Malignant Cartilaginous Tumors Research Articles

Chondrosarcoma Resistance to Radiation Therapy: Origins and Potential Therapeutic Solutions

Chondrosarcoma is a malignant cartilaginous tumor that is particularly chemoresistant and radioresistant to X-rays. The first line of treatment is surgery, though this is almost impossible in some specific locations. Such resistances can be explained by the particular composition of the tumor, which develops within a dense cartilaginous matrix, producing a resistant area where the oxygen tension is very low. This microenvironment forces the cells to adapt and dedifferentiate into cancer stem cells, which are described to be more resistant to conventional treatments. One of the main avenues considered to treat this type of tumor is hadrontherapy, in particular for its ballistic properties but also its greater biological effectiveness against tumor cells. In this review, we describe the different forms of chondrosarcoma resistance and how hadrontherapy, combined with other treatments involving targeted inhibitors, could help to better treat high-grade chondrosarcoma.

Benign cartilaginous tumors of the hand, a five-year retrospective study.

Benign and malignant cartilaginous bone tumors of the hand are rare findings, however representing a particular pathology due to the capacity to induce significant functional impairment. Even though a large proportion of tumors of the hand and wrist are benign, these may present destructive characteristics, deforming adjacent structures until compromising function. The most appropriate surgical approach for most benign tumors is intralesional lesion resection. Malignant tumors often require wide excision, up to segment amputation to obtain tumor control. A five-year retrospective study was performed on patients admitted in our Clinic with benign cartilaginous tumors of the hand, in which 15 patients were admitted within this period, 10 presenting with enchondroma, four presenting with osteochondroma, and lastly one with chondromatosis. After clinical and imaging evaluation, all the aforementioned tumors were surgically removed. Definitive diagnosis for all bone tumors, either benign or malignant, was established by tissue biopsy and histopathological examination, dictating therapeutic strategy.

Secondary chondrosarcoma of humerus with osteosarcomatous de-differentiation: The importance of being on guard

Dedifferentiated chondrosarcoma is a highly aggressive but fortunately a rare variant of chondrosarcoma. It is characterized by juxtaposed elements of malignant cartilaginous tumor proliferation alongside mesenchymal tumor of the high malignancy. Careful radiological assessment coupled with sampling of different areas of the biopsy is important for planning treatment. We are reporting a case of secondary chondrosarcoma of humerus which underwent dedifferentiation to fibrosarcoma and osteosarcoma with a fatal outcome.

Concordance between Radiological Features and Histopathological Diagnosis of Cartilaginous Lesions of Bone among Patients at a Tertiary Care Centre, Trivandrum, Kerala

Introduction: Cartilaginous tumours comprise a large, heterogeneous group of mesenchymal neoplasms. They pose a challenge in terms of accurate diagnosis and management. Histopathological findings have direct implications for treatment outcomes. Aim: To determine the concordance between the radiological features and the histopathological diagnosis of cartilaginous lesions of bone. Materials and Methods: This was a retrospective study conducted in the Department of Pathology, Regional Cancer Centre, Trivandrum, Kerala, India, among 109 patients with histopathologically proven benign and malignant cartilaginous tumours, received in the laboratory between January 2012 and December 2021 for a duration of 10 years, were analysed. The study was conducted between September 2019 and January 2022. The demographic data for the study, including age, tumour site, clinical findings, and radiological diagnosis, were obtained from medical records. The cases were histopathologically graded based on the World Health Organization 2020 classification of tumours of soft tissue and bone. The concordance between histopathological diagnosis and radiological features was assessed. The Chi-square test was used to find the association between two categorical variables, and the Independent sample t-test was used to find the difference between two groups with respect to mean and standard deviation. Results: There were a total of 109 cases of cartilaginous tumours, out of which 82 cases (75.22%) were diagnosed as malignant and 27 cases (24.77%) were diagnosed as benign. Among benign neoplasms, chondroblastoma and osteochondroma were the most common, with 10 cases (37.03%) each. Among malignant chondroid tumours, 73 (89.02%) were diagnosed as conventional chondrosarcoma. There were five cases (6.09%) of secondary chondrosarcomas (malignant transformation of a benign cartilaginous lesion). Among the secondary chondrosarcomas, three cases (60%) were malignant transformation in osteochondroma, 1 (20%) in enchondroma, and 1 (20%) in synovial chondromatosis. Among the 91 cases for which radiology was available, 86 (94.50%) had a concordance between radiological and histopathological diagnosis. Five cases (5.49%) had a discordant radiological diagnosis. Conclusion: For histologically benign tumours, the radiological findings in the study were identical and concordant. For histologically malignant tumours, there were discrepancies with radiological findings in this study when the lesion had an associated cyst, absence of cortical destruction, or absence of a clear cartilaginous component and extra cortical expansion. For histologically suspicious cases in the study, the final diagnosis was made based upon radiological findings, with a particular interest in cortical destruction.

