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Light and electron microscopic examination of fine-needle aspirates in the preoperative diagnosis of osteogenic tumors: a study of 21 osteosarcomas and two osteoblastomas.

Twenty-three patients with primary osteogenic tumors, two osteoblastomas and 21 osteosarcomas, underwent fine-needle aspiration biopsy in the preoperative investigation. The cytologic features in smears were compared with the light and electron microscopic findings of resin-embedded fine-needle aspirates (16 cases) and the histopathologic findings of the surgical specimens. Cytologic smears clearly indicated a primary bone malignancy in all 20 high-malignancy osteosarcomas. In the osteoblastic osteosarcomas, the diagnosis of osteosarcoma was strongly suggested by the osteoblastic appearance of the tumor cells and the presence of an osteoid-like fibrillar matrix in 6 of 11 cases in the May-Grünwald-Giemsa-stained smears. The distinction of chondroblastic osteosarcomas from high-grade chondrosarcomas and of polymorphic osteosarcomas from malignant fibrous histiocytomas is difficult in smears. Electron microscopic examination and immunocytochemistry indicating a positivity for vimentin but not for cytokeratin helped to exclude the possibility of a carcinoma in osteoblastic osteosarcomas where the tumor cells had epithelium-like features in the smears. The resin-embedding technique of fine-needle aspirates was useful for the typing since it gave additional light microscopic information about growth pattern, structure, and matrix production, as well as ultrastructural information about cell and tissue differentiation. The osteoid-like material seen in May-Grünwald-Giemsa-stained smears could be proven to represent osteoid with varying degrees of calcification at the ultrastructural examination. The fine-needle aspiration technique, especially when used for both smears and embedding, may play an important role in the preoperative investigation of bone tumors, provided that it is used with full knowledge of the clinical and radiographic findings.

Adolescent↗

Cytoplasmic and/or nuclear accumulation of the beta-catenin protein is a frequent event in human osteosarcoma.

The molecular events that precede the development of osteosarcoma, the most common primary malignancy of bone, are unclear, and concurrent molecular and genetic alterations associated with its pathogenesis have yet to be identified. Recent studies suggest that activation of beta-catenin signaling may play an important role in human tumorigenesis. To investigate the potential role of beta-catenin deregulation in human osteosarcoma, we analyzed a panel of 47 osteosarcoma samples for beta-catenin accumulation using immunohistochemistry. Potential activating mutations were investigated by sequencing exon 3 of the beta-catenin gene in genomic DNA isolated from tumor samples. Our findings revealed cytoplasmic and/or nuclear accumulation of beta-catenin in 33 of 47 samples (70.2%); however, mutation analysis failed to detect any genetic alterations within exon 3, suggesting that other regulatory mechanisms may play an important role in activating beta-catenin signaling in osteosarcoma. In our survival analysis, beta-catenin deregulation conferred a hazard ratio of 1.05, indicating that beta-catenin accumulation does not appear to be of prognostic value for osteosarcoma patients. When analyzed against other clinicopathologic parameters, beta-catenin accumulation correlated only with younger age at presentation (26.4 vs. 39.8 years). Nevertheless, our results demonstrate that the deregulation of beta-catenin signaling is a common occurrence in osteosarcoma that is implicated in the pathogenesis of osteosarcoma.

Adult↗

Annexin 2 expression is reduced in human osteosarcoma metastases.

