Presentación de un sarcoma extraóseo de Ewing como una masa mediastínica posterior / Extraskeletal Ewing's Sarcoma Presenting as a Posterior Mediastinal Mass

La familia de tumores del sarcoma de Ewing es un grupo poco habitual de neoplasias malignas que pueden localizarse en regiones tanto óseas como extraóseas. El sarcoma de Ewing extraóseo (SEE) es poco frecuente y afecta de modo predominante a los tejidos blandos del tronco o de las extremidades. Describimos a una paciente de 19 años de edad que refirió dolor en el brazo izquierdo. La radiografía de tórax simple reveló una opacidad que ocupaba casi todo el hemitórax izquierdo y, tras realizar modalidades de diagnóstico por imagen, se demostró una lesión de masa realzada para el contraste, sólida, en el mediastino posterior. Era evidente una desviación mediastínica y el pulmón izquierdo estaba colapsado. Aunque, como diagnóstico inicial, se consideró un linfoma, la paciente se sometió a una biopsia y el análisis histopatológico reveló un SEE. Entre los estudios publicados, solo se han descrito unos pocos casos de SEE localizados en el mediastino. Concluimos que, aunque es una localización insólita del SEE, debe tenerse en cuenta en el diagnóstico diferencial de las masas mediastínicas(AU)

The Ewing's sarcoma family of tumors is an uncommon group of malignant neoplasms that may be located in both skeletal and extraskeletal regions. Extraskeletal Ewing's sarcoma (EES) is quite rare and predominantly involves the soft tissues of the trunk or the extremities. Herein, we report the case of a 19-year-old female patient who complained of left arm pain. Simple chest radiography revealed an opacity occupying almost the entire left hemithorax. Diagnostic imaging techniques demonstrated a solid contrast-enhanced mass in the posterior mediastinum. There was an evident mediastinal shift, and the left lung was collapsed. Even though lymphoma was considered as an initial diagnosis, a biopsy was taken and its histopathological analysis revealed EES. In the literature, there have been only a few case reports of ESS located in the mediastinum. We conclude that, although this is an unusual location, EES should be contemplated in the differential diagnosis of mediastinal masses(AU)

Tumor neuroectodérmico primitivo (tumor de Askin) en la pared torácica / Primitive neuroectodermal tumour (Askin tumour) in the chest wall

No disponible

Sarcoma de Ewing renal primario / Primary renal Ewing`s sarcoma

OBJETIVO: Presentación de dos nuevos casos de sarcoma de Ewing / tumor neuroectodérmico primitivo renal primario, uno de ellos con trombo en cava.MÉTODO: Caracterización de los dos casos clínicos y revisión bibliográfica mediante búsqueda en pubmed.RESULTADO: Presentamos los casos de dos varones diagnosticados de sarcoma de Ewing renal primario, que han sido tratados con nefrectomía y quimioterapia adyuvante; encontrándose en remisión completa hasta la fecha.CONCLUSIÓN: El sarcoma de Ewing / tumor neuroectodérmico primitivo renal primario es una entidad rara que afecta mayoritariamente a adultos jóvenes. La historia natural de estos tumores es la evolución hacia una enfermedad metastásica y la muerte. El tratamiento es multimodal, y combina cirugía y quimioterapia. El papel de la radioterapia no está bien establecido(AU)

OBJECTIVE: To report two new cases of Ewing`s sarcoma/ primitive neuroectodermal tumor of the kidney, one of them with tumor thrombus in cava.METHOD: Characterization of two new cases and literature review by PubMed search.RESULTS: We report the cases of two men diagnosed with primary renal Ewing`s sarcoma, who have been treated with nephrectomy and adjuvant chemotherapy, being in complete remission to date.CONCLUSION: Ewing`s sarcoma / primitive neuroectodermal tumor of the kidney is a rare condition that mainly affects young adults. The natural history of these tumors is the evolution towards metastatic disease and death. Treatment is multimodal, combining surgery and chemotherapy. The role of radiotherapy is not well established

Tumores neuroectodérmicos primitivos periféricos de localización en el área orocervical: presentación de dos casos clínicos / Peripheral primitive neuroectodermal tumors located in orocervical area: presentation of two clinical cases

