Osteogenic sarcoma of the breast. A case report.

A case of primary osteogenic sarcoma of the breast is reported. It should be distinguished from carcinoma with extensive osseous metaplasia. The results of light and electron microscopy including an immunohistochemical study are presented. Immunohistochemical and ultrastructural studies proved that the lesion, in the absence of epithelial differentiation, was a primary osteogenic sarcoma of the breast rather than a carcinoma with extensive osseous metaplasia. Diagnosis may be delayed because the tumor is confused clinically and mammographically with a calcific fibroadenoma.     

Metastasis of sarcomatous lesion in regional lymph node

This is a retrospective study of 390 patients with early sarcoma admitted over a 13-year period. There were 182 bone lesions, 173 soft tissue sarcomas, and 35 visceral sarcomas. Two hundred ninety-two patients had surgical resections, and 77 had specimens of lymph node(s) examined histologically. Among the latter group, 6 of 47 patients with non-osseous sarcomas (13%) had metastasis in the regional node initially (subtypes include fibrohistiocytoma, leiomyosarcoma, rhabdomyosarcoma; synovial, anaplastic, and Kaposi sarcoma). Another two patients developed nodal metastasis subsequently (rhabdomyosarcoma). Among the 30 patients with skeletal sarcomas who had lymph nodes removed during resection, one case with osteogenic sarcoma and one chondrosarcoma had nodal metastasis initially (7%). During follow-up, one patient with Ewing's sarcoma and another with chondrosarcoma developed regional lymphadenopathy. Our findings are discussed and compared with incidences of metastatic sarcomatous lesion in lymph node reported in the literature.     

Effect of interferon administration on pulmonary osteogenic sarcomas in an experimental murine model

The iv inoculation of a suspension of osteogenic sarcoma cells induced metastatic tumor nodules in the lungs of C57BL/6 mice. The administration of 50,000-100,000 U of interferon daily for 7 days strikingly reduced the tumor mass in the lung and the number of tumor nodules present in histopathologic sections when the interferon treatment was initiated immediately after tumor cell inoculation. In some animals the development of any detectable metastatic lesion was completely prevented. Extending the therapy form 7 days to 21 days failed to improve the protective effect. Interferon therapy delayed until 7 days after tumor cell inoculation had no effect. These findings indicate the effectiveness of exogenous interferon in this murine osteogenic sarcoma model when interferon treatment is initiated within 1 hour of tumor cell inoculation, but not when it is delayed until tumor nodules are established in the lungs.     

The significance of bone scan abnormalities in patients with primary osteogenic sarcoma

The radionuclide bone scans and medical records of 62 patients with osteogenic sarcoma were reviewed to determine the significance of abnormalities demonstrated by the initial scintigraph at sites other than the primary lesion. 94% (58/62) of patients had abnormally increased tracer uptake at sites other than the primary tumor location. Eighty percent (49/62) of patients had abnormal bone scans at the ipsilateral proximal weight bearing joints. Only two of these patients later demonstrated metastatic tumor. Sixty-one percent (38/62) of patients had abnormal bone scans at joints distal to the primary tumor and none were due to tumor. Five patients ultimately developed osseous metastases at sites that were normal in the original scan. The majority of radionuclide bone scan abnormalities occurring at the time of diagnosis of osteogenic sarcoma at locations distant from the primary tumor site do not represent metastatic disease.     

Osteogenic sarcoma of the maxilla: neutron therapy for unresectable disease

Purpose. To present a case study involving the use of fast neutron therapy to treat an extensive unresectable osteogenic sarcoma arising from the left maxilla.Patient. A 14-year-old male presented with a massive tumor producing severe distortion of his facial structures. He had already received six courses of chemotherapy, which had reduced his pain, but had not measurably reduced the tumor.Methods. The patient was treated with 66 MeV fast neutrons to a dose of 20.4 Gy in 13 fractions over 35 days.Results. CT assessments indicate gradually increasing calcification and noticeable reduction of soft-tissue disease in the frontal sinus, orbit and maxillary antrum.There has been some recontouring of the facial structures.The boy conducts an active life, has no pain, and feels well. He was 17 years old at the last follow-up.Discussion. Fast neutrons have a greater biological effectiveness than conventional photon beams. Their use has been associated with improved chance for local control of unresectable disease.This case illustrates their effectiveness in controlling an unusual and aggressive osteogenic sarcoma of the facial bone and sinuses.     

