Extraskeletal Ewing's sarcoma: A clinical,morphological and ultrastructural analysis of five cases with a review of the literature

In 1969 it was recognised that tumours with light microscopic appearances indistinguishable from Ewing's sarcoma of bone may arise in extraskeletal sites (extraskeletal Ewing's sarcoma). Here, we review the available literature and report five new cases. All five received combined modality therapy with combination chemotherapy and radiotherapy to the primary site followed by surgical excision in two. All attained complete remission; after a median follow-up of 26 months, three remain disease-free but two have relapsed and died. Our experience, in accord with previous series, suggests that extraskeletal Ewing's sarcoma compared with its bony counterpart tends to occur in older subjects, has a similar incidence in males and females, usually presents with a painless mass and readily responds to combined modality therapy. We detected no light or electron microscopic features to denote a histogenetic origin. However, we suspect extraskeletal Ewing's sarcoma may occur more frequently than previously supposed.     

MR findings of primary Ewing's sarcoma of greater wing of sphenoid

Primary Ewing's sarcoma of the skull is a very rare entity. We report MRI findings in a case of Ewing's sarcoma of the greater wing of sphenoid in a 4‐year‐old patient. Magnetic resonance imaging showed markedly heterogenous signal intensity with areas of haemorrhage and necrosis. It also demonstrated the exact extent of tumour due to its multiplanar capabilities and was, therefore, helpful in planning surgery.     

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.     

Sarcoma of the Ewing Family in Pregnancy: A Case Report of Intrauterine Fetal Death after Induction of Chemotherapy

Ewing''s sarcoma is an ultra-orphan disease (2/1,000,000/year) which requires a multimodal therapy approach in high-volume centers. Treatment consists of pre-operative therapy followed by surgery and post-operative combination of chemo-radiotherapy. Experience with diagnosis and therapy of Ewing''s sarcoma in pregnancy is very limited. We herein report the case of an atypical Ewing''s sarcoma detected in the second trimester of gestation. Neoadjuvant chemotherapy was initiated and resulted in substantial tumor shrinkage and intrauterine fetal death. The rare nature of this condition underlines once more the need for a multidisciplinary team to improve the quality of care for this highly special patient collective.Key words: Ewing''s sarcoma, Pregnancy, Neoadjuvant chemotherapy, Intrauterine fetal death, Multidisciplinary team approach     

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.     

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.     

An Unusual Location of Extraosseous Ewing's Sarcoma

Ewing''s sarcoma (ES) is the second most common malignant bone tumor in children and young adults. ES also occurs as a primary soft tissue neoplasm without involvement of bone. We report the second case of extraosseous (EO) ES emerging from the omentum and a review of the relevant literature. EO ES should be included in the differential diagnosis of soft tissue neoplasms in the abdomen.Key words: Extraosseous Ewing''s sarcoma, Surgery, Chemotherapy, Multimodality care     

Periosteal Ewing's Sarcoma: Report of Two New Cases and Review of the Literature

Background. The origin of Ewing''s sarcoma in a periosteal location is rare and not clearly documented. Other malignant bone tumors appear to have a somewhat better prognosis when confined between periosteum and bone. Is it the same for periosteal Ewing''s sarcoma? Methods. We describe two new cases and comprehensively review the literature consisting of 18 documented cases since the condition was first described in 1986 (S.M. Bator.Cancer 58:1781– 4). Results. Periosteal Ewing''s sarcoma differs from the other forms of Ewing''s sarcoma in terms of sex predominance, location of tumor, surgical stage at presentation and typical imaging studies. Eighteen out of the 20 patients were reported to be alive with no evidence of disease. Conclusions. It seems that the prognosis of this rare variant of Ewing''s sarcoma family of tumors might be better but the small number of cases precludes such a firm conclusion.     

Diagnostic difficulties in extraosseous Ewing's sarcoma: A proposal for diagnostic criteria

Five cases diagnosed as extraosseous Ewing's sarcoma (EES) during a 15-year period, and the relevant literature, were reviewed. The diagnosis in these cases was difficult to confirm, mainly because the distinction between the osseous form of Ewing's sarcoma (OES) and either periosteal reactions or direct tumour invasion into adjacent bone by EES was often unclear. The literature suggests that other authors have also encountered difficulties. The authors believe that many cases reported as EES are likely to have been OES. This distinction has some importance, as the two conditions are usually treated in differing ways. The following criteria are proposed for the diagnosis of primary EES: (i) no evidence of bony involvement on magnetic resonance imaging; (ii) no evidence of increased uptake in bone or periosteum adjacent to the tumour on static isotope bone scan images; (iii) a small round cell tumour with no differentiating features on light microscopy, immunochemistry or electron microscopy; and (iv) demonstration of cytoplasmic glycogen.     

