-
Genes, Chromosomes & Cancer Nov 2022Mesenchymal chondrosarcoma (MCS) is a rare translocation-associated sarcoma, driven by a canonical HEY1::NCOA2 fusion. The tumors typically have a biphasic phenotype of...
BACKGROUND
Mesenchymal chondrosarcoma (MCS) is a rare translocation-associated sarcoma, driven by a canonical HEY1::NCOA2 fusion. The tumors typically have a biphasic phenotype of primitive small blue round cells intermixed with hyaline cartilage. The head and neck (HN) region is a common site for MCS, accounting for 12-45% of all cases reported.
AIMS
We assembled a relatively large cohort of 13 molecularly confirmed HN MCS for a detailed clinicopathologic analysis. The underlying fusion events were determined using fluorescence in situ hybridization and/or targeted RNA sequencing.
RESULTS
The median age of presentation was 19 years. Five MCSs (39%) had an intraosseous presentation (skull, maxilla, palate, and mandible), while the remaining eight cases occurred in the brain/meninges, orbit, and nasal cavity. Microscopically, HN MCSs were characterized by primitive round cells arranged in a distinctive nested architecture and a rich staghorn vasculature. A cartilaginous component of hyaline cartilage islands and/or single chondrocytes were present in 69% cases. A combined immunoprofile of CD99(+)/SATB2(+)/CD34(-)/STAT6(-) was typically noted. As this immunoprofile is non-specific, the referral diagnoses in cases lacking a cartilaginous component included Ewing sarcoma family and osteosarcoma. Among the seven patients with follow-up data, three developed distant metastasis and one died of disease.
CONCLUSION
HN MCS may arise at intra- or extra-osseous sites. The HN MCS appears to have a more prolonged survival compared other MCS sites. Testing for HEY1::NCOA2 fusion is recommended in HN tumors with nested round cell morphology and staghorn vasculature that lack a distinctive cartilaginous component.
Topics: Adult; Basic Helix-Loop-Helix Transcription Factors; Cell Cycle Proteins; Child; Chondrosarcoma, Mesenchymal; Female; Gene Fusion; Head and Neck Neoplasms; Humans; In Situ Hybridization, Fluorescence; Male; Nuclear Receptor Coactivator 2; Young Adult
PubMed: 35672279
DOI: 10.1002/gcc.23075 -
Frontiers in Oncology 2022Craniofacial bones may be the site of origin of various sarcomas. We review the various malignancies affecting this region of the body and attempt to put systemic... (Review)
Review
INTRODUCTION
Craniofacial bones may be the site of origin of various sarcomas. We review the various malignancies affecting this region of the body and attempt to put systemic treatment approaches into perspective.
MATERIAL AND METHODS
Non-systematic literature review.
RESULTS
Conventional types of osteosarcoma, Ewing sarcoma, and chondrosarcoma are the most frequent bone sarcomas occurring in craniofacial region, but variants may occur. The tumors' biologies and the resulting treatment strategies vary distinctly. As a general rule, local control remains paramount regardless of histology. The efficacy of antineoplastic chemotherapy varies by type of malignancy. It is clearly indicated in Ewing sarcoma and related tumors, potentially of benefit in high-grade osteosarcoma, undifferentiated pleomorphic sarcoma, dedifferentiated and mesenchymal chondrosarcoma, and of no proven benefit in the others.
CONCLUSIONS
Various histologies demand various and distinct treatment approaches, with local control remaining paramount in all. The efficacy of systemic treatments varies by type of tumor. Prospective trials would help in all of these to better define systemic treatment strategies.
PubMed: 36158667
DOI: 10.3389/fonc.2022.966073 -
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 -
The British Journal of Radiology Oct 2018Mesenchymal chondrosarcoma (MCS) of the orbit is a rare and aggressive form of chondrosarcoma. The purpose of this study was to retrospectively identify the imaging...
OBJECTIVE:
Mesenchymal chondrosarcoma (MCS) of the orbit is a rare and aggressive form of chondrosarcoma. The purpose of this study was to retrospectively identify the imaging features of mesenchymal chondrosarcoma of the orbit.
