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PubMed1976

Ceruloplasmin levels in sera from human patients with osteosarcoma.

Ceruloplasmin (Cp) levels in sera of osteosarcoma patients, women on chemical contraceptives, and normal individuals were determined by radial immuno-diffusion (RID) and rocket electroimmunophoresis (REP) techniques; serum copper levels (SCL) were determined by atomic absorption spectroscopy. Ratios of SCL/Cp were constant in all groups tested, indicating that the ratio of bound to unbound copper in the serum is maintained relative to normal levels both in osteosarcoma patients and in women receiving chemical contraceptives. There was a highly significant increase over normal levels in Cp concentration in sera from patients with osteosarcoma and from women on chemical contraceptives, in agreement with our previous data on SCL. Either RID or REP can be used to measure serum Cp. The latter method appears to be faster and more sensitive, whereas the former is easier to perform. It appears that the determination of serum Cp in osteosarcoma patients may be of value in differential diagnosis of the disease in selected patients, and in evaluation of the efficacy of therapy.

Ceruloplasmin↗
PubMed1980

Definitions of osteosarcoma, chondrosarcoma, and fibrosarcoma of bone.

The current definition of osteosarcoma, based on the prescence of tumor osteoid, is unsatisfactory because it fails to identify some examples of chondroblastic, fibroblastic, and anaplastic osteosarcoma having no demonstrable tumor osteoid. The tumor cells in osteosarcoma, whether osteoblastic, chondroblastic, fibroblastic, or anaplastic, contain abundant alkaline phsophatase, whereas this enzyme is scanty or absent in condrosarcoma and fibrosarcoma. It is therefore proposed that these bone sarcomas are best defined according to the origin of the constituent tumor cells and their alkaline phosphatase content: osteosarcoma--a malignant tumor of osteoblasts (alkaline phosphatase positive); chondrosarcoma--a malignant tumor of chondroblasts (alkaline phosphatase negative); and fibrosarcoma--a malignant tumor of fibroblasts (alkaline phosphatase negative).

Alkaline Phosphatase↗
PubMed1980

Intracortical osteosarcoma.

A case of osteosarcoma is described that originated within the cortex of the tibial diaphysis. This form of osteosarcoma was first described by Jaffe as "intracortical osteogenic sarcoma." A review of the literature indicates that this is probably the rarest presenting form of osteosarcoma. It appears to have a predilection for origin in the diaphysis, and its radiologic appearance may mimic a benign lesion. Follow-up information is given on the two cases originally reported by Jaffe, and the tumor is distinguished from periosteal osteosarcoma with which it has recently been confused.

Adolescent↗
PubMed1985

Osteosarcoma resembling osteoblastoma.

A series of 17 patients with osteosarcomas that histologically resembled osteoblastomas was studied. The ages of the 9 male and 8 female patients ranged from 11 to 58 years. The roentgenographic appearance was suggestive of malignancy in most cases. Two histologic features seemed most important in differentiating osteosarcoma from osteoblastoma. In the former, there is permeation of surrounding tissues and lack of "maturation" toward the edges, whereas osteoblastoma tends to show maturation peripherally and is circumscribed. Osteoblastoma-like osteosarcoma should be considered to be a malignant tumor because 7 of the 17 patients died of their disease. The authors believe that malignant osteoblastoma and aggressive osteoblastoma are really osteosarcomas that resemble osteoblastomas.

Adolescent↗
PubMed1987

Osteosarcoma of the urinary bladder. Report of a case and review of the literature.

A 65-year-old man with hematuria had a large polypoid tumor of the urinary bladder which on microscopic examination was an osteosarcoma, only the 22nd example reported in this organ. The tumor was initially misinterpreted as a transitional cell carcinoma because of an absence of osteoid in the initial slide prepared from a biopsy of the neoplasm. Most of the patients with osteosarcoma of the bladder have been male; they have ranged from 41 to 83 (average 62) years of age. The tumors have characteristically been large and polypoid and have most commonly been located in the trigone. Follow-up is available for 21 patients; 18 of them died within 6 months or less. Three patients were still alive 14 months, 18 months, and 2 years postoperatively. Osteosarcoma of the bladder should be distinguished from other bladder tumors that may be associated with bone formation such as carcinosarcomas and transitional cell carcinomas with osseous metaplasia of their stroma, both of which have a better prognosis than osteosarcoma.

Autopsy↗
PubMed1988

Postradiation multicentric osteosarcoma.

