Primitive Neuroectodermal Tumor Of Bone Research Articles

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

Carboplatin and paclitaxel adjuvant chemotherapy in primitive neuroectodermal tumor of the uterine corpus

Primitive neuroectodermal tumor of the uterine corpus (PNET) is rare and appears to have an aggressive clinical course. We report on a postmenopausal woman with optimal surgically cytoreduced advanced-stage PNET in which adjuvant combination chemotherapy with platinum and taxane agents was unsuccessful in extending her disease-free survival.

Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: a report from the Children's Oncology Group

AbstractThis study describes the magnitude of risk of therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) in 578 individuals diagnosed with Ewing sarcoma and enrolled on Children's Oncology Group therapeutic protocol, INT-0091. Between 1988 and 1992, patients with or without metastatic disease were randomized to receive doxorubicin, vincristine, cyclophosphamide, and dactinomycin (regimen A) or these 4 drugs alternating with etoposide and ifosfamide (regimen B). Between 1992 and 1994, patients with metastatic disease were nonrandomly assigned to receive high-intensity therapy (regimen C: regimen B therapy with higher doses of doxorubicin, cyclophosphamide, and ifosfamide). Median age at diagnosis of Ewing sarcoma was 12 years, and median length of follow-up, 8 years. Eleven patients developed t-MDS/AML, resulting in a cumulative incidence of 2% at 5 years. While patients treated on regimens A and B were at a low risk for development of t-MDS/AML (cumulative incidence: 0.4% and 0.9% at 5 years, respectively), patients treated on regimen C were at a 16-fold increased risk of developing t-MDS/AML (cumulative incidence: 11% at 5 years), when compared with those treated on regimen A. Increasing exposure to ifosfamide from 90 to 140 g/m2, cyclophosphamide from 9.6 to 17.6 g/m2, and doxorubicin from 375 to 450 mg/m2 increased the risk of t-MDS/AML significantly.

Therapy-related myelodysplasia/ leukemia (t-MDS/AML) following treatment of children with Ewing sarcoma and primitive neuroectodermal tumor of bone (PNET)

8514 Background: Limited information exists regarding risk of t-MDS/AML after Ewing’s sarcoma. Methods: We followed a cohort of 578 individuals less than 30 years of age, diagnosed with Ewing’s sarcoma, PNET or primitive sarcoma of bone between 1988 and 1994 (treated according to a therapeutic protocol: CCG-7881/POG-8850) to determine the incidence of t-MDS/AML and associated risk factors. Between 1988 and 1992, all patients were assigned randomly to standard chemotherapy with doxorubicin (dox), vincristine (VCR), cyclophosphamide (CPM), and dactinomycin (DACT) (Regimen A: n=262) or experimental therapy consisting of these four drugs in alternation with Ifosfamide (I) and etoposide (E) (Regimen B: n=256). Between 1992 and 1994, patients with metastatic disease were nonrandomly assigned to Regimen C (n=60). Cumulative therapeutic exposures were: Regimen A: CPM:20.4 g/2, dox:375 mg/m2; Regimen B: CPM:9.6 g/m2, dox:375 mg/2, E:5 g/m2, I:90 mg/2; Regimen C: CPM:17.6 g/m2, dox:450 mg/m2, E:5 g/m2, I:140 g/m2. Results: Median age at diagnosis (dx) was 12.0 yr. Eleven patients developed t-MDS/AML [Regimen A (n=3), Regimen B (n=2), Regimen C (n=6)] at a median of 3 yr., with a cumulative incidence of 2% at 5 years. Magnitude of risk by regimen is shown in the Table. Multiple regression analysis revealed that Regimen C (RR=15.9, 95% CI, 3.8–65.8), but not Regimen B (RR=0.6, 95% CI, 0.1–3.7) was associated with an increased risk of developing t-MDS/t-AML when compared with Regimen A. Age at diagnosis, gender, and use of radiation therapy for local control did not increase the risk of t-MDS/AML. Conclusions: The risk of t-MDS/AML after Ewing’s sarcoma is not increased after exposure to ifosfamide at a dose of 90 g/m2, or etoposide at 5 g/m2, when compared to those not exposed to ifosfamide or etoposide, but that the risk increases dramatically after exposure to ifosfamide at cumulative doses of 140 g/m2. No significant financial relationships to disclose.

