Traumatized Ischial Apophysis (Report of Six Cases)

Six boys with traumatic ischial apophysis are reported. Two cases were diagnosed as stress apophysis and four as apophyseolysis. Two of our patients were referred to the hospital as malignant bone tumours—Ewing sarcoma and osteosarcoma.     

Primary Sacral Bone Tumours in Children (Report of 16 cases with a short literature review)

16 cases of primary sacral bone tumours in children are reported. These include 13 patients with Ewing's sarcoma and 3 with very rare primary sacral bone tumours in childhood — chordoma, haemangiopericytoma and osteoblastoma. All sacral bone tumours, with the exception of Ewing's sarcoma are very rare in childhood. The possibility of a sacral tumour should be considered in a child with radiculopathy. CT and MR make the diagnosis of primary sacral bone tumours much easier with the added possibility of recognition of the true nature of the lesion in many instances. Reports of primary sacral bone tumours in children are scarce. Most of the patients are incorporated in adult series which do not specify the age of the child and the site of the tumour. The purpose of this paper is to describe 16 children with primary sacral bone tumours.     

The contrasting age-incidence patterns of bone tumours in teenagers and young adults: Implications for aetiology

Bone tumours comprise 0.2% of cancers overall but 5.7% in 15-24 year olds. To explore the relationship with adolescence we have analysed age-incidence patterns of bone tumours in a large national dataset. Data on incident cases of bone tumours in 0-84 year olds in England, 1979-2003, were extracted from national cancer registration data. Incidence rates per million person-years by 5-year age-group, sex, morphology and primary site were calculated and adjusted to the world standard population. Nine thousand one hundred forty-six cases were identified giving an overall age-standardized rate of 7.19 per million person-years. The distribution by morphology was: osteosarcoma, 34.2%; chondrosarcoma, 27.2%; Ewing sarcoma, 19.3%; other, 19.4%. The distribution varied by age. Ewing sarcoma was most common in 0-9 year olds, osteosarcoma in 10-29 year olds and chondrosarcoma in 30-84 year olds. 29.2% of all tumours occurred in 0-24 year olds. Highest incidence of osteosarcoma and Ewing sarcoma in females was in 10-14 year olds. In males, peak incidence occurred at 15-19 years and exceeded that in females. Chondrosarcoma incidence steadily increased with age. The proportions of Ewing sarcomas occurring in respective bones were consistent with those of the adult skeleton by weight. In osteosarcoma tumours of long bones of lower limb were markedly over-represented in the adolescent peak, being six times more than at any other site. Variation in incidence patterns with age and site suggests pubertal bone growth to be a key factor in osteosarcoma while different biological pathways could be relevant for Ewing sarcoma.     

Rare,Primary Iliac,Pubic and Ischial Tumours in Children (Report of 14 Cases) — Part II

14 cases of rare, primary iliac, pubic and ischial bone tumours or tumorous conditions are reported. These include aneurysmal bone cyst, eosinophilic granuloma, cavernous haemangioma, osteoid osteoma, fibrous dysplasia, fibrous dysplasia with sarcomatous degeneration, chondrosarcoma, lymphoma and atypical malignant histiocytosis. The possibilities to be considered in the accurate radiographic recognition of primary tumours of iliac, pelvic and ischial bones are discussed.     

Seltene Knochentumoren der Extremitäten

Of the various types of mesenchymal tumours of the extremities, bone neoplasms are significantly less frequent than soft tissue neoplasms. Because of their relative frequency, osteosarcomas, Ewing’s sarcomas, and chondrosarcomas, including the dedifferentiated variant, are the most significant forms of primary malignant bone neoplasms. In the first two groups, interdisciplinary multimodal treatment concepts involving combinations of neoadjuvant chemotherapy, extremity-preserving operations (when possible) and, in some circumstances, radiation therapy (Ewing’s sarcoma) have long been applied in international treatment trials (EURAMOS, Euro-BOSS, Euro-EWING) that have been initiated in the paediatric oncological sector. This has significantly improved the prognoses of these highly malignant tumours. Surgery is the principal form of treatment for chondrosarcomas. Although the relative importance of chemotherapy has not yet been established for these tumours, which are predominantly associated with adulthood, treatment options are being sought, so it is necessary to check whether these patients could be considered for treatment under the Euro-BOSS protocol. Giant cell tumours, which can cause considerable local destruction but only rarely metastasize, are generally given intralesional surgery using adjuvants or cement fillings. Modern therapeutic options using osteoclast-inhibiting substances might well produce positive results.     