Introducción: Los tumores neuroectodérmicos primitivos (PNET, de primitive neuroectodermaltumors) son una familia de neoplasias malignas de células pequeñas y redondas, quederivan de la cresta neural. Se distinguen tres tipos: PNET del sistema nervioso central,PNET del sistema nervioso autónomo y PNET periféricos. Los más frecuentes dentro delgrupo de PNET periféricos son el neuroepitelioma periférico y el sarcoma de Ewing, que seconsideran la misma neoplasia pero con diferente grado de diferenciación.Casos clínicos: Presentamos dos casos de PNET periféricos, uno de aparición en la regióncervical y otro originado en el cóndilo mandibular.Discusión: Los PNET son neoplasias muy raras y altamente agresivas. En todos ellos aparecencélulas redondas pequeñas poco diferenciadas y una traslocación cromosómica característicadel gen EWS. En general se considera que tienen un pronóstico desfavorable.Además, la baja frecuencia de estos tumores, así como la escasez de casos publicados hacendifícil valorar el tratamiento más adecuado(AU)

Introduction: Peripheral primitive neuroectodermal tumors (PNET) are a family of smallroundcell tumors of presumed neuroectodermal origin. This broad family can besubdivided into three major groups: PNET from the central nervous system, PNET from theautonomic nervous system or peripheral PNET. Ewing’s sarcoma and peripheralneuroepitelioma, the two most frequently encountered members of the peripheral PNET family, are considered to represent a spectrum according to the extent of neuroectodermaldifferentiation, ranging from the least differentiated (Ewing’s sarcoma) to the mostdifferentiated (peripheral neuroepithelioma).Case report: We present a patient with a peripheral neuroectodermal tumor located in the neckand another one with a peripheral neuroectodermal tumor of the mandibular condyle.Discussion: Peripheral neuroectodermal tumors are a very rare and aggressive tumors. Theycharacteristically reveal the presence of small round cells and a translocation of the geneEWS. The prognosis in overall is very poor. Due to the small numbers of cases publishedthe best treatment is not well defined(AU)

Sarcoma de Ewing pulmonar/tumor neuroectodérmico primitivo (PNET): aportación de un caso y revisión de la bibliografía / Pulmonary Ewing sarcoma/primitive neuroectodermal tumor: a case report and a review of the literature

Los sarcomas primarios de tórax son muy poco frecuentes. Sarcoma sinovial, angiosarcomas, leiomiosarcomas, rabdomiosarcomas y mesoteliomas sarcomatoides son las variantes intratorácicas más comunes. Aunque el sarcoma de Ewing/tumor neuroectodérmico primitivo (PNET) torácico se desarrolla habitualmente en la pared torácica, se ha descrito en la literatura médica algún caso de localización pulmonar primaria. Presentamos el caso de una mujer de 22 años diagnosticada de sarcoma de Ewing/PNET pulmonar mediante muestra broncoscópica por sus características histológicas, inmunohistoquímicas y técnicas de hibridación in situ. Se excluyó el origen metastásico mediante radiografía, gammagrafía y biopsia de médula ósea. Se inició quimioterapia según el esquema VACD-IE (vincristina, actinomicina D, ciclofosfamida, doxorrubicina, ifosfamida y etopósido), con buena respuesta. En la actualidad acude de forma regular a consultas ambulatorias(AU)

Primary thoracic sarcomas are very rare. The most common intrathoracic variants are synovial sarcoma, angiosarcoma, leiomyosarcoma, rhabdomyosarcoma, and sarcomatoid mesothelioma. Although thoracic Ewing sarcoma/primitive neuroectodermal tumor (PNET) usually develops on the chest wall, there have been reports of primary Ewing sarcoma/PNET of the lung. We present the case of a 22-year-old woman with Ewing sarcoma/PNET diagnosed following histologic, immunohistochemical, and in situ hybridization studies of a bronchial biopsy specimen. Radiography, ventilation-perfusion scintigraphy, and a bone marrow biopsy confirmed that the tumor was not metastatic. The patient was started on a chemotherapy regimen of vincristine, actinomycin, cyclophosphamide, doxorubicin, ifosfamide, and etoposide and responded well. She is now being seen regularly at our outpatient clinic(AU)

Peripheral Primitive Neuroectodermal Tumour (pPNET) in the cervical spine.

Primary spinal primitive neuroectodermal tumours are rare. We present a 45-year-old man with a peripheral primitive neuroectodermal tumour arising in the cervical spine. We believe this to be the first report of this type of tumour in the cervical spine.

An infant case of intracranial peripheral-type primitive neuroectodermal tumor with long-term survival.

