Ewing's sarcoma of bone tumor cells produces MCSF that stimulates monocyte proliferation in a novel mouse model of Ewing's sarcoma of bone

Ewing's sarcoma of bone is a primary childhood malignancy of bone that is treated with X-radiation therapy in combination with surgical excision and chemotherapy. To better study Ewing's sarcoma of bone we developed a novel model of primary Ewing's sarcoma of bone and then treated animals with X-radiation therapy. We identified that uncontrolled tumor resulted in lytic bone destruction while X-radiation therapy decreased lytic bone destruction and increased limb-length asymmetry, a common, crippling complication of X-radiation therapy. Osteoclasts were indentified adjacent to the tumor, however, we were unable to detect RANK-ligand in the Ewing's tumor cells in vitro, which lead us to investigate alternate mechanisms for osteoclast formation. Ewing's sarcoma tumor cells and archival Ewing's sarcoma of bone tumor biopsy samples were shown to express MCSF, which could promote osteoclast formation. Increased monocyte numbers were detected in peripheral blood and spleen in animals with untreated Ewing's sarcoma tumor while monocyte number in animals treated with x-radiation had normal numbers of monocytes. Our data suggest that our Ewing's sarcoma of bone model will be useful in the study Ewing's sarcoma tumor progression in parallel with the effects of chemotherapy and X-radiation therapy.     

乳腺癌术后放疗诱发性肉瘤的治疗进展

【摘要】〓放疗诱发性肉瘤(radiation induced sarcoma, RIS)是一种罕见的、恶性程度较高的肿瘤,可发生于乳腺癌、妇科肿瘤、霍奇金淋巴瘤和其他类型肿瘤放射治疗后,而其中乳腺癌放疗诱发性肉瘤占较大的比例。目前,对于此类肿瘤的治疗仍是临床上一大难题,不管是手术治疗还是手术联合辅助放化疗,其5年生存率仍较低,且治疗后局部复发率很高。为提高临床医生对放疗诱发性肉瘤治疗方案的优化选择,改善患者预后,本文对目前针对放疗诱发性肉瘤的治疗进展做一综述。     

Concurrent metastatic thymic carcinoma and postirradiation sarcoma

We present a case of concurrent metastatic thymic carcinoma and postirradiation sarcoma in the same lobe of the lung in a woman who had received partial resection of thymic carcinoma with chemoradiotherapy 11 years ago. One tumor showed similar histology to the previous carcinoma. The other tumor was a pleomorphic sarcoma, suggestive of a postirradiation sarcoma. Irradiation-induced sarcomas are rare and have not been reported in patients with thymic carcinoma. This case may serve as a model in considering the possibility of postirradiation sarcoma for patients encountering recurrent masses with the history of radiotherapy for thymic carcinoma several years ago.     

Indomethacin influences Moloney's sarcoma and associated periosteal osteogenesis in the mouse

The effect of indomethacin on periosteal osteogenesis mediated by the Moloney sarcoma virus was studied using a mouse model. In the indomethacin-treated animals, the development of sarcoma was inhibited, as evaluated by the tumor incidence, tumor size, and maximal tumor duration. Periosteal osteogenesis mediated by this sarcoma was lower than in saline-treated control mice.     

Primary sarcoma of penis

A case of primary sarcoma of the penis is reported. A very slow growth rate of this tumor was observed and prompted conservative treatment. A review of the literature is included. More cases of penile sarcoma should be reported in order to study the not well-documented natural history of this disease.     

Primary pulmonary artery sarcoma

Primary pulmonary artery sarcoma is an uncommon tumor. We report a case of a 73-year-old male patient with a two-week history of palpitations and shortness of breath, aggravated for two days and was believed to be pulmonary hypertension. Emergency heart ultrasound after admission presented a massive pulmonary embolism in the pulmonary artery. The patient's condition was successfully managed with urgent pulmonary artery embolectomy. The patient demonstrated improvement in hemodynamics after the operation. Histologic and immunohistochemical assays were performed and a diagnosis was made as primary pulmonary artery sarcoma arising from the left pulmonary artery. Resection of the tumor is recommended for the treatment of this rare malignant tumor. The corresponding chemotherapy, follow-up and prognosis are described as well in this case report.     

