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Neuroendocrinology 2020Skull base chordomas account for less than 0.2% and chondrosarcomas for less than 0.15% of all intracranial tumors. Although their clinical and imaging presentations are... (Review)
Review
Skull base chordomas account for less than 0.2% and chondrosarcomas for less than 0.15% of all intracranial tumors. Although their clinical and imaging presentations are similar, they derive from different origins. Chordomas arise from embryonic remnants of the primitive notochord and chondrosarcomas from primitive mesenchymal cells or from the embryonic rest of the cranial cartilaginous matrix. Both entities are characterized by infiltration and destruction of the surrounding bone and soft tissue and a high locoregional recurrence rate. Chondrosarcomas, when treated with similar complex strategies, display a much better prognosis than chordomas. The overall survival is approximately 65% for chordomas and 80% for chondrosarcomas at 5 years and 30 and 50%, respectively, at 10 years. Chordomas are divided into the following 3 histological types: classical (conventional), chondroid, and dedifferentiated. Chondrosarcomas have conventional, mesenchymal, clear cell, and dedifferentiated subgroups. Both tumor entities often present with nonspecific symptoms, and headaches are the most reported initial symptom. Computed tomography and magnetic resonance imaging are required to determine the tumor localization and the extent of tumor growth. The treatment philosophy is to maximize tumor resection, minimize morbidity, and preserve function. Neurosurgical approaches commonly used for the resection of intracranial chordomas and chondrosarcomas are transsphenoidal, transbasal, cranio-orbitozygomatic, transzygomatic extended middle fossa, transcondylar, and transmaxillary approaches. Chordomas and chondrosarcomas are not sensitive to chemotherapy and there are no approved drugs for their treatment. The present treatment concept is a combination of surgical resection with a maximal excision and preserving patients' quality of life by adjuvant radiotherapy for both chordomas and chondrosarcomas.
Topics: Chondrosarcoma; Chordoma; Humans; Skull Base Neoplasms
PubMed: 32541136
DOI: 10.1159/000509386 -
International Journal of Molecular... Jan 2023This review provides an overview of histopathology, clinical presentation, molecular pathways, and potential new systemic treatments of high-grade chondrosarcomas (CS),... (Review)
Review
This review provides an overview of histopathology, clinical presentation, molecular pathways, and potential new systemic treatments of high-grade chondrosarcomas (CS), including grade 2−3 conventional, dedifferentiated, and mesenchymal CS. The diagnosis of CS combines radiological and histological data in conjunction with patient clinical presentations. Conventional CS is the most frequent subtype of CS (85%) and represents about 25% of primary bone tumors in adults; they can be categorized according to their bone location into central, peripheral, and periosteal chondrosarcomas. Central and peripheral CS differ at the molecular level with either IDH1/2 mutations or EXT1/2 mutations, respectively. CDKN2A/B deletions are also frequent in conventional CS, as well as COL2A1 mutations. Dedifferentiated CS develops when low-grade conventional CS transforms into a high-grade sarcoma and most frequently exhibits features of osteosarcoma, fibrosarcoma, or undifferentiated pleomorphic sarcoma. Their molecular characteristics are similar to conventional CS. Mesenchymal CS is a totally different pathological entity exhibiting recurrent translocations. Their clinical presentation and management are different too. The standard treatment of CSs is wide en-bloc resection. CS are relatively radiotherapy resistant; therefore, doses >60 Gy are needed in an attempt to achieve local control in unresectable tumors. Chemotherapy is possibly effective in mesenchymal chondrosarcoma and is of uncertain value in dedifferentiated chondrosarcoma. Due to resistance to standard anticancer agents, the prognosis is poor in patients with metastatic or unresectable chondrosarcomas. Recently, the refined characterization of the molecular profile, as well as the development of new treatments, allow new therapeutic options for these rare tumors. The efficiency of IDH1 inhibitors in other malignancies suggests that these inhibitors will be part of IDH1/2 mutated conventional CS management soon. Other treatment approaches, such as PIK3-AKT-mTOR inhibitors, cell cycle inhibitors, and epigenetic or immune modulators based on improving our understanding of CS molecular biology, are emerging.
Topics: Adult; Humans; Chondrosarcoma; Bone Neoplasms; Radiography; Osteosarcoma; Biology
PubMed: 36674874
DOI: 10.3390/ijms24021361 -
Cureus Jul 2020Chondrosarcoma is a unique kind of tumor that originates from the cartilage-producing neoplastic mesenchymal cells and appears in both the appendicular and atlantoaxial...