Imaging features of cartilaginous tumors of the head and neck.

There is a wide spectrum of head and neck cartilaginous lesions which include both neoplastic and nonneoplastic processes. Cartilaginous tumors of the head and neck are uncommon, posing a diagnostic challenge. Benign cartilaginous tumors that may occur in the head and neck include chondroma, chondroblastoma, chondromyxoid fibroma, osteochondroma, and synovial chondromatosis. Chondromesenchymal hamartoma is a rare non-neoplastic cartilaginous lesion that is included for the 1first time in the new WHO classification and radiologically can mimic a tumor. Malignant cartilaginous tumors include chondrosarcoma and chondroid variant of chordoma. Characteristic tumor locations, internal chondroid matrix calcification, and typical T2 hyperintense signal secondary to high-water content within the extracellular matrix of the hyaline cartilage are useful imaging features that narrow the differential diagnosis and help in diagnosing these diseases. This article presents a narrative review of the anatomy of the head and neck cartilaginous structures, discusses the current knowledge and imaging spectrum of benign and malignant cartilaginous tumors and tumor-like lesions of the head and neck.

Diagnostic Value of CT- and MRI-Based Texture Analysis and Imaging Findings for Grading Cartilaginous Tumors in Long Bones.

ObjectiveTo confirm the diagnostic performance of computed tomography (CT)-based texture analysis (CTTA) and magnetic resonance imaging (MRI)-based texture analysis for grading cartilaginous tumors in long bones and to compare these findings to radiological features.Materials and MethodsTwenty-nine patients with enchondromas, 20 with low-grade chondrosarcomas and 16 with high-grade chondrosarcomas were included retrospectively. Clinical and radiological information and 9 histogram features extracted from CT, T1WI, and T2WI were evaluated. Binary logistic regression analysis was performed to determine predictive factors for grading cartilaginous tumors and to establish diagnostic models. Another 26 patients were included to validate each model. Receiver operating characteristic (ROC) curves were generated, and accuracy rate, sensitivity, specificity and positive/negative predictive values (PPV/NPV) were calculated.ResultsOn imaging, endosteal scalloping, cortical destruction and calcification shape were predictive for grading cartilaginous tumors. For texture analysis, variance, mean, perc.01%, perc.10%, perc.99% and kurtosis were extracted after multivariate analysis. To differentiate benign cartilaginous tumors from low-grade chondrosarcomas, the imaging features model reached the highest accuracy rate (83.7%) and AUC (0.841), with a sensitivity of 75% and specificity of 93.1%. The CTTA feature model best distinguished low-grade and high-grade chondrosarcomas, with accuracies of 71.9%, and 80% in the training and validation groups, respectively; T1-TA and T2-TA could not distinguish them well. We found that the imaging feature model best differentiated benign and malignant cartilaginous tumors, with an accuracy rate of 89.2%, followed by the T1-TA feature model (80.4%).ConclusionsThe imaging feature model and CTTA- or MRI-based texture analysis have the potential to differentiate cartilaginous tumors in long bones by grade. MRI-based texture analysis failed to grade chondrosarcomas.

