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Intracortical osteosarcoma is the rarest type of osteosarcoma. In most instances the tumor arises in the cortex of the femur, less commonly, in the tibia. We describe an 11-year-old patient with intracortical osteosarcoma of the tibia in whom the tumor was present for 2 years and became painful 3 months prior to presentation.
A rare case of chondroblastic osteosarcoma arising from the ethmoid sinus is reported. The patient, a 34-year-old woman, presented with diminished visual acuity of the left eye. CT and MR imaging showed a heterogeneous left-sided nasoethmoidal mass destroying the medial orbital wall. Biopsy revealed a chondroblastic osteosarcoma containing malignant chondroid elements and calcified malignant osteoid. Treatment consisted of craniofacial resection followed by radiotherapy and chemotherapy with symptomatic improvement. We briefly discuss ethmoidal osteosarcomas.
Extraskeletal osteosarcoma is a rare malignancy, which accounts for 1-2% of all soft tissue sarcomas; occurrence of these tumors in the head and neck is extremely rare. We present a case of extraskeletal osteosarcoma arising in the subcutaneous tissue of the jaw angle, the central portion of which displayed calcification. Imaging findings were interesting in terms of a high grade malignancy in that the tumor was small and well circumscribed; its appearance mimicked a calcified lymph node. The differential diagnosis of this lesion as well as the imaging and pathological features of extraskeletal osteosarcoma are discussed.
Although osteosarcoma is the most common primary bone malignancy of childhood and adolescence that is not related to marrow cells, involvement of the short tubular bones is uncommon. In contrast to more conventional sites, where the tumor is usually high grade and found in adolescents, osteosarcoma of the small bones is more likely to be low grade, and is often seen in older individuals. We present a case of low-grade primary osteosarcoma of a metatarsal bone in a 25-year-old woman.
Osteosarcomas arising in irradiated tissues are uncommon but important complications of radiotherapy. Radiation-induced osteosarcomas generally occur 3-30 years after exposure and are most common after radiotherapy for cervical or breast carcinoma. These tumors are usually rapidly growing, extremely painful, and histologically high grade. In this paper, we report two cases of high-grade post-radiation osteosarcoma of the scapula. Despite being almost identical radiologically and pathologically, one case had a typical clinical presentation whereas the second case had two unusual features, being non-painful and arising in a field initially irradiated for bronchogenic carcinoma.
In this report, we describe the clinical, imaging, and pathologic findings in a case of diaphyseal telangiectatic osteosarcoma arising 23 years after successful treatment of bilateral retinoblastomas. To our knowledge, telangiectatic osteosarcoma occurring as a second tumor in this setting, outside the radiation treatment field, has not been previously reported. The association of the RB-1 gene defect with retinoblastomas and other tumors is discussed. Also, the computed tomography and magnetic resonance imaging findings in telangiectatic osteosarcoma are described and discussed.
OBJECTIVE: This study investigated whether dynamic MRI could determine microscopic intraosseous invasion in osteosarcoma. PATIENTS: Six patients with osteosarcoma who underwent total resection of the tumor after chemotherapy were studied. DESIGN: The steepest slope value of the time-intensity curve was calculated on the basis of the first-pass method on dynamic MRI performed after chemotherapy. Slope value modified log = [100.(SIb - SIa)/(Tb - Ta)/SIa], where SIa and SIb represent the signal intensity at time points Ta and Tb when the steepest slope started and ended, respectively. The slope value was correlated with the histological findings of the surgical specimens. The findings on conventional MRI were also reviewed. RESULTS AND CONCLUSIONS: In five of six patients microscopic tumor invasion ranging from 1 to 3.5 cm in depth was pathologically proven. The slope value within the microscopic invasion (-0.052 +/- 0.267) was significantly greater than that of tumour-free marrow (-0.609 +/- 0.220) and less than that in areas showing macroscopic tumor invasion (0.595 +/- 0.483) (P < 0.001). Histological examination disclosed the dilatation of small vessels within the macroscopic and microscopic invasion. Findings on conventional MRI varied among patients; microscopic invasion was not detected in one, underestimated in two, and overestimated in two. It is concluded that calculation of the slope value on dynamic MRI can discriminate regions of microscopic invasion from tumor-free marrow in patients with osteosarcoma after chemotherapy.
