Peripheral Neuroepithelioma Research Articles

Ewings Sarcoma Mimicking a Schwannoma: MRI Findings of a Rare Case

Ewing’s sarcoma is among the most frequent yet highly aggressive neoplasms of the bones presenting in adolescents and children under the age of ten with a slight male predilection. It is now broadly categorized into a set of tumors recognized as Ewing’s sarcoma family based on the same histology and genotype of these tumors. This group of tumors includes Ewing’s sarcoma of bones, the 2nd most frequent bone malignancy, Askin tumors, PNET, and those rarely occurring extraosseous Ewing sarcoma (peripheral neuroepithelioma). Extra-osseous Ewing’s is a rare presentation occurring in only 5% of patients. Here we present such a case of an extra-osseous Ewing’s sarcoma in a 13-year-old female presenting to our hospital with a large mass in the sacral region. The interesting imaging findings and his histopathology are discussed.

Ewing Sarcoma in the Sciatic Nerve: Case Report

AbstractEwing 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.

A Short note on Ewings sarcoma

Ewing’s sarcoma was first distinguished as “diffuse endothelioma of bone”. The cause is still unknown the but mostly theories suggest that these tumors arise from a primitive cell obtained either from an embryologic tissue which is called the neural crest, or from mesenchymal stem cells that are capable to become one of a variety of tissue types. Pathologists have studied that Ewing sarcoma is almost alike to an even rarer soft tissue tumor called primitive neuroectodermal tumor (PNET).ES and PNET were having similar features when observed under microscope, in more than 95% of cases also had a similar genetic abnormality called as translocation. Hence they were grouped into class of cancers entitled Ewing’s Sarcoma Family of Tumor (ESFT).This family includes, Ewing’s sarcoma of the bone, Extraosseus Ewing’s sarcoma, Primitive neuroectodermal tumor (PNET),Peripheral neuroepithelioma, Askin’s tumor and Atypical Ewing’s sarcoma. The translocation in ESFT is between chromosomes 11 and 22 and is referred to as t (11;22). The gene from chromosome 22 encodes the Ewing sarcoma gene (EWS) whose function is not well-understood. The gene FLI1 from chromosome 11, is involved in turning other genes on and off. EWS/FLI is a fused gene, which encodes an altered fusion protein which controls the regulation of other genes that can give rise to cancers when inappropriately expressed.

Extraosseus Ewing's Sarcoma in Pancreas: A Review.

Primitive neuroectodermal tumors (PNET, previously referred to as peripheral neuroepithelioma) are rare malignant tumors with various degrees of differentiation belonging to the Ewing’s family of sarcomas. They are classified as round cell tumors arising from soft tissues. In rare instances, PNETs may arise from solid organs containing neuroendocrine cells of kidney, bladder, heart, lungs, parotid glands and pancreas. Most cases occur in the second decade of life with a slight preponderance in males. PNET of the pancreas is an aggressive tumor with multiple recurrences and a relatively poor prognosis. These tumors should be considered in the differential diagnosis, especially in a diagnosed pancreatic tumor in individuals less than 35 years of age. Due to the nature of the tumor, surgery with subsequent chemoradiation are widely accepted modalities despite the poor prognosis. In this article, we review 25 cases of extraosseous Ewing’s sarcoma (ES) of the pancreas which to the best of our knowledge, enlists most cases reported in the literature thus far.

Characteristics of human Ewing/PNET sarcoma models

Ewing/PNET (peripheral neuroepithelioma) tumors are rare aggressive bone sarcomas occurring in young people. Rare-disease clinical trials can require global collaborations and many years. In vivo models that as accurately as possible reflect the clinical disease are helpful in selecting therapeutics with the most promise of positive clinical impact. Human Ewing/PNET sarcoma cell lines developed over the past 45 years are described. Several of these have undergone genetic analysis and have been confirmed to be those of Ewing/PNET sarcoma. The A673 Ewing sarcoma line has proven to be particularly useful in understanding the biology of this disease in the mouse. The chromosomal translocation producing the EWS/FLI1 fusion transcript characterizes clinical Ewing sarcoma. Cell lines that express this genetic profile are confirmed to be those of Ewing sarcoma. The A673 Ewing sarcoma line grows in culture and as a xenograft in immunodeficient mice. The A673 model has been used to study Ewing sarcoma angiogenesis and response to antiangiogenic agents. Many Ewing sarcoma clinical specimens express the cell surface protein endosialin. Several Ewing sarcoma cell lines, including the A673 line, also express cell surface endosialin when grown as subcutaneous tumor nodules and as disseminated disease; thus the A673 is a useful model for the study of endosialin biology and endosialin-directed therapies. With the advent of tools that allow characterization of clinical disease to facilitate optimal treatment, it becomes imperative, especially for rare tumors, to develop preclinical models reflecting disease subsets. Ewing PNET sarcomas are a rare disease where models are available.

