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Human Pathology Sep 2023Clear cell chondrosarcoma (CCC), an extremely rare primary bone tumor, is currently classified by the World Health Organization as a low-grade malignant cartilaginous... (Review)
Review
Clear cell chondrosarcoma (CCC), an extremely rare primary bone tumor, is currently classified by the World Health Organization as a low-grade malignant cartilaginous neoplasm. Clinically, CCC occurs primarily in males with a peak incidence in the third to fifth decades of life, and occasionally, it presents in skeletally immature patients. Unlike conventional chondrosarcoma, CCC has a predilection for the epiphysis of long bones and often displays radiologic features reminiscent of chondroblastoma. The recommended treatment is wide operative resection. CCC has a local recurrence rate of approximately 30%, and nearly 20% cases metastasize mainly to bone and lung often a decade after surgical intervention. Incomplete excision or curettage is associated with a high rate of recurrence. Histologically, the process is characterized by infiltrative lobules and sheets of round to oval cells with abundant cleared cytoplasm and well-defined cell borders associated with trabecula of osteoid and woven bone, scattered osteoclasts, and foci of conventional low-grade chondrosarcoma in about one-half of cases. Correlation with clinical and radiologic characteristics, such as epiphyseal location and young patient age, assists in establishing a correct diagnosis. Pathologic diagnosis of CCC is complicated by the low diagnostic accuracy of core needle biopsy, overlapping histologic features with other matrix-rich primary bone tumors, and a lack of a specific immunohistochemical and molecular profile. DNA methylation-based profiling classifier (sarcoma classifier) is one recent technologic advancement that may help to confirm the histopathological diagnosis of CCC or indicate the need for thorough reassessment in cases where results contradict previous conventional findings.
Topics: Male; Humans; Chondrosarcoma, Clear Cell; Diagnosis, Differential; Bone Neoplasms; Bone and Bones; Chondrosarcoma
PubMed: 37805864
DOI: 10.1016/j.humpath.2023.06.004 -
European Journal of Orthopaedic Surgery... Oct 2019Metastases are the most common malignancy in bone. In patients with bone metastases, especially if a limited expected survival, the indications for surgical treatment... (Review)
Review
Metastases are the most common malignancy in bone. In patients with bone metastases, especially if a limited expected survival, the indications for surgical treatment are limited, immediate pain relief and improvement in the functional status are important, and complications of treatments are unwanted. Novel medical treatments can offer an effective palliative option in these patients. Advances in interventional radiology and surgery have led to the development of less invasive techniques with the aim to achieve the same clinical results with less surgical morbidity. These include embolization, electrochemotherapy, magnetic resonance imaging-guided high-intensity focused ultrasound, and thermal ablation. Less invasive techniques combine the advantages of less invasive procedures including decreased blood loss, earlier functional recovery and initiation of adjuvant medical therapies and seem to be both effective in pain relief and local tumor control.
Topics: Bone Neoplasms; Electrochemotherapy; Embolization, Therapeutic; High-Intensity Focused Ultrasound Ablation; Humans; Radiofrequency Ablation
PubMed: 31089821
DOI: 10.1007/s00590-019-02446-y -
Neuroendocrinology 2021Skeletal colonization is often regarded as a rare event in patients with neuroendocrine tumors (NETs) although both national registries and retrospective series report... (Review)
Review
Skeletal colonization is often regarded as a rare event in patients with neuroendocrine tumors (NETs) although both national registries and retrospective series report an incidence of bone metastases as high as 20% in subjects with advanced disease. While the biological mechanisms leading to bone metastatic colonization in NETs have been poorly investigated so far, key steps of osteotropic mechanisms, including the epithelial-to-mesenchymal transition, preparation of the premetastatic niche, migration of circulating tumor cells towards the bone marrow as well as the resulting alterations of the skeletal metabolism, are likely to operate also during the development of NET bone metastases. The skeleton involvement by NETs has a detrimental impact on both quality of life and patients' prognosis, leading to pain in the majority of symptomatic subjects. While it is currently unclear whether or not the earlier recognition of bone involvement by PET/CT imaging techniques employing 68Ga-DOTA-conjugated peptides might improve outcomes through the exploitation of timely treatments, the management of bone-colonizing NETs is today based only on clinical experience from other osteotropic tumors. Here, we summarize the fundamental molecular mechanisms driving bone colonization and revisit both established and novel treatments for patients with bone metastatic NETs.