Osteosarcoma is an aggressive primary bone cancer affecting primarily children and young adults. The development of valuable diagnostic indicators and therapeutic agents will be enhanced by the identification and characterization of genes that contribute to its aggressive behavior. We used representational difference analysis to isolate genes differentially expressed between primary human osteosarcoma tumors and subsequent metastatic lung lesions to identify genes potentially involved in metastatic potential. Several genes were differentially expressed between the two tumor populations, including annexin2. The levels of annexin2 mRNA and protein inversely correlated with metastatic potential in a subset of human osteosarcoma tumor specimens, as well as in a human osteosarcoma cell line selected for increased metastatic potential. Annexin2 has been described in several cellular localizations with various functional implications, many of which may be relevant to metastatic potential. Therefore, the subcellular localization of endogenous annexin2 protein was evaluated biochemically by subcellular fractionation and immunologically by flow cytometry and immunofluorescence in osteoblastic cells. Annexin2 was localized to the cytoplasm and intracellular aspect of the plasma membrane, excluded from the nucleus and undetectable on the cell surface or in the conditioned medium. Overexpression of annexin2 in osteosarcoma cells did not alter several in vitro phenotypes often used to assess metastatic potential including motility, adhesion, and proliferation. However, our previous data have implicated annexin2 in the mineralization process of osteoblastic cells in vitro. Consistent with an increase in differentiation-induced mineralization, there was diminished tumorigenicity and experimental metastatic potential of osteosarcoma cells overexpressing annexin2. These data suggest that annexin2 may downregulate osteosarcoma aggressiveness by inducing a more differentiated state in osteoblastic cells.

Animals↗

P-glycoprotein expression in osteosarcoma: a basis for risk-adapted adjuvant chemotherapy.

Previous reports on osteosarcomas treated with multi-agent chemotherapy have shown that P-glycoprotein expression is a reliable prognostic indicator. The current thinking is that, of the several agents used for the treatment of osteosarcoma, only doxorubicin is involved in drug resistance mediated by P-glycoprotein. This study examines the relationship of P-glycoprotein expression to clinical outcome in osteosarcomas, treated only with doxorubicin in addition to surgery, to determine if the prognostic significance of P-glycoprotein expression reflects the ability of osteosarcoma to respond to this drug. The expression of P-glycoprotein in tumor specimens was assessed by immunohistochemistry in 37 nonmetastatic, operable osteosarcomas treated at a single institution with doxorubicin as a single adjuvant drug. The P-glycoprotein status was analysed in relation to the length of event-free survival. A widespread pattern of P-glycoprotein expression in tumor cells at diagnosis was significantly associated with a higher rate of systemic relapse (p < 0.001). On comparison of this group of patients with a similar series of 92 patients, all treated with multi-agent chemotherapy plus surgery of the primary lesion and previously analysed for P-glycoprotein status, only P-glycoprotein-positive, doxorubicin-resistant tumors consistently benefited from the addition of drugs other than doxorubicin (p < 0.001). Osteosarcomas with different abilities to respond to adjuvant chemotherapy can be identified by the expression of P-glycoprotein in tumor cells at the clinical onset. P-glycoprotein status may serve as a basis for risk-adapted, individualized therapeutic regimens. Standard programs are sufficient for P-glycoprotein-negative osteosarcomas, whereas P-glycoprotein-positive tumors may benefit from the use of more intensive therapeutic approaches.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Osteosarcoma: histological evaluation and grading.

With 60 cases of osteosarcomas a histological evaluation from + to +++ carried out for mitoses, osteoid formation, presence of multinucleated giant cells, and tumor necrosis. A subclassification in osteoblastic, chondroblastic, and fibroblastic type of osteosarcoma (according to Dahlin) and a histological grading from + to +++ based on degree of cellular atypism was also done. In our material no relations between these three types of osteosarcoma and chance for survival became evident. There was, however, a significant correlation between grade of atypism and rate of mitoses. Grading of oestosarcomas from + to +++ showed that cases with grade III osteosarcoma remained only seldomly without metastases during the course of the disease. Grade I osteosarcomas and also grade II tumors showed a higher number of patients with 2-year survival. However, neither correlation between tumor grade and incidence of metastases, nor with chances for survival were statistically significant. Nevertheless, characterization of osteosarcomas, by a histological grading from + to +++ based on cellular atypism and mitotic count is advisable, in addition to the TNM stages. This histological grading appeared to be more practicable than subclassifications of osteosarcoma by type which had been tested by us in a previous study (Konrad et al., in press).

Humans↗

Characterization of autocrine inducible prostaglandin H synthase-2 (PGHS-2) in human osteosarcoma cells.

