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Cancers Sep 2023Mesenchymal chondrosarcoma (MCS) is a rare subtype of chondrosarcoma with a poor prognosis. Although these tumors are sensitive to radiotherapy/chemotherapy, the... (Review)
Review
Mesenchymal chondrosarcoma (MCS) is a rare subtype of chondrosarcoma with a poor prognosis. Although these tumors are sensitive to radiotherapy/chemotherapy, the standard treatment for localized MCS is only surgical resection, and there are no established treatment guidelines for patients with advanced and metastatic MCS. Due to the low incidence of MCS, the pathology of these tumors is still unknown, and other therapeutic options are lacking. Some studies show the potential role of the PDGF/PPI3K/AKT, PKC/RAF/MEK/ERK, and pRB pathways, and BCL2 overexpression in the pathogenesis of MCS. These findings provide an opportunity to use protein kinases and BCL2 inhibitors as potential therapy in MCS. In this review, we summarize the current knowledge about MCS diagnosis and treatment options. We show the immunological and molecular biomarkers used in the diagnosis of MCS. In addition, we discuss the known prognostic and predictive factors in MCS. Finally, we present the novel trends, including targeted therapies and ongoing clinical trials using protein kinase inhibitors and the death receptor 5 (DR5) agonist, which may be the focus of future MCS treatment studies.
PubMed: 37760551
DOI: 10.3390/cancers15184581 -
Skeletal Radiology Feb 2021To describe imaging and clinical features of primary mesenchymal chondrosarcoma (MCS) and evaluate for presence of a distinct biphasic pattern on imaging.
OBJECTIVE
To describe imaging and clinical features of primary mesenchymal chondrosarcoma (MCS) and evaluate for presence of a distinct biphasic pattern on imaging.
MATERIAL AND METHODS
Patients with a pathologic diagnosis of MCS were identified along with imaging of their primary tumor. Size, location, appearance (lytic, sclerotic, or mixed), presence, extent and distribution of calcifications, cortical destruction, soft tissue extension, periosteal reaction, contrast enhancement, and radiotracer uptake were recorded. The presence of T2-hyperintense tumor lobules on MRI and a biphasic morphology (distinct calcified and non-calcified components) on CT were assessed. Presence and location of metastases were documented.
RESULTS
Twenty-three patients (mean age 28.0 ± 13.8 years) were reviewed (13 skeletal, 10 extraskeletal). Overall mean tumor size was 10.2 ± 7.2 cm, 7.1 ± 7.3 cm in non-metastatic and 13.2 ± 5.9 cm (p = 0.004) in metastatic cases. Locations were extremities (n = 11), head/neck (n = 4), chest wall (n = 4), pelvis (n = 3), and retroperitoneum (n = 1). Skeletal MCS were aggressive mixed lytic and sclerotic (n = 8), purely lytic (n = 4), or juxtacortical (n = 1) lesions with cortical destruction and soft tissue extension. Chondroid calcifications were common (80%). On MRI, the presence of T2-hyperintense lobules was seen in 35%. A biphasic morphology on imaging was seen in 30%. Metastases were common (52%) with the most common site being the lungs (75%). All tumors were hypermetabolic with a mean SUVmax of 14.3 (5.6-34) on PET/CT.
CONCLUSION
Skeletal MCS commonly present as aggressive lytic bone lesions with chondroid calcifications. A biphasic morphology was seen in one-third of cases. Metastases were common at initial presentation and more commonly seen with larger tumors.
Topics: Adolescent; Adult; Bone Neoplasms; Chondrosarcoma; Chondrosarcoma, Mesenchymal; Humans; Magnetic Resonance Imaging; Positron Emission Tomography Computed Tomography; Retrospective Studies; Young Adult
PubMed: 32734374
DOI: 10.1007/s00256-020-03558-x -
The American Journal of Surgical... Jun 2023Calcified chondroid mesenchymal neoplasm is a term proposed for tumors with a spectrum of morphologic features, including cartilage/chondroid matrix formation, that...
Calcified chondroid mesenchymal neoplasm is a term proposed for tumors with a spectrum of morphologic features, including cartilage/chondroid matrix formation, that frequently harbor FN1 gene fusions. We report a series of 33 cases of putative calcified chondroid mesenchymal neoplasms, mostly referred for expert consultation out of concern for malignancy. Patients included 17 males and 16 females, with a mean age of 51.3 years. Anatomic locations include the hands and fingers, feet and toes, head and neck, and temporomandibular joint; 1 patient presented with multifocal disease. Radiologic review showed soft tissue masses with variable internal calcification, which occasionally scalloped bone but in all cases appeared indolent/benign. Tumors had a mean gross size of 2.1 cm and a homogenous rubbery to fibrous/gritty tan-white cut surface. Histology demonstrated multinodular architecture with a prominent chondroid matrix and increased cellularity towards the periphery of the nodules. The tumor cells were polygonal with eccentric nuclei and bland cytologic features and showed a variable amount of increased spindled / fibroblastic forms in the perinodular septa. The majority of cases had notable grungy and/or lacy calcifications. A subset of cases demonstrated at least focal areas of increased cellularity and osteoclast-like giant cells. Herein, we confirm the distinct morphologic and clinicopathologic features associated with this entity with the largest series to date, with a focus on practical diagnostic separation from similar chondroid neoplasms. Awareness of these features is critical in avoiding pitfalls, including a malignant diagnosis of chondrosarcoma.