Unusual Myogenic and Melanocytic Differentiation of Soft Tissue pPNETs

All of the members of the peripheral primitive neuroectodermal tumor family (Ewing sarcomas, neuroectodermal tumors of bone, peripheral neuroepitheliomas, and Askin tumors) have similar morphologic and immunophenotypical features (ie, the proliferation of small and medium-sized round cells in a fibrous background showing strong and diffuse immunohistochemical positivity for CD99), and the common cytogenetic abnormality of a nonrandom translocation involving the EWS gene and one of several members of the erythroblastosis virus transforming sequence family of transcription factors. The combination of clinical information and morphologic/immunophenotypical characteristics is usually sufficient for a correct diagnosis, but there are rare cases in which an unusual predominant or multidirectional immunophenotypical differentiation makes diagnosis a challenge and requires the use of molecular cytogenetic or molecular techniques. We describe 3 such cases in which we employed fluorescence in-situ hybridization analysis to detect translocation involving the EWS gene and reverse transcription polymerase chain reaction followed by sequencing to detect the fusion transcript EWS-FLI1.

Tumores neuroectodérmicos primitivos periféricos de localización en el área orocervical: presentación de dos casos clínicos

Introduction: Peripheral primitive neuroectodermal tumors (PNET) are a family of smallround cell tumors of presumed neuroectodermal origin. This broad family can be subdivided into three major groups: PNET from the central nervous system, PNET from the autonomic nervous system or peripheral PNET. Ewing's sarcoma and peripheral neuroepitelioma, the two most frequently encountered members of the peripheral PNET family, are considered to represent a spectrum according to the extent of neuroectodermal differentiation, ranging from the least differentiated (Ewing's sarcoma) to the most differentiated (peripheral neuroepithelioma). Case report: We present a patient with a peripheral neuroectodermal tumor located in the neck and another one with a peripheral neuroectodermal tumor of the mandibular condyle. Discussion: Peripheral neuroectodermal tumors are a very rare and aggressive tumors. They characteristically reveal the presence of small round cells and a translocation of the gene EWS. The prognosis in overall is very poor. Due to the small numbers of cases published the best treatment is not well defined.

Malignant peripheral primitive neuroectodermal (pPNET) of tongue

Primitive neuroectodermal tumors (PNETs) are relatively rare tumors. Tumors that once would have been diagnosed as Ewing's sarcoma are now often designated as peripheral neuroepithelioma or synonymously PNET. This paper reports a case of PNET located orally on the tongue, which is, to our knowledge, the first case reported in medical literature. The patient was treated with postoperative radiotherapy and chemotherapy. Multiple liver metastases occurred 5 months after the initial diagnosis and following extensive chemotherapy the patient was only able to survive for a further 10 months.

Malignant peripheral neuroepithelioma "peripheral neuroblastoma" a case report

Peripheral neuroepitheliomais a rare malignant tumour of primitive peripheral non autonomic nervous system. The tumour can occur at any age involving soft tissue mainly of lower extremities, Other sites of occurrence are the shoulder-thoracic region and the head and neck.It is a very aggressive tumour with early metastasis mainly to the lung.Herewith we report a case of 16 years old female who was presented with soft mass of labia majora of 3 years duration which has been rapidly enlarging in the last 6 months. The mass was excised and followed by administration of chemotherapy and radiotherapy. The patient developed secondaries in the lung 3 months after excision, with pleural effusion, but no local recurrence. However, eight months after the diagnosis and in January 2005, the patient died from the tumour.Keywords: Peripheral Neuroepithelioma Primitive Neuro Ectodermal Tumour "PNET" Soft tissue.

