Osteosarcoma After Hematopoietic Stem Cell Transplantation in Children and Adolescents: Case Report and Review of the Literature

Osteosarcoma as a secondary malignancy after hematopoietic stem cell transplantation (HSCT) is very rare. We present a case and review of 18 other cases reported to date. Our patient underwent HSCT for myelodysplastic syndrome at the age of 4 years. She developed osteosarcoma 13 years later. She underwent surgery after three courses of neoadjuvant chemotherapy followed by chemotherapy and mifamurtide. She has no evidence of disease 28 months after termination of chemotherapy. In 18 other cases of secondary osteosarcoma in the literature, 15 had received total body irradiation, eight had received alkylating agents, and six had received etoposide. The median interval from HSCT to the onset of osteosarcoma was 6.5 years (range 2.5–15.3), which confirms that children undergoing HSCT should be followed up for many years. In conclusion, osteosarcoma must be included in the differential diagnosis among solid tumors that may develop following HSCT.     

Primary meningeal osteosarcoma of the brain during childhood. Case report

Primary meningeal osteosarcomas are rare tumors, with only 19 reported cases in the literature; only 4 of these, including the present case, are in pediatric patients. In this report, the authors present the case of an 8-year-old boy with a history of generalized tonic-clonic seizures who was found to harbor a meningeal osteosarcoma within the sylvian fissure. Initial working diagnoses included meningioma and glioma. After tumor enlargement and progressive symptoms, the patient underwent a large frontotemporal craniotomy and complete resection of the lesion, which recurred 6 and 12 months after the initial surgery and was surgically treated after each recurrence. The rarity of primary meningeal osteosarcomas can make their diagnosis difficult, and histopathological evaluation is mandatory for diagnosis. Because of their fast progression, they must be treated aggressively by means of surgery, chemotherapy, and radiotherapy.     

Late relapse of osteosarcoma: implications for follow-up and screening

Long-term disease-free survival in patients with localised osteosarcoma treated in large multicentre randomised trials is over 50%. Most relapses occur early, usually within 2-3 years. Relapse after 5 years is uncommon and has been infrequently described. Eight patients with osteosarcoma treated at The London Bone and Soft Tissue Tumour Service since 1986 developed recurrence of disease after 5 years, the latest 14 years after the initial diagnosis. Five patients developed pulmonary metastases, two patients isolated bone metastases and one patient intra-abdominal metastases. Although a second complete remission was achieved in six patients, four patients relapsed again, all with pulmonary metastases. Two patients had co-existent brain metastases. One of those with a second recurrence has achieved a further complete remission and remains well 50 months after the most recent treatment. A second patient is disease-free 24 months after complete excision of an isolated pulmonary metastasis and one further patient is disease-free 6 months after chemotherapy and pneumonectomy for pleural and pulmonary metastases. Five patients have died of disease with a median survival from the date of relapse of 17 months (2-68 months). Current data looking at long-term outcome of patients with osteosarcoma is limited. Reports of late relapse are rare as numbers are small, thus long-term surveillance of patients is essential. It is possible that sites of relapse are more unusual, and more extensive staging may be necessary when late relapse occurs.     

Childhood osteosarcoma of greater wing of sphenoid: case report and review of literature

Primary osteosarcoma of skull base is extremely rare. We present a case of primary osteosarcoma arising in greater wing of sphenoid in a child. Our patient had an incomplete excision after which he received adjuvant chemotherapy and radiotherapy. There was good response to adjuvant chemoradiotherapy and the patient is disease free at a follow-up of 18 months. Treatment of skull base osteosarcomas is difficult, as complete excision is often not possible. To the best of our knowledge, this is the first case of sphenoid wing osteosarcoma in childhood to be reported in literature.     