METHODS:
This study included five patients with histologically confirmed MCS of the orbit who had undergone either CT, MRI, or both. Images were evaluated for the following: location, size, margin, CT density and presence or absence of calcification and/or ossification, MRI findings including dynamic contrast-enhancement and time-intensity curves.
RESULTS:
CT was performed in four of the five patients, and all four (100%) demonstrated calcification and ossification of the mass. MRI was performed in all five patients. In two patients (40%), the mass demonstrated areas of hyperintensity on T weighted images.
CONCLUSION:
The presence of a well-defined, orbital mass with calcification and ossification on CT and, marked heterogenous enhancement and a rapid-washout pattern on dynamic MRI indicate a high probability of MCS of the orbit. In addition, MCS of the orbit can demonstrate areas of hyperintensity on T weighted images, representing bone marrow fat tissue of ossification.
ADVANCES IN KNOWLEDGE:
MCS of the orbit is a highly malignant tumor, and early diagnosis by imaging is important. Radiologists should be aware of the imaging features of MCS of the orbit.
Topics: Adolescent; Adult; Calcinosis; Child; Chondrosarcoma, Mesenchymal; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Neoplasm Metastasis; Orbital Neoplasms; Ossification, Heterotopic; Retrospective Studies; Tomography, X-Ray Computed; Young Adult
PubMed: 29975155
DOI: 10.1259/bjr.20170579 -
PloS One 2015Mesenchymal chondrosarcoma(MCS) is a rare high-grade variant of chondrosarcoma. Consensus has not been reached on its optimal management. Resection with wide margins is... (Review)
Review
BACKGROUND
Mesenchymal chondrosarcoma(MCS) is a rare high-grade variant of chondrosarcoma. Consensus has not been reached on its optimal management. Resection with wide margins is usually recommended, but the effect of margins has been demonstrated by little positive evidence. Moreover, the effectiveness of adjuvant chemo- and/or radiotherapy remains controversial.
OBJECTIVES
To describe the clinical characteristics and outcomes of MCS of bone and soft tissue, to assess the efficacies of surgery, chemotherapy and radiation, and finally to deliver a more appropriate therapy.
MATERIALS AND METHODS
We reviewed EMBASE-, MEDLINE-, Cochrane-, Ovid- and PubMed-based to find out all cases of MCS of bone and soft tissue described between April 1994 and April 2014. Description of treatment and regular follow-up was required for each study. Language was restricted to English and Chinese. Issues of age, gender, location, metastasis, and treatment were all evaluated for each case. Kaplan-Meier Method and Cox Proportional Hazard Regression Model were used in the survival analysis.
RESULTS
From the 630 identified publications, 18 meeting the inclusion criteria were selected, involving a total of 107 patients. Based on these data, the 5-, 10-and 20-year overall survival are 55.0%, 43.5% and 15.7% respectively. The 5-, 10-, 20- year event-free survival rates are 45.0%, 27.2% and 8.1%, respectively. Treatment without surgery is associated with poorer overall survival and event-free survival. Negative surgical margins could significantly bring down the local-recurrence rate and are associated with a higher event-free survival rate. Chemotherapy regime based on anthracyclines does not benefit the overall survival. The addition of radiation therapy is not significantly associated with the overall or event-free survival. However, we recommend radiation as the salvage therapy for patients with positive margin so as to achieve better local control.
CONCLUSIONS
This review shows that surgery is essential in the management of MCS of bone and soft tissue. Appropriate adjuvant therapy may reduce local recurrence, but cannot benefit the overall survival.
Topics: Bone Neoplasms; Chondrosarcoma, Mesenchymal; Humans; Soft Tissue Neoplasms; Treatment Outcome
PubMed: 25849226
DOI: 10.1371/journal.pone.0122216 -
Calcified Tissue International Feb 2018Bone sarcomas are tumours belonging to the family of mesenchymal tumours and constitute a highly heterogeneous tumour group. The three main bone sarcomas are... (Review)
Review
Bone sarcomas are tumours belonging to the family of mesenchymal tumours and constitute a highly heterogeneous tumour group. The three main bone sarcomas are osteosarcoma, Ewing sarcoma and chondrosarcoma each subdivided in diverse histological entities. They are clinically characterised by a relatively high morbidity and mortality, especially in children and adolescents. Although these tumours are histologically, molecularly and genetically heterogeneous, they share a common involvement of the local microenvironment in their pathogenesis. This review gives a brief overview of their specificities and summarises the main therapeutic advances in the field of bone sarcoma.