Topics: Bone Neoplasms; Humans; Neuroendocrine Tumors
PubMed: 32403104
DOI: 10.1159/000508633 -
Frontiers in Immunology 2024Bone is a common organ for solid tumor metastasis. Malignant bone tumor becomes insensitive to systemic therapy after colonization, followed by poor prognosis and high... (Review)
Review
Bone is a common organ for solid tumor metastasis. Malignant bone tumor becomes insensitive to systemic therapy after colonization, followed by poor prognosis and high relapse rate. Immune and bone cells constitute a unique immune microenvironment, which plays a crucial role in the context of bone metastasis. This review firstly focuses on lymphatic cells in bone metastatic cancer, including their function in tumor dissemination, invasion, growth and possible cytotoxicity-induced eradication. Subsequently, we examine myeloid cells, namely macrophages, myeloid-derived suppressor cells, dendritic cells, and megakaryocytes, evaluating their interaction with cytotoxic T lymphocytes and contribution to bone metastasis. As important components of skeletal tissue, osteoclasts and osteoblasts derived from bone marrow stromal cells, engaging in 'vicious cycle' accelerate osteolytic bone metastasis. We also explain the concept tumor dormancy and investigate underlying role of immune microenvironment on it. Additionally, a thorough review of emerging treatments for bone metastatic malignancy in clinical research, especially immunotherapy, is presented, indicating current challenges and opportunities in research and development of bone metastasis therapies.
Topics: Humans; Tumor Microenvironment; Neoplasm Recurrence, Local; Bone and Bones; Bone Neoplasms; Macrophages
PubMed: 38464516
DOI: 10.3389/fimmu.2024.1335366 -
Advances in Protein Chemistry and... 2024Osteosarcoma is a malignant osseous neoplasm. Osteosarcoma is a primary bone malignancy capable of producing osteoid tissue or immature bones. A subsequent malignant... (Review)
Review
Osteosarcoma is a malignant osseous neoplasm. Osteosarcoma is a primary bone malignancy capable of producing osteoid tissue or immature bones. A subsequent malignant degeneration of the primary bone pathology occurs less frequently in adults. The over-expression of several proteins, including Heat shock proteins, Cofilin, Annexins, Insulin-like growth factor, transforming growth factor-β, Receptor tyrosine kinase, Ezrin, Runx2, SATB2, ATF4, Annexins, cofilin, EGFR, VEGF, retinoblastoma 1 (Rb1) and secreted protein, has been associated to the development and progression of osteosarcoma. These proteins are involved in cell adhesion, migration, invasion, and the control of cell cycle and apoptosis. In genomic studies, osteosarcoma has been associated with several genetic abnormalities, including chromosomal rearrangements, gene mutations, and gene amplifications. These differentially expressed proteins could be used as early identification biomarkers or treatment targets. Proteomics and genomics play significant parts in enhancing our molecular understanding of osteosarcoma, and their integration provides essential insights into this aggressive bone cancer. This review will discuss the tumour biology that has assisted in helping us better understand the causes of osteosarcoma and how they could potentially be used to find new treatment targets and enhance the survival rate for osteosarcoma patients.