Supratentorial primitive neuroectodermal tumors (S-PNET) that develop in children have recently been classified into two types: central-type PNET (C-PNET), which has been reported over the years, and peripheral-type PNET (P-PNET), which develops intracranially and was referred to as Ewing's sarcoma in the past. P-PNET is fundamentally a malignant tumor, but the patient reported here represents a case of long-term survival from onset without recurrence. At the age of 21 months, a male infant developed a cranial bone deformity and symptoms of high intracranial pressure. A CT scan revealed a cystic tumor attaching to the falx, and cyst drainage operation was immediately performed. The intracranial tumor was then resected. The tumor was an intradural extramedullary tumor, and it was totally excised with the falx attachment. The tumor was initially diagnosed as a neuroblastoma, and postoperative treatment consisted of administration of radiotherapy and chemotherapy using cyclophosphamide and vincristine. Twenty years have now passed without any recurrence. Recent repeated performance of histopathological analysis resulted in a diagnosis of P-PNET. In recent years, studies in molecular biology have demonstrated that P-PNET involves the EWS-FLI1 chimeric gene, and immunohistochemical staining has shown P-PNET to be MIC2 positive. P-PNET also differs from C-PNET with regard to prognosis, and for this reason it is believed that P-PNET and C-PNET should be considered separate entities. That is, in spite of the fact that P-PNET is a malignant tumor, patient survival can be comparatively long. Because P-PNET originates intracranially, it is fundamentally an intradural extramedullary tumor. For this reason, treatment should consist of surgical excision that is as complete as possible, followed by appropriate radiotherapy and chemotherapy. This approach can be expected to result in the patient's long-term survival.

Primary Ewing´s sarcoma/primitive neuroectodermal tumor of the kidney. An infrequent finding / Sarcoma de Ewing primario/Tumor neuroectodérmico primitivo renal. Un hallazgo infrecuente

Objetive: Ewing's sarcoma/Primitive neuroectodermal tumor (ES/PNET) is an extraordinarily rare primary tumor in the kidney. We report herein the clinical, histological, and immunohisto-chemical features of a primary renal ES/PNET. Methods: A 19-year old male referred a two weeks history of constant, colic, left flank pain, and fever. A left radical nephrectomy was performed. Gross pathologic examination showed pink-tan, lobulated solid tumor, localized at the superior pole. Results: Histologically, the tumor was solid with necrosis. The neoplastic cells showed a small amount of clear cytoplasm, and had vesicular nuclei with small nucleoli. Immunohistochemical studies showed strongly and diffusely positive staining for CD99 in a membranous pattern. Conclusions: This case represents a typical ES/PNET, affecting a young male patient. Adequate diagnosis is important because this neoplasm has an aggressive behaviour (AU)

El sarcoma de Ewing/Tumor Neuroectodermico Primitivo (SE/TNEP) del riñón es una neoplasia extremadamente rara en el riñón. Presentamos los hallazgos clínicos, histológicos e inmunohistoquímicos de un SE/TNEP primario renal. Métodos: Un paciente varón de 19 años refirió historia de dos semanas de dolor tipo cólico, constante, en el flanco izquierdo y fiebre. Se hizo nefrectomía radical izquierda. El examen macroscópico mostró un tumor sólido, lobulado, pardo-rosado, localizado en el polo superior. Resultados: Histológicamente el tumor era sólido con necrosis. Las células neoplásicas mostraron citoplasma escaso claro y poseían un núcleo vesicular con nucléolo pequeño. Los estudios inmunohistoquímicos mostraron una fuerte y difusa positividad para el CD99 en un patrón membranoso. Conclusiones: Este caso representa un típico SE/TNEP, afectando a un varón joven. Es importante un diagnóstico adecuado debido a que esta neoplasia tiene una conducta agresiva (AU)

Peripheral primitive neuroectodermal tumor with postchemotherapy neuroblastoma-like differentiation.

We report the case of an 11-year-old girl with a retroperitoneal tumor in the left upper quadrant. The girl was admitted to hospital with weight loss and a painless abdominal mass that on biopsy was diagnosed as a peripheral primitive neuroectodermal tumor/Ewing sarcoma (pPNET/EWS) of the soft tissue. The patient underwent chemotherapy followed by surgical resection of the tumor 5 months after diagnosis. The posttreatment residual viable tumor showed a morphologic appearance resembling a neuroblastoma. Interphase and metaphase fluorescent in situ hybridization (FISH) studies performed on the pretreatment and posttreatment samples showed the presence of a t(11;22) rearrangement resulting in EWSR1/FLI1 gene fusion consistent with pPNET/EWS in both specimens. This case is unusual in the sense of showing the typical gene fusion for pPNET/EWS both in the pretherapy sample with the typical morphological appearance of this tumor and in the posttherapy specimen showing neural differentiation suggestive of a neuroblastoma.

Peripheral primitive neuroectodermal tumor/Ewing's sarcoma of the craniospinal vault: case reports and review.