Survival after recurrence of osteosarcoma: a 20-year experience at a single institution

BACKGROUND: Approximately one-third of patients with osteosarcoma who have a complete response to their initial treatment can be expected to relapse. It is important to define what host, tumor, or treatment characteristics determine outcome after relapse. We present findings in 59 patients treated at our institution from 1974 to 1996 who have relapsed one or more times after their initial response. METHODS: Host and tumor characteristics at diagnosis and relapse, therapeutic interventions and survival outcomes were determined from examination of medical records and a follow-up questionnaire. RESULTS: Of the 59 patients, 37 initially presented with localized disease of the extremity, 11 with localized non-extremity disease, and 11 with metastatic disease. This report focuses on those with localized disease of the extremity. For these patients, median time from original diagnosis to first recurrence was 14 months. Median survival after first recurrence was 31 months. The median post initial relapse survival was the same for patients whose first relapse occurred before or after 14 months from original diagnosis. Seventeen of 29 patients with systemic metastasis at first recurrence had complete removal of their disease and had a median post-op survival of 2.5 years, while the remaining 12 patients with no surgery, had a median survival of 2 years. Of the 37 patients who presented with primary disease only in the extremities and relapsed: 31 died (2 more than 6 years from first recurrence) and 6 are alive from 6 to 24 years from first recurrence (5 without disease and 1 with disease). Three of the five disease-free survivors had three or more relapses. CONCLUSION: With a long follow-up time, we found 15% of patients with relapsed osteosarcoma who originally presented with localized disease in the extremity are alive with no evidence of disease at 10 years from first recurrence (Kaplan-Meier estimate). Even patients with multiple relapses may have long-term disease-free survival after salvage therapy. Chemotherapy and time to first recurrence were unrelated to survival after relapse in this study. Complete surgical removal of metastatic disease may be important for long-term survival.     

Metastatic osteosarcoma to the liver after treatment for synovial sarcoma: a case report

Metastatic osteosarcoma most commonly affects the lungs and other bones. Hepatic metastasis at the time of diagnosis is extremely rare. A 14-year-old boy with synovial sarcoma of the left popliteal fossa was treated with surgical resection, radiotherapy for microscopic residual disease, and 1 year of chemotherapy (vincristine, cyclophosphamide, dactinomycin, and doxorubicin). Approximately 10 years after the initial diagnosis, a secondary osteosarcoma developed in the left proximal tibia. Computed tomography at presentation showed bilateral pulmonary metastases and large ossified nodules in the liver that demonstrated abnormal avidity on ^99m TcMDP bone scan indicating hepatic metastasis. Despite chemotherapy (cisplatin, ifosfamide, high-dose methotrexate, and dacarbazine), the patient died of progressive disease 4 months after the diagnosis of the second cancer. Hepatic metastasis was found at the time of diagnosis of a secondary osteosarcoma and manifested as ossified nodules. The risk of radiation-induced osteosarcoma should always be considered in decisions about treatment for soft-tissue sarcoma.     

METASTATIC OSTEOSARCOMA TO THE LIVER AFTER TREATMENT FOR SYNOVIAL SARCOMA: A Case Report

Metastatic osteosarcoma most commonly affects the lungs and other bones. Hepatic metastasis at the time of diagnosis is extremely rare. A 14-year-old boy with synovial sarcoma of the left popliteal fossa was treated with surgical resection, radiotherapy for microscopic residual disease, and 1 year of chemotherapy (vincristine, cyclophosphamide, dactinomycin, and doxorubicin). Approximately 10 years after the initial diagnosis, a secondary osteosarcoma developed in the left proximal tibia. Computed tomography at presentation showed bilateral pulmonary metastases and large ossified nodules in the liver that demonstrated abnormal avidity on ^99m TcMDP bone scan indicating hepatic metastasis. Despite chemotherapy (cisplatin, ifosfamide, high-dose methotrexate, and dacarbazine), the patient died of progressive disease 4 months after the diagnosis of the second cancer. Hepatic metastasis was found at the time of diagnosis of a secondary osteosarcoma and manifested as ossified nodules. The risk of radiation-induced osteosarcoma should always be considered in decisions about treatment for soft-tissue sarcoma.     

