TIPE1 inhibits the growth of Ewing’s sarcoma cells by suppressing Wnt/B-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/β-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. Method 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/β-catenin signaling. Conclusions Our results demonstrated the anti-tumor function of TIPE1 in Ewing’s sarcoma and reveal a novel therapeutic target (AU)

Ewing's Sarcoma of the Zygoma: A Very Rare Location.

Ewing's sarcoma is a rare and aggressive neoplasm that typically affects the long bones. The presence of a primary tumor in the facial bones is extremely uncommon. Here, we present a case of a 21-year-old male with Ewing's sarcoma of the zygoma. To date, only a few such cases have been reported worldwide in the literature.

Prognostic profiling of the immune cell microenvironment in Ewing´s Sarcoma Family of Tumors.

Ewing´s Sarcoma Family of Tumors (ESFT) are clinically aggressive bone and soft tissue tumors in children and young adults. Analysis of the immune tumor microenvironment (TME) provides insight into tumor evolution and novel treatment options. So far, the scarcity of immune cells in ESFT has hindered a comprehensive analysis of rare subtypes. We determined the relative fraction of 22 immune cell types using 197 microarray gene expression datasets of primary ESFT tumor samples by using CIBERSORT, a deconvolution algorithm enumerating infiltrating leucocytes in bulk tumor tissue. The most abundant cells were macrophages (mean 43% of total tumor-infiltrating leukocytes, TILs), predominantly immunosuppressive M2 type macrophages, followed by T cells (mean 23% of TILs). Increased neutrophils, albeit at low number, were associated with a poor overall survival (OS) (p = .038) and increased M2 macrophages predicted a shorter event-free survival (EFS) (p = .033). High frequency of T cells and activated NK cells correlated with prolonged OS (p = .044 and p = .007, respectively). A small patient population (9/32) with combined low infiltrating M2 macrophages, low neutrophils, and high total T cells was identified with favorable outcome. This finding was confirmed in a validation cohort of patients with follow up (11/38). When comparing the immune TME with expression of known stemness genes, hypoxia-inducible factor 1 α (HIF1α) correlated with high abundance of macrophages and neutrophils and decreased T cell levels. The immune TME in ESFTs shows a distinct composition including rare immune cell subsets that in part may be due to expression of HIF1α.

[Neuroectodermic renal tumor. Case report and bibliographic review.] / Tumor renal neuroectodérmico. A propósito de un caso tratado en nuestra unidad. Revisión de la literatura.

We report the case of a 16 year old female who underwent left radical nephrectomy for a 13.2 cm neuroectodermic renal tumor and posterior chemo and radiotherapy in the Quiron Hospitals in Madrid and Complejo Hospitalario de Toledo, with a current survival of 14 months. Medical literature was reviewed for the historical, clinical, etiopathogenic, diagnostic, prognostic, therapeutic and survival features. We estimate the number of published cases to date. We also address the treatment performed and its results under a critical view.

Se presenta el caso de una adolescente de 16 años de edad a la que practicamos nefrectomia radical izquierda por un tumor neuroectodérmico renal de 13,2 cm y tratada posteriormente mediante quimioterapia y radioterapia en los Hospitales Quirón de Madrid y Complejo Hospitalario de Toledo, con una supervivencia actual de 14 meses. Se revisa la literatura médica en los aspectos históricos, clínicos, etiopatogénicos, diagnósticos, pronósticos, terapéuticos y de supervivencia. Se realiza una estimación de la cantidad de casos publicados hasta la fecha. Abordamos además con una visión descriptiva y crítica el tratamiento realizado y su resultado.

Ewing sarcoma of the mobile spine; predictive factors for survival, neurological function and local control. A Scandinavian sarcoma group study with a mean follow-up of 12 years.

