Cushing's syndrome caused by Ewing's sarcoma secreting corticotropin releasing factor-like peptide.

Procedures were carried out in a 12-year-old girl to relate Ewing's sarcoma of the left tibia with Cushing's syndrome. Computed tomography revealed a normal pituitary and hypothalamus but bilateral adrenal hyperplasia without focal enlargement, thus readily excluding hypothalamic-pituitary-adrenal tumor. Negative results from a high-dose dexamethasone suppression test do not support pituitary-dependent Cushing's disease. Ewing's sarcoma was diagnosed on tibial biopsy. The regression of the physical and biochemical findings of Cushing's syndrome subsequent to amputation of the left lower leg strongly suggests ectopic Cushing's syndrome caused by Ewing's sarcoma. Immunohistochemical studies of the resected bone were negative for corticotropin but positive for corticotropin releasing factor-like peptide. We conclude that this is the first reported case of ectopic Cushing's syndrome in a child that is caused by Ewing's sarcoma secreting corticotropin releasing factor-like peptide.     

Primary bone tumours of the hand

Twenty-one primary bone tumours of the hand in children from 8 paediatric hospitals are reported. Osteochondromas and enchondromas were not included. Our material consisted of 16 patients with common tumours (3 Ewing's sarcoma, 5 aneurysmal bone cyst, 6 osteoid osteoma and 2 epidermoid cyst) and 5 patients with uncommon tumours (osteoma, simple bone cyst, haemangiopericytoma, capillary angiomatous tumour and benign ossifying fibroma or osteoblastoma). The X-ray diagnosis of the common tumours should have high concordance with histology, whereas that of uncommon tumours is much more difficult and uncertain. The characteristic features of Ewing's sarcoma are stressed as all our children with this tumour had a delayed diagnosis and a fatal outcome. Differential diagnosis with other short tubular bone lesions of the hand - specifically osteomyelitis - is discussed and the possibilities of microscopic diagnosis are stressed.     

Cooperative Ewing's Sarcoma Studies 81/86: pathologico-anatomic and immunohistochemical findings and differential diagnosis of Ewing sarcoma

158 cases of the Cooperative Ewing's Sarcoma Trials (CESS 81/86), which have been documented at the Pediatric Tumor Registry, Kiel, were studied by conventional light microscopy and immunohistochemistry. There were 77 cases of typical Ewing's sarcoma with 70 cases being located in the skeleton and 7 in soft tissues. Of the 14 cases of atypical Ewing's sarcoma 7 cases each were localized in bone and in soft tissue, respectively. In contrast to typical Ewing's sarcoma, cells of atypical Ewing's sarcoma were larger and displayed more heterochromatin. Both, typical and atypical Ewing's sarcoma reacted positively for vimentin. Other stains were negative, notably the neuron specific enolase (NSE). In 55 cases a diagnosis of malignant peripheral neuroectodermal tumor (MPNT) was made. Histologically most of these tumors resembled atypical Ewing's sarcoma. By immunohistochemistry positive reactions were found for NSE, vimentin, protein S-100, neurofilaments and glial fibrillary acidic protein. In 3 cases a diagnosis of small cell osteosarcoma was made. There were 2 cases of undifferentiated sarcoma of bone, 2 cases of soft tissue sarcoma of undetermined histogenesis and 2 cases of rhabdomyosarcoma. Of the 4 tumors which could be investigated for response to polychemotherapy, 1 each corresponded to grade II and III, respectively, and 2 to grade IV according to the classification of histologic grade of regression established by Salzer-Kuntschik et al. (1983).     

Ewing's sarcoma

This patient had Ewing's sarcoma of the femur, which was originally misinterpreted by radiograph and by biopsy as osteomyelitis. For approximately 1 year the patient was treated for osteomyelitis. The lesion was slowly progressive and near the end of the first year became more active, and pulmonary metastases appeared. The natural behavior of this one case of Ewing's sarcoma demonstrates that it is not necessarily an overwhelmingly aggressive tumor. In addition, the point is made that pathologists should pay careful attention to necrotic material so that the suggestion of necrotic tumor can be made rather than dismissing the biopsy as nondiagnostic.     

Pulmonary metastases in children: an analysis of surgical spectrum.

