Peripheral Primitive Neuroectodermal Tumor Research Articles

Peripheral primitive neuroectodermal tumor in a two-year-old paint horse

A 2-year-old gelding presented with a history of lethargy and anorexia. Physical examination revealed pleural and abdominal fluid, as well as several masses in the scrotum. The horse became acutely dyspneic despite 7 days of supportive care. Because of the poor prognosis, the owners elected euthanasia. Gross necropsy findings included multiple masses in the scrotum and inguinal canals and along the dorsal peritoneal cavity. The neoplasm infiltrated the kidneys, liver, spleen, mesenteric lymph nodes, mesentery, and abdominal surface of the diaphragm. Histologically, the neoplasm is composed of spindle to round cells arranged in densely cellular areas, vague streams, and rare rosettes. Neoplastic cells were immunoreactive for S-100 protein, glial fibrillary acidic protein, neuron-specific enolase, neurofilament protein, and synaptophysin. Based on gross, histological, and immunohistochemical findings, a diagnosis of peripheral primitive neuroectodermal tumor was made. Primitive neuroectodermal tumors are rarely described in horses that were associated with the eyes.

Magnetic Resonance Imaging Characteristics of Primary Intraspinal Peripheral Primitive Neuroectodermal Tumour

PurposeThe purpose of our study was to describe the salient magnetic resonance imaging (MRI) findings in primary intraspinal peripheral primitive neuroectodermal tumour (PNET). MethodsA retrospective review of the clinical and MRI images of 7 pathologically proven cases of intraspinal peripheral PNETs was performed. The various parameters, such as vertebral level of involvement; tumour location, size, focality, and margin; signal intensity of the lesion; the presence of hemorrhage or calcification; any signal voids; assessment of the adjacent cord for cord compression; cord dilatation; the presence of paraspinal tissue mass; or vertebral or other bony changes, were analysed. ResultsAll 7 patients had lesions in the thoracolumbar region. Three patients had extradural lesions, 4 had intradural extramedullary lesions, and none had intramedullary lesions. Six lesions were well circumscribed. Only 1 patient had multifocal involvement. All lesions were of hypointense or isointense signal on T1-weighted imaging, whereas all but one were hyperintense on T2-weighted imaging. Lesions enhanced heterogeneously except 1 intradural extramedullary lesion, which enhanced homogeneously. A paraspinal mass was noticed in 2 patients. Vertebral collapse was present in 1 patients. ConclusionIntraspinal peripheral PNETs are rare spinal tumours. Although imaging characteristics are not specific, a focal circumscribed lesion in a young individual at the intramedullary, extramedullary intradural, or extradural spinal location that shows hypointense and hyperintense signal on T1- and T2-weighted images, respectively, requires PNET to be considered in the differentials.

A rare, highly aggressive primitive neuroectodermal tumor of the kidney: Case report and literature review

We report a case of a 14-year-old boy who initially suffered from a sudden onset of abdominal pain for 2 weeks with a protrusive soft mass over the left upper abdomen. No obvious symptomatic symptoms or body weight loss were observed. However, early lung metastasis was detected after an initial computed tomographic examination. Even after we performed salvage en bloc resection of the huge retroperitoneal tumor after primary neoadjuvant chemotherapy, the final outcome was still poor. A diagnosis according to radiologic findings was uncharacteristic. Finally, a pathologic diagnosis based on histologic and immunohistochemical results revealed a rare renal peripheral primitive neuroectodermal tumor.