The human osteosarcoma 143.98.2 cell line was found to express high levels of prostaglandin synthase-2 (PGHS-2) without detectable levels of prostaglandin synthase-1 (PGHS-1) as measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblot analysis. Maximal levels of PGHS-2 induction were attained when the cells were grown beyond confluence. The osteosarcoma cells also secrete IL-1 alpha, IL-1 beta and TNF alpha in the culture medium. PGHS-2 expression was inducible by the exogenous addition of these cytokines as well as conditioned media from auto-induced cultures and inhibitable by treatment with dexamethasone. In contrast, undifferentiated U937 cells selectively express PGHS-1 as analyzed by RT-PCR and Western blotting. The effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the cellular PGE2 production mediated by each isoform of human PGHS were determined using osteosarcoma and undifferentiated U937 cells. When cells were preincubated with inhibitors to allow time-dependent inhibition prior to arachidonic acid stimulation, NS-398, CGP 28238, L-745,337, SC-58125 all behaved as potent (IC50 = 1-30 nM) and selective inhibitors of PGHS-2, in contrast to indomethacin, flurbiprofen or diclofenac which are potent inhibitors of enzymes. DuP-697 and sulindac sulfide were also potent inhibitors of PGHS-2 but both compounds inhibited cellular PGHS-1 activity at higher doses (IC50 = 0.2-0.4 microM). Time-dependent inhibition of PGE2 production in osteosarcoma cells was observed for indomethacin, diclofenac and etodolac. The synthesis of PGE2 by U937 cells was strongly dependent on exogenous arachidonic acid (100-fold stimulation) whereas confluent osteosarcoma cells also produced PGE2 without exogenous stimulus (7-fold stimulation by arachidonic acid). Osteosarcoma cells grown beyond confluence released more PGE2 from endogenous substrate than arachidonic acid stimulated undifferentiated U937 cells. These results indicate that osteosarcoma cells selectively express PGHS-2 with an autocrine regulation and effective utilization of endogenous arachidonic acid for PGE2 synthesis.

Arachidonic Acid↗

[Is the elimination of osteosarcoma cells with intraoperative "mesh autotransfusion" and leukocyte depletion filters possible?].

UNLABELLED: Intraoperative autotransfusion is contraindicated in cancer surgery because of the possible risk of systemic tumor spread. The aim of the present study was to investigate whether a cell saver in combination with a white blood cell depletion filter can remove osteosarcoma cells. METHODS: A defined number of osteosarcoma cells from an established cell line were added to red cell concentrates and Ringer solution. The tumor cell concentration was 1000/ ml in the first five experiments, 7111/ml in test no. 6, 1667/ml in test no. 7 and 167/ml in test no. 8. Following thorough mixing, each unit was processed separately by a cell saver (DIDECO BT 795/P) in its normal operation mode to produce a red cell concentrate. This red cell concentrate was filtered using a leukocyte depletion filter (PALL BPF 4). Samples were taken before and after processing with the autotransfuser and after filtration with the white cell depletion filter. Cytospin specimens from all samples were examined for osteosarcoma cells by three different methods (Papanicolaou stain, Vimentin antibodies, DNA analysis). RESULTS: After processing with the autotransfuser, tumor cells were identified in the red cell concentrate. No osteosarcoma cells were evident after the combined use of cell saver and leukocyte depletion filter. CONCLUSION: The sole use of the autotransfuser DIDECO BT 795/P during osteosarcoma surgery is not recommended because of the potential danger of retransfusion of malignant cells. In combination with the leukocyte depletion filter PALL BPF 4, no osteosarcoma cells were identified in the red cell concentrate. Since the adhesiveness of tumor cells from established cell lines may be different from that of tumor cells in the intraoperative salvaged blood, further studies with blood from the surgical field are necessary to determine the efficacy of white cell depletion filters to eliminate osteosarcoma cells.

Blood Transfusion, Autologous↗

Synchronous multicentric osteosarcoma: the case for metastases.

