[Ewing sarcoma/primitive hepatic neuroectodermal tumor]. / Sarcoma de Ewing/tumor neuroectodérmico primitivo hepático.

Ewing sarcoma (ES) and primitive neuroectodermal tumor (PNET) belong to the group of neoplasms called small round cell tumors. PNETs have been divided into central and peripheral. ES and peripheral PNETs arise from bones, soft tissues, or peripheral nerves. We present a case of hepatic ES/PNET in a healthy man that began four months before consultation with abdominal symptoms and weight loss. Upper gastrointestinal endoscopy and laboratory tests revealed no notable findings. The abdominal tomography revealed an enlarged liver due to a solid lesion that involved all its segments with intravenous contrast enhancement and large areas of necrosis. It compressed and displaced neighboring structures. Core needle biopsy of the liver lesion was performed: small round cell neoplasm. Immunohistochemistry revealed negativity for CD45, CKA1/A3, chromogranin, synaptophysin, and cytokeratins CK7 and CK20. Dim CD56 expression and CD99, FLI-1, and NKX2 positivity. He underwent chemotherapy treatment with carboplatin and etoposide for 6 cycles with clinical improvement and tolerance. Control images showed reduction of the mass with involvement of the right hepatic lobe, involvement of the inferior vena cava, infiltration of the right adrenal gland and upper pole of the right kidney. He was referred to hepatobiliary surgery for surgical resection of the residual lesion. The patient rejected the proposed surgical procedure. Our objective is to highlight the clinical and histological diagnostic challenge of this entity that requires ruling out other clinical entities.

El sarcoma de Ewing (ES) y el tumor neuroectodérmico primitivo (PNET) pertenecen al grupo de neoplasias denominadas tumores de células pequeñas y redondas. Los PNET se dividen en centrales y periféricos. El ES y los PNET periféricos surgen del tejido óseo, de los tejidos blandos o nervios periféricos. Presentamos un caso de ES/PNET hepático en un hombre sano que inició cuatro meses antes de la consulta con síntomas abdominales y pérdida de peso. La endoscopia digestiva alta y la analítica no revelaron hallazgos relevantes. En la tomografía de abdomen se evidenció hígado aumentado de tamaño a expensas de lesión sólida que comprometía todos sus segmentos con realce al contraste endovenoso y grandes áreas de necrosis. Comprimía y desplazaba estructuras vecinas. Se realizó biopsia con aguja gruesa de la lesión hepática: neoplasia de células pequeñas y redondas. La inmunohistoquímica reveló negatividad para CD45, CKA1/A3, cromogranina, sinaptofisina y citoqueratinas CK7 y CK20. Expresión tenue de CD56 y positividad de CD99, FLI-1 y NKX2. Realizó tratamiento quimioterápico con carboplatino y etopósido por 6 ciclos con mejoría clínica y tolerancia al mismo. En imágenes de control se evidenció reducción de la masa con afección del lóbulo hepático derecho, compromiso de la vena cava inferior, infiltración de la glándula suprarrenal y polo superior del riñón derechos. Se remitió a cirugía hepatobiliar para resección quirúrgica de la lesión residual. El paciente rechazó el procedimiento quirúrgico. Nuestro objetivo es destacar el desafío diagnóstico clínico e histológico de esta entidad que obliga a descartar otras entidades clínicas.

Proximal femur alloprosthesis in a pediatric patient with Ewing sarcoma: Case report.

INTRODUCTION AND IMPORTANCE: Ewing sarcoma is a primary malignant tumor of bone and, to a lesser extent, soft tissues. Within oncological management, surgery with extensive local control and reconstruction is the most accepted option, however, the size, extension of the tumor, the age of the patient and distant involvement can make this option difficult. CASE PRESENTATION: We present a clinical case of a 3-year-old infant with Ewing sarcoma in the proximal femur, who was managed with wide resection of the tumor plus proximal humerus allograft, which acted as a proximal femur for 2 years and then presented joint failure due to what was done was the application of a cemented stem over the remnant of the allograft to save the hip. CLINICAL DISCUSSION: In the presented case, similar to the report by Zoccali a malignant tumor in the proximal femur of a pediatric patient is documented. In these cases, where the distal femoral growth plate is disease-free, a reconstruction technique preserving the growth plate is proposed. CONCLUSION: The technique of proximal femoral allograft with a proximal humeral graft is an acceptable reconstructive treatment alternative for young patients with Ewing sarcoma, especially when conventional treatment options are limited. This approach helps avoid limb-threatening surgeries such as amputation or rotationplasty, providing a viable and functional solution for limb salvage in these cases.