Pulmonary surgery is frequently used for the treatment of metastasis or nodules in children with various types of malignancies. However, the indications and effectiveness of pulmonary metastatectomy have not been evaluated recently. Therefore, a retrospective study was conducted to analyse the results of pulmonary metastatectomy in children. Children who underwent pulmonary metastatectomy at our department between 1990 and 2000 were reviewed. Eighteen children consisting of 11 boys and 7 girls (age range, 3 to 18 years) underwent thoracotomy for pulmonary metastasis excision. The primaries were osteosarcoma (n = 2), synovial sarcoma (n = 1), fibrosarcoma (n = 1), Ewing's sarcoma (n = 2), mesenchymal chondrosarcoma (n = 1), Wilms' tumour (n = 4), clear-cell sarcoma (n = 1), Hodgkin lymphoma (n = 3), hepatoblastoma (n = 1), hepatocellular carcinoma (n = 1) and haemangioendotheliosarcoma (n = 1). Pulmonary metastases were encountered either at the time of initial diagnosis (22 %) or occurred within 6 months to 5 years. They were frequently nodular (94 %), unilateral (94 %) and located in the right lung (70 %). The number of metastases were frequently one (56 %) or two (28 %). Excision was done by means of wedge resection (88 %), segmentectomy (6 %), and lobectomy + wedge resection (6 %). The nodules contained tumour cells in most cases (n = 14) (78 %), mature nephrogenic elements (6 %) and no tumour tissue (16 %) in the remaining cases. Histology was similar to that of the original tumour in 12 cases. However, synovial sarcoma was encountered in metastasis in one case with fibrosarcoma primary. Re-thoracotomy was performed in 22 % of cases for the recurrent lesion, which in only one case was a true local recurrence. Overall disease-free survival rate was 56 % during the follow-up period (mean, 36.4 +/- 31.8 months). Pulmonary metastatectomy may increase survival in carefully selected children, though it is unlikely to cure the patient. Therefore combined therapies such as chemotherapy and/or radiotherapy should be continued in the postoperative period.     

Lenticular lesions: not always an epidural hematoma

Ewing's sarcoma is a tumor of the bone, which occurs most often in the diaphysis of long and flat bone. The most common sites of metastasis are the lungs and bones. Less frequently, the primary site is an intracranial or pelvic lesion (either as a soft tissue or a bone lesion). We report a case of a 16-year-old female with an extraosseous intracranial lesion, who presented with a history of minor trauma, unilateral facial swelling, and head pain. Though head computed tomography scan showed a lesion consistent with an epidural hematoma, further exploration revealed Ewing's sarcoma.     

High-dose melphalan therapy for the treatment of children with refractory neuroblastoma and Ewing's sarcoma

Neuroblastoma and Ewing's sarcoma are examples of pediatric cancers in which disseminated disease is often present at diagnosis or develops later in spite of combination therapy. The demonstration that marrow-ablative doses of chemotherapy can increase tumor cell kill, and that autologous bone marrow can be cryopreserved and reinfused into the patient to reverse such marrow ablation, has stimulated interest in this approach to refractory childhood cancers. We present results of treating eighteen patients with recurrent neuroblastoma and Ewing's sarcoma resistant to conventional therapy. We used supralethal doses of melphalan, supported by reinfusion of previously cryopreserved autologous bone marrow. Seven of 10 neuroblastoma and six of eight Ewing's sarcoma patients had complete or partial responses, lasting for a median of 6 months (neuroblastoma) and 3 months (Ewing's sarcoma). Prolonged hospitalization, pancytopenia complicated by sepsis, and reversible gastrointestinal toxicity were the major side effects. These results suggest this approach should be tested in therapeutic trials at an earlier disease stage in children who have cancers with a predictably bad prognosis.     

Megachemotherapy followed by autologous stem cell transplantation in children with Ewing's sarcoma

Twenty-one children with high-risk Ewing's tumor received high-dose chemotherapy with a PBSCT. Aim of the study was evaluation of efficiency and safety of this procedure. All but three patients have meta-static disease at presentation. There were 11 females and the median age at diagnosis was 12 yr (range 4.5-18 yr). Megachemotherapy consisted of melphalan 140 mg/m2/busulfan 16 mg/kg in 12 patients, melphalan 140 mg2/treosulfan 10.0 g/m2 in two patients and melphalan with other drugs in seven patients. Eight of 11 patients transplanted in CR survived with a median follow-up 24 month (range 14-60) and probability of 2-year OS is 0.68 and DFS is 0.63. There was no severe regimen-related toxicity in this group. Children transplanted without remission died: Two of them due to transplant related causes and eight had progression of disease in a median time 7 month after PBSCT. Megachemotherapy with PBSCT is a safe procedure in children with Ewing's sarcoma in remission. Autologos transplantation in children with metastatic Ewing's sarcoma seems to improve their outcome. Patients with Ewing's sarcoma, resistant to conventional therapy and with recurrent disease did not benefit from megachemotherapy. New approaches such as anti-tumor vaccination or using of imatinib are reasonable to introduce in patients with relapsed or resistant to therapy Ewing's tumor.     