A system-level approach identifies HIF-2\u03b1 as a critical regulator of chondrosarcoma progression

Chondrosarcomas, malignant cartilaginous neoplasms, are capable of transitioning to highly aggressive, metastatic, and treatment-refractory states, resulting in significant patient mortality. Here, we aim to uncover the transcriptional program directing such tumor progression in chondrosarcomas. We conduct weighted correlation network analysis to extract a characteristic gene module underlying chondrosarcoma malignancy. Hypoxia-inducible factor-2α (HIF-2α, encoded by EPAS1) is identified as an upstream regulator that governs the malignancy gene module. HIF-2α is upregulated in high-grade chondrosarcoma biopsies and EPAS1 gene amplification is associated with poor prognosis in chondrosarcoma patients. Using tumor xenograft mouse models, we demonstrate that HIF-2α confers chondrosarcomas the capacities required for tumor growth, local invasion, and metastasis. Meanwhile, pharmacological inhibition of HIF-2α, in conjunction with the chemotherapy agents, synergistically enhances chondrosarcoma cell apoptosis and abolishes malignant signatures of chondrosarcoma in mice. We expect that our insights into the pathogenesis of chondrosarcoma will provide guidelines for the development of molecular targeted therapeutics for chondrosarcoma.

Incidence and survival rates and trends of skull Base chondrosarcoma: A Population-Based study

IntroductionChondrosarcomas are extremely rare, locally invasive, and potentially mortal malignant cartilaginous tumors. In this study, we aimed to evaluate the incidence and survival rates and trends of skull base chondrosarcomas (SBC). MethodsData from SBC patients between 1975 and 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The age-adjusted incidence rates (AAR) were calculated for the overall cases and based on gender, age, race, and histology. Furthermore, the relative survival rates for one, three, and five years, and the rates stratified to the aforementioned selected variables were computed. Besides, we conducted a joint point regression analysis to calculate the annual percent change (APC) and its associated standard error (SE) for AAR and mortality. ResultsThe AAR rate of SBC was 0.019 per 100,000. Higher AAR rates were observed in patients who were in the 65−74-year-age-group, females, Caucasians, and had none mesenchymal subtype. The relative one-year, three-year and five-year-survival rates were 99.58 %, 93.67 %, and 89.10 %, respectively. Lower survival rates were noted in patients who were males, African Americans, and had a mesenchymal subtype. The trend analysis has shown a significant yearly increase (P < 0.001) in AAR of SBC (APC ± SE = 0.0005 %±0.0001), along with a significant yearly decline in mortality rates (APC ± SE= -0.0202 %±0.0029). ConclusionDespite the increase in AAR over time, there has been a significant decline in mortality rates over time, which might have been due to the advancement of treatment modalities, improvement in diagnostic imaging, and modification in disease grading.

Inhibiting Monocyte Recruitment to Prevent the Pro-Tumoral Activity of Tumor-Associated Macrophages in Chondrosarcoma.

Chondrosarcomas (CHS) are malignant cartilaginous neoplasms with diverse morphological features, characterized by resistance to chemo- and radiation therapies. In this study, we investigated the role of tumor-associated macrophages (TAM)s in tumor tissues from CHS patients by immunohistochemistry. Three-dimensional organotypic co-cultures were set up in order to evaluate the contribution of primary human CHS cells in driving an M2-like phenotype in monocyte-derived primary macrophages, and the capability of macrophages to promote growth and/or invasiveness of CHS cells. Finally, with an in vivo model of primary CHS cells engrafted in nude mice, we tested the ability of a potent peptide inhibitor of cell migration (Ac-d-Tyr-d-Arg-Aib-d-Arg-NH2, denoted RI-3) to reduce recruitment and infiltration of monocytes into CHS neoplastic lesions. We found a significant correlation between alternatively activated M2 macrophages and intratumor microvessel density in both conventional and dedifferentiated CHS human tissues, suggesting a link between TAM abundance and vascularization in CHS. In 3D and non-contact cu-culture models, soluble factors produced by CHS induced a M2-like phenotype in macrophages that, in turn, increased motility, invasion and matrix spreading of CHS cells. Finally, we present evidence that RI-3 successfully prevent both recruitment and infiltration of monocytes into CHS tissues, in nude mice.