Simultaneous osteosarcoma lung metastasis and second primary lung cancer

Second malignant neoplasms (SMNs) after treatment of children and adolescent cancers have been extensively studied. Lung cancer as an SMN is rare in all type of primary cancer in children and in osteosarcoma as well. The authors reviewed all cases of osteosarcomas treated at their institution from 1975 to 2000 and found 22 cases of SMN, only 1 involving lung cancer. The authors describe this latter case, a 17-year-old girl with a localized osteosarcoma of the tibia who developed simultaneously lung metastases of osteosarcoma and a primitive lung adenocarcinoma only 18 months from the diagnosis. Lung cancer is unusual in youths as a primary malignancy or as a second primary malignancy. The occurrence of a primitive lung cancer together with lung metastases from osteosarcoma is even more unusual, and examination of all new lung nodules is highly recommended.     

Osteosarcoma of the rib

Primary osteosarcomas arising from the rib are very rare. The authors report an 11-year-old boy with a primary fibroblastic osteosarcoma of the rib, who underwent wide excision and reconstruction of the chest wall followed by chemotherapy. He is disease free after a follow up of 24 months. The relevant literature is reviewed briefly     

Paratesticular metastasis from Wilms tumor associated with a hydrocele

Metastatic sites other than the lungs, lymph nodes, and liver are unusual for Wilms tumor (WT). Intra-scrotal metastasis is very rare. We report a 3-year-old boy with stage IIA WT, who experienced paratesticular metastasis 2 months after surgery for an abdominal recurrence. He had right scrotal hydrocele at initial diagnosis. The patient underwent right radical orchiectomy, and pathological examination revealed paratesticular WT metastasis. Intra-abdominal and peritoneal disseminated metastases followed. We considered that tumor cells spread through the patent processus vaginalis and grew at paratesticular space in hydrocele. One month after the end of 12 months of salvage chemotherapy and abdominal radiotherapy, the patient has no evidence of disease.     

Intraoperative radiotherapy in the multidisciplinary treatment of bone sarcomas in children and adolescents.

From September 1984 to December 1989, 38 patients of pediatric age with localized bone sarcomas received intraoperative radiotherapy (IORT) as part of a multidisciplinary treatment program. The age ranged from 6 to 21 years. The tumor histologies were 22 osteosarcomas and 16 Ewing's sarcomas. Thirty-four had initial primary disease (90%) and 4 were treated for local recurrence (10%). IORT was used on 32 untreated patients and in 6 previously treated with external beam radiotherapy (EBR). The IORT field included the surgically exposed tumor bed area. Single radiation doses ranging from 10 to 20 Gy were delivered, using 6-20 MeV electron beams. The median follow-up time for the entire group is 25 months (2-65+ months). The projected 5-year disease-free and overall survival rates are 65% and 69%, respectively. One patient developed a local recurrence in each histological group: one chondroblastic osteosarcoma and one cervical Ewing's sarcoma. Six patients died from metastatic progression: 3 initially recurrent tumors and three primary disease cases. Severe neuropathy and soft tissue necrosis were seen in some patients as IORT related complications. IORT is a feasible technique to be integrated in multidisciplinary programs that may promote local control in pediatric and adolescent patients with bone sarcomas. Peripheral nerves are dose-limiting tissue structures for IORT.     

Skip metastasis in osteosarcoma

Skip metastasis is rare in high-grade osteosarcoma and indicates a very poor prognosis. The authors describe two patients who had high-grade osteosarcoma and skip metastasis. MRI detected the skip lesion in both patients, and both lesions were confirmed by histology. The patients were treated with adjuvant chemotherapy and radical surgical resection. Both are alive and free of disease 3 and 6 years from diagnosis.     

Second neoplasms in pediatric patients treated for cancer: a center's 30-year experience

To investigate the incidence and outcome of secondary neoplasms in pediatric patients treated for childhood cancer. Between December 1971 and January 2000, a total of 5859 patients younger than age 17 were diagnosed and treated for childhood cancers in our center. Of this group, 1511 (36%) patients were followed for more than 36 months. These long-term survivors were included in this analysis. Twenty-six patients developed a secondary malignancy with an overall risk of 1.7% in this cohort. The male:female ratio was 17:10, with a median age of 7.66 at diagnosis (range, 2 to 16 y). Four patients (14.8%) with Hodgkin lymphoma; 3 each (11.1%) with retinoblastoma and rhabdomyosarcoma; 2 each (7.4%) with Wilms tumor, Ewing sarcoma, medulloblastoma, ganglioneuroblastoma, and non-Hodgkin lymphoma; and 1 each (3.7%) with ependymoma, nasopharyngeal carcinoma, osteosarcoma, astrocytoma had a secondary malignant disease during the long-term follow-up period. Secondary malignant diseases were osteosarcoma in 6 patients, acute lymphoblastic leukemia in 2, acute myelogenous leukemia in 2, and rare malignant disease in others. Four patients with osteosarcoma developed disease within the radiation field. Osteosarcoma was the most frequently occurring secondary neoplasm. Less toxic treatment modalities should be used to decrease the risk of secondary malignant diseases.     