The oncogenic effects of radiation are well-established. Osteosarcomas and fibrosarcomas are the two most common histologic types of secondary sarcoma. In this article a case of postradiation osteosarcoma is presented in which four discrete foci of sarcomatous transformation have occurred in the tibia and fibula after irradiation for a rhabdomyosarcoma of the calf 8 years earlier. A review of the literature reveals no similar case. Although synchronous, multifocal osteosarcoma without prior radiation has been described, this case differs in clinical, radiographic, and pathologic features; it best fits the description of postradiation multicentric osteosarcoma.

Bone Neoplasms↗
PubMed1988

Mediastinal osteosarcoma with extension to lungs in a patient treated for Hodgkin's disease.

This article reports a patient with Hodgkin's disease in remission after combined modality therapy who developed metastatic pulmonary osteosarcoma, subsequently found to originate in soft tissue of the mediastinum, within a field irradiated 11 years previously. This patient developed a series of radiotherapy-induced complications in addition to osteosarcoma. Only 16 cases of extraskeletal osteosarcoma after radiation treatment have been reported, none originating in the mediastinum. To the authors' knowledge, this is the first reported case of extraskeletal osteosarcoma occurring in a patient previously treated for Hodgkin's disease and with the sarcoma originating within the irradiated field.

Adult↗
PubMed1990

Osteosarcoma of the maxilla in Hong Kong Chinese postirradiation for nasopharyngeal carcinoma. A report of four cases.

Postirradiation osteosarcoma of the maxilla was seen in four Hong Kong Chinese patients treated for nasopharyngeal carcinoma. These cases represent four of 42 (9%) cases of osteosarcoma at all sites in this institution during the period 1979 to 1989, when more than 1000 patients were treated with radiotherapy for nasopharyngeal carcinoma. The latent periods varied from 8 to 11 years from completion of radiotherapy treatment to development of osteosarcoma. The radiation dosage varied from 6000 to 6280 cGy in three of the patients. These cases fit the criteria for diagnosis of postirradiation sarcomas. Maxillary osteosarcomas after irradiation for nasopharyngeal carcinoma do not appear to have been described. The very high incidence of nasopharyngeal carcinoma (for which radiotherapy is the treatment of choice) in Hong Kong Chinese would make the occurrence of such tumors more likely in Hong Kong, although the small risk does not contraindicate the use of radiation in the treatment of nasopharyngeal carcinoma in view of its well-documented efficacy.

Adult↗
PubMed1991

Osteosarcoma in young children.

The clinicopathologic features of osteosarcoma in 12 children younger than 16 years of age treated at The Children's Hospital and Dana-Farber Cancer Institute, Boston, during a 70-year time period are presented. Only one of six children treated before 1972 is a long-term survivor. Four of six children (67%) treated after 1972 are disease-free with an average follow-up of 8.8 years. The year 1972 marked the onset of use of effective chemotherapy in osteosarcoma, namely, high-dose methotrexate and leucovorin rescue. It would appear that the pathologic features and behavior of osteosarcoma in young children is similar to that of osteosarcoma in older children and adolescents. A combination of complete (wide) surgical resection or amputation and aggressive chemotherapy offers the best chance of long-term survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Spontaneous regression of lung metastases from osteosarcoma.

BACKGROUND: Spontaneous regression of malignancy is infrequent, but in osteosarcoma, such occurrence is extremely rare. Through a survey of many university hospitals and cancer centers in Japan, two patients with such regression were found. METHODS: In both patients, radiograms of the primary sites and histologic specimens were studied carefully for accurate diagnosis. The clinical records, serum alkaline phosphatase values, and changes in the pulmonary metastasis on chest radiograms were followed for 26 years and 13 years, respectively. In the second patient, metastatic lesions were studied histologically. RESULTS: The patients, a 19-year-old man and an 11-year-old boy each with osteosarcoma in the distal femur. Each was treated by amputation. Pulmonary metastases were found on routine checkup 5 months and 12 months after the surgery, respectively, despite adjuvant chemotherapy. The metastatic nodules of both patients became denser and smaller 12 and 5 months, respectively, after detection, and the alkaline phosphatase concentration returned to normal, without special treatment. To date, the patients are alive and well. In the second patient, histologic examination of the metastatic nodules showed no remarkable infiltration of lymphocytes that would suggest an immunologic response; however there was florid bone formation indicating maturation of the tumor cells. CONCLUSION: Cases that have been reported as spontaneous regression of pulmonary metastases from osteosarcoma often show equivocal pathologic or clinical signs, and some have shown only temporary regression of the lesions. The two patients presented here are unique, however, because they had a definite diagnosis of osteosarcoma and showed extraordinarily long-lasting regression, which presumably occurred spontaneously, not as a direct effect of chemotherapy.