Radiation-induced breast sarcoma

BACKGROUND: The purpose of this study was to examine the presentation, treatment, and prognosis of patients with radiation-induced sarcomas after adjuvant radiotherapy for breast cancer. METHODS: This was a retrospective review from 1975 to 2001 of patients who presented with a sarcoma in an irradiated field after surgical treatment for breast cancer. RESULTS: Thirty-four women were included. Six had undergone breast-conserving therapy and 28 had mastectomy for primary breast carcinoma. All patients received postoperative radiation. The mean time to diagnosis of sarcoma was 152 months (range 40 to 372). Twenty-three of 34 patients (68%) had recurrence of the sarcoma after resection, and 22 patients (65%) died of their disease. Patients with no evidence of disease at follow-up had a mean tumor size of 4.2 cm +/- 0.7 (n = 6), compared with 8.1 cm +/- 1.2 (n = 10) for patients who died of their disease (P = 0.030). CONCLUSIONS: Radiation-induced sarcoma is a late complication of definitive treatment for breast carcinoma. The prognosis of such patients is poor, with two thirds dying of their disease. In the present series, improved survival was associated with smaller tumor size at presentation.     

Pulmonary metastases in childhood sarcoma

A retrospective analysis of 56 patients less than 19 years old with pulmonary metastases from previously diagnosed sarcomas was performed. Thirty patients had primary osteogenic sarcoma. Eighteen of them underwent a total of 37 thoracotomies. Overall survival was 20%. Twelve patients were noted to have metastatic Wilms' tumor, and 5 of them underwent 7 thoracotomies. This group had a 25% overall survival. Six patients had pulmonary metastases from Ewing's sarcoma. Four of these required pulmonary resection. The overall survival in these patients was 50%. The remaining 8 patients had pulmonary resection for various soft tissue malignancies, with an overll survival of 50%. The results of this review indicate a role for aggressive pulmonary resection in patients in whom the primary tumor is controlled and there is no other evidence of metastatic disease. The frequency of bilaterality and multicentric implants in patients with osteogenic sarcoma and Wilms' tumor suggest the efficacy of a median sternotomy approach in these patients.     

Synovial sarcoma in clinical practice--description of selected cases

Clinically, synovial sarcoma becomes apparent as a growing mass. Initial presentation and the course may be variable. We discuss 4 characteristic patients. CASE 1: A 37 year-old female patient presented with a mass in her thigh after two consecutive resections of a malignant hemangioendothelioma. Histology: Biphasic synovial sarcoma (G II). CASE 2: A tumor was enucleated in the adductors of a 42 year-old female patient. Histology: Biphasic synovial sarcoma (G I). 2 years later local tumor recurrence (G I) occurred. Treatment was provided by wide resection and radiotherapy. CASE 3: Resection of a suspected neurinoma in the thigh of a 34 year-old male patient. Histology: Biphasic synovial sarcoma, positive margins. CASE 4: A 74 year- old female patient receiving anticoagulants was symptomatic due to intracranial tumor hemorrhage of a metastasis of a previously unknown synovial sarcoma of her popliteal fossa. The primary tumor was initially misdiagnosed as Baker's cyst, causing a deep vein thrombosis. Histology: Angioinvasive synovial sarcoma (G II). Survival: 11 months. Therapy: Wide resection and postoperative irradiation in cases 1-3. Indication for the irradiation in case 2 and 3 was due to the inadequate operation. An amputation was performed in case 4 because of infiltration of the neurovascular structures. CONCLUSION: The presentation of synovial sarcoma does not differ from other soft tissue sarcomas. Patients should be treated in specialized centers to reduce inadequate operations. Outcome and rate of metastatic disease suggest the need for improved adjuvant treatment modalities.     

Spindle cell sarcoma of the penis: a case report

A 75-year-old man, with a past history of radiation therapy for prostatic carcinoma ten years ago, was referred to our hospital with complaints of penile tumor. After pathological examination by core biopsy, the patient was treated by radical penectomy for a penile tumor. Pathological examinations demonstrated that the tumor was composed of pleomorphic spindle cells without any differentiation tendency and diagnosed as spindle cell sarcoma. Although the patient had a past history of radiation therapy for the prostate, the causal relation of development of penile sarcoma with the radiation therapy was uncertain because the main tumor was very near but outside of the irradiation field. The sarcoma rarely occurs in the penis, and this is the first report of penile spindle cell sarcoma, to our knowledge.     