Object: Many patients with Ewing sarcoma (ES) of the mobile spine present with neurologic symptoms leading to emergency decompressive surgery. Only rarely is optimal treatment involving neo-adjuvant chemotherapy followed by en bloc excision possible. The purpose of this study was to study treatment, neurologic and oncologic outcome in patients with ES of the mobile spine. Methods: Twenty-four patients diagnosed between 1986 and 2012 were identified through the Scandinavian Sarcoma Group registry. Charts were reviewed in order to assess details in patient characteristics, neurologic status, treatment and outcome. Prognostic factors were analyzed with respect to local control, disease-free survival and overall survival. Results: Neurologic symptoms were frequently observed at presentation, being present in 19/23 patients with documented neurologic status. Most (13/19) patients had a complete neurologic recovery regardless of whether or not emergency decompressive surgery was performed. The majority (18/24) of patients were treated with definitive radiotherapy. However, only 9/17 received the recommended dose of  ≥  50.4 Gy. The disease-free and overall survival rates were 48% and 57% at 5 and 10 years, respectively. The local recurrence rates were 19% and 27% at 5 and 10 years, respectively. Only year of diagnosis, categorized into periods with significant changes in chemotherapy protocols, was a significant factor for local recurrence, but there was a trend (p = 0.06) for an increased risk of a local recurrence if emergency decompressive surgery was performed. Conclusion: Patients with ES of the mobile have a relatively favorable prognosis. Nonetheless, local recurrence rate is high for this group of patients for which local treatment mainly relies on definitive radiotherapy. Emergency decompressive surgery may increase the risk for local recurrence.

Ewing`s sarcoma of the mandible misdiagnosed as periodontal inflammation: Report of three cases.

Balkaya E, Bozkurt C, Aksu AE, Özmen S, Incesoy-Özdemir S, Sahin G. Ewing`s sarcoma of the mandible misdiagnosed as periodontal inflammation: Report of three cases. Turk J Pediatr 2017; 59: 704-707. Ewing`s sarcoma (ES) is the second most common childhood primary malignant tumor of the bone. The most popular locations of ES are long bones and pelvis. The involvement of the mandible is very rare in childhood. In last 10 years, we met with three cases of ES of the mandible in our department. Initially the patients had symptoms similar to periodontal inflammation. The involvement of the mandible might be considered with periodontal inflammation in its initial stages, what frequently leads to delayed treatment. Although this tumor has an aggressive clinical behavior and rapid growth, early diagnosis can reduce patient`s morbidity and mortality and thus it is important to distinguish from periodontal inflammation.

Tumor neuroectodérmico de seios paranasais: diagnóstico e tratamento / Primitive neuroectodermal tumor of paranasal sinuses: diagnosis and treatment

Tumores neuroectodérmicos primitivos (PNET) são neoplasias raras e extremamente agressivas encontradasprincipalmente em crianças e adultos jovens. São classificados em periféricos ou centrais, de acordo com sua origem. O diagnóstico baseia-se na história clínica, sendo essenciais exames de imagem, como tomografia computadorizada e ressonância magnética, e, para a confirmação, estudo anatomopatológico. É importante distingui-los de outros tumores de células redondas pequenas,como linfoma, sarcoma de Ewing extraósseo e rabdomiossarcoma,exigindo diferenciação imunoistoquímica através de marcadores específicos. O tratamento envolve cirurgia, quimioterapia e radioterapia, sendo o prognóstico pobre e a sobrevida bastante reservada. O objetivo deste artigo é discutir as características clínicas, radiográficas ehistológicas dos tumores neuroectodérmicos primitivos e seu tratamento...

Primitive neuroectodermal tumours (PNET) are rare and highly aggressive neoplasms found mainly in children and young adults. They are classified in peripheral or central according to their origin. The diagnosis is based on clinical history, computed tomography and magnetic resonance imaging, but the pathological study is the only way to confirm it. It´s very important to distinguish the PNET from other small cell round cell tumors - such as lymphoma, Ewing´s sarcoma and rhabdomyosarcoma – through immunohistochemical specific markers. The treatment includes surgical resection, chemotherapy and irradiation. The prognosis is poor and the survival rate is variable. This article aims to discuss the clinical, imagingand histological features of the primitive neuroectodermal tumors and their treatment...

Tumor neuroectodérmico primitivo: relato de caso / Primitive neuroectodermal tumor: case report

JUSTIFICATIVA E OBJETIVOS: O tumor neuroectodérmico primitivo (PNET) pertence a um grupo de tumores de pequenas células redondas e, devido a sua semelhança biológica com os sarcomas de Ewing, tem sido incluído nesta família. O objetivo deste estudo foi descrever o quadro clínico, características de imagem e evolução de um caso de processo expansivo em coxa direita, com histologia consistente com sarcoma de Ewing extraesquelético. RELATO DO CASO: Paciente do sexo feminino, 21 anos, branca, apresentava queixa de dificuldade para deambular e dor na perna direita há aproximadamente seis meses. Ao exame físico foi detectada massa sólida na raiz da coxa direita. Exames de imagens identificaram formação expansiva sólida, sendo o estudo histopatológico/imuno-histoquímico compatível com PNET/sarcoma de Ewing extraesquelético. Foi instituído tratamento quimioterápico, que nãofoi suspenso mesmo após diagnóstico de gestação. A gravidez evoluiu com oligodramnia e óbito fetal. Dois meses após o diagnóstico, a paciente apresentou depressão, piora do estado geral e óbito. CONCLUSÃO: O estudo relatado reflete a agressividade desta doença apesar da possibilidade de multimodalidade terapêutica. A aplicação da genética molecular em estudos recentes correlaciona o rearranjo genético da translocação entre os cromossomas 11e 22 com o prognóstico.