Stemness and Cell Cycle Regulators and Their Modulation by Retinoic Acid in Ewing Sarcoma.

Retinoic acid (RA) regulates stemness and differentiation in human embryonic stem cells (ESCs). Ewing sarcoma (ES) is a pediatric tumor that may arise from the abnormal development of ESCs. Here we show that RA impairs the viability of SK-ES-1 ES cells and affects the cell cycle. Cells treated with RA showed increased levels of p21 and its encoding gene, CDKN1A. RA reduced mRNA and protein levels of SRY-box transcription factor 2 (SOX2) as well as mRNA levels of beta III Tubulin (TUBB3), whereas the levels of CD99 increased. Exposure to RA reduced the capability of SK-ES-1 to form tumorspheres with high expression of SOX2 and Nestin. Gene expression of CD99 and CDKN1A was reduced in ES tumors compared to non-tumoral tissue, whereas transcript levels of SOX2 were significantly higher in tumors. For NES and TUBB3, differences between tumors and control tissue did not reach statistical significance. Low expression of CD99 and NES, and high expression of SOX2, were significantly associated with a poorer patient prognosis indicated by shorter overall survival (OS). Our results indicate that RA may display rather complex modulatory effects on multiple target genes associated with the maintenance of stem cell's features versus their differentiation, cell cycle regulation, and patient prognosis in ES.

Histone Methyltransferases G9a/Ehmt2 and GLP/Ehmt1 Are Associated with Cell Viability and Poorer Prognosis in Neuroblastoma and Ewing Sarcoma.

Changes in epigenetic programming have been proposed as being key events in the initiation and progression of childhood cancers. HMT euchromatic histone lysine methyltransferase 2 (G9a, EHMT2), which is encoded by the G9a (Ehmt2) gene, as well as its related protein GLP, which is encoded by the GLP/Ehmt1 gene, participate in epigenetic regulation by contributing to a transcriptionally repressed chromatin state. G9a/GLP activation has been reported in several cancer types. Herein, we evaluated the role of G9a in two solid pediatric tumors: neuroblastoma (NB) and Ewing sarcoma (ES). Our results show that G9a/Ehmt2 and GLP/Ehmt1 expression is higher in tumors with poorer prognosis, including St4 International Neuroblastoma Staging System (INSS) stage, MYCN amplified NB, and metastatic ES. Importantly, higher G9a and GLP levels were associated with shorter patient overall survival (OS) in both NB and ES. Moreover, pharmacological inhibition of G9a/GLP reduced cell viability in NB and ES cells. These findings suggest that G9a and GLP are associated with more aggressive NB and ES tumors and should be further investigated as being epigenetic targets in pediatric solid cancers.

A logical model of Ewing sarcoma cell epithelial-to-mesenchymal transition supports the existence of hybrid cellular phenotypes.

Ewing sarcoma (ES) is a highly aggressive pediatric tumor driven by the RNA-binding protein EWS (EWS)/friend leukemia integration 1 transcription factor (FLI1) chimeric transcription factor, which is involved in epithelial-mesenchymal transition (EMT). EMT stabilizes a hybrid cell state, boosting metastatic potential and drug resistance. Nevertheless, the mechanisms underlying the maintenance of this hybrid phenotype in ES remain elusive. Our study proposes a logical EMT model for ES, highlighting zinc finger E-box-binding homeobox 2 (ZEB2), miR-145, and miR-200 circuits that maintain hybrid states. The model aligns with experimental findings and reveals a previously unknown circuit supporting the mesenchymal phenotype. These insights emphasize the role of ZEB2 in the maintenance of the hybrid state in ES.

Ewing's sarcoma of the head and neck: A systematic review.