Primary Bone Tumours of the Pelvis in Childhood—Ewing's Sarcoma of the Ilium,Pubis and Ischium. (Report of 30 cases) (Part I)

30 children with Ewing's sarcoma, the most common malignant pelvic tumour in childhood, were analysed. The diagnosis of Ewing's sarcoma is relatively easy and can be established in most of the cases on plain radiography. The diagnostic radiographic features of the tumour are discussed. The two most important conditions in differential diagnosis are eosinophilic granuloma and the rare primary bone lymphoma. Osteomyelitis should rarely cause confusion unless the clinico-radiographic findings are not properly evaluated.     

Incidence and survival of childhood bone cancer in northern England and the West Midlands, 1981�C2002

There is a paucity of population-based studies examining incidence and survival trends in childhood bone tumours. We used high quality data from four population-based registries in England. Incidence patterns and trends were described using Poisson regression. Survival trends were analysed using Cox regression. There were 374 cases of childhood (ages 0–14 years) bone tumours (206 osteosarcomas, 144 Ewing sarcomas, 16 chondrosarcomas, 8 other bone tumours) registered in the period 1981–2002. Overall incidence (per million person years) rates were 2.63 (95% confidence interval (CI) 2.27–2.99) for osteosarcoma, 1.90 (1.58–2.21) for Ewing sarcoma and 0.21 (0.11–0.31) for chondrosarcoma. Incidence of Ewing sarcoma declined at an average rate of 3.1% (95% CI 0.6–5.6) per annum (P=0.04), which may be due to tumour reclassification, but there was no change in osteosarcoma incidence. Survival showed marked improvement over the 20 years (1981–2000) for Ewing sarcoma (hazard ratio (HR) per annum=0.95 95% CI 0.91–0.99; P=0.02). However, no improvement was seen for osteosarcoma patients (HR per annum=1.02 95% CI 0.98–1.05; P=0.35) over this time period. Reasons for failure to improve survival including potential delays in diagnosis, accrual to trials, adherence to therapy and lack of improvement in treatment strategies all need to be considered.     

Ewing sarcoma-family tumors that arise after treatment of primary childhood cancer

BACKGROUND: Unlike osteosarcoma, the Ewing sarcoma family of tumors (ESFT) has rarely been reported as secondary malignant neoplasms after treatment of childhood cancer. ESFT arising as a second cancer was reviewed and characterized at our childhood cancer center. METHODS: A retrospective review was undertaken of 11,183 patients age <21 years who were treated for a primary cancer between March 1962 and December 2003 at St. Jude Children's Research Hospital. All cases of ESFT were confirmed to have a rearranged EWS gene. RESULTS: Six cases of ESFT (1.3% of 479 second cancers) were identified in patients previously treated for lymphoma (n = 3), leukemia (n = 1), retinoblastoma (n = 1), or Wilms tumor (n = 1). None of these patients had a family history suggestive of a familial cancer syndrome. The median time between diagnosis of primary cancer and diagnosis of ESFT was 5.9 years (range, 3.1-18.3 years). ESFT occurred in typical anatomic locations: rib (n = 2), chest wall soft tissues (n = 2), pelvis (n = 1), and extremity (n = 1). One tumor arose at the margin of a previous radiotherapy field and 1 arose distant from previous radiotherapy fields; all other patients had not received radiotherapy. Three patients are alive at the time of this report, including 2 whose ESFT was diagnosed more than 8 years ago. CONCLUSIONS: ESFT occurs rarely after treatment of a primary cancer during childhood, and most cases do not appear to be related to radiation therapy. Long-term survival can be achieved in some patients, and therefore secondary ESFT should be treated with curative intent.     

Malignant change secondary to fibrous dysplasia

Background Malignant change in fibrous dysplasia (FD) is very rare. This study was carried out to establish some characteristic clinical information about this disorder. Methods Four cases with a malignant change in FD out of 128 cases with FD were surgically treated and followed up for a median period of 61.3 months. The mean age of the patients was 39.8 years. Clinical features, radiological findings, and the outcome were analyzed for each of the four cases. Results and conclusion The sites of the lesions were tibia (2 cases), femur (1 case), and rib (1 case). The forms of FD were monostotic in one case and polyostotic in three cases. Radiologically, plain films and computed tomography (CT) showed osteolytic lesions with poorly delineated margins within and/or near areas having a ground-glass appearance. In the osteolytic lesions, simple cystic changes associated with old FD could be excluded by enhanced magnetic resonance imaging (MRI). Histopathologically, two cases were osteosarcoma, one case was malignant fibrous histiocytoma (MFH), and one case was fibrosarcoma. The management of this disease should be decided according to the type of primary high-grade bone sarcoma. One patient, with MFH, was dead of lung metastasis 13 months after surgery. The others are alive without disease.     

