Osteocondromatosis sinovial de rodilla: una causa infrecuente de gonalgia en edad pediátrica / Synovial chondromatosis of the knee. A rare cause of knee pain in pediatric age

La osteocondromatosis sinovial es una metaplasia benigna de la membrana sinovial que afecta a 1 de cada 100 000 personas, en su mayoría adultos, y es extremadamente infrecuente en edad pediátrica. Predomina en grandes articulaciones, sobre todo la rodilla, y la sintomatología es, por lo general, inespecífica. Dado que la radiografía simple no suele ser concluyente, se recurre a la resonancia magnética nuclear y a la tomografía axial computarizada para orientar el diagnóstico. Se expone el caso de una paciente de 10 años de edad con gonalgia y dismorfia en la patela izquierda de seis meses de evolución, con diagnóstico de osteocondromatosis sinovial. Se presenta el caso dado que se trata de una entidad muy rara en niños, pero que requiere un tratamiento quirúrgico precoz para evitar sus posibles complicaciones, como la destrucción articular progresiva o la malignización a condrosarcoma.

Synovial osteochondromatosis consists of a synovial metaplasia which affects 1 per 100 000 people. It is a very rare disease among children. It typically affects large joints of the body, especially the knee. Due to the lack of specificity of the signs and symptoms and X-Ray images, imaging tests such as nuclear magnetic resonance or computerized tomography are frequently needed for diagnosis.We report a case of a ten-year-old female patient with a six months history of pain and deformity of left patella which was diagnosed with synovial osteochondromatosis. This case highlights the importance of clinical suspicion, not only because it is an extremely rare disease in children, but also because it needs a surgical treatment as soon as possible in order to avoid consequences it might have in pediatric age, as joint destruction or malignization to chondrosarcoma.

Risk factors for metastasis at presentation with conventional chondrosarcoma: a population-based study.

PURPOSE: The aim of the study was to investigate risk factors for metastasis at diagnosis. METHODS: We collected patients diagnosed with conventional chondrosarcoma between 1983 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) database. Each patient was classified as having metastatic or localized disease. Univariate and multivariate logistic regression analyses were applied to determine which characteristics were risk factors for metastasis at diagnosis. RESULTS: Two thousand three hundred forty-nine patients were collected and 180 patients had metastasis at presentation. Data on age, gender, primary site, grade, and tumour size were enrolled into the multivariate logistic analysis. Greater age (60 years or older: OR = 1.872, 95% CI, 1.206 to 2.904), axial or craniofacial location (spine: OR = 1.775, 95% CI, 1.188 to 2.651; thoracic cage: OR = 2.034, 95% CI, 1.321 to 3.134; craniofacial bones: OR = 5.507, 95% CI, 3.001 to 10.107), higher grade (grade II: OR = 1.849, 95%CI, 1.181 to 2.895; grade III: OR = 4.016, 95%CI, 2.513 to 6.418), and larger tumour size (size over 10 cm: OR = 7.135, 95%CI, 2.130 to 23.893) were associated with an increased risk of metastasis at presentation. CONCLUSIONS: Conventional chondrosarcoma patients with greater age, axial or craniofacial tumour location, higher grade, and larger tumor size were more likely to have metastasis at diagnosis.

Delayed malignant transformation of petroclival meningioma to chondrosarcoma after stereotactic radiosurgery.

Stereotactic radiosurgery (SRS) is often used as adjuvant treatment for residual or recurrent tumor following microsurgical resection of posterior fossa meningiomas. SRS is associated with excellent rates of local control, however long-term complications remain unclear. Secondary malignancy is an often discussed but rarely described complication of SRS. We present a 56-year-old woman who underwent near total resection of a petroclival meningioma, followed by two episodes of SRS over the ensuing 8 years for local recurrence. She returned 14 years after initial diagnosis with neurologic deterioration and was found to have massive recurrence. Pathology was consistent with high-grade chondrosarcoma. The tumor continued to progress despite debulking and proton-beam therapy and the patient died of medical complications. To our knowledge this is the first report of malignant transformation of a meningioma to high-grade chondrosarcoma, further notable due to the remarkable clinical course and delayed presentation after initial surgery and radiosurgery. Though this may have been a de novo tumor, it is also possible that this represents a case of radiation-induced neoplasm. Although SRS continues to gain favor as a treatment modality, delayed malignant degeneration is a potential complication and physicians should counsel patients of this risk.

Potential application of titanium dioxide nanoparticles in the prevention of osteosarcoma and chondrosarcoma recurrence.