Primary cardiac synovial sarcoma —A case report—

We report a case of cardiac synovial sarcoma, a very rare primary tumor of the heart. The patient was a 29-year-old man with chief complaint of dyspnea. On echocardiography, a tumor 42 mm in diameter occupying the most space of the left atrium was found. The tumor was obstructed the opening of the mitral valve. He was diagnosed with heart failure due to disturbance of the pulmonary venous return and hemodynamic mitral valve stenosis, and underwent surgery. The tumor was a 5-cm sphere originating in the left atrial posterior wall, and was covered with a sheath and solid. The atrial posterior wall was covered with a peel that appeared to be tumor tissue, and this tissue expanded toward the openings of the pulmonary veins bilaterally and the posterior cusp of the mitral vavle. The tumor was resected together with the posterior wall. On pathologic examination, the tumor was diagnosed as a synovial sarcoma. Since no other primary focus was found, this tumor was judged to be a primary sarcoma of the heart. The patient was discharged with elimination of symptoms. The sarcoma recurred after 4 months, and the patient underwent a second operation. The recurrent tumor began from the site of resection of the previous operation and expanded up to the inferior pulmonary veins bilaterally. A wide area of the left atrial wall including the tumor was resected, and he was discharged again. The sarcoma recurred again, and he died of progression of heart failure and aggravation of general conditions after 8 months from the first operation.     

Primary Ewing's sarcoma of the temporal bone.

Primary cranial Ewing's sarcoma is exceptionally rare. Only ten cases of such a tumor had been reported heretofore in the literature. We describe a case of primary Ewing's sarcoma occurring in the temporal bone. The tumor was surgically excised, and the patient underwent radiation and chemotherapy. Neither recurrence nor distant metastasis was noted at 12 months after surgery. Although the prognosis of Ewing's sarcoma in general is often poor because of early metastasis to the lungs and/or to other bones, a review of the literature suggested that the same tumor occurring in the cranium can often be successfully managed by intensive therapy with radical excision and radiochemotherapy. This inference was supported by the case reported here.     

Undifferentiated carcinoma of the vulva mimicking epithelioid sarcoma.

We report an undifferentiated sweat gland carcinoma of the vulva in an 80-year-old woman. The tumor, which was located in the right labium majus, resembled an epithelioid sarcoma histologically; it had a granulomatous appearance with multiple tumor nodules containing epithelioid tumor cells. The tumor also contained rhabdoid cells; a large cluster of them showed histological features indistinguishable from those of a malignant rhabdoid tumor. Immunohistochemically, the tumor cells reacted not only for epithelial markers such as cytokeratins, EMA, and CEA, which are known to be expressed by epithelioid sarcoma, but also for CA125 and with monoclonal antibodies recognizing sweat gland structures--namely, EKH5 and EKH6. For comparison, two epithelioid sarcomas and two extrarenal malignant rhabdoid tumors were also studied. Of these tumors, only one extrarenal rhabdoid tumor reacted with EKH5, and none reacted for CA125. Electron-microscopic examination of the present tumor showed the presence of discontinuous basal laminae and tonofibril-like structures as well as primitive cell junctions and interdigitating filopodia. From these findings, we conclude that the tumor was an undifferentiated sweat gland carcinoma mimicking an epithelioid sarcoma. Findings in this case support the idea of the diverse histogenesis of extrarenal malignant rhabdoid tumors and indicate that electron microscopy is important for differentiating epithelioid sarcoma from skin adnexal carcinoma.     

Hemangiopericytoma-like synovial sarcoma of the lumbar spine. Case report

The purpose of this report is to demonstrate that synovial sarcoma should be included in the differential diagnosis of tumors originating from the lumbar spine, especially if they show hemangiopericytoma-like pathological characteristics. A synovial sarcoma is a mesenchymal spindle cell tumor that displays variable epithelial differentiation including glandular formation. It is unrelated to a synovium. More than 80% of these lesions arise in the deep soft tissue of the extremities. The tumor frequently arises adjacent to joints or tendon sheaths. The authors describe a young woman with a hemangiopericytoma-like tumor of the lumbar spine. During repeated operation, this lesion was shown to be a synovial sarcoma, which had invaded the dura mater. The tumor metastasized to the mediastinum and the intradural cervical spine and, finally, to the brain and the lungs. To the authors' knowledge, this is the first reported case of a synovial sarcoma originating from the lumbar spine.     