OBJECTIVE: The aim of the present study was to conduct a systematic review of head and neck Ewing sarcoma (ES) concerning patients' demographic and clinical features, histopathological findings, treatment, follow-up, and survival rate. MATERIALS AND METHODS: An electronic search was undertaken in four databases. Articles describing case reports or case series were included. Outcomes were evaluated by the Kaplan-Meier method along with Cox regression. RESULTS: The search yielded 186 studies describing 227 ES cases. The mean age was 22.7 years, and males were slightly more affected. Interestingly, more than half the cases were diagnosed up to 20 years. The respiratory tract was the most reported site, followed by the jawbones. Clinically, symptomatic swelling or nodules were described, with a mean duration of 4 months. Management involved multimodal treatment regimens. Local recurrence, lymph node and distant metastasis were observed in 10.7%, 12.6%, and 20.3% of cases, respectively. Statistical analysis revealed that older patients with distant metastasis had a lower overall survival rate (p < 0.05). CONCLUSION: This study provides an overall view of head and neck ES that can assist oral and maxillofacial pathologists with the diagnosis and extend the knowledge of surgeons and oncologists about this condition.

The Extended-Sphenoid Ridge Approach: A New Technique for the Surgical Treatment of Skull Base Tumors in Pediatric Patients.

The sphenoid ridge approach (SRA) was initially described as a surgical technique for treating vascular pathologies near the Sylvian fissure. However, limited studies have systematically explored the use of skull base techniques in pediatric patients. This study investigated an extended variation in the sphenoid ridge approach (E-SRA), which systematically removed the pterion, orbital walls (roof and lateral wall), greater sphenoid wing, and anterior clinoid process to access the base of the skull. OBJECTIVE: This report aimed to evaluate the advantages of the extradural removal of the orbital roof, pterion, sphenoid wing, and anterior clinoid process as a complement to the sphenoid ridge approach in pediatric patients. PATIENTS AND METHODS: We enrolled 36 patients with suspected neoplastic diseases in different regions. The E-SRA was performed to treat the patients. Patients were included based on the a priori objective of a biopsy or a total gross resection. The surgical time required to complete the approach, associated bleeding, and any complications were documented. RESULTS: Our results demonstrated that the proposed a priori surgical goal, biopsy, or resection were successfully achieved in all cases. In addition, using the E-SRA technique was associated with a shorter operative time, minimal bleeding, and a lower incidence of complications. The most frequently encountered complications were related to dural closure. CONCLUSIONS: The extended sphenoid ridge approach represents a safe and effective option for managing intracranial tumors in pediatrics.

Sarcoma de Ewing multifocal: presentación de un caso pediátrico / Multifocal Ewing sarcoma: presentation of a pediatric case / Sarcoma de Ewing Multifocal: apresentação de um caso pediátrico

Introducción: el Sarcoma de Ewing es una neoplasia maligna de origen mesenquimático. Al momento del diagnóstico el 75% se presentan en forma localizada. Objetivo: comunicar un caso que por su presentación multifocal, generó dificultades diagnósticas. Caso clínico: niña de 6 años. Consulta por traumatismo de mano derecha tras caída de su altura 24 horas previas, constatándose en mano y puño derecho edema, calor y eritema, movilidad conservada. No fiebre. Radiografía: aumento del diámetro del tercer metacarpiano, imagen esmerilada, no trazos de fracturas. Ingresa con planteo de celulitis. Anemia leve microcítica, hipocrómica. Proteína C reactiva 82 mg/l. Recibe clindamicina intravenosa 72 horas, completa 14 días vía oral. Persistencia de alteraciones en puño y mano derecha, agrega tumoración de raíz nasal con desviación del eje, indolora. Fosfatasa alcalina, lactato deshidrogenasa, fosfatemia, calcemia normales. Resonancia magnética: alteración morfoestructural de radio, olecranon y tercer metacarpiano, fractura de olecranon y radio, reacción perióstica. Pet-Scan: lesión extensa ósea en macizo facial, tibias, cúbitos, humero derecho y clavícula. Biopsia 3er metacarpiano: tumor de células pequeñas, redondas azules, CD99 y vimentina positivo. Comienza poliquimioterapia y radioterapia sin complicaciones. Conclusiones: es frecuente que las manifestaciones clínicas iniciales sean confundidas con entidades más frecuentes, como post-traumáticas y/o inflamatorias, tal como ocurrió en este caso. Posteriormente, la aparición de nuevas lesiones y compromiso del estado general orientó el abordaje diagnóstico de la patología tumoral. La confirmación exige el estudio anatomopatológico con estudio inmunohistoquímico. La presencia de metástasis óseas constituye un factor de mal pronóstico y dificulta el abordaje terapéutico.