Results of treatment of primary metastatic Ewing sarcoma. A retrospective analysis of 48 patients

The clinical presentation of the disease and the results of treatment in 48 patients with metastases at diagnosis of Ewing's sarcoma, entered into the Cooperative Ewing's Sarcoma Studies (CESS) 1981 and 1986 of the German Society of Pediatric Oncology (GPO), were analysed. The period of observation ranged from 1 to 82 months, the median relapse-free time was 26 months. There was a male predominance of 35 to 13, which was even more pronounced in patients older than 15 years. The predominant localization of the primary tumor was the pelvic region, followed by the extremities, the chest wall, and the spine. The most common site of primary metastases were the lungs, followed by bone and bone marrow. Nine patients presented with combined metastases. The disease-free survival according to Kaplan-Meier life-table analysis was 18% after 7 years. Best results were obtained in patients with pulmonary metastases only, who underwent surgical resection of the primary tumor and received radiation to the lungs. Without bone marrow transplantation the prognosis of patients with bone metastases was extremely poor.     

Ewing's sarcoma of the rib

In addition to eosinophilic granuloma, chondroma, osteochondroma, aneurysmatic bone cyst, and osteomyelitis, the differential diagnosis of primary costal tumors in children must also include Ewing's sarcoma. Radiologic diagnostic problems in localizing the tumor, in differential diagnosis, and the importance of imaging procedures are discussed with reference to a 16-year-old female patient.     

Ewing's sarcoma/primitive neuroectodermal tumor of the chest wall

Ewing's sarcoma/primitive neuroectodermal tumor is the most common tumor of the chest wall in children and adolescents. It is extremely malignant with a high frequency of both metastatic spread and of local recurrence. Cure requires intensive therapy to control both distant and local disease. Surgery and high-dose radiotherapy can achieve equivalent local control; however, radiation is associated with the additional morbidities of second malignancy and a significant adverse impact on both cardiac and pulmonary function. The optimal therapeutic sequence is initial biopsy followed by induction chemotherapy with subsequent resection of the primary tumor. This approach will achieve the lowest incidence of tumor present at the margins of resection and, hence, need for postoperative radiotherapy. The chest wall is a rare site for tumors in children and adolescents. In a series reported from St Jude's Children's Research Hospital, chest wall tumors constituted only 1.8% of the solid childhood tumors. They are primarily mesenchymal in origin and the Ewing's sarcoma/primitive neuroectodermal tumors (PNET) predominate. This report concentrates on the later tumors. They are recognized to be extremely malignant, and cure in those who present with metastatic disease is very difficult to achieve. Recent advances in our understanding of their cytogenetic basis and optimal treatment are presented.     

儿童输尿管肿瘤的诊治分析

目的 总结儿童输尿管肿瘤的病理类型、临床表现、诊断、治疗和预后,提高对该病的认识.方法 回顾性分析2011年1月至2015年10月我院收治的5例输尿管肿瘤患儿的临床资料,结合文献总结儿童输尿管肿瘤的病理类型、临床表现、诊断、治疗及预后.5例患儿均为男性,输尿管炎性肌纤维母细胞瘤3例,2例以腹痛就诊,分别为6岁和10岁,肿瘤位于输尿管下段,均行输尿管下段肿物切除+输尿管端端(输尿管膀胱)吻合,1例以尿痛并血尿就诊,年龄1岁9月龄,肿物来源于下段输尿管,经输尿管膀胱连接部长入膀胱,继发膀胱输尿管积水,经输尿管和膀胱联合切除肿物+输尿管膀胱再植术.结果 术后随访5~48个月,未见肿瘤复发及转移.恶性横纹肌样瘤1例6岁,以左下腹痛2周就诊,输尿管肿瘤边界不清与腰大肌肉和后腹膜粘连,切除肿物行输尿管端端吻合,术后ICE方案化疗一疗程后局部复发,放弃治疗,术后233d死亡.尤文/原始神经外胚层瘤1例12岁,以右侧腰痛10d就诊,肿瘤位于输尿管髂血管水平,行输尿管肿瘤切除术+输尿管端端吻合术,术后予CAV+IE化疗12个月,随访56个月,未见转移及复发.结论 输尿管肿瘤在儿童发病率极低,文献曾报道的病理类型包括炎性肌纤维母细胞瘤、恶性横纹肌样瘤、尤文/原始神经外胚层瘤、横纹肌肉瘤,术前无特异方法诊断,手术完整切除肿瘤并重建输尿管是治疗的主要方法,确诊需要结合病理检查,根据病理类型决定是否化疗,治疗后均需要长期随访.     