Contribution of Raman Spectroscopy to Diagnosis and Grading of Chondrogenic Tumors

In the last decade, Raman Spectroscopy has demonstrated to be a label-free and non-destructive optical spectroscopy able to improve diagnostic accuracy in cancer diagnosis. This is because Raman spectroscopic measurements can reveal a deep molecular understanding of the biochemical changes in cancer tissues in comparison with non-cancer tissues. In this pilot study, we apply Raman spectroscopy imaging to the diagnosis and grading of chondrogenic tumors, including enchondroma and chondrosarcomas of increasing histologic grades. The investigation included the analysis of areas of 50×50 μm2 to approximately 200×200 μm2, respectively. Multivariate statistical analysis, based on unsupervised (Principal Analysis Components) and supervised (Linear Discriminant Analysis) methods, differentiated between the various tumor samples, between cells and extracellular matrix, and between collagen and non-collagenous components. The results dealt out basic biochemical information on tumor progression giving the possibility to grade with certainty the malignant cartilaginous tumors under investigation. The basic processes revealed by Raman Spectroscopy are the progressive degrading of collagen type-II components, the formation of calcifications and the cell proliferation in tissues ranging from enchondroma to chondrosarcomas. This study highlights that Raman spectroscopy is particularly effective when cartilaginous tumors need to be subjected to histopathological analysis.

Malawer limb salvage surgery for large chondrosarcoma of scapula with functional outcome – A case report

Chondrosarcoma is a malignant cartilaginous bone tumor. It commonly occurs in the pelvis and femur. However, scapula primary is relatively rare, accounting for 5%–7% of all the chondrosarcomas. Although wide local excision with negative margins is sufficient for chondrosarcoma, amputation is commonly performed for large tumors at the scapula location. Malawer limb salvage surgery can be performed in a large-sized tumor in order to retain the function. Here, we report a case of large scapular chondrosarcoma in a 53-year-old male, and the case was successfully treated with Malawer limb salvage surgery without any residual or positive margin. The patient was on regular follow-up with a well-preserved anatomical function of the shoulder girdle and without any recurrence of the disease after 24 months of surgery.

Intracellular cholesterol biosynthesis in enchondroma and chondrosarcoma.

Enchondroma and chondrosarcoma are the most common benign and malignant cartilaginous neoplasms. Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are present in the majority of these tumors. We performed RNA-seq analysis on chondrocytes from Col2a1Cre;Idh1LSL/+ animals and found that genes implied in cholesterol synthesis pathway were significantly upregulated in the mutant chondrocytes. We examined the phenotypic effect of inhibiting intracellular cholesterol biosynthesis on enchondroma formation by conditionally deleting SCAP (sterol regulatory element-binding protein cleavage-activating protein), a protein activating intracellular cholesterol synthesis, in IDH1 mutant mice. We found fewer enchondromas in animals lacking SCAP. Furthermore, in chondrosarcomas, pharmacological inhibition of intracellular cholesterol synthesis significantly reduced chondrosarcoma cell viability in vitro and suppressed tumor growth in vivo. Taken together, these data suggest that intracellular cholesterol synthesis is a potential therapeutic target for enchondromas and chondrosarcomas.

The Role of Imagistics in the Diagnosis of Chondrosarcomas

Abstract Chondrosarcomas are malignant cartilaginous tumors, with many histological subtypes and three grades based on cellularity. They are the second most common primary malignant tumors of the bone. From the histopathologically proved clinical cases, we are reviewing the imaging semiology - size, type of calcifications, cortical breach, endosteal scalloping, permeative or moth eaten bone appearance, and revealing other differentiation elements like location, age, and pain. A special point is the frequent difficulty in distinguishing between enchondromas and low grade conventional chondrosarcomas - as the lesions are very similar both histologically and radiographically. The radiologist should point the area to aim on the biopsy - at areas that may harbor foci of high-grade tumor, such as the ones of endosteal scalloping, soft-tissue components, or diffusely enhancing areas with minimal mineralization. It is known that with cartilaginous tumors, histopathologic examination of the biopsy specimen alone does not permit an accurate classification of the tumor. We emphasized the role of imaging in positive and differential diagnosis, management, and therapy of these bone tumors.