Introduction: Ewing's sarcoma is a malignant neoplasm of mesenchymal origin. At the time of diagnosis 75% of the cases are localized. Objective: to report a case that, due to its multifocal presentation, generated diagnostic difficulties. Clinical case: 6-year-old girl. She consulted for right hand trauma after a fall from her height 24 hours earlier, with edema, warmth and erythema in the right hand and fist, with preserved mobility. No fever. X-ray: increase in the diameter of the 3rd metacarpal, frosted image, no traces of fractures. Admitted with cellulitis. Mild microcytic anemia, hypochromic. C-reactive protein 82mg/l. Receives intravenous clindamycin 72 hours, completes 14 days orally. Persistence of alterations in fist and right hand, adds tumor of nasal root with deviation of the axis, painless. Alkaline phosphatase, lactate dehydrogenase, phosphatemia, normal calcemia. MRI: morphostructural alteration of radius, olecranon and 3rd metacarpal, fracture of olecranon and radius, periosteal reaction. Pet-Scan: extensive bone lesion in facial mass, tibiae, ulnae, right humerus and clavicle. Biopsy 3rd metacarpal: small cell tumor, blue round, CD 99 and vimentin positive. Polychemotherapy and radiotherapy were started without complications. Conclusions: it is frequent that the initial clinical manifestations are confused with more frequent entities, such as post-traumatic and/or inflammatory, as occurred in this case. Subsequently, the appearance of new lesions and compromise of the general condition guided the diagnostic approach of the tumor pathology. Confirmation requires anatomopathological study with immunohistochemical study. The presence of bone metastases constitutes a poor prognostic factor and hinders the therapeutic approach.

Introdução: O sarcoma de Ewing é um neoplasma maligno de origem mesenquimatosa. No momento do diagnóstico, 75% dos casos são localizados. Objetivo: Relatar um caso que, devido a sua apresentação multifocal, causou dificuldades diagnósticas. Caso clínico: Menina de 6 anos. Ela consultou por traumatismo à mão direita após cair de sua altura 24 horas antes, com edema, calor e eritema na mão direita e punho, com mobilidade preservada. Sem febre. Raio-X: aumento do diâmetro do 3º metacarpo, imagem fosca, sem vestígios de fraturas. Admitido com a sugestão de celulite. Anemia microcítica leve, hipocrómica. Proteína C reativa 82mg/l. Recebe clindamicina intravenosa por 72 horas, completa 14 dias por via oral. Persistência de alterações no punho e mão direita, tumor indolor da raiz nasal com desvio do eixo. Fosfatase alcalina, desidrogenase láctica, fosfataemia, calcemia normal. IRM: alteração morfo-estrutural do rádio, olecrânio e 3º metacarpo, fratura do olecrânio e do rádio, reação periosteal. Pet-Scan: extensa lesão óssea na massa facial, tíbia, ulnae, úmero direito e clavícula. Biópsia do 3º metacarpo: tumor de pequenas células, redondo azul, CD 99 e vimentina positiva. Ela iniciou a poli-quimioterapia e radioterapia sem complicações. Conclusões: É comum que as manifestações clínicas iniciais sejam confundidas com entidades mais freqüentes, tais como pós-traumáticas e/ou inflamatórias, como ocorreu neste caso. Posteriormente, o aparecimento de novas lesões e o envolvimento do quadro geral levaram a uma abordagem diagnóstica da patologia tumoral. A confirmação requer um estudo anatomopatológico com estudo imuno-histoquímico. A presença de metástases ósseas é um fator de mau prognóstico e dificulta a abordagem terapêutica.

Replication Timing Aberration of KIF14 and MDM4 / PI3KC 2 ß Alleles and Aneuploidy as Markers of Chromosomal Instability and Poor Treatment Response in Ewing Family Tumor Patients.

