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PubMed2000

Two primary osteosarcomas in a patient with Rothmund-Thomson syndrome.

Rothmund-Thomson syndrome is an autosomal recessive disorder characterized by poikilodermatous skin changes that develop in infancy. Associated manifestations include juvenile cataracts, sparse hair, short stature, skeletal defects, dystrophic nails and teeth, and hypogonadism. An increased incidence of malignancy, including osteosarcoma, has been reported in patients with Rothmund-Thomson syndrome. The molecular basis of the disorder is not known. This report describes a patient with Rothmund-Thomson syndrome in whom two primary osteosarcomas developed 12 years apart. The presentation, diagnosis, and treatment of osteosarcoma in this patient with Rothmund-Thomson syndrome are described. Cytogenetic and molecular analysis of peripheral blood and skin fibroblasts had low level mosaicism for trisomy of chromosomes 2 and 8. Although several patients have been described with mosaic trisomy 8 and i(2q) (mosaic isochromosome for the long arm of chromosome 2), the patient described here is the first to have mosaic trisomy for the entire chromosomes 2 and 8. The cytogenetic findings in this patient are consistent with an underlying defect in chromosomal stability.

Bone Neoplasms↗

PubMed2001

Selective drug resistant human osteosarcoma cell lines.

Chemotherapy in combination with surgery has been shown to be effective for the control of osteosarcoma. Development of resistance to chemotherapeutic agents is a recurring clinical problem. To investigate this phenomena, human osteosarcoma cells, TE-85, were exposed to increasing doses of Taxol or Taxotere during a 9-month period. Highly resistant subclones (TE-85TXL; TE-85TXR, respectively) were developed. Chemosensitivities are presented for TE-85 cell line and these new lines to Taxol, Taxotere, doxorubicin, cisplatin, and topotecan. Drug concentrations that inhibited cell growth by 50% compared with untreated cells were determined. The TE-85TXL cells showed resistance greater than 1,000-fold to Taxol and Taxotere and 60-fold to doxorubicin. The TE-85TXR cells showed resistance greater than 1,000-fold to Taxol, 800-fold to Taxotere, and 90-fold to doxorubicin. There was little cross resistance to topotecan and enhanced sensitivity to cisplatin. The role of P-170 glycoprotein in Taxol and Taxotere resistance was explored. Coincubation with verapamil, to block the actions of P-170 glycoprotein, partly reversed resistance to Taxol, Taxotere, and doxorubicin in both cell lines. Anti-P-170 glycoprotein antibodies revealed positive staining in TE-85TXL and TE-85TXR cell lines. Flow cytometry revealed reduced accumulation of doxorubicin in resistant cells. These data indicate that a human osteosarcoma cell line will develop resistance to Taxol and Taxotere, which is mediated in part by the P-170 glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Histologic response of high-grade nonmetastatic osteosarcoma of the extremity to chemotherapy,.

In 510 patients with osteosarcoma of the extremity treated at the authors' institute between March 1983 and June 1995 with different regimens of neoadjuvant chemotherapy, factors that influenced the histologic response were investigated. The rate of total necrosis was not related to the patients' gender, age, site, size of tumor, serum of alkaline phosphatase values, or route of cisplatin administration. The histologic response significantly and independently correlated with the number of drugs administered before surgery and with the histologic subtype of the tumor. According to the number of drugs used, the percentage of total necrosis was 31% for a four-drug regimen, 18% for a three-drug regimen, and only 1.5% for a two-drug regimen. According to the histologic type, the rates of total necrosis were 41% for telangiectatic tumors, 36% for fibroblastic tumors, 15% for osteoblastic tumors, and 3% for chondroblastic tumors. The authors concluded that in neoadjuvant therapy of osteosarcoma, the histologic response to preoperative treatment, which correlates with prognosis, depends on the effectiveness of the chemotherapy regimen and on some features intrinsically inherent to the tumor. These data should be considered when selecting the type of treatment (adjuvant or neoadjuvant) and the combinations of drugs to be used in preoperative treatment of patients with osteosarcoma.

Adolescent↗

PubMed2002

Analysis of organ selectivity in the metastatic behavior of Dunn osteosarcoma.