The peripheral primitive neuroectodermal tumor/Ewing's sarcoma family tumor (pPNET/ESFT) group includes small round cell tumors of the bone, soft tissue, and nerve with morphological attributes of the germinal neuroepithelium. Peripheral PNETs/ESFTs also occur within the craniospinal vault, a region including the central nervous system, the meninges, and the cranial and spinal nerve roots. Gene rearrangements between the EWS gene on chromosome 22q12 and members of the ETS gene family are common in and specific to pPNETs/ESFTs. Another defining characteristic of pPNETs/ESFTs is their membranous expression of the MIC2 gene product. We describe 2 cases of pPNETs within the craniospinal vault. An intradural tumor arising from the nerve roots of the cauda equina was discovered in a 32-year-old man presenting with radiculopathic back pain and lower-extremity weakness. An intracranial pPNET that mimicked a meningioma was found in a 21-year-old man presenting with headache and visual disturbances. MIC2 gene product expression and EWS/ETS gene rearrangement were detected in both case patients. The literature with regard to pPNETs/ESFTs arising within the craniospinal vault is reviewed.

Two successful spontaneous pregnancies in a patient with a primary primitive neuroectodermal tumor of the ovary.

OBJECTIVE: To describe a patient with primary primitive neuroectodermal tumor of the ovary with two successful spontaneous pregnancies. DESIGN: Case report. SETTING: Tertiary center for gynecologic oncology. PATIENT(S): A 25-year-old woman with two spontaneous pregnancies 5 months after and 2 years after conservative treatment of International Federation of Gynecology and Obstetrics stage IC primary primitive neuroectodermal tumor of the ovary. INTERVENTION(S): Assessment of extraovarian spread with staging laparotomy. Four courses of BEP (bleomysin, etoposide, cisplatin) and, for recurrent disease, six courses of salvage VIP (vinblastin, iphosphamide, mesna, cisplatin) chemotherapy. MAIN OUTCOME MEASURE(S): Two successful deliveries and no residual ovarian cancer. RESULTS(S): A healthy, normal female infant weighing 3600 g was delivered by cesarean section at 38 weeks' gestation. Sixteen months later another infant, a healthy, normal male weighing 3500 g, was delivered by cesarean section at 38 weeks' gestation. No residual cancer was detected at follow-up 12 months after the last delivery. CONCLUSION(S): Conservative fertility-preserving treatment might be considered in patients with primary primitive neuroectodermal tumor of the ovary. Without any assisted reproductive technologies, spontaneous pregnancies might occur.

Fibroblast growth factor 2 induces differentiation and apoptosis of Askin tumour cells.

Peripheral primitive neuroectodermal tumour (PNET)/Ewing's sarcoma (ES) and neuroblastoma (NB) are related tumours of neural crest origin with primitive neural characteristics. Fibroblast growth factor 2 (FGF2) is a critical signalling molecule for primitive neural crest cells. The treatment of NB cells with FGF2 variably affects biological characteristics such as growth and differentiation, while in PNET/ES, FGF2 predominantly induces apoptosis. The JK-GMS Askin tumour cell line can be induced to differentiate upon treatment with nerve growth factor (NGF), indicating the integrity of the cellular machinery necessary for differentiation. The present study assesses whether FGF2 can induce differentiation in JK-GMS cells. JK-GMS cells expressed high-affinity FGF receptors (FGFRs), and treatment with FGF2 induced phosphorylation of FGFR1 together with activation of extracellular signal-regulated kinases (ERK1/ERK2) and c-Jun N-terminal kinase (JNK). Subsequent biological effects were growth inhibition, neuronal differentiation, and apoptosis, and these changes were associated with increased expression of neurofilaments, reduction of c-myc and bcl-2 expression, and activation of caspase 3. Treatment of the cells with a specific inhibitor of the MAPK/extracellular signal-regulated kinase (MEK)-1, PD98059, predominantly inhibited the effects of FGF2 on growth, differentiation, and apoptosis, while an inhibitor of JNK reduced apoptosis, indicating that the ERK1/2 and JNK pathways are critical components of FGF2-mediated effects in JK-GMS cells. Additional comparative analyses of FGF2-mediated effects in two ES cell lines (CADO-ES, RD-ES) and a PNET cell line (SK-N-MC) showed pronounced differentiation in SK-N-MC, but not in CADO-ES or RD-ES cells. This study demonstrates that FGF2 can induce neuronal differentiation of PNET including Askin tumour. These findings clearly indicate that the FGF2-mediated signalling pathway plays a critical role in controlling the major properties of PNET cells and may provide a potential therapeutic target for PNET.

Alternative EWS-FLI1 fusion gene and MIC2 expression in peripheral and central primitive neuroectodermal tumors.