Topics: Bone Neoplasms; Female; Giant Cell Tumor of Bone; Humans; Male; Sarcoma; Tumor Microenvironment
PubMed: 29238848
DOI: 10.1007/s00223-017-0372-2 -
Annals of Palliative Medicine Nov 2021Intracranial mesenchymal chondrosarcoma (IMC) is a rare primary malignant tumor in the skull, but mostly originates from the abnormal residual chondrocytes in the... (Review)
Review
Intracranial mesenchymal chondrosarcoma (IMC) is a rare primary malignant tumor in the skull, but mostly originates from the abnormal residual chondrocytes in the embryonic period, which grow slowly, and primarily occurs at the junction of the cartilage of the skull base. IMC is difficult to diagnose by preoperative imaging and is easily misdiagnosed. It needs to be differentiated from meningiomas, gliomas, hemangioma, fibroids, etc.; this article introduces a case of primary IMC in a 38-year-old female teacher, and reviews the literature on the diagnosis and treatment of symptoms. The patient suffered from persistent severe headaches without nausea and vomiting. There was no obvious abnormality in the physical examination. Magnetic resonance imaging (MRI) of the head showed a circular space-occupying lesion on the right frontal bone and forehead; the mass was approximately 5.9 cm × 5.2 cm × 5.5 cm, and there was a large edema band surrounding it. The space-occupying effect was obvious; bilateral ventricles were compressed, and on the right side, the midline structure was shifted to the left. The patient was initially diagnosed with simple meningioma. After admission, the right frontal lobe meningioma was resected under general anesthesia, and the tumor tissue was completely removed in blocks. The postoperative pathology report stated: malignant tumor of the right frontal lobe; consider mesenchymal chondrosarcoma. Following a difficult pathological consultation at the Provincial Medical Association, the tumor was found to be consistent with mesenchymal chondrosarcoma. Intracranial chondrosarcoma is a very rare malignant tumor. Other intracranial masses, such as meningioma and glioma, should be distinguished through differential diagnosis. At present, more attention is paid to surgical intervention and combined radiotherapy and chemotherapy for the treatment of IMC, which should also be the future treatment option.
Topics: Adult; Bone Neoplasms; Chondrosarcoma; Chondrosarcoma, Mesenchymal; Female; Humans; Magnetic Resonance Imaging; Skull
PubMed: 34872324
DOI: 10.21037/apm-21-2290 -
Journal of Cancer Research and... Apr 2024Bone sarcomas encompass a group of spontaneous mesenchymal malignancies, among which osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma are the most common... (Review)
Review
Bone sarcomas encompass a group of spontaneous mesenchymal malignancies, among which osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma are the most common subtypes. Chondrosarcoma, a relatively prevalent malignant bone tumor that originates from chondrocytes, is characterized by endogenous cartilage ossification within the tumor tissue. Despite the use of aggressive treatment approaches involving extensive surgical resection, chemotherapy, and radiotherapy for patients with osteosarcoma, chondrosarcoma, and chordoma, limited improvements in patient outcomes have been observed. Furthermore, resistance to chemotherapy and radiation therapy has been observed in chondrosarcoma and chordoma cases. Consequently, novel therapeutic approaches for bone sarcomas, including chondrosarcoma, need to be uncovered. Recently, the emergence of immunotherapy and immune checkpoint inhibitors has garnered attention given their clinical success in various diverse types of cancer, thereby prompting investigations into their potential for managing chondrosarcoma. Considering that circumvention of immune surveillance is considered a key factor in the malignant progression of tumors and that immune checkpoints play an important role in modulating antitumor immune effects, blockers or inhibitors targeting these immune checkpoints have become effective therapeutic tools for patients with tumors. One such checkpoint receptor implicated in this process is programmed cell death protein-1 (PD-1). The association between PD-1 and programmed cell death ligand-1 (PD-L1) and cancer progression in humans has been extensively studied, highlighting their remarkable potential as biomarkers for cancer treatment. This review comprehensively examines available studies on current chondrosarcoma treatments and advancements in anti-PD-1/PD-L1 blockade therapy for chondrosarcoma.