Late effects of chemotherapy and radiotherapy in osteosarcoma and Ewing sarcoma patients: The Italian Sarcoma Group Experience (1983-2006)

BACKGROUND:

Patients with osteosarcoma and Ewing sarcoma have achieved longer survival over the past decades, but late side effects of chemotherapy and radiotherapy have become important concerns.

METHODS:

The authors reviewed all patients with localized osteosarcoma or Ewing sarcoma who had been enrolled in the Italian Sarcoma Group neoadjuvant protocols from 1983 through 2006. Data were updated in December 2010 to determine 3 endpoints: the incidence of a secondary primary cancer (designated as “second malignant neoplasm” [SMN]), infertility, and cardiotoxicity.

RESULTS:

Data were available on 883 patients with osteosarcoma and 543 patients with Ewing sarcoma. In the osteosarcoma group, there were 39 SMNs (4.4%) in 36 patients; in the Ewing sarcoma group, 15 patients (2.8%) experienced a single SMN each. The cumulative 10‐year and 20‐year incidence of an SMN (±standard error) was 4.9% ± 0.9% and 6.1% ± 1.2%, respectively, in the osteosarcoma group and 3.4% ± 0.9% and 4.7% ± 1.6%, respectively, in the Ewing sarcoma group. The most common SMN in the osteosarcoma group was breast cancer (n = 11), and the most common SMN in the Ewing sarcoma group was radiotherapy‐induced osteosarcoma (n = 6). After 20 years, the risk of developing an SMN increased, whereas the risk of a recurrence of the primary tumor decreased. Permanent sterility was more common in males than in females. Doxorubicin cardiotoxicity occurred in 18 patients with osteosarcoma (2%) and in 7 patients with Ewing sarcoma (1.3%).

CONCLUSIONS:

The awareness of late side effects in long‐term survivors of primary bone cancers should encourage longer follow‐up. Cancer 2012. © 2012 American Cancer Society.     

Knochentumoren des Kindes- und Jugendalters

Malignant bone tumors are the most common solid tumors in children and adolescents. Osteosarcoma and Ewing’s sarcoma are the commonest malignant bone tumors in this age group. Only 30 years ago the outcome for patients suffering from malignant bone tumors was extremely poor. Currently two-thirds of patients can be cured if they undergo early and appropriate therapy. This requires a precise and early diagnosis made by specialized radiologists and pathologists. Furthermore the good prognosis depends on the precondition that patients are referred to selected medical centres with an interdisciplinary team of specialized oncologists, surgeons and radiotherapists. Still, clinicians and practitioners whose primary focus is not oncology must be aware of the typical but distinct signs and symptoms of malignant bone tumors, the basic diagnostic procedures and treatment schedules and possible late effects of treatment.     

单纯髂骨切除术治疗髂骨原发恶性骨肿瘤

目的：探讨单纯髂骨切除术治疗髂骨原发恶性肿瘤的手术方法,分析其肿瘤学结果及骶髂关节连续性对患者肢体功能的意义。方法回顾分析1983年6月至2011年6月,诊断为髂骨原发恶性肿瘤并于我院骨肿瘤科行单纯髂骨切除术且资料完整的患者25例。分析该术式对髂骨恶性肿瘤的治疗效果及手术后骶髂关节连续性对患者肢体功能的影响。结果25例均于我院进行手术治疗,男19例,女6例。病例分布为软骨肉瘤13例,骨肉瘤6例,尤文肉瘤2例,梭形细胞肉瘤2例,未分化多形性肉瘤2例。随访14.2～127.9个月,平均41个月。截止随访期末,18例未发现肿瘤复发或转移。1例骨肉瘤患者于术后9个月出现肺转移,行胸腔镜肺部病灶切除,1例尤文肉瘤患者术后58个月出现肺部转移,行化疗,1例软骨肉瘤患者术后23个月出现局部复发,再次手术切除,此3例目前均存活。4例死亡,1例骨肉瘤患者术后10个月出现肺部转移,术后18个月死亡;1例软骨肉瘤患者术后12个月出现肺部转移,术后15个月死亡;1例术后29个月发现局部复发及肺部转移,术后39个月死亡;1例骨肉瘤患者术后26个月因肝功能衰竭死亡。15例可行MSTS评分系统进行评分,平均为27.5（24～30）分。其中10例骶髂关节连续性存在,MSTS评分平均为28.8分,5例骶髂关节连续性破坏,MSTS评分为25.0分。结论单纯髂骨切除术是治疗髂骨原发恶性肿瘤的有效术式,骶髂关节失去连续性对行走功能有一定影响。其功能可满足日常生活需要。     