Malignant ectomesenchymoma in children and adolescents: Report from the Cooperative Weichteilsarkom Studiengruppe (CWS)

Malignant ectomesenchymoma (MEM) is a soft tissue tumor with heterologous rhabdomyoblastic components believed to arise from pluripotent migratory neural crest cells. To date merely 50 cases have been published and the knowledge about the course of disease and optimal treatment is limited. Six patients with MEM were registered 1996-2009. The diagnosis was confirmed according to current criteria. Their treatment and outcome was analyzed. The median age of the three females and three males was 0.6 years (range, 0.2-13.5). The mesenchymal component in all tumors was rhabdomyosarcoma (RMS), the neural component ganglioneuroblastoma/neuroblastoma (n = 5) and peripheral primitive neuroectodermal tumor in one case. Five patients presented with localized, one with metastatic disease. All but one patient received multiagent chemotherapy during their initial treatment. The tumors of 4/5 patients with localized MEM were at least grossly resected at best surgery; the patient without gross resection was additionally irradiated. Three of four evaluable tumors responded well to induction chemotherapy. All patients achieved a first complete remission (CR), but three recurrences (two local, one systemic) occurred. The individual with metastatic MEM did not survive, but all five patients with localized MEM are currently alive in CR with a median follow-up of 5 years (range: 2.1-13.7). Risk-factors and outcome of MEM appear to be comparable with other highly malignant pediatric soft tissue sarcoma when a multimodal treatment strategy including chemotherapy and adequate local treatment is pursued. We propose that treatment of patients with MEM be done according to pediatric protocols similar to other rhabdomyosarcoma-like soft tissue sarcoma.

Abstract 1421: Down-regulation of neuronal repressor gene REST inhibits tumor growth in Ewing's sarcoma

Abstract Ewing's sarcoma is a peripheral primitive neuroectodermal tumors (PNET). The abnormal differentiation of neuronal stem cells may relate to tumorigenesis of Ewing's sarcoma. The RE1-silencing transcription factor (REST) is a neuronal repressor gene which regulates neuronal stem cell differentiation. The aim of this study is to investigate the role of REST in Ewing's sarcoma. Our results demonstrated that three human Ewing's sarcoma cell lines TC71, A4573 and SK-ES expressed high levels of REST. Six of seven tumor samples from patients with Ewing's sarcoma were shown REST positive. Transfection of EWS-FLI-1 into mesenchymal stem cells up-regulated REST expression. Down-regulation of EWS-FLI-1 using si-RNA inhibited REST expression in TC71 cells, suggesting EWS-FLI-1 fusion protein regulates REST expression in Ewing's sarcoma. The siRNA-REST stable transfected cell line was established to down-regulate REST expression in TC71 Ewing's sarcoma cells. In vivo experiments indicated that Ewing's sarcoma tumor growth was significantly inhibited in the mice injected with si-REST-TC71 cells compared to the mice injected with si-control cells. Down-regulation of REST inhibited cell proliferation and induced apoptosis in TC71 tumors. The immunohistochemical staining indicated that the tumor vessels and pericyte marker expression were reduced in si-REST tumor tissues. Inhibition of REST decreased the early neural differentiation marker MSX-1 expression and up-regulated the terminal neural differentiation marker β-Tubulin III (Tuj) expression. These data suggesting that neuronal repressor gene REST plays an important role in tumor development of Ewing's sarcoma. Inhibition of REST suppressed tumor growth and altered neuronal differentiation marker expression in Ewing's sarcoma. REST is a potential target for treatment of Ewing's sarcoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1421. doi:1538-7445.AM2012-1421

Clinical study of peripheral primitive neuroectodermal tumors of the spinal cord

Objective To investigate the clinical characteristics of the peripheral primitive neuroectodermal tumors (pPNET) of the spinal cord.Method Four cases of pPNET of the spinal cord were treated in our hospital between Nov.2006 and Mar.2010.The clinical characteristics and outcome of them were reviewed.Results There were 1 male and 3 female patients.The age of presentation ranged from 4 to 20 years.Neck hurt was the first clinical symptom,and the symptoms developed rapidly.The preoperative images were impressing.All 4 lesions were given operations,and one lesion was totally removed,2 lesions were subtotally resected,and one was grossly removed.Two patients were dead at last follow - up.Conclusions pPNETs of the spinal cord are rare lesions occuring in young adults.Immunocytochemical staining(CD99)offers an easy way of making a differential diagnosis between cPNET and pPNET.Surgery combined with chemo - radiotherapy is the first treatment choice.The lesions carry a poor prognosis. Key words: Neuroectodermal tumors, primitive; Spinal cord neoplasms ; Treatment; Prognosis