Mesenchymal Mandibular Chondrosarcoma: A Case Report and Review of Literature

Introduction: Chondrosarcomas (CS) are malignant cartilaginous tumors of rare maxillary localization. Their evolution is generally slow in time. They have a high tendency for locoregional recurrence after surgical treatment. Their prognosis depends on their degree of differentiation and the quality of resection. The authors report a clinical case of mesenchymal mandibular chondrosarcoma (MC), which is considered to be a subtype of CS, and specify the epidemiological, diagnostic, therapeutic and evolutionary features of this tumor. Case Report: A 73-year-old woman reported in February 2018 in our department complained of a slowly enlarging mass involving the right part of the lower jaw for the last 18 months. On examination a firm multilobular painful mass was palpated with cortical expansion, occupying the right side. A CT scan with 3D reconstruction was achieved and showed osteolysis lesions and cortical thickening. The mass biopsy for histological examination found a grade I well-differentiated bone chon-drosarcoma. We performed a hemi-mandibulectomy with complete resection of the tumor. The anatomopathologic examination of the resection specimen was in favour of a grade II mesenchymal chondrosarcoma. No radiotherapy was needed. The patient’s follow up was uneventful. Discussion: CS grading is the key to its management. Low grade CS (grades I and II) of the facial skeleton are luckily the most common, they are best treated with a local resection using 1.5 cm margins for bone and soft tissue. According to published literature, CS was historically considered as a radio resistant tumor. Radiotherapy and chemotherapy were therefore mainly reserved for high-grade tumors and for non-operable lesions. However, radical local surgery appears to be the treatment of choice for low grade chondrosarcoma. Conclusion: CS’s definitive diagnosis depends on appropriate radiographic evaluation along with adequate biopsy with meticulous histopathological examination and adjunctive immunohistochimical analysis. Neither chemotherapy nor radiotherapy is indicated as primary treatment. A long period follow-up should be advised as recurrence and metastasis are very frequent.

Primary Intracranial Myxoid Chondrosarcoma: A case report

Objective: Intracranial extraskeletal myxoid chondrosarcoma is a rare tumor; up to date, only ten cases have been reported. Case report: We present a case report of a 65-year-old female admitted for right side hemiplegia of gradual onset and progressive course over three weeks. Magnetic resonance imaging (MRI) revealed left intra-axial parieto-occipital space occupying lesion, hypodense with ring enhancement surrounded by diffuse edema. The patient underwent subtotal resection of the mass using sonar guided craniotomy. The histopathological and immunohistochemical evaluation confirmed a diagnosis of extraskeletal myxoid chondrosarcoma. One month after initial discharge, the patient underwent radiotherapy. A follow-up examination 6 months after surgery revealed that the patient was deteriorated and died. Conclusion: intracranial extraskeletal myxoid chondrosarcoma is a rare malignant cartilaginous tumor. Pathological diagnosis is the gold standard and radical excision is the standard treatment

Primary Intracranial Myxoid Chondrosarcoma: A case report

Objective: Intracranial extraskeletal myxoid chondrosarcoma is a rare tumor; up to date, only ten cases have been reported. Case report: We present a case report of a 65-year-old female admitted for right side hemiplegia of gradual onset and progressive course over three weeks. Magnetic resonance imaging (MRI) revealed left intra-axial parieto-occipital space occupying lesion, hypodense with ring enhancement surrounded by diffuse edema. The patient underwent subtotal resection of the mass using sonar guided craniotomy. The histopathological and immunohistochemical evaluation confirmed a diagnosis of extraskeletal myxoid chondrosarcoma. One month after initial discharge, the patient underwent radiotherapy. A follow-up examination 6 months after surgery revealed that the patient was deteriorated and died. Conclusion: intracranial extraskeletal myxoid chondrosarcoma is a rare malignant cartilaginous tumor. Pathological diagnosis is the gold standard and radical excision is the standard treatment

Familial solitary chondrosarcoma resulting from germline EXT2 mutation.