In the current study, the authors established a novel metastatic model to analyze organ selective metastasis by osteosarcoma, using a murine cell line, Dunn osteosarcoma. The lung, liver, kidney, and spleen were resected from syngeneic donor mice, and a tissue fragment of the respective organs was transplanted subcutaneously into a recipient mouse. Two weeks later, tumor cells were injected intravenously and the formation of metastatic deposits in the ectopic transplants was examined. Ectopic lung transplants had a significantly higher incidence of metastasis than either liver or kidney transplants. When enzymatically dispersed organ cells that were embedded in agar gel were transplanted, intravenous injection of tumor cells also resulted in a higher metastatic rate in lung transplants than in either liver or kidney transplants. Photomicrographs and microangiographs of the transplants showed equivalent revascularization of the different organs. Radiolabeled tumor cells were deposited in equivalent amounts in the ectopic transplants of the different organs after intravenous injection. In addition, in vitro growth of tumor cells was stimulated by medium conditioned with lung tissue in a dose-dependent manner. These results suggest that organ selective metastasis by osteosarcoma is not defined anatomically or hemodynamically, but may be caused by tumor cells responding to possible paracrine factors emanating from the lung.

Angiography↗

PubMed1983

The role of time-factor and RBE for the induction of osteosarcomas by incorporated short-lived bone-seekers.

In a large series of experiments, fractionated injections of short-lived bone-seekers have been shown in many cases to cause a remarkable increase of the osteosarcoma incidence compared with a single administration of the same total skeletal dose. This effect has been observed with both alpha- and beta-emitters. In addition the latency period was shortened by protracting the dose. The total skeletal doses investigated ranged between 0.9 and 20 Gy for alpha-emitters (224Ra and 227Th) and between 28 and 112 Gy for the beta-emitter (177Lu). In all cases the protracted dose had higher or at least equal effects when compared with a single application. Reference experiments with long-lived alpha- and beta-emitting bone-seeking nuclides (226Ra and 90Sr) showed that the incidence of osteosarcomas per Gy was sometimes lower than that observed when the same skeletal dose was applied by protraction of short-lived radionuclides. The dependence of osteosarcoma incidence on dose-time distribution, duration of internal irradiation, and radiation quality is discussed. In this context the possibility that the critical initial dose rate may be related to the initiating event within the multi-stage hypothesis of carcinogenesis is considered.

Animals↗

PubMed1997

Osteosarcoma metastatic to the ovary: a case report and review of the literature.

A 23-year-old black woman presented with abdominal pain of sudden onset, high fever, chills, and an elevated serum alkaline phosphatase level. Examination revealed a tender abdominopelvic mass consistent with an ovarian mass. Her medical history was significant for an osteosarcoma of the left humerus removed 7 years earlier and excision of multiple pulmonary and chest wall metastases 2 years earlier. Exploratory laparotomy revealed a solid hemorrhagic left ovarian mass and ascites. There was no other evidence of disease. A left salpingo-oophorectomy was performed. Pathological examination of the mass showed metastatic osteosarcoma. Four months later, the patient died of widespread osteosarcoma. The clinicopathologic features of ovarian osteogenic sarcomas reported in the literature are reviewed. Pain, fever, and elevated serum alkaline phosphatase levels may be the presenting clinical features of this rare ovarian tumor.

Adult↗

PubMedDate not supplied

MRI of extraskeletal osteosarcoma.

We report four cases of extraskeletal osteosarcoma of the thigh to illustrate MRI findings of this rare neoplasm. Calcifications or osteoid material were not discernible in these tumors on MRI or conventional radiography. Three tumors were well demarcated on MRI and corresponded to pseudoencapsulation on radiologic-pathologic correlation. These three tumors were heterogeneous in appearance and were hyperintense to muscle on T1-weighted imaging and demonstrated high signal intensity on T2-weighted imaging. In the fourth tumor, which occupied almost the entire thigh, MRI before and after intravenous gadopentetate dimeglumine administration revealed cystic, hemorrhagic, and solid components. Pathological examination revealed a cystic hemorrhagic cavity containing necrotic and viable tumor and a large solid tumor component. The MRI findings in extraskeletal osteosarcoma are non-specific. However, in the appropriate age group the differential diagnosis of a soft-tissue mass in the thigh should include extraskeletal osteosarcoma, even in the absence of radiographically discernible calcifications or osteoid material within the soft-tissue mass.

Aged↗

PubMed1989

Radiation-induced osteosarcoma of the sphenoid bone.

The case of a patient who developed osteosarcoma in the sphenoid bone 15 years after radiation therapy for a craniopharyngioma is reported. Radiation-induced osteosarcoma of the sphenoid bone has not been reported previously. Reported cases of radiation-induced osteosarcomas are reviewed.

Bone Neoplasms↗

PubMed1988

Uptake of 99Tcm-MDP in lung metastasis from osteosarcoma: clinical and animal studies.