Intraoperative radiotherapy in the multidisciplinary treatment of bone sarcomas in children and adolescents

From September 1984 to December 1989, 38 patients of pediatric age with localized bone sarcomas received intraoperative radiotherapy (IORT) as part of a multidisci plinary treatment program. The age ranged from 6 to 21 years. The tumor histologies were 22 osteosarcomas and 16 Ewing's sarcomas. Thirty-four had initial primary disease (90%) and 4 were treated for local recurrence (10%). IORT was used on 32 untreated patients and in 6 previously treated with external beam radiotherapy (EBR). The IORT field included the surgically exposed tumor bed area. Single radiation doses ranging from 10 to 20 Gy were delivered, using 6–20 MeV electron beams. The median follow-up time for the entire group is 25 months (2–65+ months). The projected 5-year disease-free and overall survival rates are 65% and 69%, respectively. One patient developed a local recurrence in each histological group: one chondroblastic osteosarcoma and one cervical Ewing's sarcoma. Six patients died from metastatic progression: 3 initially recurrent tumors and three primary disease cases. Severe neuropathy and soft tissue necrosis were seen in some patients as IORT related complications. IORT is a feasible technique to be integrated in multidisciplinary programs that may promote local control in pediatric and adolescent patients with bone sarcomas. Peripheral nerves are dose-limiting tissue structures for IORT.     

Pediatric myositis ossificans mimicking osteosarcoma

Myositis ossificans (MO) is a rare benign cause of heterotopic bone formation in soft tissue that most commonly affects young adults, typically following trauma. We report the case of an 11‐year‐old girl who developed MO mimicking osteosarcoma in her right shoulder. Plain radiography and computed tomography showed poorly defined flocculated densities in the soft tissue and a periosteal reaction along the proximal humerus. On magnetic resonance imaging, the mass displayed an ill‐defined margin and inhomogeneous signal change. Histologically, the mass had a pseudosarcomatous appearance. Based on these findings, the patient was initially misdiagnosed with osteosarcoma at another hospital. The diagnosis was difficult because the patient was 11 years old and had no trauma history, with atypical radiographic changes and a predilection for the site of origin for osteosarcomas. We finally made the correct diagnosis of MO by carefully reviewing and reflecting on the pathological differences between stages.     

Prognosis in children with metastatic rhabdomyosarcoma

Distant metastases were documented in 83 of 161 children with rhabdomyosarcoma seen between 1953 and 1974. Of these, 31 had metastases at diagnosis (Group IV) and 7 were noted to have metastases only at autopsy. Only 6 are living with no evidence of disease activity at 6, 20, 77, 85, 105, and 112 months from time of metastasis. One child is living with disease at 98 months. Late deaths occurred in 2 at 31 and 41 months after metastasis. Sixty-four of the 66 deaths occurred within 24 months. The median durations of life after metastasis were less than 9 months in Groups I and II patients, less than 6 months in Group III patients, and about 12 months in 31 Group IV patients. The median time to metastasis in Groups I, II, and III patients was 9 months.     

Metastatic osteosarcoma to the small bowel with resultant intussusception: a case report and review of the literature

Intussusception resulting from osteosarcoma metastasis to the small bowel is a rare diagnosis. This case report describes a patient with this diagnosis, demonstrates the CT appearance of this lesion, and reviews the literature.     