Late Events in Pediatric Patients With Ewing Sarcoma/Primitive Neuroectodermal Tumor of Bone

The outcome for 82 pediatric patients with Ewing sarcoma (ES) and primitive neuroectodermal tumor (PNET) of bone is reported; the patients were treated at the Dana-Farber Cancer Institute (DFCI) and Children's Hospital (CH) in Boston, MA (USA) from 1971-1988. The charts of all patients with ES/PNET of bone treated during this period were reviewed for disease status, therapy, sites of relapse, information on second malignancies, and survival status. Eighty-two patients with ES/PNET of bone treated at DFCI/CH were identified. The 10-year event-free survival (EFS) rates were 12% (95% confidence interval [CI] 0, 27%) and 38% (95% CI 26, 51%) for patients with and without metastases, respectively (P = 0.002); the overall survival (OS) rates were 17% (95% CI 1, 33%) and 48% (95% CI 35, 61%) for patients with and without metastases (P = 0.001). Median follow-up for surviving patients is 10.2 years. Primary site in the pelvis also was associated with a poor outcome for patients with no metastatic disease (P = 0.006 OS, P = 0.03 EFS). Thirty-one patients survived in first remission at least 5 years from diagnosis, and of these, five experienced relapse of original disease, and five experienced secondary malignancies. Pediatric patients treated for ES/PNET of bone remain at risk for life-threatening events into the second decade of follow-up. After 5 years, the risk of second malignant neoplasm is at least as high as the risk of late relapse. Prolonged follow-up of patients with ES and PNET of bone is indicated.

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.

The Ewing's sarcoma family of tumors: Ewing's sarcoma and peripheral primitive neuroectodermal tumor of bone and soft tissue.

In 1921 James Ewing described a radiosensitive tumor of the forearm composed of small round cells that he believed to be of endothelial origin [1]. These small round cell tumors of bone came to be known as Ewing’s sarcomas. Soft tissue variants are called extraosseous Ewing’s sarcoma [2, 3] and the Askin tumor [4]. Bone and soft tissue tumors, which are quite similar to Ewing’s sarcoma under the light microscope but which have notable neural differentiation, have been denoted peripheral primitive neuroectodermal tumors (PNETs) or peripheral neuroepithelioma. The distinction between Ewing’s sarcoma of bone and soft tissue and other small round blue cell tumors of childhood was essentially a diagnosis of exclusion until current immunohistochemical and molecular genetic techniques gave us tools to better delineate these tumors. These tumors are defined by a common molecular marker, the (11;22)(q24;q12) translocation, or its variants. It is now thought that these tumors are all related and compose a spectrum of neuroepithelial tumors ranging from the least differentiated (Ewing’s sarcoma) to the most differentiated variants (PNET). It has been suggested that these tumors be considered a family of tumors called the Ewing’s sarcoma family of tumors (ESFT).KeywordsTotal Body IrradiationDesmoplastic Small Round Cell TumorSmall Round Cell TumorPeripheral Primitive Neuroectodermal TumorEwing Family TumorThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

The World Health Organization's histologic classification of bone tumors. A commentary on the second edition

The World Health Organization's histologic classification of bone tumors was revised in 1993. The first edition was reviewed by an international panel of pathologists from nine countries and modified to incorporate advances made in the twenty years since it appeared. The framework and concept of the classification remain the same (i.e., based on histologic criteria in terms of differentiation shown by the tumor cells via conventional light microscopy supplemented by immunohistochemistry). New entities not described in the first edition include, for example, benign and malignant fibrous histiocytomas, well differentiated osteosarcoma, round-cell osteosarcoma, clear cell chondrosarcoma, primitive neuroectodermal tumor of bone, osteofibrous dysplasia, and giant cell reparative granuloma. The revised and expanded classification reflects advances in our knowledge, but is similar in concept and framework to the original version to allow comparisons between data collected in the past and future.