Bone scintigraphy was performed in 17 patients with previously known lung metastases of osteosarcoma. 99Tcm-MDP uptake was observed in all primary bone lesions but lung metastatic lesions were positive in only six patients (35%). 99Tcm-MDP uptake by lung metastases was significantly correlated with bone and osteoid formation in the metastatic lesions and preoperative serum ALPase values. These clinical observations were confirmed by using nude mice transplanted with human lung metastatic osteosarcoma. 99Tcm-MDP scintigraphy appears to be useful for detecting lung metastases of osteosarcoma only in a selected group of patients.

Adolescent↗

PubMed1996

Loss of heterozygosity and microsatellite instability at the retinoblastoma locus in osteosarcomas.

Studies of osteosarcoma cell lines or frozen tissue have detected loss of heterozygosity (LOH) at the retinoblastoma (RB) locus by Southern blot analysis or restriction fragment length polymorphism. Most archived clinical specimens cannot be analyzed by these techniques. We analyzed formalin-fixed, paraffin-embedded samples from 19 cases of osteosarcoma for molecular changes at the RB locus using polymerase chain reaction amplification of polymorphic short tandem repeat sequences (microsatellite repeats). Four repeat sequences, two within and two flanking the RB gene, were analyzed. Fourteen of 18 informative cases (78%) showed molecular changes at the RB locus. LOH was identified in 13 cases (72%). Unexpectedly, microsatellite instability (MI) was found in eight cases (44%). All of the cases of MI involved alterations of more than one repeat unit, and six of eight were associated with LOH. LOH was identified at three unlinked loci in one case and at a single locus in another Microsatellite analysis of archival tissue yields prevalence rates of LOH comparable to those found by other methods and has the added advantage of showing MI. The ability to use formalin-fixed, paraffin-embedded tissue extends genetic analysis to routinely processed surgical material and may permit molecular confirmation of challenging cases of osteosarcoma.

Bone Neoplasms↗

PubMedDate not supplied

Multifocal osteosarcoma in a patient with Fanconi anemia.

PURPOSE: The purpose of this report is to present a case of multifocal osteosarcoma in a patient with Fanconi anemia. PATIENTS AND METHODS: A nine year old girl with known Fanconi anemia presented with a pathologic femur fracture. Imaging studies confirmed soft tissue and bony involvement in the femur, ipsilateral tibia, and possibly contralateral femur. RESULTS: Biopsy and subsequent amputation confirmed the presence of classic osteosarcoma in the involved femur and ipsilateral tibia. The patient died seven months later of pulmonary failure secondary to metastases. CONCLUSION: Fanconi anemia is known to be associated with malignancies such as leukemias. We report a new association of Fanconi anemia with osteosarcoma.

Bone Neoplasms↗

PubMedDate not supplied

Lack of prognostic significance of intratumoral angiogenesis in nonmetastatic osteosarcoma.

BACKGROUND: A need exists to stratify patients with nonmetastatic osteosarcoma into risk subcategories to administer risk-adapted therapy. Intratumoral angiogenesis determined at diagnosis may have a prognostic significance in this malignancy. PATIENTS AND METHODS: The authors performed a retrospective immunohistochemical study on archival pathologic material from patients with nonmetastatic osteosarcoma, excluding patients with purely chondroblastic tumors associated with hypovascularity of the cartilaginous stroma. Representative sections from the diagnostic biopsies were stained with a murine monoclonal antibody directed against CD34, an endothelial cell marker. Two pathologists unaware of the patients' long-term outcome counted microvessels in 10 microscopic fields from the most active areas of neovascularization. RESULTS: Between March 1988 and December 1996, 15 girls and 14 boys (median age 12.6 y, range 4.3-18.3) were identified. Seven patients had died of metastatic disease at a median of 3.4 years (range 0.8-7.4) after diagnosis; 22 were alive with no evidence of disease at a median follow-up of 6.8 years (range 2.7-11.4). There was no significant difference in the number of microvessels per field (pathologist 1, median 19 vs. 18.5; pathologist 2, median 15 vs. 10) between survivors or patients who died of metastatic disease. The correlation between the measurements of the two pathologists was excellent (correlation coefficient 0.87). CONCLUSIONS: Intratumoral neovascularization determined at diagnosis does not correlate with long-term outcome in patients with nonmetastatic osteosarcoma. A prospective study is necessary to confirm these results.

Adolescent↗

PubMed2003

A chemosensitive pediatric extraosseous osteosarcoma: case report and review of the literature.