Intracortical osteosarcomas originate in the bone cortex and represent the rarest type of osteosarcoma. We describe the clinical, radiological and histological features of an intracortical osteosarcoma occurring in the femur of a young man and discuss the pertinent features of this tumour compared to those previously reported.
OBJECTIVE: The purpose of our study was to report the imaging characteristics of 12 high-grade surface osteosarcomas, diagnosed, staged, treated and followed up in a single institution. DESIGN AND PATIENTS: There were 3 females and 9 males ranging in age from 15 to 34 years (mean 20 years). The radiological documents (plain films in all patients, CT scans in 8 and MR images in 6) were reviewed and compared with the histological findings. RESULTS: Disease sites were the femur (7), tibia (4) and fibula (1). Tumor size varied from 6 to 17 cm. The cortex appeared normal in two patients, thick in seven and/or thin in five. The tumor showed dense ossification in all except in one case where ossification was slight. Minimal marrow involvement was visible in two cases on CT/MRI. Only one case exhibited a satellite nodule in a previous biopsy tract. Two cases radiologically mimicked periosteal osteosarcoma. CONCLUSION: High-grade surface osteosarcomas are often characterized by the presence of an ossified mass contiguous with and originating from the cortical bone with no or minimal marrow involvement.
Primary tumors developing in immunocompetent hosts escape immunosurveillance by acquiring immune evasive properties. This raises the prospect that metastases derived from such tumors will also evade immunity. To investigate whether immune surveillance plays a role in preventing metastases, we studied a murine model which mimics the clinical progression of osteosarcoma: primary tumor growth in the lower extremity, amputation, minimal residual disease followed by the development of overt metastases. K7M2 implants readily escaped immune surveillance since normal BALB/c mice, T cell deficient SCID and T/NK cell deficient SCID-bg mice showed no difference in the rate of growth of primary osteosarcomas. However, both SCID and SCID-bg mice had higher rates of metastases than immunocompetent mice. Similarly, immune reconstitution following transfer of naive T cells to SCID or SCID-bg mice did not impact primary tumor growth, but significantly diminished metastatic recurrence. T cells in osteosarcoma bearing mice produced IFNgamma in response to tumor and IFNgamma production by immune reconstituting T cells was required to prevent metastases. These results demonstrate an important role for T cell based immune surveillance in preventing metastases, even when metastases develop from tumors that adeptly evade immunosurveillance. The results further suggest that T cell depleting cancer therapies may eliminate beneficial immune responses and that immune reconstitution of lymphopenic cancer patients could prevent metastatic recurrence of solid tumors.
Osteosarcoma is the commonest malignant tumour of the bones. The presence of micrometastases at the time of primary diagnosis is associated with poor prognosis. Despite developments in surgery and aggressive chemotherapy, about 50% of the patients still succumb to the disease. Thus, there is a need to develop alternative treatment modalities. One such strategy is to use antibodies with improved effector functions. The two monoclonal antibodies, TP-1 and TP-3, recognize a tumour-associated antigen on human osteosarcoma cells. In the present study, we describe the cloning of the TP-1 variable genes, and the production of complete chimeric mouse/human monoclonal antibodies. Constructs containing the constant genes from human IgG1, IgG3 or a mutant IgG3 with a shortened hinge region, called m15, were expressed in the mouse myeloma cell line, NS0. The m15 mutant has been shown to be very potent in triggering complement-mediated lysis. Our goal was to investigate whether this mutant could overcome the complement protection on human osteosarcoma cells, which is generally present on all human cells. We found that the target cells expressed several membrane-bound complement inhibitors, and that masking of these inhibitors rendered the cells sensitive to lysis. The m15 mutant exhibited greater lytic activity than both IgG3 and IgG1, although it could not cause extensive killing of the target cells alone.