A case of primitive neuroectodermal tumor of the ovary

Peripheral primitive neuroectodermal tumor (PNET) is a small round tumor belonging to the PNET/Ewing’s sarcoma family classified based on location in the body. There have been a small number of case reports of PNET arising in the ovary. We present extremely rare case of PNET of the ovary occurring in a 32-year-old pregnant woman, which was detected during her second Cesarean section. She had a past history of oophorectomy due to a huge mature solid teratoma in left ovary during her first Cesarean section. She got the operation of right salpingoophorectomy during the second Cesarean section at local gynecologic clinic and referred to our institute. Magnetic resonance imaging and positron emission tomography revealed the PNET was metastased to the peritoneum and the lymph nodes. We had persecuted vincristine, doxorubicin, cyclophosphamide, and etoposide/ifosfamide 8 cycles. There has been no evidence of local tumor recurrence and metastasis after the chemotherapy until now.

Peripheral primitive neuroectodermal tumor of the cervical spine

Background:Primitive neuroectodermal tumor (PNET) is a malignant neoplasm that generally arises from bone and soft tissues, with predilection for young adults. This neural crest origin tumors share biologic and histologic features with Ewing's sarcoma (ES).Case Description:We present a case of a 22-year-old woman with history of severe progressive neck pain, without radiation, associated with paresthesia in the right arm, and palpable right posterior cervical mass. Neurological examination showed increased reflexes in all four limbs, bilateral Hoffman's sign, right Babinski's sign, and right hemi-hypoesthesia. Neuroimaging revealed a right posterior cervical lesion with heterogeneous contrast enhancement extending to the neural foramina of the atlas and axis. Patient underwent microsurgical removal of the lesion, and histopathological and immunohistochemical analysis confirmed the diagnosis of peripheral primitive PNET (pPNET). The patient had adjuvant treatment with radiotherapy and chemotherapy. After twelve months, neuroimaging showed no signs of tumor regrowth and the patient had no neurological deficits. However, three months later, the patient developed hydrocephalus and cerebrospinal fluid (CSF) was positive for neoplastic cells. No other treatment was administered and the patient died.Conclusion:pPNET is a rare malignant tumor with poor prognosis, although promising results with multimodal treatment-surgery, radiotherapy, and chemotherapy. Diagnosis requires immunohistochemical analysis, with identification of neuronal differentiation markers.

A Rare Case of Peripheral Primitive Neuroectodermal Tumor Arising from the Minor Salivary Gland in a Young Woman

A Rare Case of Peripheral Primitive Neuroectodermal Tumor Arising from the Minor Salivary Gland in a Young Woman

Clinical features and outcomes in patients with Ewing sarcoma and regional lymph node involvement

A minority of patients with Ewing sarcoma present with regional lymph node involvement. We investigated if patient characteristics and outcomes differ between patients with Ewing sarcoma with and without regional node involvement. Patients <40 years of age with Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) reported to the SEER database from 1973 to 2008 were evaluated based on the presence (n = 91) or absence (n = 1,361) of regional node involvement. Patient characteristics were analyzed using Fisher exact tests. Overall survival was estimated by Kaplan-Meier methods and evaluated using log-rank tests and Cox models. Patients with regional node involvement were more likely to have extraskeletal primary tumors (65.9% vs. 31.2%; P < 0.001) and axial tumors (71.1% vs. 59.6%; P = 0.03) compared to patients without regional node involvement. The incidence of regional node involvement was 12.4% for patients with extraskeletal primary tumors compared to 3.2% for patients with skeletal tumors. Five-year overall survival from diagnosis was inferior for patients with regional node involvement compared to those without regional node involvement (45.9% vs. 60.3%; P < 0.001). On multivariate analysis, regional node involvement was predictive of inferior overall survival independent of age, metastatic status, tumor site, and soft tissue origin (hazard ratio 1.59; 95% CI 1.16-2.19). Patients with extraskeletal Ewing sarcoma should undergo evaluation for regional node involvement. If validated, our findings indicate that regional node involvement may be an independent adverse prognostic factor in Ewing sarcoma, and potentially useful in risk-stratifying patients with otherwise localized disease.