OBJECTIVE: There is a current debate whether multicentric osteosarcoma represents synchronous multiple primary osteosarcomas or metastatic disease. The purpose of this report is to evaluate the etiology, presentation, and classification of this entity. DESIGN AND PATIENTS: Six patients ranging in age from 7 to 29 years were studied. The clinical, radiographic, and pathologic findings are reported. In addition, a review of the literature was undertaken. RESULTS: The clinical courses of our six patients as well as a review of the literature suggest that multicentric osteosarcoma represent one extreme of a continuous scale of metastatic osteosarcoma rather than multiple synchronous primary tumors. The presentation is unusual and the clinical behavior distinctive, but the mechanism of spread remains the same: blood-borne and lymphatic-borne. CONCLUSIONS: Our experience with these six patients supports the concept in the recent literature that synchronous osteosarcoma is one extreme of the spectrum of metastatic osteosarcoma. Its unique features are: (1) multiple radiodense lesions that present simultaneously with or without pulmonary metastases; (2) a single "dominant" lesion with multiple smaller lesions; and (3) a uniformly rapid, fatal prognosis. Osteosarcoma should be regarded as a metastatic disease, even when only a single primary lesion is found at the initial presentation.

Adolescent↗

[Periosteal osteosarcoma. Histologic characteristics, preparation technique, growth pattern and differential diagnosis].

Periosteal osteosarcoma is a distinct bone tumor entity with characteristic morphological features within the group of juxtacortical osteosarcoma. Periosteal osteosarcoma is predominantly located in the long tubular bones, especially in the tibia and femur and is situated on the outer circumference of the tumor-bearing bone (saucerization phenomenon). In contrast to parosteal osteosarcoma, periosteal osteosarcoma is less differentiated and is believed to have a worse prognosis. In this work the histological features are described with predominantly chondroblastic differentiation of 14 cases with periosteal osteosarcoma. A horizontal preparation technique of periosteal osteosarcoma specimens allows comparison with computed tomography and is the optimal method to detect an invasion of the medullary cavity. Further studies are necessary to clarify if neoadjuvant chemotherapy could improve the prognosis of certain patients.

Adolescent↗

In vitro culture of human osteosarcoma cell lines: a comparison of functional characteristics for cell lines cultured in medium without and with fetal calf serum.

PURPOSE: Experimental in vitro models including well-characterised cell lines can be used to identify possible new therapeutic targets for the treatment of osteosarcoma. Culture media including inactivated serum is often recommended for in vitro culture of osteosarcoma cells, but the serum component then represents a nonstandardised parameter including a wide range of unidentified mediators. To improve the standardisation we have investigated whether serum-free culture media can be used in experimental in vitro studies of osteosarcoma cell lines. METHODS: The seven osteosarcoma cell lines Cal72, SJSA-1, Saos-2, SK-ES-1, U2OS, 143.98.2, and KHOS-32IH were cultured in vitro in various serum-free media and media supplemented with 10% heat-inactivated fetal calf serum (FCS). RESULTS: Although proliferation often was relatively low in serum-free media (X-vivo 10, X-vivo 15, X-vivo 20, Stem Span SFEM), some cell lines (Cal72, KHOS-32IH, Saos-2) showed proliferation comparable with the recommended FCS-containing media even when using serum-free conditions. The optimal serum-free medium then varied between cell lines. We also compared 6 different FCS-containing media (including Stem Span with 10% FCS) and the optimal FCS-containing medium varied between cell lines. However, all cell lines proliferated well in Stem Span with FCS, and this medium was regarded as optimal for four of the lines. FCS could not be replaced by fatty acids or low density lipoprotein when testing the Stem Span medium. The release of a wide range of soluble mediators showed only minor differences when using serum-free and FCS-containing media (including Stem Span with and without FCS), and serum-free Stem Span could also be used for in vitro studies of mitogen-stimulated T cell activation in the presence of accessory osteosarcoma cells. The use of Stem Span with 10% FCS allowed the release of a wide range of chemokines by osteosarcoma cell lines (Cal72, SJSA-1), and the chemokine release profile was very similar to the fibroblast lines Hs27 and HFL1. CONCLUSIONS: Serum-free culture media can be used for in vitro studies of several osteosarcoma cell lines, but the optimal medium varies between cell lines and thus depends on: (i) the cell lines to be investigated/compared; (ii) the functional characteristic that is evaluated (proliferation, cytokine release); and (iii) whether coculture experiments are included.