Osteogenic sarcoma associated with Paget's disease of bone. A clinicopathologic study of 65 patients

Among 1177 osteogenic sarcoma patients diagnosed and treated at Memorial Hospital, 65 (5.5%) were associated with either monostotic or polyostotic Paget's disease. The overall median age was 64 years (range, 39-82 years). In those patients older than 40 years of age, the frequency of sarcomatous transformation rose to 27%. There were slightly more men (55%) than women. The most common skeletal sites were the pelvic bones (34%), the humerus (22%), the femur (19%), and the craniofacial bones (14%). Unrelenting pain and tender swelling were the most common presenting symptoms (85%), with pathologic fracture in 14 (22%) patients. In two-thirds of the cases, the radiographic presentation was that of a lytic destructive lesion; while in the others it showed a sclerotic, mixed, or permeative character. In almost one-half of the cases, the histologic appearance of the osteogenic sarcomas was either fibrohistocytomatous or osteoblastic. In spite of radical surgical amputations, only three patients survived longer than 5 years. The prognosis of Paget's sarcoma is significantly less favorable than in osteogenic sarcoma arising de novo in patients of comparable age.     

Lung resection for metastatic osteogenic sarcoma.

Osteogenic sarcoma, excluding the paraosteal osteosarcoma, has a grave prognosis, half of the patients dying within 1 year following ablative surgery of the primary lesion. Once pulmonary metastasis is detected, most patients do not survive more than 3 years. Various attempts by investigators to prolong patient survival, including surgery, chemotherapy, immunotherapy, radiation therapy, and combined modalities, have met with some success. This report is a summary of 13 patients who underwent lung resections and received adjuvant chemo- and/or immunotherapy for metastatic osteogenic sarcoma in our intstitute in the past 7 years.     

Influence of doxorubicin dose intensity on response and outcome for patients with osteogenic sarcoma and Ewing's sarcoma.

The goal of this study was to use dose-intensity analyses of published Ewing's sarcoma and osteogenic sarcoma trials to determine which agents were most closely associated with a favorable response. The percentage of patients with more than 90% tumor necrosis following neoadjuvant chemotherapy was the end point for analysis of osteogenic sarcoma trials, and disease-free survival and percentage of patients with distant-only relapse were the end points for analysis of Ewing's sarcoma trials. The data were analyzed using logistic regression analysis to circumvent the distortion of univariate analysis resulting from the correlation between doxorubicin dose intensity and the dose intensity of other agents. Our analysis suggests that doxorubicin dose intensity is an important determinant of favorable outcome for both Ewing's sarcoma and osteogenic sarcoma and that the dose intensities of other agents do not contribute as significantly to outcome as does doxorubicin dose intensity. Increasing dactinomycin dose intensity was associated with a poorer outcome in treatment of osteogenic sarcoma and Ewing's sarcoma, most likely resulting from regimens with a higher dactinomycin dose intensity having a lower doxorubicin dose intensity. While our analysis of osteogenic sarcoma trials is consistent with significant activity for cisplatin and high-dose methotrexate (and likely ifosfamide), a rank ordering of the efficacy of these agents when given with doxorubicin in multiagent regimens is not possible. Our analysis illustrates the importance of analyzing the contributions of individual agents to combination chemotherapy regimens. In the design of future clinical trials for osteogenic sarcoma and Ewing's sarcoma, careful attention should be given to optimizing doxorubicin dose intensity in regimens to be tested.     

Combination chemotherapy with bleomycin, cyclophosphamide and dactinomycin for the treatment of osteogenic sarcoma.

Thirteen patients with osteogenic sarcoma were treated with multiple drug chemotherapy consisting of bleomycin, cyclophosphamide and dactinomycin. The dosage schedule used was: bleomycin 12 mg/m2/day, cyclophosphamide 600 mg/m2/day, and dactinomycin 450 microgram/m2/day. All drugs were given intravenously for two consecutive days. Treatment was repeated every 2 weeks. Toxicity included severe nausea and vomiting (managed with antiemetics and intravenous hydration) and manifestations of bone marrow depression. Of 13 patients, eight were previously treated with high dose methotrexate with citrovorum factor rescue, cyclophosphamide and Adriamycin. Of these eight, three patients had objective evidence of tumor regression (37.5%). Five of five previously untreated patients had objective evidence of tumor regression. The overall response rate in osteogenic sarcoma patients to BCD was 61.5%. The combination of BCD appears to be more active against osteogenic sarcoma than cyclophosphamide alone or Adriamycin alone. The relative safety with which BCD can be administered makes this combination a valuable adjunct to high dose methotrexate with citrovorum factor rescue and Adriamycin in the treatment of osteogenic sarcoma.     

Parosteal osteogenic sarcoma.