Chondrosarcoma is a unique kind of tumor that originates from the cartilage-producing neoplastic mesenchymal cells and appears in both the appendicular and atlantoaxial skeleton. It is the second most prevalent neoplastic bone tumor, with an occurrence of 0.79/100,000/year. The biological presentation of this cancer fluctuates extensively, depending on the grade and anatomical location. Since chondrosarcoma is predominantly resistant to conventional chemo- and radiation therapy, surgical resection remains the sole curative treatment, although at present new treatment modalities are under investigation.
PubMed: 32789094
DOI: 10.7759/cureus.9158 -
Translational Cancer Research Dec 2022
PubMed: 36644194
DOI: 10.21037/tcr-22-2284 -
JCI Insight May 2023Mesenchymal chondrosarcoma affects adolescents and young adults, and most cases usually have the HEY1::NCOA2 fusion gene. However, the functional role of HEY1-NCOA2 in...
Mesenchymal chondrosarcoma affects adolescents and young adults, and most cases usually have the HEY1::NCOA2 fusion gene. However, the functional role of HEY1-NCOA2 in the development and progression of mesenchymal chondrosarcoma remains largely unknown. This study aimed to clarify the functional role of HEY1-NCOA2 in transformation of the cell of origin and induction of typical biphasic morphology of mesenchymal chondrosarcoma. We generated a mouse model for mesenchymal chondrosarcoma by introducing HEY1-NCOA2 into mouse embryonic superficial zone (eSZ) followed by subcutaneous transplantation into nude mice. HEY1-NCOA2 expression in eSZ cells successfully induced subcutaneous tumors in 68.9% of recipients, showing biphasic morphologies and expression of Sox9, a master regulator of chondrogenic differentiation. ChIP sequencing analyses indicated frequent interaction between HEY1-NCOA2 binding peaks and active enhancers. Runx2, which is important for differentiation and proliferation of the chondrocytic lineage, is invariably expressed in mouse mesenchymal chondrosarcoma, and interaction between HEY1-NCOA2 and Runx2 is observed using NCOA2 C-terminal domains. Although Runx2 knockout resulted in significant delay in tumor onset, it also induced aggressive growth of immature small round cells. Runx3, which is also expressed in mesenchymal chondrosarcoma and interacts with HEY1-NCOA2, replaced the DNA-binding property of Runx2 only in part. Treatment with the HDAC inhibitor panobinostat suppressed tumor growth both in vitro and in vivo, abrogating expression of genes downstream of HEY1-NCOA2 and Runx2. In conclusion, HEY1::NCOA2 expression modulates the transcriptional program in chondrogenic differentiation, affecting cartilage-specific transcription factor functions.
Topics: Animals; Mice; Bone Neoplasms; Cell Differentiation; Chondrosarcoma, Mesenchymal; Core Binding Factor Alpha 1 Subunit; Mice, Nude; Oncogene Proteins, Fusion
PubMed: 37212282
DOI: 10.1172/jci.insight.160279 -
Cancers Mar 2023Chondrosarcomas can be classified into various forms according to the presence or absence of a precursor lesion, location, and histological subtype. The new 2020 World... (Review)
Review
Chondrosarcomas can be classified into various forms according to the presence or absence of a precursor lesion, location, and histological subtype. The new 2020 World Health Organization (WHO) Classification of Tumors of Soft Tissue and Bone classifies chondrogenic bone tumors as benign, intermediate (locally aggressive), or malignant, and separates atypical cartilaginous tumors (ACTs) and chondrosarcoma grade 1 (CS1) as intermediate and malignant tumors. respectively. Furthermore, the classification categorizes chondrosarcomas (including ACT) into eight subtypes: central conventional (grade 1 vs. 2-3), secondary peripheral (grade 1 vs. 2-3), periosteal, dedifferentiated, mesenchymal, and clear cell chondrosarcoma. Most chondrosarcomas are the low-grade, primary central conventional type. The rarer subtypes include clear cell, mesenchymal, and dedifferentiated chondrosarcomas. Comprehensive analysis of the characteristic imaging findings can help differentiate various forms of chondrosarcomas. However, distinguishing low-grade chondrosarcomas from enchondromas or high-grade chondrosarcomas is radiologically and histopathologically challenging, even for experienced radiologists and pathologists.