Primitive neuroectodermal tumour of the mandible

Primitive neuroectodermal tumors (PNETs) are relatively rare tumors. Tumors that once would have been diagnosed as Ewing's sarcoma are now often designated as peripheral neuroepithelioma or synonymously PNET. Herein we report the first case of PNET of the mandible in a 6-year-old female who was admitted to the hospital with a two-months history of painless, progressively enlarging lower jaw mass.

Primitive Neuroectodermal Tumor Of The Spermatic Cord

Primitive neuroectodermal tumor (PNET) originates from neural crest cells and is classified into the group of small round cell tumors with high morbidity and mortality. PNET is also a member of the family of Ewing tumors, which include Ewing’s sarcoma, peripheral neuroepithelioma and Askin tumor.1 These tumors typically develop in children and arise from the central nervous system, lungs and soft tissues. We report a case of PNET arising from the spermatic cord that was treated with resection and chemoradiotherapy. CASE REPORT A 53-year-old man presented with a recurrent left inguinal mass, which had originally been resected by another surgeon. At the previous operation the nature of the tumor was unclear on routine pathological examination. The patient had a palpable mass measuring approximately 7 cm. that extended from the left inguinal region to the scrotum. Abdomino-pelvic computerized tomography revealed a homogeneous solid mass measuring 2.4 2.7 7 cm. that was related to the left spermatic cord. On magnetic resonance imaging the mass demonstrated hypointensity on T1weighted images and hyperintensity on T2-weighted images (fig. 1, A). Tumor markers were negative for -fetoprotein, carcinoembryonic antigen, -human chorionic gonadotropin, and neuron specific enolase. No metastases were detected. Preoperative workup was done and informed consent was obtained. Left radical orchiectomy with complete excision of the mass was performed. The tumor was adherent to the spermatic cord, but was easily separated from the muscle tissue and pubic bone. The lesion was firm and had a whitish cut face (fig. 1, B). Histological examination revealed the monotonous proliferation of small round cells (fig. 2, A). Immunohistochemical staining was nonspecific and was negative for CD99, which is often positive in tumors of the Ewing’s sarcoma family. However, staining for S-100 protein was positive, CD56 was positive and FLI1 gene product was weakly positive. Electron microscopy showed primitive cells with neurosecretory granules in the cytoplasm (fig. 2, B), indicating neuronal differentiation and confirming the diagnosis of PNET. We did not detect EWS-FLI1 or EWS-ERG fusion gene transcripts in tumor tissue using the reverse transcription polymerase chain reaction method. Postoperatively, the patient received 2 cycles of adjuvant chemotherapy using the CyVADIC protocol2 (cyclophospha

Neuroectodermal and neuroendocrine tumors principally seen in children.

Neuroectodermal tumors comprise a large proportion of childhood neoplasms. Neuroblastic tumors, including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma, are the most frequent extracranial solid cancers of childhood, occurring primarily in infants and toddlers. Primitive neuroectodermal tumors, including Ewing sarcoma and peripheral neuroepitheliomas, occur most frequently in older children and adolescents, and as pediatric sarcomas are second in frequency only to rhabdomyosarcomas. Rarer neuroectodermal tumors include desmoplastic small cell tumors, esthesioneuroblastomas, and melanotic neuroectodermal tumors, the first two entities occurring as rather site-specific lesions in the abdomen and nose, respectively. Diagnosis can be difficult due to the undifferentiated nature of many of these cancers, but ancillary studies, including electron microscopy, immunohistochemistry, cytogenetics, and molecular genetics, enhance their recognition. The molecular nature of childhood neuroectodermal tumors is as diverse as their histology, ranging from the fusion genes characterizing the Ewing sarcoma family of tumors to the proto-oncogene amplification seen in aggressive neuroblastomas.

Non-hematopoietic cutaneous metastases in children and adolescents: thirty years experience at St. Jude Children's Research Hospital.