Imaging features of peripheral primitive neuroectodermal tumors

Objective To investigate the X-ray,CT and MRI features of peripheral primitive neuroectodermal tumors (pPNETs).Methods 14 patients were pathologically diagnosed with pPNETs.The imaging of X-ray (twelve image),Computed Tomography(eleven image) and Magnetic Resonance Imaging(five image) were retrospectively analyzed.Results Of 14 patients,there were two sites of tumour:soft tissue( eight patients) and bones( six patients).For tumoura of the soft tissue region,the appearance of X-ray and CT imaging showed equal or lower density soft mass without dear boundary.In some cases,tumours invaded adjacent bones.The appearance of MRI imaging showed large heterogeneous masses inside soft tissue without clear boundary.Tumours displaced adjacent cortical bone and cavitas medullaris.All masses were heterogeneous enhancement on contrast images.For tumours of bone region,X-ray and CT scan showed large scale osteolysis osteoclasia in bone surrounding with soft tissue masses of various size.The lesions were equal or lower signal on T1 WI.All masses were intermediate or hyperintense signal with heterogeneous midrange or obvious enhancement on T2WI.Conclusion Imaging characteristics of pPNETs were described.X-ray,CT and MRI were useful in understanding the property,extent and staging of tumor and very useful in the diagnosis. Key words: Bone neoplasms; Neuroectodermal tumor, peripheral; Tomography, X-ray computed; Magneticresonance imaging

Peripheral primitive neuroectodermal tumour of the liver: A case report and review of the literature

Peripheral primitive neuroectodermal tumour (PNET) is a malignant mesenchymal tumour. Although PNETs can occur in numerous solid organs, it is an extremely rare tumour entity, specially involving the liver. We report a 19-year-old boy with Hepatitis B Virus (HBV) infection who was diagnosed with a primary PNET of the liver.

A zebrafish transgenic model of Ewing’s sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis

SUMMARYEwing’s sarcoma, a malignant bone tumor of children and young adults, is a member of the small-round-blue-cell tumor family. Ewing’s sarcoma family tumors (ESFTs), which include peripheral primitive neuroectodermal tumors (PNETs), are characterized by chromosomal translocations that generate fusions between the EWS gene and ETS-family transcription factors, most commonly FLI1. The EWS-FLI1 fusion oncoprotein represents an attractive therapeutic target for treatment of Ewing’s sarcoma. The cell of origin of ESFT and the molecular mechanisms by which EWS-FLI1 mediates tumorigenesis remain unknown, and few animal models of Ewing’s sarcoma exist. Here, we report the use of zebrafish as a vertebrate model of EWS-FLI1 function and tumorigenesis. Mosaic expression of the human EWS-FLI1 fusion protein in zebrafish caused the development of tumors with histology strongly resembling that of human Ewing’s sarcoma. The incidence of tumors increased in a p53 mutant background, suggesting that the p53 pathway suppresses EWS-FLI1-driven tumorigenesis. Gene expression profiling of the zebrafish tumors defined a set of genes that might be regulated by EWS-FLI1, including the zebrafish ortholog of a crucial EWS-FLI1 target gene in humans. Stable zebrafish transgenic lines expressing EWS-FLI1 under the control of the heat-shock promoter exhibit altered embryonic development and defective convergence and extension, suggesting that EWS-FLI1 interacts with conserved developmental pathways. These results indicate that functional targets of EWS-FLI1 that mediate tumorigenesis are conserved from zebrafish to human and provide a novel context in which to study the function of this fusion oncogene.