Chest wall epithelioid sarcoma

Two relatively rare cases of epithelioid sarcoma located in the chest wall are reported herein. The first was a tumor, 3.8 x 5.5 x 2.4 cm in size, originating in the left erector spinae muscle of a man 64 years of age. He experienced local recurrence 3 times even after wide resections, and he died of systemic metastasis 22 months after the initial surgery. The second was a tumor, 2.2 x 2.0 x 1.5 cm in size, originating in the left seventh intercostal muscle of a woman 24 years of age. A metastatic tumor occurred in the same muscle, and wide resection including the seventh and eighth intercostal muscles was performed. There has been no recurrence for 1.5 years since surgery. Metastasis of chest wall epithelioid sarcoma in the muscle in which the primary lesion resides should be considered, even if the primary lesion is small.     

Antitumor immune response following injection of neuraminidase-treated sarcoma cells.

Mice inoculated with MCA-10 sarcoma cells which had previously been incubated with Vibrio cholerae neuraminidase (VCN) demonstrated a significantly lower tumor incidence (9/26) than mice injected with untreated sarcoma cells (10/10) or sarcoma cells incubated with heat-inactivated neuraminidase (28/29) p less than .05. Rechallenge of nontumor-bearing mice from the VCN group with untreated sarcoma cells resulted in a low tumor incidence (4/11), indicating that these mice had developed systemic immunity following the initial injection of VCN-treated tumor cells. These mice also demonstrated significant lymphocytotoxicity against MCA-10 target cells compared with normal control mice (p less than .05). Subsequent cytotoxicity experiments, utilizing groin lymph node and splenic lymphocytes from mice five days following leg injection of VCN-treated, heat-inactivated VCN-treated or untreated MCA-10 cells, demonstrated that the mice injected with VCN-treated tumor cells demonstrated greater antitumor immunity both locally and systemically. This magnification of tumor immunity is postulated as the mechanism by which neuraminidase treated MCA-10 sarcoma cells grew less well in C57 mice than cells incubated with heat-inactivated VCN or cells left untreated.     

Adult urological sarcoma.

From July 1982 to December 1989, 43 of 1,583 adults (2.7%) with soft tissue sarcoma admitted to the Memorial Sloan-Kettering Cancer Center (MSKCC) had tumors arising from the urinary tract and male genital tract (urological sarcoma). The most common site of origin of the tumor was paratesticular (14 patients), followed by the prostate/seminal vesicle (12), bladder (10) and kidney (7). The most common histological type was leiomyosarcoma (19 patients), followed by rhabdomyosarcoma (14), liposarcoma (5) and 5 other histological sarcoma categories (angiosarcoma, malignant fibrous histiocytoma, mesenchymoma and 2 undifferentiated sarcomas). Most of the tumors were high grade (86%) and more than half (56%) were greater than 5 cm. in diameter. A total of 9 patients (21%) presented with metastatic disease, 8 of whom had rhabdomyosarcoma. Complete resection with negative microscopic margins was possible in 58% of the patients. Actuarial relapse-free survival for all patients at 3 and 5 years was 55% and 40%, respectively. There were no significant differences in survival based on patient age, sex or histological tumor type. Favorable prognostic variables by univariate analysis included tumor diameter less than 5 cm., low histological grade, paratesticular or bladder tumor site and complete surgical resection. Application of the MSKCC sarcoma staging system, which is based on grade, size, depth and presence or absence of metastasis, was useful to predict survival. In our experience patients with stage 3 (high grade, greater than 5 cm., 15 patients) or stage 4 (metastatic disease, 9 patients) had a combined 3-year relapse-free survival rate of only 26% and they should be considered candidates for adjuvant treatment protocols.     

Case of proximal-type epithelioid sarcoma of the perineum

A 31-year-old man was referred to our department for investigation and treatment of a rapidly-growing mass in the perineal region. MRI showed a periurethral tumor in the perineal region measuring 3.5cm in maximum diameter and bilateral inguinal lymph nodes enlargement. Therefore, the tumor was extirpated immediately with bilateral inguinal lymphadenectomy. The pathological examination with immunohistochemistry revealed that the tumor was proximal-type epithelioid sarcoma. Multidisciplinary therapy with irradiation, chemotherapy, and tumor ablation with a microwave tissue coagulator, was not effective for local recurrence and metastasis, and finally he died of progressive disease 14 months after the operation. Epithelioid sarcoma originating from the thigh or trunk is classified into the proximal-type, which shows significantly poorer prognosis than the distal-type that develops in the distal extremities. The proximal-type epithelioid sarcoma of the perineum is rare and, to our knowledge, the present report is the fourth case in the Japanese literatures.