BACKGROUND AND OBJECTIVES: Primitive neuroectodermal tumor (PNET) belongs to a family of small round cell tumors, and because of their biological similarity has been includedin the family of Ewing's sarcomas. The objective of this case was to describe the clinical, imaging characteristics and outcome of a case of an expansive process in the right thigh, with histology consistent with extraskeletal Ewing's sarcoma. CASE REPORT: Female patient, 21 years, white, featured a complaint of difficulty in walking and pain in his right leg for about six months. On examination a solid mass was detected at the root of the right thigh. Imaging techniques identified an expansive solid mass and histopathology was compatible with PNET/extra-skeletal Ewing's sarcoma. Chemotherapy was instituted, which was not suspended even after pregnancy diagnosis. It progressed with oligohydramnios and fetal death. In two months, the patient had depression, poor general condition and death. CONCLUSION: The study reported reflects the aggressive nessof this disease despite multimodality therapy. The application of molecular genetics in recent studies correlating the genetic rearrangement of the translocation between chromosomes 11:22 prognosis.

Metástasis de calota / Calvarial metastasis

Objective. To describe five cases of cranial vault metastasis. Materials and methods. Clinical records and images of five patients with cranial vault metastasis were reviewed at the “Hospital de Clinicas” and “Hospital Español” from Buenos Aires, between January 2009 to June 2010. Results. Case 1, 63 years old female, complains for headache with aleatory response to medical therapy; MRI: right occipital bone lession; Pathological Finding: breast carcinoma metastasis. Case 2, 70 years old female, complains for palpable lession of the scalp; MRI: right fronto-parietal intraxial lession and right parietal cranial vault lession; Pathological Finding: endometrial carcinoma metastasis (primary, diagnosed 4 months before). Case 3, 76 years old female, with palpable lession in the scalp; MRI: left parietal cranial vault lesion. Pathological Finding: kidney carcinoma metastasis (primary, diagnosed in 2008). Case 4, 50 years old female and Case 5, 78 years old male, both complains for bone pain; serological findings and marrow bone biopsy compatible with multiplemyeloma; screening of the long bones and cranial vault demonstrate evidence of bone infiltration. Conclusion. Metastasis at the cranial vault often presents with headache or pain upon inspection of a palpable scalp lession. Images of the CNS involves CT scan (delimitate lession and differentiates litic from blastic metastasis) and MRI (shows the degree of dural and brain infiltration). Prevalence of cranial vault metastasis is greater than brain metastasis, but this underdiagnosis is due that the first are frequently course without symptoms.

Metástasis de calota / Calvarial metastasis

Objective. To describe five cases of cranial vault metastasis. Materials and methods. Clinical records and images of five patients with cranial vault metastasis were reviewed at the ¶Hospital de Clinicas÷ and ¶Hospital Español÷ from Buenos Aires, between January 2009 to June 2010. Results. Case 1, 63 years old female, complains for headache with aleatory response to medical therapy; MRI: right occipital bone lession; Pathological Finding: breast carcinoma metastasis. Case 2, 70 years old female, complains for palpable lession of the scalp; MRI: right fronto-parietal intraxial lession and right parietal cranial vault lession; Pathological Finding: endometrial carcinoma metastasis (primary, diagnosed 4 months before). Case 3, 76 years old female, with palpable lession in the scalp; MRI: left parietal cranial vault lesion. Pathological Finding: kidney carcinoma metastasis (primary, diagnosed in 2008). Case 4, 50 years old female and Case 5, 78 years old male, both complains for bone pain; serological findings and marrow bone biopsy compatible with multiplemyeloma; screening of the long bones and cranial vault demonstrate evidence of bone infiltration. Conclusion. Metastasis at the cranial vault often presents with headache or pain upon inspection of a palpable scalp lession. Images of the CNS involves CT scan (delimitate lession and differentiates litic from blastic metastasis) and MRI (shows the degree of dural and brain infiltration). Prevalence of cranial vault metastasis is greater than brain metastasis, but this underdiagnosis is due that the first are frequently course without symptoms.(AU)