Disseminated Intracranial Ewing's Sarcoma in an Adult: A Rare and Difficult Diagnosis

The Ewing sarcoma family of tumors comprises a rare class of cancers of mesenchymal origin. Cases of Ewing''s sarcoma in the central nervous system – specifically, intracranial Ewing''s – are extremely rare. Almost all reported cases have occurred in children. However, this rare presentation can also occur in the adult population. It is important to distinguish these tumors from primitive neuroectodermal tumors at the time of diagnosis. Testing for EWSR1(22q12) gene rearrangement using fluorescence in situ hybridization is a useful tool for making the distinction between these 2 similar but distinct entities. We present here the case of a middle-aged male patient with intracranial Ewing''s sarcoma, and discuss diagnostic challenges and potential new treatment approaches for this rare disease.Key Words: Ewing''s sarcoma, intracranial; Magnetic resonance imaging; Primitive neuroectodermal tumor     

Ifosfamide and Actinomycin-D,Added in the Induction Phase to Vincristine,Cyclophosphamide and Doxorubicin,Improve Histologic Response and Prognosis in Patients with Non Metastatic Ewing's Sarcoma of the Extremity

Abstract

The role of ifosfamide as first-line chemotherapy treatment of non metastatic Ewing's sarcoma of the extremity is still under discussion. The purpose of this paper is to report the results achieved in a neoadjuvant protocol (REN-3) in which ifosfamide, added to the conventional VACA regimen, was employed since the induction phase. Induction chemotherapy consisted of vincristine, cyclophosphamide, doxorubicin, actinomycin-D and ifosfamide. After local treatment, patients received the drugs used in the induction phase and etopo-side. Between November 1991 and November 1994, 61 patients with non metastatic Ewing's sarcoma of the extremity were treated. Forty-nine patients underwent surgery and 73.5% of them had a good histologic response. At a median follow-up of 60 months (range 32-76), 48 patients (79%) remained continuously disease-free. The 5-year event-free and overall survival were 77% and 87%, respectively. These results were significantly better both in terms of histologic response or event-free and overall survival than those obtained in 58 patients with non metastatic Ewing's sarcoma of the extremity treated in a previous protocol (REN-2) in which the same drugs were used, but ifosfamide was employed only in the maintenance phase. The present study suggests the importance of early use of ifosfamide in the treatment of patients with non metastatic Ewing's sarcoma of the extremity.     

Clinical oncology: Case presentations from oncology centres 1. Ewing's sarcoma: The London bone tumour service

The management of a case of Ewing's sarcoma of the left proximal humerus in a 15-year-old girl is presented, and the radiological and pathological findings are described. The chemotherapeutic, radiotherapeutic and surgical management of Ewing's sarcoma are discussed with reference to the case.     

A biochemical and immunohistological study of collagen synthesis in Ewing's tumour.

The synthesis and localization of collagen have been studied on material from a total of 16 primary Ewing''s tumours. The predominant collagen extracted from the tissues and synthesized in short-term cultures was type I. The proportion of type III collagen was relatively small and variable (0-8%) in the direct tumour extracts, but a higher proportion (29-38% of the total collagens) was synthesized in culture. Immunofluorescence studies showed that positive staining for all types of collagen tested (types I, III, IV and V) was restricted to stroma; there was no evidence of collagen either within the tumour cells or in their pericellular matrix, a finding endorsed by negative staining for reticulin in the same areas. The absence of any evidence for type IV or V collagen synthesis by Ewing''s cells argues against an endothelial origin for the tumour, and indicates that collagen analysis is unlikely to be of value in the diagnosis of this particular sarcoma.     

Expression of interleukin 15 (IL-15) in human rhabdomyosarcoma,osteosarcoma and Ewing's sarcoma

Interleukin 15 (IL-15) is a recently discovered cytokine that stimulates lymphocyte proliferation and migration via a trimeric receptor sharing the β and γ signal transducing chains with the IL-2 receptor. IL-15 is typically produced by normal cells that do not release IL-2, but little information is currently available on human tumors. To assess whether human musculo-skeletal sarcomas produce IL-15, we analyzed surgical specimens and cell lines obtained from rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma. IL-15 mRNA was present in 9/9 surgical specimens (3 Ewing's sarcomas, 5 osteosarcomas and 1 rhabdomyosarcoma). The analysis of a panel of cell lines (7 derived from Ewing's sarcoma, 12 from osteosarcoma and 5 from rhabdomyosarcoma) showed that all rhabdomyosarcoma and osteosarcoma cell lines expressed IL-15 mRNA at levels ranging from low to high, while Ewing's sarcoma cells contained little or no IL-15 message. ELISA assays showed IL-15 release in a subset of rhabdomyosarcomas and osteosarcomas, but not in Ewing's sarcoma. The highest production of IL-15, in the picogram/ml range, was found in rhabdomyosarcoma cell lines RH30 and RD. Int. J.Cancer 71:732-736, 1997. © 1997 Wiley-Liss Inc.     