PURPOSE: The significance of preoperative cisplatin (CDDP) as a single agent has not been assessed in terms of its effect on prognosis. The purpose of this multi-institution study was to assess the local effect of preoperative CDDP as a single agent as well as its impact on the prognosis of limb osteosarcoma. PATIENTS AND METHODS: The study group comprised 44 patients with stage IIB limb osteosarcoma who were treated with single-agent CDDP as initial preoperative chemotherapy. Two to five courses of CDDP (mean 2.4 courses) were administered intravenously and/or intraarterially as an initial preoperative treatment. The mean dose of CDDP was 3.0 mg/kg (2.5-3.4 mg/kg). The effect of the treatment was evaluated clinically and histologically. RESULTS: The clinical and histological response rates to preoperative CDDP were 56.8% and 47.6%, respectively. The survival rate was 59.1% among all patients in the study, 64.0% among those with a grade III or IV clinical response, and 52.6% among those with a grade I or II clinical response, with no significant differences between the groups. The survival rate was 70% among patients with a grade III or IV histological response, and 54.5% among those with a grade I or II histological response, with no statistical differences between the groups. CONCLUSIONS: We consider that CDDP is a useful chemotherapeutic agent for preoperative induction therapy for osteosarcoma because of the excellent local effect observed. Good responders to preoperative CDDP showed a better survival rate, but a correlation between the local response to CDDP and the survival rate was not demonstrated statistically. Systemic multidrug chemotherapy should follow preoperative CDDP to diminish the microscopic foci of metastatic disease.
Activation of the mitogen-activated protein kinases ERK1/2 by the chemotherapeutic agent cisplatin has been shown to result in either survival or cell death. The downstream mediators of these opposing effects are unknown, as are the upstream signaling molecules. Activation of ERK is required for accumulation and phosphorylation of p53 following cisplatin treatment. We studied the role of ERK activation after cisplatin treatment under p53-negative and p53-positive conditions using a tetracycline-dependent expression vector in Saos-2 osteosarcoma cells. Dose-dependent activation of ERK first occurred 3-6 h after a 2-h cisplatin incubation and declined after 12-24 h in several tumor cell lines. Incubation of cell lines with the MEK1 inhibitors PD98059 or UO126 after, but not during, cisplatin treatment completely inhibited cisplatin-induced activation of ERK. The activation of ERK by cisplatin was inhibited by transient transfection with dominant-negative Ras-N17 in Saos-2 cells. Treatment of cells with PD98059 or UO126 after cisplatin incubation or inhibition of signaling through ERK by tetracycline-regulated expression of dominant-inhibitory ERK enhanced resistance to cisplatin in p53-negative osteosarcoma cells and reduced cisplatin-induced apoptosis. P53 was stabilized and phosphorylated in a MEK1-dependent manner after cisplatin incubation in Kelly neuroblastoma cells. Inhibition of signaling through ERK increased cell survival after cisplatin treatment in these cells as well. Expression of functional p53 did not change the proapoptotic effects of ERK activation in response to cisplatin in Saos-2 cells. Our results suggest that cisplatin-induced activation of ERK is mediated by Ras. ERK activation increased cisplatin-induced cell death independently of p53 in osteosarcoma and neuroblastoma cell lines.
PURPOSE: To elucidate the role of extracellular matrix (ECM) in repopulation capacity of osteosarcoma cells after doxorubicin treatment. METHODS: OSCORT cells established in our laboratory from a human osteosarcoma, were treated with doxorubicin in monolayer for 4 h, then cells were further incubated either in monolayer or in ECM-containing three-dimensional cell-culture (3-DCC), apoptosis induction and changes in cell number were measured. Alkaline comet assay was applied to estimate DNA damage, immunoblot technique and immunocytochemistry were used to investigate p53 protein synthesis, and the repopulating capacity in monolayer culture and in ECM-based 3-DCC, after doxorubicin treatment was measured. In addition to OSCORT culture five other human cell lines (HT-1080, PC-3, MDA-MB231, A-431 and ZR-75-1) were used to compare the antimigratory and antiproliferative effects of doxorubicin. RESULTS: The apoptotic index, the extent of DNA damage and the representation of p53 were much lower in the OSCORT cell cultures if the cells were exposed to ECM after treatment with doxorubicin. The doxorubicin-treated OSCORT cells transferred from the monolayer culture were not able to proliferate at all, at the same time, the cytoprotection provided by ECM prevailed upon transferring the cells into plastic dish, and resulted in potent repopulation capacity of the cells. CONCLUSIONS: Present data indicate that ECM contributes to failure in therapy of human osteosarcoma in clinical situation. Overall, the application of ECM-based 3-DCC could be suggested as an appropriate model system for the better understanding of antitumor drug action and hereby to set the stage for promising novel pharmacological approaches in cancer therapy.