Sarcoma de Ewing extraesquelético que semeja abdomen agudo / Extra-skeletal Ewing's sarcoma resembling acute abdomen: case report

Introducción: El sarcoma de Ewing extraóseo es un tumor raro de origen neuroectodérmico que se ha presentado principalmente en las partes blandas de las extremidades y del tórax; histológicamente es similar al sarcoma de Ewing en el tejido óseo. Caso clínico: Paciente con abdomen agudo y leucocitosis, en quien por imagen (ultrasonido y tomografía axial computarizada) se diagnosticó enfermedad diverticular complicada del colon, por lo que fue intervenido quirúrgicamente, encontrando lesión localizada en el espacio de Retzius con extensión a la cavidad abdominal de 20 x 15 x 15 cm. El tratamiento consistió en extirpación del tumor, separándolo de las vísceras adyacentes y el paciente fue tratado con quimioterapia: epirrubicina, ciclofosfamida y vincristina por seis ciclos; la tomografía abdominal de control mostró actividad tumoral en el retroperitoneo, adyacente al colon ascendente y ciego, por lo que se requirió nuevo tratamiento resectivo. Conclusiones: En la revisión de la literatura no hay informes previos de sarcoma de Ewing extraóseo cuya presentación sea abdomen agudo. Por la rareza de esta lesión, en la literatura solo hay registro de casos o algunas series de casos, por lo que no fue posible llevar a cabo comparaciones; la extirpación de la lesión es el pilar del tratamiento. No se define el papel de la quimioterapia preoperatoria. La biopsia percutánea guiada por algún método de imagen es de utilidad para otorgar al paciente un tratamiento óptimo que le permita un mejor pronóstico.

BACKGROUND: Extraosseous Ewing's sarcoma is a rare tumor of neuroectodermal origin. It presents mainly in the soft tissue of the extremities and thorax. Histologically, it is similar to Ewing's sarcoma of the bone. CLINICAL CASE: We present the case of a male who arrived at the emergency room with acute abdomen, leucocytosis and imaging techniques (abdominal ultrasound and computed tomography) suggestive of complicated diverticular disease. He was treated with emergency surgery. Intraoperative findings were an unsuspected tumor (20 x 15 x 15 cm). Treatment consisted of extirpation of the tumor, separating it from the adjacent viscera and followed by chemotherapy based on epirubicin, cyclophosphamide and vincristine for six cycles. Because the control abdominal CT demonstrated tumor activity in the retroperitoneum adjacent to the ascending colon and cecum, further resection was decided upon. CONCLUSIONS: In a review of the literature, no previous reports of extraosseous Ewing's sarcoma were found presenting as acute abdomen. Due to the rarity of this tumor, only case reports or series have been found in the literature without randomized or comparative studies. Surgery was the cornerstone of treatment, without reports of preoperative chemotherapy. If the patient's condition permits, percutaneous needle biopsy is mandatory to obtain optimum treatment as well as to improve prognosis.

Radioterapia como tratamiento de las metástasis tumorales: reporte de dos casos / Radiotherapy as treatment of tumor metastasis: report of two cases

Se presentan dos casos de pacientes con neuroblastoma y sarcoma de Ewing respectivamente, los cuales presentan lesiones metastásicas. El primer caso presenta una lesión a nivel de cuerpo vertebral, el cual a su vez le produjo un síndrome de compresión medular. El paciente presenta alteración en la movilidad y sensibilidad de miembros inferiores, y alteración en el control de sus esfínteres. En el segundo caso se encontró una lesión metastásica a nivel de tejidos blandos en la zona parietal derecha. En ambos cuadros se valora el tratamiento por medio de la radioterapia para el control y reversión de los síntomas

Extraskeletal Ewing`s sarcoma Extraskeletal Ewings Sarcoma Arising in the Chest Wall / 결핵

Extraskeletal Ewing's sarcoma is a very rare tumor which was first reported by Angervall and Enzinger in 1975. The common sites of extraskeletal Ewing s sarcoma are bony structures of lower extremities, paravertebral region, and pelvis, but rarely chest walL Microscopically, extraskeletal Ewing's sarcoma is indistinguishable from the Ewing's sarcoma of bone. We present here a case of extraskeletal Ewing's sarcoma of the left lateral chest wall in a 19-year-old male. Wide extirpation and postoperative combined chemotherapy were done, and we discuss the clinical picture, histopathology, therapeutic management, and prognosis with review of the literature.