surgical treatment of intramedullary chondrosarcoma of the extremities, to provide a new reference and research basis for the surgical treatment of CS. METHODS: We recruited 36 patients with intramedullary CS who underwent MWA assisted extended curettage. Preoperative patient demographics and clinical data were recorded. Surgery was independently assisted by a medical team. Patients were followed up strictly and evaluated for oncological prognosis, radiological results, limb joint function, pain, and complications. RESULTS: We included 15 men and 21 women (mean age: 43.5 ± 10.1). The average length of the lesion was 8.1 ± 2.5 cm. Based on preoperative radiographic, clinical manifestations, and pathological results of puncture biopsy, 28 patients were preliminarily diagnosed with CS-grade I and eight patients with CS-grade II. No recurrence or metastasis occurred in the postoperative follow-up. The average Musculoskeletal Tumor Society score was 28.8 ± 1.0, significantly better than presurgery. Secondary shoulder periarthritis and abduction dysfunction occurred in early postoperative stage CS of the proximal humerus in some, but returned to normal after rehabilitation exercise. Secondary bursitis occurred at the knee joint in some due to the internal fixation device used in treatment; however, secondary osteoarthritis and avascular necrosis of the femoral head were not observed. Overall, oncological and functional prognoses were satisfactory. CONCLUSIONS: The application of MWA assisted degradation therapy in intramedullary CS can achieve satisfactory oncology and functional prognosis, providing a new option for the limited treatment of CS.

Complications and local recurrence of chondrosarcoma and chordoma treated by total tumor resection in thoracic and lumbar spine.

BACKGROUND: En bloc resection of spinal tumors is challenging and associated with a high incidence of complications; however, it offers the potential to reduce the risk of recurrence when a wide margin is achieved. This research aims to investigate the safety and efficacy of en bloc resection in treating thoracic and lumbar chondrosarcoma/chordoma. METHODS: Data from patients diagnosed with chondrosarcoma and chordoma in the thoracic or lumbar region, who underwent total en bloc or piecemeal resection at our institution over a 7-year period, were collected and regularly followed up. The study analyzed overall perioperative complications and compared differences in complications and local tumor recurrence between the two surgical methods. RESULTS: Seventeen patients were included, comprising 12 with chondrosarcoma and 5 with chordoma. Among them, 5 cases underwent intralesional piecemeal resection, while the remaining 12 underwent planned en bloc resection. The average surgical time was 684 min (sd = 287), and the mean estimated blood loss was 2300 ml (sd = 1599). Thirty-five complications were recorded, with an average of 2.06 perioperative complications per patient. 82% of patients (14/17) experienced at least one perioperative complication, and major complications occurred in 64.7% (11/17). Five patients had local recurrence during the follow-up, with a mean recurrence time of 16.2 months (sd = 7.2) and a median recurrence time of 20 months (IQR = 12.5). Hospital stays, operation time, blood loss, and complication rates did not significantly differ between the two surgical methods. The local recurrence rate after en bloc resection was lower than piecemeal resection, although not statistically significant (P = 0.067). CONCLUSIONS: The complication rates between the two surgical procedures were similar. Considering safety and local tumor control, en bloc resection is recommended as the primary choice for patients with chondrosarcoma/chordoma in the thoracic and lumbar regions who are eligible for this treatment.

Clival chordomas and chondrosarcomas in Denmark-Outcomes in 33 patients following the national centralization of treatment in 2010.