Adult↗
PubMed1995

A review of 40 patients with extraskeletal osteosarcoma.

BACKGROUND: Extraskeletal osteosarcomas are rare malignancies that account for about 1% of all soft tissue sarcomas. Few large series have been reported. METHODS: Clinical records and histologic slides of all patients with extraskeletal osteosarcomas treated at the Mayo Clinic between 1915 and 1988 were reviewed. RESULTS: The study group consisted of 40 patients, most of whom presented in the sixth and seventh decades of life (mean age, 50.7 years). There was a male predominance (male-to-female ratio, 1.9:1). The lower limbs most commonly were involved (68%), usually the thigh and buttock regions. Ninety-three percent of tumors presented as an enlarging soft tissue mass, with a history of trauma in nine patients. In nine patients, the lesions were initially interpreted histologically as benign, most commonly as myositis ossificans. Histologically, all were high grade osteosarcomas. Multiple local recurrences (45%) are a feature of this tumor. All recurrences occurred within 3 years. Distant metastasis (65%) is also common and is usually to the lungs (81%). Radical resections appear to be the best option for local control, with resection of the pulmonary metastasis occasionally producing a cure. By univariate analysis of Kaplan-Meier survival curves, the patients with predominantly chondroblastic tumors fared better than those with predominantly osteoblastic tumors (P = 0.03). Analysis of survival differences of the three main subtypes together (osteoblastic, chondroblastic, and fibroblastic) was not significant. A small-sized initial lesion did not equate with better survival. Seventy-three percent died of the disease, with a mean follow-up of 5.9 years. CONCLUSION: Extraskeletal osteosarcoma is a high grade malignant tumor associated with a 5-year survival rate of 37% (95% confidence interval, 28%-59%). Local recurrences and distant metastasis are common and usually occur by 3 years after excision. Patients with the chondroblastic subtype survive longer than those with the osteoblastic subtype.

Adult↗
PubMed2001

Amplification of the HER-2/neu oncogene is uncommon in pediatric osteosarcomas.

BACKGROUND: Recent reports have described overexpression of p185(c-erbB2), the product of the HER-2/neu oncogene, in more than 40% of archival osteosarcomas that were examined by immunohistochemistry (IHC). However, IHC can be influenced by the method of fixation, extent of antigen retrieval, specificity and sensitivity of the antibody clone, and the use of an arbitrary semiquantitative scoring system. In contrast, fluorescence in situ hybridization (FISH) assays that assess HER-2/neu gene copy numbers in individual cells are more consistent, more reproducible, and less subjective than IHC. METHODS: The authors examined pretreatment nondecalcified archival tissue from 21 high-grade pediatric osteosarcomas for amplification of the HER-2/neu oncogene using an Food and Drug Administration (FDA)-approved FISH assay (PathVysion, Vysis Inc., Downers Grove, IL). Additionally, IHC for p185(c-erbB2) was performed in all cases using the Dako polyclonal antibody clone A0485 (Dako Co., Carpinteria, CA). RESULTS: None of the 21 osteosarcomas had evidence of HER-2/neu gene amplification by FISH, whereas p185(c-erbB2) IHC was negative in all cases. CONCLUSIONS: HER-2/neu gene amplification appeared to be an uncommon event in pediatric osteosarcomas. The reason(s) for discordance between previous IHC data and the current FISH and IHC results was unknown, but might reflect intrinsic variations in antibody clones, or might suggest that, in some cases, the occurrence of protein overexpression is independent of gene amplification.

Bone Neoplasms↗
PubMed2003

Reduced folate carrier protein expression in osteosarcoma: implications for the prediction of tumor chemosensitivity.