The spectrum of cutaneous metastasis of non-hematopoietic neoplasms in the pediatric population is not well documented. We report the histologic diversity of this unusual process over a 30-year period at a tertiary care center for pediatric malignancy (St. Jude Children's Research Hospital, Memphis, TN, USA). Of 1,971 pathology accessions which included histologic material on skin (1,604 surgical cases and 367 autopsy cases) we found 40 cases (2% of total skin accessions) coded for metastatic non-hematopoietic malignancy. The patients (n=34) ranged in age from 1 month to 20 years (mean=9.8 years) and had a male:female ratio of 1:1. The histologic diagnoses were as follows: rhabdomyosarcoma NOS (6 cases), embryonal rhabdomyosarcoma (4 cases), alveolar rhabdomyosarcoma (4 cases), neuroblastoma (8 cases), osteosarcoma (2 cases), choriocarcinoma (2 cases), peripheral neuroepithelioma or Ewing's sarcoma (2 cases), malignant rhabdoid tumor (1 case), paraganglioma (1 case), nasopharyngeal carcinoma (1 case), sarcoma NOS (1 case), colon adenocarcinoma (1 case), and malignant melanoma (1 case). Cutaneous or subcutaneous metastasis of non-hematopoietic malignancies in children and adolescents is a rare occurrence but in a high percentage of cases may be the first manifestation of disease. The tumors most likely to metastasize to the skin in children are rhabdomyosarcoma and neuroblastoma and they are more likely than adult malignancies to disseminate to multiple distant sites.

Ewing's Sarcoma and Peripheral Primitive Neuroectodermal Tumor of Bone and Soft Tissue

The histological diagnosis of Ewing's sarcoma (Es) continues to be a difficult task for pathologists. A number of new Es varieties has been described, leading to further complexity. Conventional Es, atypical Es, and peripheral neuroectodermal tumor (pPNET), including peripheral neuroepithelioma, belong genetically to the same family of neoplasms, displaying common chromosomal rearrangements and analogous gene reorganizations. The main translocations are t(11;22) and t(21;22), with genes EWS, FLI-1 and ERG being involved, as well as other members of the ETS family of transcription factors. The prevalence of morphology should be maintained with the use of conventional histological techniques and supported with the analysis of the expression of CD99 Mic2 (HBA 71, 0.13) antigen, which is present in over 90% of cases, as well as with FLI-1 rearranged gene derived protein. Moreover, FISH and RT-PCR in paraffin-embedded tumor tissue may be of use in extremely difficult cases for differential diagnosis. Nevertheless, a number of mixed tumor types, such as primitive sarcoma or biphenotypic sarcoma, may show structural and genetic diversity, thus rendering their diagnosis even more complex.

Peripheral neuroepithelioma in the abdominal wall developed in the patient with hepatocellular carcinoma: A case report.

An abdominal wall tumor was discovered in a 65-year-old man when he was admitted to our hospital for the treatment of hepatocellular carcinoma. The needle biopsy specimen indicated peripheral neuroepithelioma. The patient underwent a simple resection of the tumor and reconstruction of the abdominal wall with artificial peritoneum and Dexon mesh. He has survived with liver cirrhosis for 31 months after the operation. Peripheral neuroepithelioma in the abdominal region is rare and thus the reported English literature is discussed.

Interference of proteins involved in the cytoplasmic sequestration of p53 with human papillomavirus E6-mediated degradation.

The oncogenic human papillomaviruses (HPVs) are able to efficiently target p53 for degradation by the ubiquitin pathway. We previously demonstrated inefficient HPV E6-mediated degradation and resulting high steady-state levels of p53 in cell hybrids between a peripheral neuroepithelioma cell line and a cervical carcinoma cell line (HeLa). We now show that the p53 protein in these cell hybrids was cytoplasmically sequestered and exhibited sporadic punctate staining, which is characteristic of the p53 expression pattern observed in neuroblastic neuroblastoma (NB) cell lines, in which p53 is also sequestered. We hypothesized that the cytoplasmic sequestration of p53 in the cell hybrids might correlate with its inability to be rapidly degraded by HPV E6. Using NB cell lines as a model system to test this hypothesis, we demonstrated that the introduction of HPV E6 into two NB cell lines resulted in p53 insensitivity to HPV E6-mediated degradation. This was assessed by both pulse-chase analysis of p53 in metabolically labeled NB cells and western blotting. The enhanced stability of p53 was not due to a lack of HPV E6 expression or to a mutant conformation of the p53 protein. Our results therefore suggest that proteins involved in the cytoplasmic sequestration of p53 may also interfere with the ability of HPV E6 to target p53 for degradation.