MIC2 Detection in Tumors of Bone and Adjacent Soft Tissues

The diagnosis of Ewing's sarcoma has been based classically in large part on the exclusion of other similar small round-cell tumors by light microscopic and histochemical criteria. This study was undertaken to explore the use of a recently developed immunohistochemical stain directed against the glycoprotein p30/32MIC2 antigen (the gene product of MIC2), as a diagnostic tool and as a probe for the examination of potential interrelationships among the putative members of the family of peripheral primitive neuroectodermal tumors. Fifty-six small round-cell tumors of bone were selected for study from the files of the Armed Forces Institute of Pathology and Rhode Island Hospital; all tissues had been formalin fixed and paraffin embedded. Nine of 10 Ewing's sarcomas were MIC2 positive, as were 2 of 3 atypical Ewing's sarcomas (small round-cell tumors that diverged from the classic pattern of Ewing's sarcoma by exhibiting a greater degree of cytologic atypia and pleomorphism), and 7 of 8 Askin tumors of the thoracopulmonary region. Ten of 11 mesenchymal chondrosarcomas, 1 primitive neuroectodermal tumor of bone, 10 small cell osteosarcomas, 10 malignant lymphomas, and 3 sarcomas of bone (not additionally subclassified) were negative. The finding of MIC2 positivity in the majority of Ewing's sarcomas and Askin tumors provides additional support for earlier proposals (based on a shared cytogenetic abnormality, among other criteria) that these lesions be considered members of the same family, the peripheral primitive neuroectodermal tumors. The present study, drawing on archival and current case material (including decalcified and undecalcified specimens), indicates that neither the specimen age nor the application of any of a variety of decalcification solutions appears to adversely influence MIC2 staining of paraffin-embedded tissues. This suggests that this antibody has use in retrospective and prospective studies. The rare occurrence of false negative (in the case of Ewing's sarcoma) and positive results in tumors other than peripheral primitive neuroectodermal tumors (as in 1 of the mesenchymal chondrosarcomas) suggests that MIC2 staining should not be relied on as the sole criterion for identification or exclusion of Ewing's sarcomas and related tumors.

Proceedings of the tumor board of the childrens hospital of los angeles. Malignant fibrous histiocytoma of bone following primitive neuroectodermal tumor of bone

Proceedings of the tumor board of the childrens hospital of los angeles. Malignant fibrous histiocytoma of bone following primitive neuroectodermal tumor of bone

EWING'S SARCOMA

Ewing's sarcoma is a highly malignant tumor of uncertain origin. A strong relationship is suggested between Ewing's sarcoma and tumors of neural origin. The radiologic manifestation of Ewing's sarcoma are protean and lesions may be lytic, mixed lytic-sclerotic, or rarely, predominantly sclerotic. The lower extremity long bones are predominantly affected and most lesions are diaphyseal or metadiaphyseal. CT and particularly MR imaging are invaluable in further delineating the extent of disease not readily manifested on plain radiographs. Gallium scintigraphy and gadolinium-enhanced MR images are best for following the response to therapy. Ewing's sarcoma must be distinguished from other round cell tumors including lymphoma, neuroblastoma, and primitive neuroectodermal tumor of bone as well as from osteosarcoma.

Primary neuroblastoma of a vertebra: an unusual location for a variant of primitive neuroectodermal tumor of bone.

Primary neuroblastoma of a vertebra: an unusual location for a variant of primitive neuroectodermal tumor of bone.

Establishment and characterization of a primitive neuroectodermal tumor of bone continuous cell line (LAP‐35)

A continuous tumor cell line (LAP-35) was established from a primitive neuroectodermal tumor of bone from the right tibia of a 12-year-old female. The neural character of the cell line was documented by the spontaneous growth of neurites and by the presence of several neural markers, including neuron-specific enolase (NSE), S-100 protein, neurofilaments, chromogranin A, synaptophysin and positivity to monoclonal antibodies UJ127.11, UJ13A, UJ181.4. Cell-sorter analysis showed a high expression of nerve growth factor receptor (NGFr) and major histocompatibility complex class I-related molecules. A unique cytogenetic profile was observed, including a reciprocal chromosomal translocation (rct) 11:22 (q24;q12), typically associated with Ewing's sarcoma and neuroepithelioma, and deletion of the short arm of chromosome 1 (lp-), otherwise a feature of neuroblastoma. N-myc proto-oncogene was neither amplified nor expressed, whereas the expression of c-myc was documented by northern blot analysis. These features distinguish this new cell line from previously reported neuroectodermal cell lines, identifying LAP-35 as a unique model of a group of neural bone tumors that share characteristics of neuroblastoma as well as neuroepithelioma.