BACKGROUND: High-dose methotrexate (MTX) is an important component of current protocols for the treatment of osteosarcoma. Although MTX uptake proceeds primarily through the reduced folate carrier (RFC) protein and efflux occurs via multidrug resistance protein 1 (MRP1), RFC protein expression in osteosarcoma remains unexamined. METHODS: RFC and MRP1 expression (normalized to beta-actin expression) was examined with Western blot analysis in 11 osteosarcoma specimens obtained at diagnosis and 9 osteosarcoma specimens obtained on recurrence. RESULTS: The average RFC level in specimens obtained on recurrence was significantly higher than the level in specimens obtained at diagnosis (P = 0.0005). Furthermore, in all three matched pairs of diagnosis and recurrence specimens, RFC levels were higher in recurrence specimens than in the corresponding diagnosis specimens. Potential correlations between RFC and MRP1 expression and histologic response to preoperative chemotherapy were examined. Tumors with poor histologic responses (i.e., </= 90% necrosis) had significantly lower RFC levels than did those with favorable responses to chemotherapy (P = 0.0016). In contrast, there was no correlation between MRP1 levels at diagnosis and histologic response to chemotherapy (P = 0.8764). The elevated MRP1 levels in specimens obtained on recurrence relative to MRP1 levels in specimens obtained at diagnosis were not statistically significant (P = 0.2056). CONCLUSIONS: The significant correlation between low RFC levels at diagnosis and poor histologic response to preoperative chemotherapy suggests that RFC levels at diagnosis may be a useful predictor of chemosensitivity and warrants large-scale studies. In addition, postchemotherapy progression to recurrence is associated with a significant increase in RFC expression. To our knowledge, the current study is the first to examine RFC protein levels in tumor specimens. Cancer 2003.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Outcome after local recurrence of osteosarcoma: the St. Jude Children's Research Hospital experience (1970-2000).

BACKGROUND: Despite improvements in therapy for osteosarcoma, approximately 4-10% of patients experience a local recurrence and have a poor prognosis. METHODS: The authors analyzed prognostic factors for survival in 26 patients with a local recurrence of osteosarcoma who were treated between 1970 and 2000. RESULTS: The initial surgical procedure was amputation in 20 patients (76.9%) and limb salvage in 6 patients (23.1%). The median time from the diagnosis of osteosarcoma to local recurrence was 1.2 years (range, 1.2 months-6.1 years). Eleven patients (42.3%) developed an isolated local recurrence and 15 patients (57.7%) developed local and distant recurrence. The 5-year estimate of postrecurrence survival (PRS) (+/- 1 standard error) for the 26 patients was 19.2% +/- 7.7%. Recurrence > or = 2 years from the time of diagnosis was found to predict a better outcome (5-year PRS of 50.0% +/- 20.4%) compared with earlier recurrence (10.0% +/- 5.5%) (P = 0.037). Patients with negative margins after initial surgery were found to have improved survival (5-year PRS of 33.3% +/- 13.6%) compared with patients with positive margins (7.1% +/- 4.9%) (P = 0.015). Patients who underwent complete surgical resection at the time of recurrence were found to have a better PRS (5-year PRS of 41.7% +/- 14.2%) compared with patients who did not undergo surgery (0% +/- 0%) (P < 0.001). CONCLUSIONS: The prognosis for patients after local recurrence of osteosarcoma is poor. Complete surgical resection at the time of recurrence is essential for survival. Positive margins at the time of initial surgical resection and early recurrence appear to be poor prognostic factors.

Adolescent↗
PubMed2006

Metastatic osteosarcoma.

BACKGROUND: The outcome of patients with metastatic osteosarcoma treated in two consecutive trials from 1986 to 1997 was analyzed to evaluate the efficacy of carboplatin-based multiagent chemotherapy and to identify prognostic factors. The initial study (OS-86) used ifosfamide, cisplatin, doxorubicin, and high-dose methotrexate, and the subsequent study (OS-91) used the same agents at similar doses, but carboplatin was substituted for cisplatin. METHODS: Twelve patients (median age, 15.1 yrs) were treated in OS-86 for osteosarcoma metastatic to the lung only (11 patients) or bone only (1 patient), and 17 patients (median age, 15.1 yrs) were treated in OS-91 for osteosarcoma metastatic to the lung only (12 patients), bone only (2 patients), lung and bone (2 patients), or other site (1 patient). RESULTS: Patients with metastatic disease enrolled in OS-86 and those with metastatic disease enrolled in OS-91 did not differ in terms of demographic features, histologic subtype, site of primary tumor, or site of metastases. There was a difference in survival according to treatment protocol (P = 0.054). All survivors (four of whom were enrolled in OS-86 and one of whom was enrolled in OS-91) had lung metastases only. Five-year survival estimates for patients with lung metastases only were 45.5 +/- 13.7% (OS-86) and 8.3 +/- 5.6% (OS-91) (P = 0.084). Unilateral lung metastases (P = 0.006), no more than three lung nodules (P = 0.014), and surgical remission (P = 0.001) were associated with improved survival probability. CONCLUSIONS: The poor outcome of patients with metastatic osteosarcoma treated in OS-91 justifies the use of cisplatin with its associated toxicity in patients with high-risk disease.