A clinicopathologic study of 79 patients with parosteal osteogenic sarcoma revealed that more females than males were affected and that most of the patients were in the second to the fourth decades of life. Sixty-eight percent of the patients had involvement of the posterior aspect of the lower femoral shaft. The roentgenogram characteristically showed a large, dense lobulated mass attached by a broad base to the underlying bone but with no involvement of bone itself. Microscopically, the tumor presented as well-formed bands of osteoid within a hypocellular spindle cell stroma. Seven of the lesions had foci of high-grade osteogenic sarcoma within an otherwise typical parosteal osteogenic sarcoma. Six of the 79 lesions showed involvement of the medullary cavity at surgery. Thirty-one patients had excision as their initial treatment; four of the 31 required nv further therapy. Ten patients had resection initially; three of the ten had recurrence. Only four of 27 patients who underwent amputation initially developed pulmonary metastasis. The presence of histologically "active" tumor and medullary involvement seemed to affect the prognosis adversely. Our data indicate that complete radical removal of the tumor is the treatment of choice, with resection when feasible and amputation when necessary.     

Regional chemotherapy with the use of cisplatin and doxorubicin as primary treatment for advanced sarcomas in shoulder, pelvis, and thigh

Eight patients who had large sarcomas in the hip, thigh, or shoulder girdle have been described. Three had osteogenic sarcomas, and one each had Ewing's sarcoma, biphasic synovial sarcoma, pleomorphic liposarcoma, undifferentiated spindling sarcoma, and malignant fibrous histiocytoma. All eight tumors showed evidence of regression after intraarterial infusion of cisplatin and Adriamycin (doxorubicin) given over 48 hours at 3-week intervals, for a total of between three and seven courses. Tru-cut needle biopsy specimens of five of the lesions were normal after chemotherapy. However, after resection of the regressed fibrotic tumor in seven of the patients, four contained foci of probably viable malignant cells. These cell foci were intraosseous in three cases and in the wall of a cyst in one case. In the remaining case, tumor in the distribution of the infused artery regressed, but tumor in a region supplied by an artery that was not infused continued to enlarge. In one patient with osteogenic sarcoma in the pelvis, despite a good response to intraarterial chemotherapy that was followed by surgical resection and radiotherapy, tumor recurred in an adjacent area in tissues supplied by an artery not infused. A hindquarter amputation subsequently was required. With the exception of the two cases in which adequate tumor arterial infusion was not achieved, local primary tumor control was accomplished by intraarterial infusion chemotherapy followed by local resection or radiotherapy and local resection in all patients. Four patients are well without evidence of residual or metastatic sarcoma 3.5 years after presentation in the case of an osteogenic sarcoma of shoulder, 2.5 years after presentation in the case of a large pleomorphic liposarcoma of thigh and groin, 20 months after presentation in the case of lower-thigh malignant fibrous histiocytoma, and 1 year after presentation in a child with an osteogenic sarcoma of lower femur.     

The characteristics of eicosanoid synthesis in osteogenic sarcoma in children at puberty]

Levels of prostaglandin E (PGE), prostaglandin F2 alpha, prostacyclin A2, thromboxan B2 and leucotriene B4 assayed radioimmunologically were compared in 42 samples of osteogenic sarcoma and 22 samples of benign tumors and tumor-like lesions from children at the pubertal period. In osteogenic sarcoma samples, PGE and prostaglandin F2 alpha levels were higher than those of thromboxan B2, prostacyclin A2 and leucotriene B4. Osteogenic sarcoma revealed higher levels of the eicosanoids as compared to benign tumors and tumor-like lesions of the bone. An inverse correlation was established between PGE level and time of dissemination of osteogenic sarcoma. The role of eicosanoids in the pathogenesis of growth and dissemination of osteogenic sarcoma is discussed. The use of non-steroid anti-inflammatory drugs in complex treatment of osteogenic sarcoma of children at the pubertal period is suggested.     

Sex and pituitary hormone secretion in adolescents with osteogenic sarcoma and retarded sexual development]

Basal levels of secretion of total testosterone, estradiol-17 beta, their free, albumin-binding and sex steroid-binding globulin (SSBG)--binding fractions, luteinizing hormone, follicle-stimulating hormone, prolactin and somatotropic hormone were measured in blood serum in the following groups of adolescents: (1) healthy, (2) suffering primary osteogenic sarcoma of the bone, (3) osteogenic sarcoma patients with pubertal retardation, and (4) pubertal retardation. A significant increase in total testosterone fraction, free androgen index and a decrease in blood SSBG level were established in osteogenic sarcoma patients as compared to corresponding controls, irrespective of pubertal status. No difference in the above indexes for estrogens was established between osteogenic sarcoma patients and controls in both pubertal status subgroups. The role of sex steroid hormones, particularly, androgens in the pathogenesis of osteogenic sarcoma is discussed.     