Retrospective analysis of ploidy in primary osseous and extraosseous Ewing family tumors in children.

To retrospectively study the DNA content in a series of childhood Ewing Family Tumors (EFT), and to investigate its prognostic value. The study was performed on a series of 27 EFTs (osseous Ewing's sarcoma, 18 cases; extraosseous Ewing's sarcoma, 2; peripheral neuroepithelioma, 4; Askin Rosai tumors, 3). Ploidy was investigated using both flow cytometry (FCM) and image cytometry (ICM) on tumor cell suspensions from formalin-fixed paraffin-embedded specimens or fresh frozen tissue obtained from the primary tumor at diagnosis. Ploidy was evaluable by FCM in all cases, and by ICM in 23/27. When fresh frozen tissue and paraffin-embedded samples from the same tumor were available for analysis, they yielded equal results. The rate of agreement between FCM and ICM was 82%. The majority of cases were diploid, and in the present series aneuploidy seemed to be associated with a poor outcome. These results suggest that aneuploidy could be an indicator of a bad prognosis in EFT; however, the small number of cases precludes any conclusion of statistical value. Larger retrospective studies on ploidy using archival material could be performed and their reliability is supported by the concordance of results from fresh and formalin-fixed tissue.

Failure of HPV E6 to rapidly degrade p53 in human HeLa×PNET cell hybrids

The ability of the E6 protein from high risk human papillomaviruses (HPVs) to degrade p53 via the ubiquitin pathway plays a major role in the development of cervical carcinomas. We have previously generated cell hybrids between a p53 null peripheral neuroepithelioma (PNET) cell line and a cervical carcinoma HeLa cell line which exhibits efficient E6-mediated degradation of p53. All of the resulting hybrids expressed HPV 18 E6 from the HeLa parent and some of the hybrids additionally expressed HPV 16 E6. Surprisingly, in spite of abundant E6 expression, the hybrids expressed relatively high steady-state levels of the wild-type p53 protein. We then examined the hybrids to determine whether other components of the E6-mediated degradation pathway were missing or nonfunctional. Specifically, we determined that the E6-associated protein (E6-AP), essential for E6-mediated degradation, was expressed. We further verified that these hybrids had a functional ubiquitination pathway, which suggests that this phenomenon is not due to a general defect in this pathway. We therefore conclude that other unidentified, possibly cell-specific factors can play a role in the E6-mediated degradative process and may act to inhibit this process.

Value of Immunohistochemistry in a Subset of Small Round Blue Cell Tumors

A patient with a retroperitoneal mass extending into the liver had a core needle biopsy that showed a small, round, blue cell tumor of uncertain origin by light microscopy. The tumor cells stained with antibodies against vimentin, neuron specific enolase, and the S-100 protein. The cells did not stain with antibodies to muscle specific actin, chromogranin A, cytokeratin cocktail, or leukocyte common antigen. Based upon these histologic and immunohistochemical findings, consideration was given to either an extra-osseous Ewing's sarcoma or a peripheral neuroepithelioma, and a diagnosis of “consistent with peripheral neuroepithelioma” was rendered. The role of immunohistochemistry in resolving this differential and the resulting prognostic implications are discussed. (The J Histotechnol 20:67, 1997)

Value of Immunohistochemistry in a Subset of Small Round Blue Cell Tumors

A patient with a retroperitoneal mass extending into the liver had a core needle biopsy that showed a small, round, blue cell tumor of uncertain origin by light microscopy. The tumor cells stained with antibodies against vimentin, neuron specific enolase, and the S-100 protein. The cells did not stain with antibodies to muscle specific actin, chromogranin A, cytokeratin cocktail, or leukocyte common antigen. Based upon these histologic and immunohistochemical findings, consideration was given to either an extra-osseous Ewing's sarcoma or a peripheral neuroepithelioma, and a diagnosis of “consistent with peripheral neuroepithelioma” was rendered. The role of immunohistochemistry in resolving this differential and the resulting prognostic implications are discussed. (The J Histotechnol 20:67, 1997)