Adolescent↗
PubMed2002

Utility of fine-needle aspiration in the diagnosis of primary osteosarcoma.

Fine-needle aspiration (FNA) is a reliable, safe, and cost-effective procedure with a well-established role in the diagnosis of various solid tissue neoplasms. The role of FNA in the diagnosis of primary bone tumors, including osteosarcoma (OGS), is controversial and has yet to be established. We reviewed our experience with the use of FNA as a diagnostic technique over the past 8 yr at our institution. Diagnosis was conclusive in 26 (65%) of 40 patients, 18 of whom went to neoadjuvant therapy and/or resection based solely on the FNA interpretation of either "high grade sarcoma" or "osteosarcoma." Of the remaining 14 (25%) patients, 12 had inconclusive diagnosis and two (5%) were false-negatives. An inconclusive diagnosis was most likely to be an inadequate or paucicellular aspirate, seen in six (15%) patients. An additional six patients had variants of osteosarcoma (four chondroid, one "giant cell rich," one parosteal) that made definitive diagnosis impossible. The two that were incorrectly classified were diagnosed as fracture callus and plasmacytoma. FNA is an accurate and cost-effective tool for the initial diagnosis of primary osteosarcoma with a sensitivity of 65% and accuracy of 95%. Inconclusive diagnoses are likely to be due to insufficient sample cellularity or the presence of OGS variant. In our experience, FNA is sufficient to provide the diagnosis of OGS prior to definitive treatment when interpreted in conjunction with imaging studies and clinical findings. In those cases where FNA fails to yield a diagnostic sample, a traditional biopsy can be performed.

Adolescent↗
PubMed2005

Osteosarcoma metastatic to adrenal gland diagnosed by fine-needle aspiration.

Osteosarcoma, a primary malignant tumor of the long bones, frequently metastasizes to the lungs. We report an unusual case of osteosarcoma metastatic to the right adrenal gland in a 37-yr-old male who presented 8 yr after remission with an adrenal mass. A preoperative diagnosis was made by fine-needle aspiration (FNA) biopsy. FNA biopsy revealed pleomorphic oval cells with prominent nucleoli, spindle cells, and giant tumor cells. Diagnostic osteoid was readily seen on smears and was also detected by polarization of cell-block section. Immunocytochemical stains revealed positivity of tumor cells for vimentin and osteonectin. Cytokeratin stains were negative. The cytologic diagnosis of metastatic Osteosarcoma was made, which was later confirmed upon resection of tumor by histology. Although the role of FNA in the diagnosis of primary bone tumors, including osteogenic sarcoma (OGS), remains controversial, this case, however, demonstrates the value of FNA biopsy combined with immunocytochemistry performed on the aspirated material in diagnosing osteosarcoma from an unusual location such as the adrenal gland.

Adrenal Gland Neoplasms↗
PubMed2003

Identification of drug-regulated genes in osteosarcoma cells.

The introduction of systemic chemotherapy improved significantly the prognosis of osteosarcoma. Despite this success, approximately 30-40% of patients will relapse. Cytotoxic drugs have been shown to induce apoptosis in the target cells independent of their primary effects. The underlying molecular mechanisms and the intracellular mediators, however, are still largely unknown. Therefore, the purpose of our study was to identify drug-regulated genes in osteosarcoma cells useful as prognostic factors and for the development of new therapeutic strategies. Using suppressive subtractive hybridization (SSH) the gene expression pattern of untreated Saos-2 cells was compared to cells treated with cisplatin, methotrexate and doxorubicin, respectively. We identified 8 genes that are regulated >2-fold in drug-treated osteosarcoma cell lines. Expression of ferritin light chain, rhoA, inosine monophosphatdgehydrogenase II, ribonucleotide reductase M2, pro2000 and pro1859 were increased after drug treatment, whereas prohibitin and alpha-actinin expressions were significantly downregulated. Differential expression of the identified genes was verified by Northern blot analysis of 3 different osteosarcoma cell lines. In addition, the effects on chemosensitivity of 4 selected genes was analyzed by overexpression of recombinant constructs in Saos-2 cells and subsequent quantification of drug-induced apoptosis. Overexpression of prohibitin and rhoA reduced significantly drug sensitivity to approximately 52% and 59% indicating a crucial role in the modulation of drug-induced cell death.

Actinin↗