Liver tumours

Primary hepatic tumours in children represent an heterogeneous group of neoplasms. Malignant tumours are more common (60% of primary liver tumours), but account for only 1.2–5% of all paediatric neoplasms. There are two main types of malignant tumour, those of epithelial origin, hepatoblastoma (HB) and hepatocellular carcinoma (HCC), and the rarer mesenchymal tumours, e.g. rhabdomyosarcoma and undifferentiated sarcoma, (Weinberg AG, Finegold, MJ. Primary hepatic tumours of childhood. Hum Pathol 1983, 14, 512–532[1]). Vascular tumours e.g. haemangioendotheliomas are the most common of the benign tumours followed by mesenchymal hamartoma and the rare hepatic adenoma and focal nodular hyperplasia. This article will concentrate on the malignant epithelial tumours.     

Twenty-year outcome of prevalence,incidence, mortality and survival rate in patients with malignant bone tumors

Malignant bone tumors are a group of rare malignant tumors and our study aimed to update the recent epidemiologic estimates based on the Surveillance, Epidemiology and End Results database. Patients diagnosed with malignant bone tumors from 2000 to 2019 were included and their characteristics were retrospectively described. The limited-duration prevalence, annual age-adjusted incidence and mortality were calculated, and the annual percentage changes were analyzed to quantify the rate change. Finally, observed survival and relative survival rate were illustrated. Subgroup analysis across tumor type, age, gender, tumor Grade, primary tumor site and stage was also performed. As for results, a total of 11 655 eligible patients with malignant bone tumor were selected. Osteosarcoma was the most common tumor type, followed by chondrosarcoma, Ewing sarcoma and chordoma. The estimated limited-duration prevalence of malignant bone tumors increased from 2000 (0.00069%) to 2018 (0.00749%). Steady age-adjusted incidence was observed in all patients during the study period while the highest rate occurred in osteosarcoma. Mortality rates differed in subgroups while elder patients (older than 64 years) presented the highest mortality rate compared to other age groups. In all bone tumors, the 10-year observed survival and relative survival rates were 58.0% and 61.9%, respectively. Chondrosarcoma patients had the best survival outcome, followed by osteosarcoma, Ewing sarcoma, chordoma and other bone tumors. In conclusion, different epidemiologic performance in incidence and mortality was observed across tumor type as well as other demographic and clinicopathological variables, which provide potential suggestion for further adjustment of medical resource.     

Tumeurs PNET/Ewing : prise en charge actuelle et perspectives

Ewing tumours are characterised as tumours consisting of small, blue, round malignant cells that may exhibit varying degrees of neural differentiation. Most of them arise in bony sites, and they represent the second commonest primary osseous malignancy in and adolescence and young adults. During the past 30 years, chemotherapy has increased survival from less than 5% to 65–70% in localized tumours and to 25–30% in primary metastatic tumours. Surgery is a major tool, whereas advances in imaging techniques have improved treatment indication and optimization. Radiotherapy remains useful, either alone or in addition to surgery, and new techniques (conformational RT and IMRT) will reduce short-term toxic effects. However, long-term toxic effects are also of major concern. Clinical and biological prognostic factors has been clearly identified and should guide the therapeutic choice for these patients. The metastatic Ewing tumours are of extremely poor prognosis, and impose the development of new therapeutic agents. This article is a review of the data available in 2009 concerning Ewing's sarcoma either as biologic aspects or as therapeutic aspects.     

Ewing sarcoma dissemination and response to T-cell therapy in mice assessed by whole-body magnetic resonance imaging

Background:

Novel treatment strategies in Ewing sarcoma include targeted cellular therapies. Preclinical in vivo models are needed that reflect their activity against systemic (micro)metastatic disease.

Methods:

Whole-body magnetic resonance imaging (WB-MRI) was used to monitor the engraftment and dissemination of human Ewing sarcoma xenografts in mice. In this model, we evaluated the therapeutic efficacy of T cells redirected against the Ewing sarcoma-associated antigen G_D2 by chimeric receptor engineering.

Results:

Of 18 mice receiving intravenous injections of VH-64 Ewing sarcoma cells, all developed disseminated tumour growth detectable by WB-MRI. All mice had lung tumours, and the majority had additional manifestations in the bone, soft tissues, and/or kidney. Sequential scans revealed in vivo growth of tumours. Diffusion-weighted whole-body imaging with background signal suppression effectively visualised Ewing sarcoma growth in extrapulmonary sites. Animals receiving G_D2-targeted T-cell therapy had lower numbers of pulmonary tumours than controls, and the median volume of soft tissue tumours at first detection was lower, with a tumour growth delay over time.