Germline mutations of EXT2, encoding Exostosin Glycosyltransferase 2, are associated with multiple osteochondromas (MO), an autosomal dominant disease characterized by the development of multiple peripheral cartilaginous benign tumors with a weak risk of malignant transformation. We report here a family with a remarkable clinical presentation characterized by the development of isolated chondrosarcomas, mostly located in ribs. Comparative analysis of exomes from two third-degree affected relatives led us to identify a single common disruptive variation, corresponding to a stop mutation (c.237G > A, p.Trp79*; (NM_000401.3); c.138G > A, p.Trp46*; (NM_207122.1)) within exon 2 of the EXT2 gene. Interestingly, no obvious sign of MO was detected in affected members by radiological examination. This report shows that germline mutations of EXT2 can result, not only in the development of multiple benign osteochondromas, but also in the development of isolated malignant cartilaginous tumors including central tumors, and that the presence of germline EXT2 mutation should be considered in patients suspected to have an inherited predisposition to chondrosarcoma, even in the absence of MO. © 2016 Wiley Periodicals, Inc.

Expression of insulin-like growth factor ІI mRNA binding protein 3 (IMP3) in enchondroma and chondrosarcoma

Atypical cartilaginous tumor and enchondroma are similar in histopathologic aspects. Although the clinical course, radiologic and pathologic examinations enable distinction in most cases, difficulties are still encountered by the pathologists. There is no known biomarker to help make a distinction between benign and malignant cartilaginous tumors. Insulin-like growth factor II mRNA binding protein (IMP3) is a member of an oncofetal family of proteins that is expressed in different human malignancies and rapidly emerging as a prognostic and diagnostic marker in surgical pathology. In this study, IMP3 expression was examined by immunohistochemistry in 36 enchondromas and 42 chondrosarcomas of different histologic grades. The results showed that all 36 cases of enchondroma were negative for IMP3, while it was overexpressed in 15 of 42 chondrosarcomas (36%) (P<0.01). Significant higher levels of IMP3 were detected in grade III chondrosarcomas (6 of 7; 85.7%) when compared to low-grade tumors (6 of 19; 31.5% in grade II and 3 of 16; 18.7% in Atypical Cartilaginous Tumor). We proved statistically significant difference in IMP3 expression between enchondromas and ACTs (P=0.025). Our study clearly demonstrated differentiation-dependent expression of IMP3 in chondrosarcoma, and suggests IMP3 as a novel marker for differentiating problematic cases of enchondroma from well-differentiated chondrosarcomas. To our knowledge, this study is the first study to clarify expression of IMP-3 in chondromas and chondrosarcomas.

Comparative analysis between growth factors of epiphyseal plate (SOX-9, PTH-rP) and expression of apoptotic modulation factor (BCL-2) in benign and malignant cartilaginous tumors: Correlation with clinical and morphological findings

Comparative analysis between growth factors of epiphyseal plate (SOX-9, PTH-rP) and expression of apoptotic modulation factor (BCL-2) in benign and malignant cartilaginous tumors: Correlation with clinical and morphological findings

A rare case of extraskeletal pulmonary myxoid chondrosarcoma

Primary malignant cartilaginous tumors of the lung are rare with limited reports in the literature. Here we describe the case of a69-year-old male who presented with a lobulated left upper lobe mass. Preoperative percutaneous biopsy was consistent with amucinous adenocarcinoma. Final pathology demonstrated a primary extraskeletal pulmonary myxoid chrondrosarcoma. Theclinical presentation and histologic characteristics are described.