Primitive neuroectodermal tumors (PNET) occur either in the central nervous system (CNS; central PNET, cPNET) or in the peripheral sites (peripheral PNET, pPNET). Recent molecular approaches have been defining a new concept of PNET, that is, the pPNET including Ewing's sarcoma (ES) which expresses MIC2 glycoprotein and shows the specific chimeric gene of EWS-FLI1. The expression of MIC2 and the genetic rearrangement of EWS-FLI1 are considered to be highly specific to the pPNET/ES. This study examined the expression of MIC2 and EWS-FLI1 gene by means of immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) on various small round cell tumors originating in the CNS or non-CNS organs. All peripheral PNET tested expressed MIC2 and were positive for EWS-FLI1 (11/11). In contrast, all cPNET and other blastic CNS tumors were negative for MIC2: medulloblastoma (0/3), cerebral PNET (0/2), spinal PNET (0/2), glioblastoma (0/2), retinoblastoma (0/3), and pineoblastoma (0/2). These MIC2-negative tumors were also negative for the chimeric gene product of EWS-FLI1. Interestingly, one PNET originating in the intracranial dura mater was positive for both MIC2 and EWS-FLI1 fusion gene. The results indicate that cPNET lacks any genetic or protein markers, except for a meningeal PNET which falls into the same phenotypic spectrum of pPNET.

Ganglioside patterns in neuroepithelial tumors of childhood.

To elucidate a relationship between neuronal anaplasia, tumor proliferation, and ganglioside contents, we quantified gangliosides by HPTLC in tumors of neuroepithelial tissues at different grade, i. e. peripheral primitive neuroectodermal tumor (PPNET, grade IV), ependymoma (EPEN, grade III), neuroblastoma (NB, grade IV), and dysembryoplastic neuroepithelial tumor (DNT, grade I). PPNET, the most undifferentiated tumor examined had lowest concentration of total lipid-bound sialic acid. GM3 was the major ganglioside in all undifferentiated tumors (46-72.7% of total lipid-bound sialic acid). GD3 was an another component in PPNET and EPEN (7.2-17.3%). Concentration of a complex gangliosides GM1 was decreased in all tumor tissues and those of GT1a, GD1b and GT1b were decreased in tumors of high grade. The results suggest that the composition of gangliosides could be of considerable value in refining the classification of neuroepithelial tumors in infancy and childhood.

Small round blue cell tumors in bone: prognostic factors correlated to Ewing's sarcoma and neuroectodermal tumors.

Ewing's sarcoma and peripheral neuroectodermal tumors are the most common small round blue cell tumors of bone. Accurate prognostic factors are required to define guidelines to standardize the treatment modalities and to adapt these modalities to the potential evolution of the disease. The various factors that have emerged in the literature as influences on the outcome of patients with Ewing's sarcoma or peripheral neuroectodermal tumors of bone are considered in this review. The presence of metastases at the clinical onset of the disease represents the most adverse prognostic factor. For nonmetastatic patients, axial location appears to be the most unfavorable factor, despite initial tumor volume, by showing that the tumor burden could be a more appropriate indicator of patient outcome. The importance of a local control of the disease by surgery has been emphasized, and the value of the histopathologic evaluation of the response to chemotherapy has been stressed.

Insulin-like growth factor I expression by tumors of neuroectodermal origin with the t(11;22) chromosomal translocation. A potential autocrine growth factor.

Expression of insulin-like growth factor I (IGF-I) mRNA by some tumor cell lines of neuroectodermal origin has been described. To further explore the significance of IGF-I mRNA expression in these tumors, a more extensive analysis was performed. Most (9 of 10) neuroectodermal tumor cell lines with a t(11;22) translocation (primitive neuroectodermal tumor [PNET], Ewing's sarcoma, esthesioneuroblastoma) expressed IGF-I mRNA, whereas 0 of 15 cell lines without the translocation (PNET, neuroblastoma) expressed IGF-I. Furthermore, inasmuch as all neuroblastoma (12 of 12) cell lines examined expressed IGF-II RNA, the pattern of IGF expression could distinguish between these closely related tumors. CHP-100, a PNET cell line with the t(11;22) translocation, was shown to secrete both IGF-I protein and an IGF binding protein, IGFBP-2. This cell line also expressed the type I IGF receptor mRNA, and blockade of this receptor by a monoclonal antibody (alpha IR3) inhibited serum-free growth. These data demonstrate that IGF-I expression is a property of neuroectodermal tumors with a t(11;22) translocation and that interruption of an IGF-I autocrine loop inhibits the growth of these tumor cells.