Sonographic Evaluation of Chest Masses in Children

The sonographic appearances of 12 intrathoracic masses in children are presented. Seven out of 12 masses were malignant and presented with opaque hemithorax on chest X-ray. Different types of masses encountered were: Lymphoma, Neuroblastoma, Ewing's sarcoma, metastatic Ewing's sarcoma, Teratocarcinoma, Pseudotumor of the lung, Neuroenteric duplication cyst, Bronchogenic cyst and tubercular mediastinal lymph nodes.     

Ewing's sarcoma of the phalangeal bone

A rare case of Ewing's sarcoma of the toe bone is described and compared with three reported cases of phalangeal Ewing's sarcoma. The lesion in two cases was initially treated as infection and the diagnosis was delayed for several months. Roentgenographic and aspiration cytology examinations in cases with clinically unresolving infection of the hands and feet may prevent delayed diagnosis. Radical surgery alone may be curative if no metastases are found preoperatively in careful clinical investigations.     

Importance of studying primitive neuroectodermal tumors and extraosseous Ewings sarcoma of the vagina and vulva

Primitive neuroectodermal tumor (PNT) and Ewing''s sarcoma are rare, round-cell tumors, characterized by the presence of the t(11; 22)(q24; q12) chromosomal translocation. A review of the literature revealed only 38 previously reported cases of vulvar PNT and Ewing''s sarcoma and 15 vaginal PNT and Ewing''s sarcoma. Although rare, these types of tumors should be taken into consideration when making a differential diagnosis for vulvar or vaginal tumors. The currently available data is limited, and therefore, case reports are essential for improving knowledge and management of these types of extremely rare tumors. However, further molecular and histopathological studies are essential for an improved understanding of these conditions and for an early, correct diagnosis. Although the gathered and presented data from the present review are limited, the literature demonstrates that the outcome of these types of cancer are more favorable compared with outcomes observed for carcinomas in more typical locations.     

Malignant round-cell tumours of bone: an analytical histological study from the Cancer Research Campaign's bone tumour panel.

A study of 40 cases of malignant round-cell tumour of one was made from the files of the Cancer Research Campaign''s Bone Tumour Panel. Five pathologists made a careful study of observer error, involving repeated examination of routine paraffin sections, to determine whether the cases were a homogeneous group or a collection of differing sub-groups. Cell outline, nuclear staining, nuclear pleomorphism, conspicuous nucleoli, reticulin pattern and intracellular glycogen were the histological features selected for study. For each feature, the results were analysed to assess the importance of differences between tumours, between samples of tissue from the same tumour, and between observers. It is concluded that round-cell tumours of bone are a heterogeneous group, although completely distinct sub-groups could not be identified. Certain histological features tend to be associated, and it is reasonable to distinguish on histological grounds between Ewing''s sarcoma and reticulum-cell sarcoma, although some tumours are not typical of either group.     

The role of surgery in children with head and neck rhabdomyosarcoma and Ewing's sarcoma

Rhabdomyosarcoma and Ewing's sarcoma are relatively common malignant tumours in paediatric population. In the past, surgery was the mainstay of treatment and survival rates were poor. Afterwards, the development of multi-agent chemotherapy protocols during the past four decades resulted in a dramatic improvement in long-term survival. As a consequence, the significance of surgery has been the subject of critical discussion in the literature. Nowadays the standard treatment of rhabdomyosarcoma and Ewing's sarcoma consists in a multimodal therapy involving chemotherapy, radiotherapy and surgery. Nevertheless, the role of surgery still remains controversial. In particular, the cure of head and neck localizations presents debatable aspects since defined criteria to establish the risks and the benefits of surgical treatment do not exist at this time. This article reviews the role of surgery in children with head and neck rhabdomyosarcoma and Ewing's sarcoma. Indications, feasibility and timing criteria of surgical treatment have been reviewed and extracted from literature. Our case series is also presented.