10 chondrosarcomas and 10 osteosarcomas were examined using cytogenetics and DNA-image-cytometry. Cytogenetically 6 of 10 chondrosarcomas and 4 of 10 osteosarcomas showed hyperdiploid tumorcells. By DNA-cytometry in 8 of 10 chondrosarcomas and 9 of 10 osteosarcomas hyperdiploid tumorcells resp. hyperdiploid stemlines were detected. This discrepancy reflects an in-vitro-selection depending on the different entities. In 7 aneuploid clones of chondrosarcomas the chromosomal ploidy was calculated using the relative length of the chromosomes and compared with the DNA-ploidy of the native tumor. There was a close relation between both parameters of nuclear DNA-content. The interpretation of cytogenetic results is improved using a combination of karyotypic and DNA-cytometric examination. This is particularly important for the search for relations between numeric chromosomal aberrations and morphological parameters (grading).
Primary cardiac osteosarcomas are uncommon tumors. Their growth pattern is aggressive and the prognosis is poor. A 34-year-old, 7-month pregnant woman with a primary cardiac osteosarcoma associated with the anterior mitral leaflet and connected to the interatrial septum, causing nearly subtotal obstruction of the mitral valve, presented with a clinical picture of heart failure. Transthoracic echocardiography demonstrated an abnormal mass located in the mitral anterior leaflet, prolapsing into the left ventricle. Radical resection of the mass and replacement of the mitral valve were performed under cardiopulmonary bypass. Histopathology showed a low-grade osteosarcoma. The postoperative course was uneventful, and the patient was discharged on the 16th day after surgery. She gave birth after 2 months to a healthy baby after the successful operation. She and her baby did not have any problem during 3 months of follow-up.
PURPOSE: In patients with an osteosarcoma, the prognosis is still poor. The aim of the present study was to investigate whether routinely tested biochemical parameters or additional parameters on bone scintigraphy could be identified which can select prognostic subgroups at the time of diagnosis. METHODS: A retrospective study was performed in 115 consecutive patients (70 male, 45 female) (mean age: 25.6 years; range: 3.50-78.0 years) who were referred for bone scintigraphy prior to treatment from March 1986 to September 2000 because of a newly diagnosed osteosarcoma. All bone scans were reassessed for the intensity and pattern of uptake and a bone-scan index. All pre-treatment general, histological, biochemical, and scintigraphic data were correlated with clinical outcome during follow-up. RESULTS: During follow-up 54 patients died. Tumour volume and GGT showed significance as independent variables for metastases. Patients with metastases demonstrated a significantly lower survival rate (23% 5-year survival) than patients without metastases (98% 5-year survival). Tumours of the humerus and femur had a significantly lower survival rate. With respect to significant biochemical parameters (ALP, GGT, ASAT), it was not possible to determine a cut-off value that could be used to differentiate between high- and low-risk patients. Additional parameters assessed on bone scintigraphy were not important for prognostic stratification. CONCLUSION: The strongest predictor of survival in osteosarcoma is the presence or absence of metastasis. Some biochemical parameters have prognostic value, but they cannot be used for the unequivocal identification of subgroups. Additional scintigraphic parameters are irrelevant for prognostic stratification.
Hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are markers of collagen absorption and LP is specific for collagen type I in bone. In the present study we evaluated the concentration of HP and LP in urine of patients with osteosarcoma ( n=20; age range 16-49 years) and chondrosarcoma ( n=15; age range 18-70 years). The values were compared with those obtained from 74 healthy controls (age range 16-83 years). The range and upper limit of normal values (HP(max) and LP(max)) were measured in our control group. High performance liquid chromatography (HPLC) was used to determine concentrations of HP and LP (nmol/mmol creatinine). The average urinary HP concentrations were significantly increased in patients with osteosarcoma ( p=0.001) and chondrosarcoma ( p<0.001), whereas HP remained within the normal range in approximately half of the patients. The average urinary LP concentrations were not increased in osteosarcoma and chondrosarcoma patients as compared with the control group. Further studies in a large group of patients are necessary to evaluate whether HP might be a valuable marker of prognosis, and if its urinary concentration can be correlated to tumour burden.