Acute Disease↗

NFS1 activates PI3K/AKT/mTOR signaling to upregulate GPX4 expression and enhance ferroptosis resistance in osteosarcoma.

Osteosarcoma continues to exhibit poor survival outcomes due to chemoresistance and metastasis, with metabolic reprogramming and ferroptosis resistance being key features of tumor heterogeneity, yet their upstream regulators remain poorly defined. NFS1, a cysteine desulfurase essential for iron-sulfur cluster biogenesis, protects multiple cancers from ferroptosis, but its role in osteosarcoma is unknown. In this study, we performed a transcriptomic meta-analysis and found that NFS1 expression was significantly upregulated in osteosarcoma tissues, with further elevation in metastatic lesions, and high NFS1 expression correlated with poor overall survival. Genome&#x2011;wide CRISPR screening data revealed a marked NFS1 dependency in osteosarcoma cell lines. Functionally, NFS1 promoted cell proliferation, migration, and invasion, whereas its knockdown suppressed these phenotypes. Using single&#x2011;cell RNA sequencing data from 27 osteosarcoma specimens, we applied a multi&#x2011;algorithm glycolytic scoring framework and observed NFS1 enrichment in highly glycolytic malignant cells, along with an association with PI3K/AKT/mTOR pathway activation. Mechanistically, NFS1 selectively enhanced PI3K, AKT, and mTOR phosphorylation without altering total protein levels, and upregulated GPX4, a central ferroptosis suppressor, leading to elevated ferroptosis resistance scores in NFS1&#x2011;high malignant cells. Collectively, these findings identify a previously unrecognized NFS1-PI3K/AKT/mTOR-GPX4 regulatory axis in osteosarcoma, linking metabolic reprogramming to ferroptosis resistance, and suggest that NFS1 functions as an oncogenic driver, as well as a promising prognostic biomarker and therapeutic target in osteosarcoma.

Humans↗

An orthotopic model of human osteosarcoma growth and spontaneous pulmonary metastasis.

Osteosarcoma is the most common primary malignancy of bone and patients often develop pulmonary metastases. In order to investigate the pathogenesis of human osteosarcoma, there is a great need to develop a clinically relevant animal model. Here we report the development of an osteosarcoma animal model using three related human osteosarcoma lines, the parental TE-85 and two derivative lines MNNG/HOS and 143B. In vitro characterization demonstrated that the 143B line had the greatest cell migration and the least cell adhesion activities among the three lines. The 143B line also exhibited the greatest ability for anchorage independent growth. When GFP-tagged osteosarcoma cells were injected into the proximal tibia of athymic mice, we found that 143B cells were highly tumorigenic and metastatic, and MNNG/HOS cells were tumorigenic but significantly less metastatic. TE85 cells were neither tumorigenic nor metastatic. The number of pulmonary metastases was found 50-fold higher in 143B injected animals than that in MNNG/HOS injected mice. No pulmonary metastases were detected in TE85 injected animals for up to 8 weeks. Primary tumors formed by MNNG/HOS and 143B cells could be visualized by whole body fluorescence imaging, while the pulmonary metastases were visualized on the necropsied samples. The GFP tagged 143B cells (and to a lesser extent, MNNG/HOS cells) were readily recovered from lung metastases. This clinically relevant model of human osteosarcoma provides varying degrees of tumor growth at the primary site and metastatic potential. Thus, this orthotopic model should be a valuable tool to investigate factors that promote or inhibit osteosarcoma growth and/or metastasis.

Animals↗

Low-dose methotrexate inhibits lung metastasis and lengthens survival in rat osteosarcoma.