Topics: Adult; Humans; Proteomics; Osteosarcoma; Genomics; Bone Neoplasms; Actin Depolymerizing Factors; Annexins
PubMed: 38220428
DOI: 10.1016/bs.apcsb.2023.06.001 -
Cells Apr 2020Osteosarcoma, Ewing sarcoma and chondrosarcoma are rare diseases but the most common primary tumors of bone. The genes directly involved in the sarcomagenesis, tumor... (Review)
Review
Osteosarcoma, Ewing sarcoma and chondrosarcoma are rare diseases but the most common primary tumors of bone. The genes directly involved in the sarcomagenesis, tumor progression and treatment responsiveness are not completely defined for these tumors, and the powerful discovery of genetic analysis is highly warranted in the view of improving the therapy and cure of patients. The review summarizes recent advances concerning the molecular and genetic background of these three neoplasms and, of their most common variants, highlights the putative therapeutic targets and the clinical trials that are presently active, and notes the fundamental issues that remain unanswered. In the era of personalized medicine, the rarity of sarcomas may not be the major obstacle, provided that each patient is studied extensively according to a road map that combines emerging genomic and functional approaches toward the selection of novel therapeutic strategies.
Topics: Bone Neoplasms; Genomics; Humans; Precision Medicine
PubMed: 32295254
DOI: 10.3390/cells9040968 -
Journal of Immunology Research 2021The treatment of bone metastases is a thorny issue. Immunotherapy may be one of the few hopes for patients with unresectable bone metastases. Immune checkpoint... (Review)
Review
The treatment of bone metastases is a thorny issue. Immunotherapy may be one of the few hopes for patients with unresectable bone metastases. Immune checkpoint inhibitors are the most commonly used immunotherapy drugs currently. In this review, the characteristics and interaction of bone metastases and their immune microenvironment were systematically discussed, and the relevant research progress of the immunological mechanism of tumor bone metastasis was reviewed. On this basis, we expounded the clinical application of immune checkpoint inhibitors for bone metastasis of common tumors, including non-small-cell lung cancer, renal cell carcinoma, prostate cancer, melanoma, and breast cancer. Then, the deficiencies and limitations in current researches were summarized. In-depth basic research on bone metastases and optimization of clinical treatment is needed.
Topics: Bone Neoplasms; Clinical Trials as Topic; Humans; Immune Checkpoint Inhibitors; Progression-Free Survival; Tumor Microenvironment
PubMed: 34877360
DOI: 10.1155/2021/8970173 -
Cancer Medicine Apr 2023Osteosarcoma is the most malignant and common primary bone tumor with a high rate of recurrence that mainly occurs in children and young adults. Therefore, it is vital...
OBJECTIVE
Osteosarcoma is the most malignant and common primary bone tumor with a high rate of recurrence that mainly occurs in children and young adults. Therefore, it is vital to facilitate the development of novel effective therapeutic means and improve the overall prognosis of osteosarcoma patients via a deeper understanding of the mechanisms of chemoresistance in osteosarcoma progression.
METHODS
In this research, the relationship between ITGB3 and the clinical characteristics of patients was detected through analysis of publicly available clinical datasets. The expression of ITGB3 was analysis in collected human osteosarcoma tissues. In addition, the potential functions of ITGB3 in the cisplatin resistance of osteosarcoma cells were investigated in vitro and in tumor xenotransplantation. Finally, the molecular mechanism of ITGB3 in the progression and recurrence of osteosarcoma were explored via transcriptome analysis.
RESULTS
ITGB3 was identified as a potential regulator of tumorigenicity and cisplatin resistance in relapsed osteosarcoma. Furthermore, the decreased osteosarcoma cell proliferation and migration ability in ITGB3 knockout osteosarcoma cells were related to increased apoptosis and slowing cell cycle progression. In addition, ITGB3 had a positive correlation with cisplatin resistance in cells and tumor xenografts in mice. Accordingly, ITGB3 performed the functions of proliferation and cisplatin resistance in osteosarcoma through the MAPK and VEGF signaling pathways.