PURPOSE: This 13-year consecutive case series aims to provide a comprehensive overview of all patients operated for clival chordomas and clival chondrosarcomas in Denmark since the centralization of treatment in 2010, comparing outcomes to international series. METHODS: This was a retrospective review of 33 patients with clival tumors, comprising 22 chordomas and 11 chondrosarcomas, who were treated at Copenhagen University Hospital between years 2010 and 2023. Data were collected from digital patient records and pathology reports. RESULTS: The symptoms leading to diagnosis primarily included double vision, headaches, and dizziness. In general, patients were in good health, with a mean Charlson Comorbidity Index score of 1.6. The complication rate of the index surgery was 51.5%. Adjuvant radiotherapy was applied in 51.5% of the cases. In patients with clival chordomas, the mean age was 51.1 years, ranging from 16 to 83 years. At the time of diagnosis, the mean tumor volume was 20.9 cm3 and the five-year overall survival rates were 79.1% (95% confidence interval (CI): 62.4-100). In patients with chondrosarcomas, the mean age was 48.2 years, ranging from 15 to 76 years. At the time of diagnosis, the mean tumor volume was 22.3 cm3 and the five-year overall survival 90% (95% CI: 73.2-100). CONCLUSION: The centralized treatment of clival tumors in Denmark demonstrates incidence, survival, and complication rates comparable to those found in other international series. Given the variations in treatment strategies, tumor localizations across series, and small sample sizes, the further analysis of larger compiled multicenter datasets for clival tumors could provide more solid evidence regarding the management of these rare tumors.

Advances in the multidisciplinary surgical approach to primary spinal sarcomas: insights from a retrospective case series on outcomes and survival.

INTRODUCTION: The management of spinal sarcomas is complex, given their widespread involvement and high recurrence rates. Despite consensus on the need for a multidisciplinary approach with surgery at its core, there is a lack of definitive guidelines for clinical decision-making. This study examines a case series of primary spinal sarcomas, focusing on the surgical strategies, clinical results, and survival data to inform and guide therapeutic practices. METHODS: We conducted a retrospective analysis of patients who underwent surgical resection for primary spinal sarcomas between 2005 and 2022. The study focused on gathering data on patient demographics, surgical details, postoperative complications, overall hospital stay, and mortality within 90 days post-surgery. RESULTS: The study included 14 patients with a primary diagnosis of spinal sarcoma, with an average age of 48.6 ± 12.6 years. Chondrosarcoma emerged as the most common tumor type, representing 57.1% of cases, followed by Ewing sarcoma at 35.7%, and synovial sarcoma at 7.1%. Patients with chondrosarcoma were treated with en-bloc resection, while the patient with synovial sarcoma underwent intra-lesional excision and those with Ewing sarcoma received decompression and tumor debulking. Postoperative assessments revealed significant improvements in neurological conditions. Notably, functional status as measured by the Karnofski Performance Index (KPI), improved substantially post-surgery (from 61.4 to 80.0%) The mean follow-up was 34.9 ± 9.2 months. During this time period one patient experienced fatal bleeding after en-bloc resection complications involving the vena cava. None of the patient needed further surgery. CONCLUSIONS: Our 16-year study offers vital insights into managing primary spinal sarcomas, showcasing the effectiveness of surgical intervention, particularly en-bloc resection. Despite their rarity and complexity, our multidisciplinary treatment approach yields improved outcomes and highlights the potential for refined surgical strategies to become standardized care in this challenging domain.

Treatment strategy in laryngeal chondrosarcoma: a multicenter study of 43 cases.

PURPOSE: Laryngeal chondrosarcoma is a rare tumor that mostly affects the cricoid cartilage. The aim of this study was to compare outcomes between the various treatments of this pathology as there are no official guidelines for this pathology. METHODS: A retrospective analysis of the pathology database of nine French tertiary care centers was conducted. Outcomes of patients treated by total laryngectomy were compared with those treated by more conservative approaches (endoscopic debulking, median thyrotomy, partial laryngectomy). Two Kaplan-Meier survival analyses were performed: one to assess the overall survival rate and the other to assess laryngeal preservation over time. RESULTS: A total of 43 patients were enrolled: 12 with total laryngectomy as the initial treatment, and 31 who initially underwent laryngeal-preserving treatment. With conservative treatment, laryngeal function was preserved in 96% and 75% of patients at 1 and 5 years, respectively. Conservative treatment did not reduce the overall survival rate. CONCLUSION: These results suggest that laryngeal preservation should be considered as the initial treatment in cases of laryngeal chondrosarcoma.