Replication timing of allelic gene pairs is strictly regulated according to expression, genome stability, and epigenetic changes, and tumorigenesis may be associated with changes in the allelic replication in various tumors. Our aim was to determine whether such alterations had a prognostic value in Ewing's family tumor (EFT) patients. The KIF14 and MDM4 / PI3KC 2ß and the centromeric satellite sequence of chromosomes 8 and 12 were used for replication timing assessments. Aneuploidy was assessed by enumerating the copy numbers of chromosomes 8 and 12. Replication timing and aneuploidy were detected cytogenetically using multicolors fluorescence in situ hybridization assay applied in 135 EFT. Patients with trisomy 8 presented an association with an asynchronous replication pattern (SD) of MDM4 / PI3KC 2ß genes ( p = 0.013). Trisomy 12 was associated with a synchronous pattern (DD) of KIF14 probe signals ( p = 0.04). The DD synchronous replication pattern of KIF14 showed a correlation with age ( p < 0.0001), and the SS synchronous replication pattern of the same locus showed a correlation with lung metastatic ( p = 0.012). The subgroup of patients presenting with multiplet signals of MDM4 / PI3KC 2ß showed an association with treatment response ( p = 0.045) and age ( p = 0.033). Replication pattern of KIF14 may, significantly, be associated with chromosomal instability as MDM4 / PI3KC 2ß may be a considerably new marker of poor treatment response in EFT patients.

TIPE1 inhibits the growth of Ewing's sarcoma cells by suppressing Wnt/ß-catenin signaling.

BACKGROUND: Ewing's sarcoma is the second most common bone and soft tissue malignancy in children and adolescents. Tumor necrosis factor-α-induced protein 8-like 1 (TIPE1) functions as a tumor suppressor in several cancers. Activation of Wnt/ß-catenin signaling in subpopulations of tumor cells contributes to phenotypic heterogeneity and disease progression in Ewing's sarcoma. The exact role of TIPE1 in Ewing's sarcoma remains to be elucidated. PURPOSE: This study aimed to assess the expression and function of TIPE1 in Ewing's sarcoma. METHODS: TIPE1 expression in Ewing's sarcoma cells was determined by qPCR and western blotting. Furthermore, the Ewing's sarcoma cell line RD-ES was transfected with a lentivirus-based TIPE1 expression system to upregulate the expression of TIPE1. The Cell Counting Kit 8 was used to assess the effect of TIPE1 on cell proliferation. The effects of TIPE1 on cell migration and invasion was detected by Transwell assay. Flow cytometry was performed to detect apoptosis. RESULTS: Our results suggested lower TIPE1 expression in Ewing's sarcoma cell lines compared with normal osseous cells. TIPE1 remarkably inhibited the growth and proliferation of Ewing's sarcoma cell; TIPE1 also induced apoptosis and inhibited invasion in vitro. TIPE1 inhibited Ewing's sarcoma growth, motility, and survival through regulation of Wnt/ß-catenin signaling. CONCLUSIONS: Our results demonstrated the anti-tumor function of TIPE1 in Ewing's sarcoma and reveal a novel therapeutic target.

Successful extracorporeal membrane oxygenation therapy in a child with coronavirus 2019 disease-associated ARDS and chemotherapy for Ewing's sarcoma.

Most children and adolescents with SARS-CoV-2 infection show no or mild symptoms, but those with medical histories can be susceptible to more severe forms of disease. There are few reported cases of extracorporeal membrane oxygenation (ECMO) in pediatric patients with coronavirus disease 2019 (COVID-19). We present a previously healthy 13-year-old male diagnosed with metastatic Ewing's sarcoma at the same time as catastrophic acute respiratory distress syndrome due to COVID-19, who was successfully supported by venovenous-ECMO while he received the corresponding chemotherapy protocol.ECMO can be used as salvage therapy in oncology pediatric patients with respiratory failure secondary to COVID-19. In addition, successful chemotherapy can be administered while patients are supported on ECMO.

Cancer Stem Cells and Chemoresistance in Ewing Sarcoma.