Osteosarcoma arising in soft tissues is exceedingly rare in children. The tumor most often affects older adults, involves the lower extremity, responds poorly to chemotherapy, and carries a grave prognosis. The authors describe a 12-year-old girl with an extraosseous osteosarcoma of the left sternocleidomastoid muscle with pulmonary metastases. The patient responded well to neoadjuvant chemotherapy and remains disease-free nearly 3 years after her initial diagnosis. The authors review available information about this disease in children and adults. Children with extraosseous osteosarcoma may have a more favorable response to treatment than adults; thus, a curative approach using combined modality therapy appears warranted.

Adolescent↗

PubMed2003

An adolescent with ovarian osteosarcoma arising in a cystic teratoma.

A 14-year-old girl had an abdominal mass with the characteristics of an ovarian germ cell tumor on computed tomography scan. The mass, arising from the left ovary, was completely resected and found to be osteosarcoma arising from a mature cystic teratoma. A metastatic lesion in the abdomen did not respond to 2 courses of cisplatin, doxorubicin, ifosfamide, and high-dose methotrexate, and was resected. Seven months after completion of chemotherapy, there were simultaneous local recurrence and lung metastases. Previously, 10 cases of ovarian osteosarcoma have been reported in the literature: 5 were primary osteosarcoma of the ovary, 4 were associated with teratomas, and 1 was part of a malignant mixed mesodermal tumor of the ovary. Of the 10, there are only 2 long-term survivors, both of whom were treated with adjuvant chemotherapy following complete resection.

Adolescent↗

PubMed2004

Low-voltage electrochemotherapy with low-dose methotrexate enhances survival in mice with osteosarcoma.

Methotrexate plays a key role in adjuvant chemotherapy for treatment of osteosarcoma, but is used at a high dose because it can pass through a cell membrane only with difficulty. Therefore, if the drug delivery of methotrexate to the tumor could be enhanced, antitumor effect and survival would improve. We examined whether enhancement of the antitumor effect of electrochemotherapy was feasible by using low-dose methotrexate in mice with osteosarcoma. The tumor-bearing mice were divided into four groups: no treatment, methotrexate treatment alone, electroporation alone, and methotrexate treatment followed by electroporation. In single-treatment series, the size of the tumors in mice treated with electrochemotherapy decreased substantially 6 days after treatment, whereas continuous growth was observed in the other groups. In the series of treatments repeated three times at 6-day intervals, the original tumors in the electrochemotherapy group decreased consistently and the tumors disappeared in four of seven animals within 16 days. In the other groups, the tumors continued to grow and all host animals died within 58 days. These results show the usefulness of electroporation to enhance the effects of low-dose methotrexate and the potential benefits of electrochemotherapy for the treatment of human osteosarcoma.

Animals↗

PubMed2005

Case report: A rare case of Ewing's sarcoma and osteosarcoma at different sites 10 years apart.

Ewing's sarcoma of bone and osteosarcoma are rare tumors. A combination of high-grade osteosarcoma and Ewing's sarcoma of bone in anatomically unrelated sites is unique, especially in the absence of previous radiation or retinoblastoma. We present a patient with a rare case of Ewing's sarcoma of the scapula that showed no evidence of recurrence (after 10 years of continued followup) and who subsequently presented with a primary osteosarcoma of the femur.

Adult↗

PubMed2005

Case Reports: osteosarcoma of the hand: one case and a literature review.

Osteosarcoma of the hand is rare. We present a case report and a literature review that indicates an older median age of onset than conventional osteosarcoma. The predilection for these lesions to manifest in the metacarpophalangeal joints, particularly in the second and third digits, is in contrast to the more symmetrical distribution of metastatic cancer and correlates with the sites of most active growth during development of conventional osteosarcoma.

Aged↗

PubMed2006

Vascular endothelial growth factor expression in osteosarcoma.

UNLABELLED: Vascular endothelial growth factor expression by osteosarcomas at biopsy has been shown to have a negative influence on survival. Whether it continues to be expressed and influence outcome in tumors after neoadjuvant chemotherapy has not been determined. To determine if a high-degree of vascular endothelial growth factor expression by the surviving osteosarcoma cells in the resected tumor has a negative influence on prognosis, we retrospectively reviewed 52 patients with Stage IIB osteosarcoma around the knee, 48 of whom received neoadjuvant chemotherapy. Vascular endothelial growth factor expression by the surviving tumor cells in the surgically resected specimens was determined by immunohistochemical staining. Followup was for a minimum of 92 months. The presence of vascular endothelial growth factor expression in greater than 25% of tumor cells was independently associated with a reduced overall and disease-free survival rate. LEVEL OF EVIDENCE: Prognostic study, Level II (retrospective study). See the Guidelines for Authors for a complete description of levels of evidence.

Adolescent↗