PubMed: 36980590
DOI: 10.3390/cancers15061703 -
Cancer Medicine Jan 2023Mesenchymal chondrosarcoma (MCS) is an ultra-rare sarcoma that follows a more aggressive course than conventional chondrosarcoma. This study evaluates prognostic...
BACKGROUND
Mesenchymal chondrosarcoma (MCS) is an ultra-rare sarcoma that follows a more aggressive course than conventional chondrosarcoma. This study evaluates prognostic factors, treatments (surgery, chemotherapy, and radiation), and outcomes in an Australian setting.
METHODS
We collected demographics, clinicopathological variables, treatment characteristics, and survival status from patients with MCS registered on the national ACCORD sarcoma database. Outcomes include overall survival (OS) and progression-free survival (PFS).
RESULTS
We identified 22 patients with MCS between 2001-2022. Median age was 28 (range 10-59) years, 19 (86%) had localised disease at diagnosis of whom 16 had surgery (84%), 11 received radiation (58%), and 10 chemotherapy (53%). Ten (52%) developed recurrence and/or metastases on follow-up and three patients with initial metastatic disease received surgery, radiation, and chemotherapy. At a median follow-up of 50.9 (range 0.4-210) months nine patients had died. The median OS was 104.1 months (95% CI 25.8-182.3). There was improved OS for patients with localised disease who had surgical resection of the primary (p = 0.003) and those with ECOG 0-1 compared to 2-3 (p = 0.023) on univariate analysis.
CONCLUSIONS
This study demonstrates contemporary Australian treatment patterns of MCS. The role of chemotherapy for localised disease remains uncertain. Understanding treatment patterns and outcomes help support treatment decisions and design of trials for novel therapeutic strategies.
Topics: Humans; Child; Adolescent; Young Adult; Adult; Middle Aged; Chondrosarcoma, Mesenchymal; Bone Neoplasms; Australia; Soft Tissue Neoplasms; Sarcoma; Cohort Studies; Retrospective Studies
PubMed: 35603739
DOI: 10.1002/cam4.4849 -
Cancers Nov 2023Sarcomas are a heterogeneous group of malignant mesenchymal tumors, including soft tissue and bone sarcomas. Macrophages in the tumor microenvironment, involved in... (Review)
Review
Sarcomas are a heterogeneous group of malignant mesenchymal tumors, including soft tissue and bone sarcomas. Macrophages in the tumor microenvironment, involved in immunosuppression and leading to tumor development, are called tumor-associated macrophages (TAMs). TAMs are very important in modulating the microenvironment of sarcomas by expressing specific markers and secreting factors that influence immune and tumor cells. They are involved in many signaling pathways, such as p-STAT3/p-Erk1/2, PI3K/Akt, JAK/MAPK, and JAK/STAT3. TAMs also significantly impact the clinical outcomes of patients suffering from sarcomas and are mainly related to poor overall survival rates among bone and soft tissue sarcomas, for example, chondrosarcoma, osteosarcoma, liposarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma. This review summarizes the current knowledge on TAMs in sarcomas, focusing on specific markers on sarcoma cells, cell-cell interactions, and the possibly involved molecular pathways. Furthermore, we discuss the clinical significance of macrophages in sarcomas as a potential target for new therapies, presenting clinical relevance, possible new treatment options, and ongoing clinical trials using TAMs in sarcoma treatment.
PubMed: 37958467
DOI: 10.3390/cancers15215294 -
International Journal of Surgery Case... Feb 2022Chondrosarcomas of the head and neck are extremely rare, accounting for approximatively 0.1% of all head and neck malignant tumors. Mesenchymal chondrosarcomas are...
INTRODUCTION
Chondrosarcomas of the head and neck are extremely rare, accounting for approximatively 0.1% of all head and neck malignant tumors. Mesenchymal chondrosarcomas are particularly aggressive, with a high propensity for recurrence.
CASE REPORT
We report the case of a 25 years old man with no prior medical history, who presented to our facility with an aggressive tumor of the left maxilla. Upon radiologic and histopathological examinations, the tumor was revealed to be a mesenchymal chondrosarcoma. The patient was treated using surgical excision of the tumor, neoadjuvant chemotherapy and adjuvant radiotherapy.
CONCLUSION
Due to the high risk of recurrence and the possibility of metastasis occurring long after the initial diagnosis, it is important that patients with mesenchymal chondrosarcomas receive close and regular follow-ups after treatment.
PubMed: 35074656
DOI: 10.1016/j.ijscr.2021.106696