Resistance to chemotherapy poses a major challenge for cancer treatment. Reactivating a stem cell program resembling that seen in embryonic development can lead cancer cells to acquire a stem-cell phenotype characterized by expression of stemness genes, pluripotency, high self-renewal ability, and tumor-initiating capability. These cancer stem cells (CSCs) are usually resistant to anticancer drugs and are likely involved in treatment failure in many cancer types. Ewing sarcoma (ES) is a pediatric cancer type typically resulting from a typical genetic alteration affecting bone or soft tissues. Despite advances in treatment, survival prognostic remains poor for patients with refractory or recurrent disease. Here, we review the increasing evidence indicating that ES tumors contain a CSC subpopulation expressing stem cell genes, including BM1, OCT3/4, NANOG, and SOX2, that plays a role in resistance to drug treatment, and current experimental strategies that successfully counteract chemoresistance mediated by CSCs in ES.

Ewing Sarcoma in the Sciatic Nerve: Case Report / Sarcoma de Ewing no Nervo Ciático: Relato de Caso

Ewing sarcoma (ES) is a malignant neoplasm that affects bones and soft tissues, usually in young patients. Currently, ES is grouped with other tumors that share the same histological and genotypic characteristics, forming the Ewing Sarcoma Family of Tumors (ESFT), which includes ES of bone, extraosseous ES (peripheral neuroepithelioma), Askin tumor, and peripheral primitive neuroectodermal tumor (PNET). Its origin in peripheral nerves is extremely rare, making its diagnosis and treatment very challenging. We describe a case of a 27-year-old male with extraosseous ES originating in the sciatic nerve, which was surgically removed, and discuss the difficulties encountered in the management of this patient.

O sarcoma de Ewing (SE) é uma neoplasia maligna que acomete ossos e partes moles, geralmente em pacientes jovens. Atualmente, o SE é agrupado com outros tumores que compartilham as mesmas características histológicas e genotípicas, formando os Tumores da Família do Sarcoma de Ewing (TFSE), que incluem o SE ósseo, o SE extraósseo (neuroepitelioma periférico), o tumor de Askin, e o tumor neuroectodérmico primitivo (TNEP) periférico. Sua origem em nervos periféricos é extremamente rara, o que torna o seu diagnóstico e tratamento um grande desafio. Descrevemos o caso de um homem de 27 anos com SE extraósseo originário no nervo ciático, que foi removido cirurgicamente, e discutimos as dificuldades encontradas no manejo desse paciente.

[Mesencephalic Ewing sarcoma: Case report]. / Sarcoma de Ewing mesencefálico: reporte de caso.

Ewing's sarcoma is a malignant neoplasm mainly occurring in the bone, with other locations being exceptional. In the case of primary intracranial presentations, it is essential to rule out metastatic lesions as well as other neuroectodermal tumors that may require different diagnostic and therapeutic approaches. We present a 14-year-old patient who consulted for upper eyelid ptosis of left eye associated with a 2-month history of diplopia, with imaging evidence of extra-axial tumor lesion, located at the level of the interpeduncular cistern. Complete excision was performed, with a pathological diagnosis of Ewing's sarcoma of midbrain location.

El sarcoma de Ewing es una neoplasia de origen más frecuentemente óseo; otras localizaciones son excepcionales. En el caso de las presentaciones primarias intracraneales, resulta imprescindible descartar que se trate de un secundarismo así como también de otros tumores neuroectodérmicos que puedan requerir distintos abordajes diagnósticos y terapéuticos. Se presenta a una paciente de 14 años que consultó por ptosis palpebral de ojo izquierdo asociado a diplopía de 2 meses de evolución; los estudios por imágenes mostraron una lesión tumoral extraaxial situada a nivel de la cisterna interpeduncular. Se realizó la exéresis completa, con diagnóstico anatomopatológico de sarcoma de Ewing de ubicación mesencefálica.

BRCA1-associated RING domain-1 (BARD1) loss and GBP1 expression enhance sensitivity to DNA damage in Ewing sarcoma.