Granulocytic sarcoma presenting as pneumonia in a child with t(8;21) acute myelogenous leukemia: diagnosis by fluorescent in situ hybridization

Granulocytic sarcoma is a soft tissue collection of leukemic cells. The authors describe a 4-year-old boy with M2 acute myelogenous leukemia (AML) who presented with fever, mild nonproductive cough, and hematemesis. Although he was initially diagnosed with nodular pneumonia, rapid resolution of a pulmonary infiltrate following induction chemotherapy was suggestive of a pulmonary granulocytic sarcoma. Interphase fluorescent in situ hybridization (FISH) of the lung biopsy specimen for the t(8;21)(q22;q22) translocation confirmed the retrospective diagnosis of a well-differentiated pulmonary granulocytic sarcoma. Pulmonary granulocytic sarcomas may be underrecognized in children with AML; this may delay anti-leukemic therapy and may lead to ineffective therapy if misdiagnosed as pneumonia.     

Monoclonal antibody MB2: a potential marker for Ewing's sarcoma and primitive neuroectodermal tumor

The small round-cell tumors of childhood present difficulties in diagnosis when differentiation is not apparent. Immunohistochemistry is helpful; however, the only antigen consistently detected in Ewing's sarcoma is vimentin, which may also be detected in the other types of small-cell neoplasms. The monoclonal antibody (MAb) MB2 is marketed as a B-lymphocyte marker that can be used on paraffin-embedded tissue. To determine its specificity, we performed immunohistochemical staining on pediatric tumors with MB2. These included 55 cases of small round-cell tumors (lymphomas, Ewing's sarcoma, peripheral primitive neuroectodermal tumors [PNET], neuroblastomas, rhabdomyosarcomas, and nephroblastomas). MB2 positivity was detected in all B-cell lymphomas and in seven of nine cases of Ewing's sarcoma and three PNET. In neuroblastomas only differentiating ganglion cells were positive. In rhabdomyosarcomas only large rhabdomyoblasts were positive. Blastema of nephroblastomas was negative. Thus, in cases of poorly differentiated small round-cell tumors, MB2 was positive in all B-cell lymphomas, most Ewing's sarcomas and all cases of PNET. Lymphomas were distinguished by staining for leukocyte-common antigen and PNET by neuron-specific enolase. Therefore, the addition of MB2 to a discrete panel of antibodies may prove useful in the diagnosis of Ewing's sarcoma and PNET.     

Leydig cell tumor after treatment for Ewing's sarcoma

Leydig cell tumors account for 3% of testicular tumors and have never been reported after treatment for Ewing's sarcoma. We report the unusual occurrence of a patient who developed a Leydig cell tumor of the testis 18 years after successful treatment for Ewing's sarcoma. Additional monitoring for second malignancies may become appropriate as long-term survival continues to improve for patients with Ewing's sarcoma.     

Bone Marrow Metastasis in Ewing's Sarcoma and Peripheral Primitive Neuroectodermal Tumor: An Immunohistochemical Study

Bone marrow metastases from small round cell tumors can present diagnostic difficulties. In this study, we assessed the value of immunohistochemistry, using two monoclonal antibodies to CD99, for the diagnosis of metastatic disease in bone marrow trephine specimens from patients with Ewing's sarcoma or primitive neuroectodermal tumor (PNET). The proportions of specimens showing metastases were 10.3% with routine staining and 20.7% with immunohistochemistry. The specimens that were negative on conventional light microscopy and positive with immunohistochemistry all showed other abnormalities. The results do not support the routine use of immunohistochemistry in specimens that are normal by conventional light microscopy, but indicate that useful information may be gained in cases where marrow histology is obscured by fibrosis, necrosis, or distortion artefact. Neither of the two antibodies tested was superior for this purpose. Received January 17, 1997; accepted May 22, 1997