Osteosarcoma and chondrosarcoma are malignant bone tumors, and they significantly affect the life quality of patients including children and adults. The main treatment method is surgical amputation of the malignant lesion, despite that recurrence often occurs. Recently, it has been observed that TiO2 NPs killed HeLa cells effectively via photocatalysis in vitro, which indicates titanium dioxide (TiO2) nanoparticles (NPs) might be used to reduce the recurrence of osteosarcoma and chondrosarcoma by inducing cytotoxicity to bone tumor cells. In this study, we investigated the potential effects of TiO2 NPs in two cancer cell lines in vitro: U-2 OS (osteosarcoma) and SW 1353 (chondrosarcoma). We assessed cell viability, the levels of reactive oxygen species (ROS) and glutathione (GSH) after exposure to TiO2 NPs at different concentrations (0.1-100 microg/ml) for varying exposure periods (12-48 hours). Compared to the NP-free control, TiO2 NPs induced cell death in a dosage-dependent and time-dependent manner. The median inhibitory concentration (IC50) of TiO2 NPs at 24 hours was 211.3 +/- 15.2 microg/ml and 5408.8 +/- 45.9 microg/ml for SW 1353 and U-2 OS cell lines, respectively. TiO2 NPs concentrations above 1 microg/ml were more efficient to reduce the cell viability of SW 1353 than U-2 OS of NPs at all exposure times. The increased ROS and reduced GSH levels indicated that TiO2 NPs killed cancer cells through oxidative stress. These results suggested that the TiO2 NPs can be potentially used to minimize/prevent the recurrence of osteosarcoma and chondrosarcoma.

Inhibition of chondrosarcoma growth by mTOR inhibitor in an in vivo syngeneic rat model.

BACKGROUND: Chondrosarcomas are the second most frequent primary malignant type of bone tumor. No effective systemic treatment has been identified in advanced or adjuvant phases for chondrosarcoma. The aim of the present study was to determine the antitumor effects of doxorubicin and everolimus, an mTOR inhibitor on chondrosarcoma progression. METHODS AND FINDINGS: Doxorubin and/or everolimus were tested in vivo as single agent or in combination in the rat orthotopic Schwarm chondrosarcoma model, in macroscopic phase, as well as with microscopic residual disease. Response to everolimus and/or doxorubicin was evaluated using chondrosarcoma volume evolution (MRI). Histological response was evaluated with % of tumor necrosis, tumor proliferation index, metabolism quantification analysis between the treated and control groups. Statistical analyses were performed using chi square, Fishers exact test. Doxorubicin single agent has no effect of tumor growth as compared to no treatment; conversely, everolimus single agent significantly inhibited tumor progression in macroscopic tumors with no synergistic additive effect with doxorubicin. Everolimus inhibited chondrosarcoma proliferation as evaluated by Ki67 expression did not induce the apoptosis of tumor cells; everolimus reduced Glut1 and 4EBP1 expression. Importantly when given in rats with microscopic residual diseases, in a pseudo neoadjuvant setting, following R1 resection of the implanted tumor, everolimus significantly delayed or prevented tumor recurrence. CONCLUSIONS: MTOR inhibitor everolimus blocks cell proliferation, Glut1 expression and HIF1a expression, and prevents in vivo chondrosarcoma tumor progression in both macroscopic and in adjuvant phase post R1 resection. Taken together, our preclinical data indicate that mTOR inhibitor may be effective as a single agent in treating chondrosarcoma patients. A clinical trial evaluating mTOr inhibitor as neo-adjuvant and adjuvant therapy in chondrosarcoma patients is being constructed.

Direct anti-cancer effect of oncostatin M on chondrosarcoma.