Imaging findings in mandibular primitive neuroectodermal tumour: a report of a rare case and review of the literature

Primitive neuroectodermal tumours (PNETs) are aggressive undifferentiated tumours that occur mainly in the central nervous system (CNS). Reviewing the literature, only six cases of primary PNET of the mandible have been reported. These rare tumours are usually overlooked in clinical practice. An 18-year-old woman who presented with dental caries and left cheek swelling was initially diagnosed with facial cellulitis, but the swelling persisted despite adequate intravenous antibiotic therapy. Subsequent ultrasound and MR examinations revealed a tumour originating from the left mandibular ramus. The ultrasonography-guided percutaneous core needle biopsy confirmed the diagnosis of peripheral PNET. The radiographic features of mandibular PNETs are similar to those of PNETs in other regions, except for haemorrhage, necrosis and calcification. In addition, this is the first reported case with sonographic and MR images of this rare tumour, and the first case that was diagnosed based on the ultrasonography-guided percutaneous core needle biopsy. Using these image characteristics, mandibular PNETs can be diagnosed more accurately.

Extraosseous Ewing’s sarcoma of the pancreas

The Ewing's family of tumors (EFT) comprises a molecularly defined group of "small round blue cell tumors", consisting of Ewing's sarcoma of bone (ESB), extraosseous Ewing's sarcoma (EES), peripheral primitive neuroectodermal tumor (pPNET), and Askin's tumor. Characteristic translocations that disrupt the EWSR1 gene located at 22q12 create novel fusion genes that are central to the pathogenesis. The EFT also shares certain clinical characteristics, such as a peak incidence during the teenage years, a tendency to spread rapidly, and responsiveness to the same chemotherapeutic regimens and radiation therapy. Nearly all patients have occult disseminated disease at diagnosis; hence, chemotherapy is routinely used. Improvements in multimodality treatment have had a dramatic impact on outcomes. EES/pPNET has been reported in a variety of sites, including the pancreas, though this is extremely rare. We describe a case of pancreatic EES/pPNET in a 35-year-old woman and provide a brief review of the relevant literature.

Pancreatic Neoplasms in Childhood and Adolescence

Pancreatic neoplasms are rare in children and adolescents; thus, our understanding of these tumors is still quite limited. We retrospectively reviewed clinical features and outcomes of all patients below 18 years of age with pancreatic neoplasms who were treated at Asan Medical Center between December 1994 and March 2010. Thirty-two patients were identified. Abdominal pain was the most common symptom. The median duration of diagnostic delay was 21 days. Nineteen patients were diagnosed with solid pseudopapillary tumors, 3 with lymphomas, 2 with pancreatoblastomas, 2 with poorly differentiated carcinomas, 2 with acinar cell cancers, 2 with endocrine tumors, 1 with peripheral (primitive) neuroectodermal tumor, and 1 with hemangioendothelioma. Gross complete resection of the primary tumor was achieved in 24 patients (75%), and 8 patients (25%) received chemotherapy. At a median follow-up of 34 months, the 5-year overall survival rate was 92.0 ± 5.5%. On multivariate analysis, histologic type was the only factor significantly predictive of survival (P=0.009). Patients with poorly differentiated carcinoma showed the worst survival probability. In cases of solid pseudopapillary tumors, surgical resection was generally curative and the prognosis was excellent. Patients with other malignant tumors, however, may require therapeutic strategies other than surgery.

Primary extraosseous intracranial Ewing′s sarcoma: Case report and literature review

Ewing's sarcoma / peripheral primitive neuroectodermal tumors occur most often in bone and soft tissues of children and young adults. The intracranial manifestation of the disease is rare, and when present, this is often misdiagnosed with other varieties of primary brain tumors. We report such a case of extraosseous Ewing's sarcoma, which was initially suspected to be a case of meningioma in an 11-year-old girl.

Expanded Access Through Cancer Trials Support Unit to Children's Oncology Group Sarcoma Trial AEWS1031 for Adolescents and Young Adults.