Conclusion:

Magnetic resonance imaging reliably visualises disseminated Ewing sarcoma growth in mice. G_D2-retargeted T cells can noticeably delay tumour growth and reduce pulmonary Ewing sarcoma manifestations in this aggressive disease model.     

Osteosarcoma: What did we learn from the paediatric experience for adolescents and young adults?

The term ‘osteosarcoma’ (OS) defines a primary malignant tumour of bone, characterised by the production of osteoid tissue or immature bone by malignant proliferating sarcomatous cells. Due to the variable biological features of different osteosarcoma, several varieties are included in the osteosarcoma family, with different grades of malignancy (Table 1). Of these variables, high grade primary central os- teosarcoma is the most common form and accounts for more than 80% of cases. About 85% of these patients have tumours located in the extremities, and about 15–20% of patients are metastatic at diagnosis. This tumour represents 0.2% of all malignant tumours with an incidence of three new cases/year per million population, and the majority of cases are in children and adolescents younger than 20 years of age. There- fore, it is a very rare tumour and during the course of their activity, orthopaedic surgeons or medical oncologists see about one patient with this tumour every 5 years. Thus, the interest in osteosarcoma for these specialists is quite limited. From a cultural point of view, however, this is an important tumour: (1) for the oncologist, because most current strategies using adjuvant and neoadjuvant treatments in other more common tumours (for instance breast cancer) have been formulated on the basis of results obtained in osteosarcoma;(2)for the orthopaedic surgeon because some of the new methods of surgical reconstruction devised for osteosarcoma may also be used in other orthopaedic pathologies.The present report is limited to primary high grade osteosarcoma of the extremity and will consider separately different presentations (localised, metastatic at diagnosis, relapsed).     

Primary spinal epidural extraosseous Ewing’s sarcoma: Report of five cases and literature review

Ewing’s sarcoma is the most common malignant bone tumour occurring in children and adolescents and exists in two different clinicopathological entities: osseous Ewing’s sarcoma (OES) and extraosseous Ewing’s sarcoma (EES). Five cases of primary epidural EES are described, which presented with non‐specific symptoms leading to a long diagnostic delay. The median age at diagnosis was 22 years (range 13–36 years). The median diagnostic delay was 3 months. All patients had one or more neurological deficits. All underwent surgical exploration with a laminectomy and partial resection followed by adjuvant radiotherapy to a dose of 46–50 Gy and chemotherapy with VAC (vincristine, adriamycin and cyclophosphamide) alternating with ICE (ifosphamide, cisplatin and etoposide) for at least six cycles. The mean follow‐up period is 21.2 months (range 11–32 months). Four of the five patients achieved a complete remission and are disease free at the time of writing this report. Two patients have a residual neurological deficit – both having presented with long history of neurological deficit. Primary spinal epidural EES should be suspected whenever young patients present with back pain and/or radicular pain, have abnormal neurology and an extradural mass is demonstrated on MRI. Surgical excision followed by adjuvant radiotherapy (50 Gy) and combination chemotherapy (VAC alternating with ICE) achieved local and systemic control in these patients. A greater number of patients and longer follow up are required to evolve a generally accepted treatment policy for this aggressive but potentially curable malignancy.     

Current treatment for Ewing’s sarcoma

Ewing’s sarcoma is the second most common primary bone tumor seen in children and adolescents, and was described by James Ewing in 1921 as a diffuse endothelioma of bone. It is one of the differential diagnoses of pediatric small round blue cell tumors. This is not a single condition, but a group of morphologically and clinically closely related disorders with similar molecular biology – expression of tumor-specific chimeric oncoproteins through balanced chromosomal translocations involving the EWS gene – often referred to as the Ewing family of tumors. This includes Ewing’s sarcoma of bone, extra-osseous Ewing’s sarcoma, Askin tumor and peripheral neuroectodermal tumor. These are aggressive neoplasms with almost 25% of patients having clinically evident metastases at presentation. Ewing’s sarcoma has therefore been considered as a systemic disease necessitating local as well as systemic treatment. An aggressive multidisciplinary approach has resulted in significant improvement in prognosis for patients with these tumors. Despite aggressive treatment, 20–40% of patients with localized disease and almost 80% of patients with metastatic disease at presentation succumb to the illness. Advances in understanding the molecular biology of these tumors will hopefully result in the development of novel treatment approaches. The aim of this article is to review the existing treatment methods and to highlight the more recent approaches to the treatment of this condition.