Lung metastasis is the most crucial event affecting the treatment of osteosarcoma and is dependent on tumor angiogenesis. To improve the prognosis for patients with osteosarcoma, prevention of lung metastasis is essential. Low-dose methotrexate is a useful drug for treating a variety of diseases. Low-dose methotrexate reportedly plays a role in antiangiogenesis for the synovial blood vessels in rheumatoid arthritis. However, whether low-dose methotrexate is correlated with tumor angiogenesis and metastasis is unclear. We investigated the inhibitory effect of methotrexate on lung metastasis in a rat osteosarcoma cell line with high metastatic potential, S-SLM. Two weeks after inoculation of S-SLM cells into male Fischer 344 rats, low-dose methotrexate (1.2 mg/kg once or twice a week) or saline was intraperitonealy injected for 4 weeks and the antimetastatic effect was evaluated. Low-dose methotrexate significantly reduced the number of lung metastatic nodules and the wet weight of the lungs. Immunohistochemical staining showed a decrease in microvessel density in the metastatic nodules. We also evaluated the effect of methotrexate on the proliferation of endothelial cells and S-SLM osteosarcoma cells in vitro. Methotrexate significantly inhibited the proliferation of endothelial cells at a lower concentration than that of S-SLM osteosarcoma cells. These data suggest that low-dose methotrexate inhibited lung metastasis of osteosarcoma through its antiangiogenic activity. Our results indicate that low-dose methotrexate is a promising drug for tumor dormancy therapy in patients with osteosarcoma and lung metastasis.

Animals↗

Ultrasonographic evaluation of osteosarcomas.

The ultrasonographic appearances of osteosarcomas and the roles of ultrasonography in the diagnosis and surgical staging of osteosarcomas were investigated. A comparative study was performed on 45 cases of osteosarcomas by ultrasonography and radiography. Bony changes, periosteal reaction and soft tissue mass were evaluated for each lesion. The results showed that ultrasonography revealed a solid mass around bone in 42 patients, bone destruction in 24 patients and periosteal reaction in 16 patients. Plain radiographs showed bony changes in 44 patients and no bony change in remaining one patient, shadowing of soft tissue swelling in 30 patients, and pulmonary metastases in 3 patients. Surgical biopsy and pathological examination confirmed osteosarcoma in all 45 patients. Soft tissue mass was confirmed in 42 patients surgically. The diagnostic accuracy of soft tissue masses by ultrasonography and radiography was 100 % (42/42) and 71.4 % (30/42), respectively. The positive rate of ultrasonography and radiography in displaying bony changes was 53.3 % (24/45) and 97.8 % (44/45), respectively. In conclusion, in the detection of soft tissue mass of osteosarcoma, ultrasonography is superior to radiography, and in displaying bony changes of osteosarcomas, radiography is superior to ultrasonography. So it may come to a conclusion that plain radiography combined with ultrasonography can completely display the bony and soft tissue lesion of osteosarcomas.

Adolescent↗

P-31 changes as a measure of therapy response in resistant and sensitive osteosarcomas implanted into nude mice.

OBJECTIVE: To determine if changes in PCr/Pi and PME can be used to predict lack of tumor response to chemotherapy in a murine model of a chemotherapy-resistant human osteosarcoma. MATERIAL AND METHODS: Cisplatin-resistant sublines were grown from high-grade cisplatin-sensitive human osteosarcoma. Surface coil localized 31P NMR spectroscopy of implanted cisplatin-resistant and sensitive osteosarcoma tumors in nude mice was performed. RESULTS: A cisplatin-resistant subline of a sensitive human osteosarcoma was developed that was five times more resistant to cisplatin than the parent cell line. Our NMR data shows a statistically significant difference in the change in the PCr/Pi ratio after treatment between sensitive and resistant osteosarcomas at the alpha = 0.05 level. Changes in PME were seen in the sensitive tumors but were not statistically significant. CONCLUSIONS: Changes in PCr/Pi predict lack of tumor treatment response in human osteosarcoma implanted into nude mice with a specificity of 70% and a sensitivity of 54%. Monitoring of PCr/Pi in human osteosarcoma patients may allow detection of response to chemotherapy before conventional imaging techniques.

Animals↗

Molecular analysis of p53, MDM2 and H-ras genes in low-grade central osteosarcoma.