Ewing sarcoma family of tumors (ESFT) is the second most common malignant tumor of bone and occurs predominantly in the adolescent and young adult age group.1 They include Ewing sarcoma, atypical Ewing sarcoma, and peripheral primitive neuroectodermal tumor of bone. Even though this malignancy arises mainly from the bone, primary extraosseous tumors also occur. These tumors are believed to be of neural crest origin and occur with almost equal incidence in the extremities and central axial sites. There is a dramatic racial variation in incidence, with almost no discernable incidence in individuals of African and Asian or Pacific island descent. Other than race, there are no known risk factors for ESFT. A EWS-ETS fusion protein is characteristic of ESFT, with over 85% of tumors expressing the EWS-FLI-1 fusion transcript.2

Computed tomography and magnetic resonance imaging findings of peripheral primitive neuroectodermal tumors of the head and neck

We aimed to analyze the computed tomography (CT) and magnetic resonance imaging (MRI) findings of peripheral primitive neuroectodermal tumor (pPNET) of the head and neck. Eight patients with pPNET of the head and neck confirmed by histopathological examination were analyzed retrospectively. The average patient age was 8 years. The tumor location in the 8 patients was as follows: maxillofacial region (right, 2; left, 1), left maxillary sinus (1), right masticator space (1), left carotid space (1), right infratemporal fossa (1), and left parotid gland (1). All 5 patients who underwent CT demonstrated ill-defined soft masses and no calcification. Three patients with tumors in the maxillofacial region showed homogeneous small masses and a mild enhancement. The patient with left maxillary sinus tumor showed a heterogeneous mass with patchy, necrotic foci and mild heterogeneous enhancement. The patient with right masticator space tumor showed a heterogeneous mass, and marked heterogeneous enhancement. The T1-weighted images of the patients with right infratemporal fossa, left carotid space, and left parotid gland tumors were isointense. The T2-weighted images were heterogeneous and mildly hyperintense in 2 patients and hyperintense in 1 patient. Heterogeneous intermediate enhancement was demonstrated in 2 patients and mild ring enhancement in 1 patient. The imaging features of pPNET of the head and neck are non-specific. An ill-defined, aggressive mass and variable enhancement on CT and MR images may suggest the diagnosis of pPNET. Peripheral PNET should be included in the differential diagnosis of children and adolescents' regional tumors.

Clinical features and outcomes in patients with extraskeletal ewing sarcoma

Ewing sarcoma can arise in either bone or soft tissue. The purpose of this study was to investigate whether patient characteristics, treatment strategies, and outcomes differ between skeletal Ewing sarcoma and extraskeletal Ewing sarcoma (EES). Patients <40 years of age with Ewing sarcoma or peripheral primitive neuroectodermal tumor reported to the United States Surveillance, Epidemiology, and End Results Program database from 1973 to 2007 were evaluated based on skeletal (n = 1519) versus extraskeletal (n = 683) site of origin. Patient characteristics were compared using Fisher exact tests. Overall survival was estimated via the Kaplan-Meier method and compared using log-rank tests and Cox proportional hazard models. Patients with EES had a higher mean age (19.5 vs 16.3 years; P < .001) and were less likely to be male (53.4% vs 63.3%; P < .001) or white (84.8% vs 92.5%; P < .001) compared with patients with skeletal tumors. Extraskeletal tumors were more likely to arise in axial locations (72.9% vs 54.2%; P = .001) but were less likely to arise specifically in the pelvis (19.8% vs 26.6%; P < .001). Metastatic status or tumor size did not differ by group. Five-year overall survival was superior for localized EES compared with localized skeletal tumors (69.7% vs 62.6%; P = .02). The hazard ratio for death in patients with localized skeletal tumors compared with localized EES was 2.36 (95% confidence interval, 1.61-3.44) beyond 24 months from initial diagnosis. Patient characteristics and outcomes differ among patients with EES compared with patients with skeletal Ewing sarcoma. These findings may have important implications for patient care.