Ewing sarcoma is a fusion oncoprotein-driven primary bone tumor. A subset of patients (~10%) with Ewing sarcoma are known to harbor germline variants in a growing number of genes involved in DNA damage repair. We recently reported our discovery of a germline mutation in the DNA damage repair protein BARD1 (BRCA1-associated RING domain-1) in a patient with Ewing sarcoma. BARD1 is recruited to the site of DNA double stranded breaks via the poly(ADP-ribose) polymerase (PARP) protein and plays a critical role in DNA damage response pathways including homologous recombination. We thus questioned the impact of BARD1 loss on Ewing cell sensitivity to DNA damage and the Ewing sarcoma transcriptome. We demonstrate that PSaRC318 cells, a novel patient-derived cell line harboring a pathogenic BARD1 variant, are sensitive to PARP inhibition and by testing the effect of BARD1 depletion in additional Ewing sarcoma cell lines, we confirm that BARD1 loss enhances cell sensitivity to PARP inhibition plus radiation. Additionally, RNA-seq analysis revealed that loss of BARD1 results in the upregulation of GBP1 (guanylate-binding protein 1), a protein whose expression is associated with variable response to therapy depending on the adult carcinoma subtype examined. Here, we demonstrate that GBP1 contributes to the enhanced sensitivity of BARD1 deficient Ewing cells to DNA damage. Together, our findings demonstrate the impact of loss-of function mutations in DNA damage repair genes, such as BARD1, on Ewing sarcoma treatment response.

Sarcoma de Ewing mesencefálico: reporte de caso / Mesencephalic Ewing sarcoma: Case report

El sarcoma de Ewing es una neoplasia de origen más frecuentemente óseo; otras localizaciones son excepcionales. En el caso de las presentaciones primarias intracraneales, resulta imprescindible descartar que se trate de un secundarismo así como también de otros tumores neuroectodérmicos que puedan requerir distintos abordajes diagnósticos y terapéuticos. Se presenta a una paciente de 14 años que consultó por ptosis palpebral de ojo izquierdo asociado a diplopía de 2 meses de evolución; los estudios por imágenes mostraron una lesión tumoral extraaxial situada a nivel de la cisterna interpeduncular. Se realizó la exéresis completa, con diagnóstico anatomopatológico de sarcoma de Ewing de ubicación mesencefálica

Ewing's sarcoma is a malignant neoplasm mainly occurring in the bone, with other locations being exceptional. In the case of primary intracranial presentations, it is essential to rule out metastatic lesions as well as other neuroectodermal tumors that may require different diagnostic and therapeutic approaches. We present a 14-year-old patient who consulted for upper eyelid ptosis of left eye associated with a 2-month history of diplopia, with imaging evidence of extra-axial tumor lesion, located at the level of the interpeduncular cistern. Complete excision was performed, with a pathological diagnosis of Ewing's sarcoma of midbrain location.

Intestinal Ewing sarcoma: An unusual presentation in the pediatric age.

BACKGROUND: Ewing's Sarcoma (ES) is the second most common type of bone cancer, with an annual incidence of 2.9:100,000. Extraosseous cases represent 15%; however, there are no reported cases of ES located in the intestine in the pediatric population. CASE REPORT: We describe the case of a 14-year-old male patient, previously healthy, who started with an anemic syndrome, weight loss, and diaphoresis of 8 weeks of evolution. After visiting a physician, who documented the presence of anemia, the patient was referred to the National Institute of Pediatrics. Physical examination showed grade III-IV systolic murmur, splenomegaly, and pain in the left hemiabdomen with no irradiation. Computed axial tomography showed a mass-dependent on the peritoneum and intestinal loop. A biopsy of the lesion showed intestinal ES. The lesion was completely resected, and the patient was treated with chemotherapy and radiotherapy. Thirty months after diagnosis, the patient has no evidence of tumor activity. CONCLUSIONS: Extraosseous presentation of ES in pediatric age is rare. There are no reports of intestinal ES in the Latin American pediatric population, although eight case reports were found in adults. ES is curable by a combination of chemotherapy, radiotherapy, and surgery. The medical literature indicates that the extraosseous presentation should receive the same treatment as the osseous presentation, which can provide a survival rate of up to 70% if there is no evidence of metastasis (which most frequently is observed in the lung).