Topics: Male; Female; Humans; Middle Aged; Neoplasms, Connective and Soft Tissue; Chondrosarcoma; Cartilage; Toes; Bone Neoplasms
PubMed: 37102574
DOI: 10.1097/PAS.0000000000002044 -
Surgical Pathology Clinics Sep 2019Bone pathology can be challenging because the skeleton is a living tissue prone to developing a diverse array of inflammatory, metabolic, genetic, reactive, circulatory,... (Review)
Review
Bone pathology can be challenging because the skeleton is a living tissue prone to developing a diverse array of inflammatory, metabolic, genetic, reactive, circulatory, and neoplastic abnormalities. Several areas of bone pathology are particularly difficult or problematic for hematopathologists given the close resemblance of some hematologic entities to primary/metastatic bone lesions; examples include plasmacytic disorders versus osteoblastic tumors and lymphoma/leukemia versus round cell tumors of bone. This article provides a conceptual and practical overview of selective bone disorders commonly encountered in the differential diagnosis of hematologic diseases.
Topics: Bone Neoplasms; Chondrosarcoma, Mesenchymal; Diagnosis, Differential; Histiocytosis, Langerhans-Cell; Humans; Mastocytosis; Osteomyelitis; Osteosarcoma; Plasmacytoma; Prognosis
PubMed: 31352990
DOI: 10.1016/j.path.2019.03.007 -
Translational Cancer Research Dec 2022
PubMed: 36644194
DOI: 10.21037/tcr-22-2284 -
The Gulf Journal of Oncology Jan 2021Mesenchymal chondrosarcoma is a rare high grade malignant neoplasm that accounts for 3-10% of all chondrosarcomas. Histopathologically, it shows biphasic population...
INTRODUCTION
Mesenchymal chondrosarcoma is a rare high grade malignant neoplasm that accounts for 3-10% of all chondrosarcomas. Histopathologically, it shows biphasic population composed of small round to ovoid with occasional spindle cells and islands of well differentiated cartilage. The study aimed at retrospectively analysing the clinical, pathological, radiological features of these cases in our institution.
MATERIALS AND METHODS
This is a retrospective descriptional study. All the cases of mesenchymal chondrosarcomas were retrieved from our archives of pathology over a period of 10 years .The demographic details including the age, clinical presentation including skeletal/extraskeletal along with radiology were noted for all these cases. The treatment details along with the follow up of the patients were archived from the medical records.
RESULTS
A total of 13 cases of mesenchymal chondrosarcoma were retrieved for our study. The mean age of presentation was 33 years with a slight male predilection. Extra skeletal soft tissue origin was noted in 3 of our cases (3/13), one case in forearm, another in pelvis. The third case was intracranial origin which presented as a dural based parieto-occipital mass and rest all had bony origin .The radiological and clinical correlation was done for all these cases.
CONCLUSION
Mesenchymal chondrosarcoma presents multiple diagnostic challenges, most common include inadequate biopsy samples which may result in errors in diagnosis, namely with small blue round cell tumours .A better understanding of this entity may help the pathologists in conferring an accurate diagnosis to the clinicians.
Topics: Adolescent; Adult; Aged; Child; Chondrosarcoma, Mesenchymal; Female; Humans; Male; Middle Aged; Retrospective Studies; Young Adult
PubMed: 33716213
DOI: No ID Found -
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 -
Diagnostics (Basel, Switzerland) Mar 2022Mesenchymal chondrosarcoma is an uncommon malignant mesenchymal tumor with an aggressive behavior. Diagnoses of mesenchymal chondrosarcoma are established based on...
Mesenchymal chondrosarcoma is an uncommon malignant mesenchymal tumor with an aggressive behavior. Diagnoses of mesenchymal chondrosarcoma are established based on histomorphological, immunohistochemical, and molecular findings. Only one case of extraskeletal mesenchymal chondrosarcoma (EMC) of the uterus has been reported. This article presents the second case of primary uterine EMC, occurring in a 33-year-old woman. We describe the histological and immunophenotypical features of EMC. Our observations will help pathologists and clinicians perform accurate histological diagnoses of uterine EMC and plan appropriate treatment strategies for this rare tumor.
PubMed: 35328196
DOI: 10.3390/diagnostics12030643 -
Cancers May 2022Bone sarcomas are rare primary malignant mesenchymal bone tumors. The three main entities are osteosarcoma, chondrosarcoma, and Ewing sarcoma. While prognosis has... (Review)
Review
Bone sarcomas are rare primary malignant mesenchymal bone tumors. The three main entities are osteosarcoma, chondrosarcoma, and Ewing sarcoma. While prognosis has improved for affected patients over the past decades, bone sarcomas are still critical conditions that require an interdisciplinary diagnostic and therapeutic approach. While radiotherapy plays a role especially in Ewing sarcoma and chemotherapy in Ewing sarcoma and osteosarcoma, surgery remains the main pillar of treatment in all three entities. After complete tumor resection, the created bone defects need to be reconstructed. Possible strategies are implantation of allografts or autografts including vascularized bone grafts (e.g., of the fibula). Around the knee joint, rotationplasty can be performed or, as an alternative, the implantation of (expandable) megaprostheses can be performed. Challenges still associated with the implantation of foreign materials are aseptic loosening and infection. Future improvements may come with advances in 3D printing of individualized resection blades/implants, thus also securing safe tumor resection margins while at the same time shortening the required surgical time. Faster osseointegration and lower infection rates may possibly be achieved through more elaborate implant surface structures.
PubMed: 35681674
DOI: 10.3390/cancers14112694 -
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