Search

Morbidity resulting from the toxicity of chemotherapeutic drugs suggests that novel approaches are worthy of investigation. Development of the use of low intensity magnetic fields as an adjuvant to current treatment regimens to prevent metastatic disease may prove to be efficacious. Using a cell culture model, we have developed a magnetic field (MF) treatment that offers the possibility of lowering the therapeutic dose of these drugs and thereby reducing morbidity. Our studies have found that a low intensity (approximately 2 gauss) MF signal and a relatively low dose (0.1 microg/ml) of Adriamycin (ADR) inhibited proliferation of human osteosarcoma cells by 82%, whereas the MF and ADR acting individually caused only 19% and 44% inhibition, respectively.

Tumor-specific chromosomal abnormalities have been identified in several histologic subtypes of sarcomas. Characterization of recurrent chromosomal abnormalities has provided direction for molecular investigations of pathogenetically important genes. Cytogenetic reports of osteosarcoma, the most common primary malignant bone tumor, are relatively rare. In this study, 73 osteosarcoma specimens from 51 patients were cytogenetically analyzed following short-term culture. Clonal chromosomal abnormalities were detected in 47 and included one haploid specimen, 18 near-diploid specimens, 17 near-triploid, 8 near-tetraploid, 1 near-hexaploid, and 2 specimens with multiple clones of different ploidy levels. Examination of the present data and previously published data (111 clonally abnormal osteosarcoma specimens) reveals that chromosomal bands or regions 1p11-13, 1q10-12, 1q21-22, 11p15, 12p13, 17p12-13, 19q13, and 22q11-13 are most frequently rearranged and the most common numerical abnormalities are +1, -9, -10, -13, and -17. Partial or complete loss of the long arm of chromosome 6 also was seen in all cases of the present study and all previously published cases describing structural abnormalities of 6q. Parosteal osteosarcoma, a prognostically favorable osteosarcoma subtype, was characterized by the presence of a ring chromosome accompanied by no or few other abnormalities. Complex karyotypes were seen nearly exclusively in the high-grade lesions. These findings indicate that specific chromosomal bands and/or regions are nonrandomly involved in osteosarcoma and may provide useful clinical information.

To test the hypothesis that fluoride is a risk factor for osteosarcoma, a case control study compared the complete residential fluoride histories of osteosarcoma patients with matched hospital-based controls. Fluoridation was not found to be a risk factor for osteosarcoma in the study population. The trend in the data from this small sample study suggests the hypothesis that a protective effect may exist against the formation of osteosarcoma for individuals consuming fluoridated water.

Three murine hybridomas (TMMR-1-3) were developed by repeated immunizations of mice with four different human osteosarcoma cell lines in an alternating sequence of inoculations. The monoclonal antibodies were screened for reactivities to cultured cell lines and tissue sections of osteosarcomas using flow cytometry and immunohistochemical techniques. TMMR-2 is a highly specific antibody (IgG1) that reacted with all 14 osteosarcoma tumors and eight human osteosarcoma cell lines tested, including the established human osteosarcoma cell lines HOS and Saos-2. Benign neoplastic cells from two osteoblastomas, osteoblasts from regions of reparative osteoid formation and neonatal new bone, are also reactive with TMMR-2. TMMR-1 has mesenchymal specificity while TMMR-3, although reactive with osseous differentiated cells, also reacted with mitotic cells of all cell types. Characterization of antigen structure by Western immunoblotting revealed that TMMR-2 reacted with a 100 degrees C heat labile mercaptoethanol-sensitive Mr 26,000 protein, and TMMR-3 recognized a mercaptoethanol-resistant Mr 97,000 protein whereas TMMR-1 reacted with a series of bands from 65,000 to 85,000 molecular weight, all of which were mercaptoethanol sensitive. TMMR-1 and TMMR-2 monoclonal antibodies showed complement-independent inhibition of [3H]thymidine incorporation into DNA, but did not exhibit cytotoxic activity. The results suggest that TMMR-2 is a specific antibody that recognizes an osteoblast/osteocyte surface antigen present in normal, reactive, and neoplastic disorders of bone. The inhibitory effects on DNA synthesis in cultured osteosarcoma cells by TMMR-2 indicate an important cell growth/proliferation role of this surface antigen. These monoclonal antibodies, in combination with other known antibodies, can be used to characterize mesenchymal cell surface antigenic structure and differentiation.

Malignant bone-forming tumors that arise from the surfaces of long bones are far less common than those that arise from within bone. These surface osteosarcomas are clinically and radiographically similar, yet histologically they are quite distinct. In reviewing the literature, we classified the tumors according to three subgroups: parosteal (juxtacortical) osteosarcoma, periosteal osteosarcoma, and high-grade surface osteosarcoma. We also studied the clinical, radiographic, and histological findings in eighty patients who had been treated for an osteosarcoma over a forty-four-year period. Adequate follow-up data existed for forty-eight of the eighty patients. The duration of follow-up ranged from two to fifteen years after the initial operation (amputation or resection). Patients who had a parosteal osteosarcoma had the best prognosis; those who had a periosteal osteosarcoma, the next best; and those who had a high-grade surface osteosarcoma, the poorest. Because of these widely varying prognoses, the lesions require different treatment.

Early magnetic resonance (MR) experience in the evaluation of 14 consecutive long bone intramedullary osteosarcomas demonstrates the need for T1 and T2 weighted pulsing sequences in the staging of this disease. Intramedullary disease is best depicted by coronal T1 weighted pulsing sequences and subtle extra-compartmental disease by T2 weighted axial imaging. Both high intensity and low intensity intra-medullary signals were noted on T2 weighting, while all T1 weighted pulsing sequences showed intra-medullary disease to have low signal intensity. Extraosseous tumor on T2 weighting usually had a high signal, and disease extent was therefore sharply demarcated from uninvolved muscle and its relationship to vessels confidently assessed. MR appears optimally suited for local staging of osteosarcoma, further enhancing the role of radiology in planning limb-salvage surgical techniques.

In defining the linear extent of a malignant tumor in a long bone, radiographs, computerized tomography, and scintigraphy are routinely employed, especially when non-ablative surgery is being considered. The drawbacks of these modalities in defining the true intracompartmental extent of disease within a bone can largely be overcome with the use of magnetic resonance imaging. We did a prospective analysis of magnetic resonance imaging in sixteen consecutive patients with a primary malignant tumor of a long bone, and it showed that this modality has clinical promise of being more precise than the other modalities in defining the true proximal and distal extent of a tumor in a long bone. Coronal images permit easier planning of surgical techniques for salvage of a limb using an allograft than do a multiplicity of transverse images.

In this review are discussed a small group of bone tumors that present the greatest and sometimes unresolved problems in diagnosis, not only for the clinician but also for the pathologist, even with full knowledge of the clinical and roentgenologic presentation. The following neoplastic lesions are described in detail: cartilage-forming tumors, bone-forming tumors (with special emphasis on aggressive or malignant osteoblastoma), and round-cell tumors of bone. This last group presents a special challenge to the pathologist even after histopathologic examination. Some newer, more sophisticated methods are discussed, especially those applied in the differential diagnosis of Ewing's sarcoma and tumors of neuroectodermal origin.