INTRODUCCIÓN: El sarcoma de Ewing (SE) es el segundo tipo cáncer más común de hueso, cuya incidencia anual es de 2.9:100,000. Los casos extraóseos representan el 15%; sin embargo, no existen reportes en la literatura de casos de SE ubicados en el intestino en la población pediátrica. CASO CLÍNICO: Se describe el caso de un paciente de sexo masculino de 14 años, previamente sano, que inició con síndrome anémico, pérdida de peso y diaforesis de 8 semanas de evolución. Acudió con un médico, quien documentó la presencia de anemia y lo refirió al Instituto Nacional de Pediatría. A la exploración física presentaba soplo sistólico grado III-IV, esplenomegalia y dolor en hemiabdomen izquierdo sin irradiaciones. La tomografía axial computarizada mostró una masa dependiente del peritoneo y asa intestinal. La biopsia de la lesión reportó SE intestinal. Se resecó por completo la lesión y el paciente recibió tratamiento con quimioterapia y radioterapia. Después de 30 meses del diagnóstico, el paciente se encuentra sin datos de actividad tumoral. CONCLUSIONES: La presentación extraósea del SE en edad pediátrica es rara. No existen reportes de presentación de SE intestinal en la población pediátrica latinoamericana, aunque se encontraron ocho reportes de caso en adultos. El SE es curable mediante la combinación de quimioterapia, radioterapia y cirugía. La literatura médica indica que la presentación extraósea debe recibir el mismo tratamiento que la ósea, lo cual puede proporcionar una sobrevida de hasta el 70% si no hay evidencia de metástasis (que ocurre más frecuentemente a pulmón).

Intestinal Ewing sarcoma: An unusual presentation in the pediatric age / Sarcoma de Ewing intestinal: presentación inusual en la edad pediátrica

Abstract Background: Ewing's Sarcoma (ES) is the second most common type of bone cancer, with an annual incidence of 2.9:100,000. Extraosseous cases represent 15%; however, there are no reported cases of ES located in the intestine in the pediatric population. Case report: We describe the case of a 14-year-old male patient, previously healthy, who started with an anemic syndrome, weight loss, and diaphoresis of 8 weeks of evolution. After visiting a physician, who documented the presence of anemia, the patient was referred to the National Institute of Pediatrics. Physical examination showed grade III-IV systolic murmur, splenomegaly, and pain in the left hemiabdomen with no irradiation. Computed axial tomography showed a mass-dependent on the peritoneum and intestinal loop. A biopsy of the lesion showed intestinal ES. The lesion was completely resected, and the patient was treated with chemotherapy and radiotherapy. Thirty months after diagnosis, the patient has no evidence of tumor activity. Conclusions: Extraosseous presentation of ES in pediatric age is rare. There are no reports of intestinal ES in the Latin American pediatric population, although eight case reports were found in adults. ES is curable by a combination of chemotherapy, radiotherapy, and surgery. The medical literature indicates that the extraosseous presentation should receive the same treatment as the osseous presentation, which can provide a survival rate of up to 70% if there is no evidence of metastasis (which most frequently is observed in the lung).

Resumen Introducción: El sarcoma de Ewing (SE) es el segundo tipo cáncer más común de hueso, cuya incidencia anual es de 2.9:100,000. Los casos extraóseos representan el 15%; sin embargo, no existen reportes en la literatura de casos de SE ubicados en el intestino en la población pediátrica. Caso clínico: Se describe el caso de un paciente de sexo masculino de 14 años, previamente sano, que inició con síndrome anémico, pérdida de peso y diaforesis de 8 semanas de evolución. Acudió con un médico, quien documentó la presencia de anemia y lo refirió al Instituto Nacional de Pediatría. A la exploración física presentaba soplo sistólico grado III-IV, esplenomegalia y dolor en hemiabdomen izquierdo sin irradiaciones. La tomografía axial computarizada mostró una masa dependiente del peritoneo y asa intestinal. La biopsia de la lesión reportó SE intestinal. Se resecó por completo la lesión y el paciente recibió tratamiento con quimioterapia y radioterapia. Después de 30 meses del diagnóstico, el paciente se encuentra sin datos de actividad tumoral. Conclusiones: La presentación extraósea del SE en edad pediátrica es rara. No existen reportes de presentación de SE intestinal en la población pediátrica latinoamericana, aunque se encontraron ocho reportes de caso en adultos. El SE es curable mediante la combinación de quimioterapia, radioterapia y cirugía. La literatura médica indica que la presentación extraósea debe recibir el mismo tratamiento que la ósea, lo cual puede proporcionar una sobrevida de hasta el 70% si no hay evidencia de metástasis (que ocurre más frecuentemente a pulmón).