Low-grade central osteosarcoma is an uncommon form that is characterized by a long premorbid history, and is compatible with prolonged survival after treatment. However, molecular abnormalities are rare in low-grade central osteosarcomas, whereas p53 mutations occur in approximately 20% of conventional high-grade osteosarcomas. In this study, 21 cases of low-grade central osteosarcoma were analyzed for mutations of the p53 gene, amplification of the MDM2 gene, and mutations of the H-ras gene using formalin-fixed, paraffin-embedded materials. We also examined the expression of p53, MDM2, and p21WAF1 protein immunohistochemically and assessed the proliferation activities using the monoclonal antibody MIB-1. One case (4.7%) showed strong p53 immunoreactivity, whereas p53 gene mutations were not detected at all. Seven cases (33.3%) showed immunoreactivity for MDM2 protein. As for gene alterations, MDM2 amplification was found in four cases (19.0%). p21WAF1 expression was detected in 12 cases (57.1%). MIB-1-LI showed very low levels in all the cases and no significant correlation with p53 or MDM2 immuno-reactivity. None of the tumors showed H-ras mutations. In conclusion, the number of p53 gene alterations in low-grade central osteosarcomas is lower than that in conventional high-grade osteosarcomas. MDM2 alterations and p21WAF1 expression might be involved in the tumorigenesis of low-grade central osteosarcomas.

Adolescent↗

[Chondroblastic osteosarcoma of the mandible: a case report with 14 years follow-up].

INTRODUCTION: Osteosarcoma, the second most frequent primary malignant bone tumor, is usually found in long bones: femur, tibia or humerus with only 6 to 7% of cases occurring in the jaws. Patients with osteosarcoma of the mandible usually complain of a swelling, which can be painful or not, accompanied by paresthesia of one of the trigeminal nerve branches in about 20% of cases. OBSERVATION: We report a case of chondroblastic osteosarcoma of the mandible affecting a 33-year-old woman with 14 years follow-up illustrating the difficulties of a rapid diagnosis. DISCUSSION: The prognosis of osteosarcoma of the mandible relies on its histological grade and the amount of time elapsing from diagnosis to treatment onset. The treatment of choice is radical surgery providing a 5-year survival rate up to 80%. The definitive surgical treatment is usually performed only after several interventions because operative-room pathology cannot be obtained due to the necessity of decalcification. In order to avoid multiple resections, an interim bridging with a reconstructive plate with a condylar head can be proposed before definitive graft reconstruction. The prognosis of osteosarcoma of the mandible is better than that of long bones. Chemotherapy or radiotherapy, which are very efficient for osteosarcoma in general, do not change the prognosis of osteosarcoma of the mandible.

Adult↗

Epiphyseal osteosarcoma: distinguishing features from clear cell chondrosarcoma, chondroblastoma, and epiphyseal enchondroma.

In a retrospective radiologic and histologic study of 286 osteosarcomas in files of a metropolitan hospital, four patients (three men and one woman) with osteosarcomas confined to the epiphysis were identified. In this series, there were also 16 metaphyseal osteosarcomas that extended to the epiphysis with penetration through the cartilaginous growth plate, a structure that ordinarily resists tumor growth. All tumors occurred in the femoral condyle. Characteristically, all four patients had histories of knee joint pain, and three reported antecedent trauma. Radiologically, the tumors showed predominantly lytic features. Histologically, three of the tumors were osteoblastic in type, and one was mostly chondroblastic. Purely epiphyseal osteosarcoma has overlapping radiologic features with clear cell chondrosarcoma, epiphyseal chondroblastoma, and epiphyseal enchondroma. The epiphyseal osteosarcomas of the distal femur reported here were characterized by a history of symptoms localized to the knee joint itself as a consequence of their epiphyseal location and joint involvement. This is in contrast to the usual metaphyseal osteosarcomas, which present with lower thigh pain and swelling. Because osteosarcomas may present as lytic tumors confined to the epiphysis, they should be included in the differential diagnosis of such lesions.

Bone Neoplasms↗