Osteogenic sarcoma in pregnant women. Prognosis, therapeutic implications, and literature review

This study of 18 pregnant women with concomitant osteogenic sarcoma of bone analyzes the important assertion whether this sarcoma and pregnancy have an adverse interaction. For comparison we matched the pregnant osteogenic sarcoma patients with nonpregnant women with the same skeletal tumor location and histologic appearance as well as similar age distribution. There was no worsening of prognosis of pregnant osteogenic sarcoma patients, and neither the pregnancy nor the disease appeared to act adversely toward the other. The 18 pregnant women with osteogenic sarcoma fared no better (nor worse) than the nonpregnant women with osteogenic sarcoma.     

脑部恶性纤维组织细胞瘤1例报道

Malignant fibrous histiocytoma (MFH) firstly described as "malignant fibrous xanthoma" by O'Brien and Stout in 1964, is the most common soft tissue sarcoma of late adult life. Uncertain histogenesis and numerous subtypes make MFH a rather controversial entity. MFH only rare arises from structures of the head and neck. When it does, it most often originates in facial structures, particularly the maxilla. This report details a case of a patient with malignant fibrous histiocytoma presenting clinically as a right-sided large indurated frontoparietal mass, three months after head trauma and eight years after radiation therapy for brain lymphoma located in the right frontal and parietal lobes. Radical excision was a surgical challenge because of the extensiveness of the lesion.     

华蟾素对MG-63骨肉瘤细胞杀伤作用的实验研究

目的探讨华蟾素（cinobufagin）对人骨肉瘤细胞株MG-63的促凋亡作用。方法采用MTT比色法、透射电镜观察、原位末端标记tunnel法、流式细胞仪检测等方法,观察和检测华蟾素对MG-63的促凋亡作用。结果华蟾素对MG-63骨肉瘤促凋亡作用明显,且呈现时间和浓度依赖性。华蟾素将MG-63细胞阻断在S期,可诱导骨肉瘤细胞凋亡。与甲氨蝶呤对照组相比,不同浓度下华蟾素对MG-63细胞促凋亡作用更显著。结论华蟾素对MG-63骨肉瘤促凋亡明显。华蟾素可用于骨肉瘤治疗。     

Incidence of regional lymph node metastasis in operable osteogenic sarcoma

Records of 182 consecutive patients with the diagnosis of operable osteogenic sarcoma, treated between 1954 through 1980 by the Breast, Bone and Mixed Tumors Department of the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru), were reviewed to study the incidence of regional lymph node metastases in this disease. All the patients included in this study had radical surgery, which means the complete resection of the bone where the tumor is located, including the proximal joint, which permitted excision of the regional lymph nodes. Nineteen patients (10.4%) had evidence of sarcoma metastatic to draining lymph nodes. A comprehensive analysis of the literature shows that the incidence of metastasis to the lymph nodes in this study, is higher than those cited in a review of the literature, probably due to the policy in the management of osteogenic sarcoma in our institution, during the period of study.     

The combination treatment of malignant bone tumors using fast neutrons

The study deals with results of a clinical trial evaluating treatment efficacy of a 6 MeV neutron beam produced by Y-120 cyclotron (Kiev). Procedures of preoperative radiotherapy and radical treatment are discussed. Radiotherapy was administered to 52 patients suffering chondrosarcoma (30 cases), osteogenic sarcoma (15) or chordoma (7). Combined treatment (radiation + surgery) was given to 22 patients whereas neutron beam therapy--to 30. All patients with osteogenic sarcoma received adjuvant combination chemotherapy. Three-year survival rate was compared to that observed in controls in whom combined treatment had included gamma-therapy. A significant increase in three-year survival rate was observed for osteogenic sarcoma and chordoma whereas for chondrosarcoma the improvement in survival proved insignificant. The use of fast neutrons in combined treatment of bone tumors was considered promising.     

Unifocal Langerhans’cell histiocytosis (eosinophilic granuloma) resembling Ewing's sarcoma

In a 9 year old boy, a destructive lesion in the diaphysis of the right femur was wrongly diagnosed as a Ewing's sarcoma on the basis of the radiologic findings and fine needle aspiration cytology report. The clinical and radiologic picture was suggestive of Ewing's sarcoma, but an open biopsy of the lesion revealed a histopathological picture of eosinophilic granuloma. A brief review of the literature is given, together with discussion on the differential diagnosis of a mid shaft femoral lesion in young patients.     

Sarcoma Following Irradiation for Breast Cancer: Report of Three Unusual Cases Including One Malignant Mesenchymoma of Bone

Three cases of sarcoma developing after irradiation for breast cancer are reported. A malignant mesenchymoma in the sternum—a combination of osteogenic sarcoma and rhabdomyosarcoma—is the first documented case of its kind occurring after radiation therapy. Of the other two tumors one was an extraskeletal osteogenic sarcoma in the soft tissues of the thoracic wall and one a rhabdomyosarcoma in the axilla.