Granulosa cell tumors of the ovary in children and adolescents. Multicenter retrospective study in 40 patients aged 7 months to 22 years]

BACKGROUND. Juvenile granulosa cell tumors (JGCT) of the ovary are rare in children. The over-all outcome after surgery is relatively good, but the indication and type of complementary treatment for severe forms are still unclear. POPULATION. A retrospective survey of the majority of patients with JGCT of the ovary admitted between 1965 and 1990 to 11 French oncologic pediatric centers was carried out. Medical records including surgical and histological data, were analyzed and each tumor was retrospectively classified by the same pathologist according to the Wollner classification. RESULTS. There were 40 patients aged 7 months to 22 years (mean: 6 years); 28 were less than 10 year old at diagnosis. Three had enchondromatosis (Ollier's disease). At diagnosis, all patients presented with an abdominal tumor, 23 had developed manifestations of precocious pseudopuberty, 2 had signs of virilization after a normal puberty and 2 had secondary amenorrhea. Surgery was always the primary treatment: unilateral ovariectomy in 35 cases, bilateral in 4 and biopsy alone in 1 case. There were 21 stage I, 1 stage II, 16 stage III and 2 stage IV cases. 13 patients received combined chemotherapy and 2 abdominal radiotherapy. 34 patients were alive and disease-free 10 months to 26 years after surgery and 6 died. All 23 patients with precocious pseudopuberty had a favorable outcome. CONCLUSIONS. This study confirms earlier reports. Unilateral ovariectomy is the first-choice therapy. There is no evidence that tumors complicated by rupture and hemoperitoneum require chemotherapy. Combined chemotherapy does not appear to improve the prognosis for the rare malignant forms. The factors of good prognosis are age less than 10 years and the presence of precocious pseudopuberty.     

Endobronchial metastases from carcinoma of the breast

We report the case histories of four patients with endobronchial metastases from breast cancer, two of whom died of resultant respiratory insufficiency. To aid in earlier diagnosis and thus permit more rapid application of specific therapy, we characterized the epidemiology and presenting symptoms of these patients and 38 additional patients with endobronchial metastases from breast carcinoma that have been reported in the literature. The average age at presentation with endobronchial metastases was 55, and the average time from diagnosis of the breast primary lesion to the endobronchial metastasis was 77 months. Cough occurred in 71% of patients; wheezing and hemoptysis occurred in 25%. Segmental atelectasis occurred in 57% on chest roentgenogram. Average survival of patients from the time of diagnosis of endobronchial metastasis was 21 months; median survival was 19 months.     

儿童骨肉瘤综合治疗的效果

目的 引用德国骨肉瘤协作组(COSS)-96方案治疗骨肉瘤,从临床疗效分析、药物剂量及给药方式、不良反应的防治方面,探讨国内治疗儿童骨肉瘤的最佳综合治疗方案.方法 对15例初诊的骨肉瘤患儿采用COSS-96方案,进行术前、术后化疗及手术综合治疗及疗效分析;检测大剂量甲氨蝶呤(HD-MTX)给药后的血清水平,根据血药水平调整HD-MTX给药剂量及甲酰四氢叶酸(CF)解救剂量及次数.结果 15例患儿术前化疗后均有局部肿块缩小及疼痛消失等症状好转及影像学改变;肿瘤坏死组织学评估Ⅰ级2例,Ⅱ级3例,Ⅲ 级6例,Ⅳ级4例; HD-MTX剂量12 g·m-2给药结束0 h血清药物水平为700～1 000 μmol·L-1.随访时间5 a 10个月,中位随访时间 3 a 2个月,肺转移3例,肺及多部位骨骼转移1例,死亡2例.5 a生存率71%,5 a无瘤生存率57%.结论 术前化疗具有清扫转移病灶,局部肿块缩小及疼痛消失、减小手术范围和难度的作用;依据术后肿瘤坏死组织学评估制定术后化疗方案,不仅达到避免患儿因化疗敏感性差使化疗方案强度不足,肿瘤易复发而生存期缩短的目的,而且可避免对化疗敏感的患儿因"过强"化疗后的不良反应及死亡的发生;血清药物水平监测下调整HD-MTX给药剂量,在确保有效杀灭瘤细胞药物剂量的同时,也为HD-MTX不良反应的防治提供客观依据.