The cytokine Oncostatin M (OSM) is cytostatic, pro-apoptotic and induces differentiation of osteosarcoma cells into osteocytes, suggesting new adjuvant treatment for these bone-forming sarcomas. However, OSM systemic over-expression could lead to adverse side effects such as generalized inflammation, neoangiogenesis and osteolysis. We determine here the effect of OSM on chondrosarcoma, another primary bone sarcoma characterized by the production of cartilage matrix and altered bone remodelling. Chondrosarcomas are resistant to conventional chemotherapy and radiotherapy, and wide surgical excision remains the only available treatment. We found that OSM blocked the cell cycle in four of five chondrosarcoma cell lines, independently of p53 and presumably through the JAK3/STAT1 pathway. In two tested cell lines, OSM induced a hypertrophic chondrocyte differentiation, with an induced Cbfa1/SOX9 ratio and induced Coll10, matrix metalloproteinase 13 (MMP13) and RANKL expression. Adenoviral gene transfer of OSM (AdOSM) in the Swarm rat chondrosarcoma (SRC) model indicated that local intra-tumoral OSM over-expression reduces chondrosarcoma development not only with reduced tumor proliferation and enhanced apoptosis but also with enhanced RANKL expression, osteoclast formation and reduced bone volumes. Flu-like symptoms were induced by the AdOSM, but there was no effect on tumor angiogenesis. Therefore, OSM could be considered as a new adjuvant anti-cancer agent for chondrosarcomas. A local application of this cytokine is presumably needed to overcome the poor vascularization of these tumors and to limit the deleterious effect on other tissues. Its side effect on bone remodeling could be managed with anti-resorption agents, thus offering potential new lines of therapeutic interventions.

COX-2 expression in chondrosarcoma: a role for celecoxib treatment?

Chondrosarcomas are resistant to conventional chemo- and radiotherapy. A subset of chondrosarcomas arises secondarily in the benign tumour syndromes enchondromatosis (EC) and multiple osteochondromas (MO), and prevention of tumour development would greatly improve prognosis. We therefore investigated the effect of selective COX-2 inhibition on chondrosarcoma growth. COX-2 expression was studied in central- and peripheral cartilaginous tumours. The effect of COX-2 inhibition was assessed in four high-grade chondrosarcoma cell lines using celecoxib and NS-398 treatment. COX-2 activity (prostaglandin E(2) (PGE(2)) ELISA) and cell viability were measured. The (prophylactic) effect of celecoxib on chondrosarcoma growth in vivo was studied for 8 weeks using a xenograft model of cell line CH2879 in immunoincompetent nude mice. High COX-2 protein expression was mainly found in solitary peripheral chondrosarcoma and in enchondromatosis-related central chondrosarcoma, which was confirmed by qPCR. After 72h of celecoxib treatment, a significant decrease in cell viability was observed in three chondrosarcoma cell lines. In vivo, celecoxib initially slowed tumour growth in chondrosarcoma xenografts; however, after prolonged treatment relapsed tumour growth was observed. Tumour volume was negatively associated with celecoxib serum levels, and seemed smaller in the high-dose prophylactic treatment group. We confirmed the expression of COX-2 in 65% of chondrosarcomas, and COX-2 inhibition by celecoxib diminished cell viability in vitro. The initial response and the decrease in tumour volume with increased celecoxib serum levels in vivo supported a role for celecoxib, although relapsed tumour growth after 6 weeks was worrisome. Also the role of high-dose prophylactic celecoxib in preventing the development of benign and malignant cartilage tumours in EC and MO patients deserves further investigation.

Condrossarcoma primário de língua em cão / Primary chondrosarcoma in the tongue of a dog

A 10 year old female Boxer was taken dead to veterinary hospital for a necropsy without any clinical history, showing a growth on the dorsal part of the tongue. Based on the histopathological findings mesenchymal chondrosarcoma was diagnosed. This report describes the first case of chondrosarcoma on the base of the tongue in veterinary medicine.

Relationship between binding affinities to cellular retinoic acid-binding protein and in vivo and in vitro properties for 18 retinoids.

A new rapid assay has been developed for measurement of the binding of [3H]retinoic acid to cellular retinoic acid-binding protein. The assay, which uses activated charcoal for the separation of bound from unbound retinoic acid, was used to determine the concentration required to inhibit the binding of [3H]retinoic acid to cellular retinoic acid-binding protein by 50% for 18 retinoids with free carboxylic acid groups. Partially purified cellular retinoic acid-binding proteins isolated from rat testes and carcinogen-induced rat mammary tumors were used for these determinations. The following parameters were also determined for some or all of the retinoids: hypervitaminosis A doses; activity against carcinogen-induced mouse skin papillomas; inhibition of growth of a rat chondrosarcoma; inhibition of growth of 3T6 cells; and differentiation of the embryonal carcinoma cell line PCC4.azaIR. While all retinoids that are potent in these biological test systems bind tightly to cellular retinoic acid-binding protein, the converse is not true. The lack of a consistent quantitative correlation between 50% inhibitory concentration and biological activity is probably due to insufficient concentrations of the retinoid in the target tissue or celll, which is a consequence of factors such as absorbability, metabolism, tissue distribution, and pharmacokinetics.