CONCLUSION
Our results will contribute to a better understanding of the function and mechanism of ITGB3 in osteosarcoma cisplatin resistance and provide a novel therapeutic target to decrease cisplatin resistance and tumor recurrence in osteosarcoma patients.
Topics: Child; Young Adult; Humans; Animals; Mice; Cisplatin; Antineoplastic Agents; Drug Resistance, Neoplasm; Apoptosis; Neoplasm Recurrence, Local; Osteosarcoma; Bone Neoplasms; Cell Line, Tumor; Cell Proliferation; Integrin beta3
PubMed: 36772869
DOI: 10.1002/cam4.5585 -
Hellenic Journal of Nuclear Medicine 2021To evaluate the clinical utility of quantitative values obtained with bone single photon emission computed tomography/computed tomography (SPECT/CT) for primary bone...
OBJECTIVE
To evaluate the clinical utility of quantitative values obtained with bone single photon emission computed tomography/computed tomography (SPECT/CT) for primary bone neoplasms.
SUBJECTS AND METHODS
Bone SPECT/CT scans of 23 patients with 19 benign bone neoplasms (5 osteoid osteomas, 4 bone giant cell tumor, 4 osteofibrous dysplasia, 3 intraosseous ganglion, 2 aneurysmal bone cyst, 1 intraosseous hemangioma) and 5 malignant bone neoplasms (2 osteosarcoma, 1 periosteal osteosarcoma, 1 malignancy in bone giant cell tumor, 1 Ewing sarcoma) were retrospectively analyzed with maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), mean SUV (SUVmean), metabolic bone volume (MBV), and total bone uptake (TBU) of primary lesions.
RESULTS
Mean SUVmax of 19 benign and 5 malignant primary bone neoplasms were 6.89±3.26 (range 3.9-15.13) and 10.31±3.19 (5.0-13.45) respectively, with statistically significant difference (P=0.048). Mean SUVpeak of those were 5.87±2.83 (range 3.5-13.63) and 9.18±3.05 (4.09-12.03) respectively, with statistically significant difference (P=0.032). Mean SUVmean of those were 4.43±2.11 (range 2.59-9.37) and 7.13±2.90 (3.3-10.42) respectively, with statistically significant difference (P=0.027). Mean MBV of those were 22.0±30.0 (range 2.47-110.61) and 27.8±39.94 (8.59-99.24) respectively, with no statistically significant difference (P=0.72). Mean TBU of those were 80.64±94.57 (range 10.50-373.57) and 166.60±203.97 (28.68-528.13) respectively, with no statistically significant difference (P=0.17).
CONCLUSION
Quantitative values obtained with bone SPECT/CT may serve as osteoblastic biomarkers for primary bone neoplasm.
Topics: Adult; Aged; Bone Neoplasms; Female; Humans; Male; Middle Aged; Retrospective Studies; Single Photon Emission Computed Tomography Computed Tomography
PubMed: 33866337
DOI: 10.1967/s002449912304 -
Advances in Anatomic Pathology May 2021Bone and soft tissue tumors of the head and neck are relatively uncommon tumors that often represent a diagnostic challenge because of the wide range of entities that... (Review)
Review
Bone and soft tissue tumors of the head and neck are relatively uncommon tumors that often represent a diagnostic challenge because of the wide range of entities that must be considered in the differential diagnosis. Over the past few years, classification of bone and soft tissue tumors has evolved primarily because of substantial contributions from molecular genetics, with the identification of new markers that are increasingly used to complement histopathologic findings in the routine diagnostic workup. This review focuses on the recently described mesenchymal tumors that preferentially involve the head and neck region, with a focus on the most relevant novel immunohistochemical and molecular findings, including gene fusions and mutations, that can help in the diagnosis and in the assessment of clinical behavior.
Topics: Biomarkers, Tumor; Bone Neoplasms; Head and Neck Neoplasms; Humans; Immunohistochemistry; Soft Tissue Neoplasms
PubMed: 33559990
DOI: 10.1097/PAP.0000000000000295