Topics: Humans; Chondrosarcoma; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Bone Neoplasms; Immune Checkpoint Inhibitors; Immunotherapy
PubMed: 38687921
DOI: 10.4103/jcrt.jcrt_2269_23 -
Frontiers in Cell and Developmental... 2022Post-translational modifications comprise series of enzymatically-driven chemical modifications, virtually involving the entire cell proteome, that affect the fate of a... (Review)
Review
Post-translational modifications comprise series of enzymatically-driven chemical modifications, virtually involving the entire cell proteome, that affect the fate of a target protein and, in turn, cell activity. Different classes of modifications can be established ranging from phosphorylation, glycosylation, ubiquitination, acetylation, methylation, lipidation and their inverse reactions. Among these, SUMOylation and NEDDylation are ubiquitin-like multi-enzymatic processes that determine the bound of SUMOs and NEDD8 labels, respectively, on defined amino acidic residues of a specific protein and regulate protein function. As fate-determinants of several effectors and mediators, SUMOylation and NEDDylation play relevant roles in many aspects of tumor cell biology. Bone represents a preferential site of metastasis for solid tumors (e.g., breast and prostate cancers) and the primary site of primitive tumors (e.g., osteosarcoma, chondrosarcoma). Deregulation of SUMOylation and NEDDylation affects different aspects of neoplastic transformation and evolution such as epithelial-mesenchymal transition, adaptation to hypoxia, expression and action of tumor suppressors and oncogenic mediators, and drug resistance. Thereby, they represent potential therapeutic targets. This narrative review aims at describing the involvement and regulation of SUMOylation and NEDDylation in tumor biology, with a specific focus on primary and secondary bone tumors, and to summarize and highlight their potentiality in diagnostics and therapeutic strategies.
PubMed: 35465332
DOI: 10.3389/fcell.2022.889002 -
Pathology Aug 2023Mesenchymal chondrosarcoma (MCS) is a rare and highly aggressive tumour of soft tissue and bone that is defined by an underlying and highly specific fusion transcript...
Mesenchymal chondrosarcoma (MCS) is a rare and highly aggressive tumour of soft tissue and bone that is defined by an underlying and highly specific fusion transcript involving HEY1 and NCOA2. Histologically, the tumours show a biphasic appearance consisting of an undifferentiated blue and round cell component as well as islands of highly differentiated cartilage. Particularly in core needle biopsies, the chondromatous component can be missed and the non-specific morphology and immunophenotype of the round cell component can cause diagnostic challenges. We applied NKX3.1 immunohistochemistry which was recently reported as a highly specific marker as well as methylome and copy number profiling to a set of 45 well characterised MCS cases to evaluate their potential diagnostic value. Methylome profiling revealed a highly distinct cluster for MCS. Notably, the findings were reproducible also when analysing the round cell and cartilaginous component separately. Furthermore, four outliers were identified by methylome profiling for which the diagnosis had to be revised. NKX3.1 immunohistochemistry showed positivity in 36% of tumours, the majority of which was rather focal and weak. Taken together, NKX3.1 expression showed a low sensitivity but a high specificity in our analysis. Methylome profiling on the other hand represents a sensitive, specific and reliable tool to support the diagnosis of MCS, particularly if only the round cell component is obtained in a biopsy and the diagnosis is not suspected. Furthermore, it can aid in confirming the diagnosis in case RNA sequencing for the HEY1::NCOA2 fusion transcript is not available.
Topics: Humans; Chondrosarcoma, Mesenchymal; Immunohistochemistry; Epigenome; Bone and Bones; Cell Differentiation; Bone Neoplasms
PubMed: 37225644
DOI: 10.1016/j.pathol.2023.03.003