Soft Tissue Ewing Sarcoma Research Articles

Soft Tissue Ewing Sarcoma Cell Drug Resistance Revisited: A Systems Biology Approach.

Ewing sarcoma is a rare type of cancer that develops in the bones and soft tissues. Drug therapy represents an extensively used modality for the treatment of sarcomas. However, cancer cells tend to develop resistance to antineoplastic agents, thereby posing a major barrier in treatment effectiveness. Thus, there is a need to uncover the molecular mechanisms underlying chemoresistance in sarcomas and, hence, to enhance the anticancer treatment outcome. In this study, a differential gene expression analysis was conducted on high-throughput transcriptomic data of chemoresistant versus chemoresponsive Ewing sarcoma cells. By applying functional enrichment analysis and protein-protein interactions on the differentially expressed genes and their corresponding products, we uncovered genes with a hub role in drug resistance. Granted that non-coding RNA epigenetic regulators play a pivotal role in chemotherapy by targeting genes associated with drug response, we investigated the non-coding RNA molecules that potentially regulate the expression of the detected chemoresistance genes. Of particular importance, some chemoresistance-relevant genes were associated with the autonomic nervous system, suggesting the involvement of the latter in the drug response. The findings of this study could be taken into consideration in the clinical setting for the accurate assessment of drug response in sarcoma patients and the application of tailored therapeutic strategies.

Prospective Study of Whole Lung Irradiation with Intensity Modulated Radiotherapy/Volumetric Modulated ARC Therapy (IMRT/VMAT) in Patients of Bone and Soft Tissue Ewing Sarcoma with Pulmonary Metastasis

<h3>Purpose/Objective(s)</h3> To evaluate the progression free survival and pulmonary failure free survival post Whole Lung Irradiation in patients of bone and soft tissue Ewing sarcoma with pulmonary metastasis and to evaluate the efficacy and early toxicities associated with Cardiac Sparing Whole Lung Irradiation in these patients. <h3>Materials/Methods</h3> In this prospective, interventional, single arm study, we recruited a total of 18 patients with bone and soft tissue Ewing sarcoma with pulmonary metastasis between January 2020 to December 2021. All the patients, after the treatment of primary disease, received Whole Lung Irradiation (WLI) - 18Gy/10#/2 weeks in patients above 18 years of age and 15Gy/10#/2 weeks in those below 18 years of age. All the patients were treated using Image guided IMRT/VMAT technique. Evaluation of pulmonary response was done with NCCT chest at 3 months and 6 months post WLI. Toxicities during and after RT was graded using the CTCAE v.5 criteria. 2-D Echo and PFT values were assessed at 3 months and at 6 months. The quality of life scores were obtained using EORTC QLQ C-30 (version 3) at 4 time points. <h3>Results</h3> Majority of the patients were adults and majority had progression during the study. Only 4 patients had pulmonary relapse as the first site of progression. The 6-month PFS and Pulmonary FFS was 50.8% and 71.4%, respectively. There was statistically significant decrease in FEV1 and FVC values post RT and most patients showed restrictive pattern in PFTs after 6 months of WLI. There was no statistically significant decrease in LVEF or any other cardiac toxicities post RT. The global health QoL scores were significantly reduced at 6 months post RT when compared to pre-RT values. Dmean of heart was 13.1Gy (12.2Gy with a total dose of 15Gy and 14.0Gy with a total dose of 18Gy), which was significantly less compared to conventional planning. No patients had acute or chronic Grade 3 or more toxicities of RT. Only few patients developed Grade 2 toxicities following RT and the proportion of patients showing Grade 2 or more toxicities was significantly less compared to 2-D conventional planning. <h3>Conclusion</h3> This prospective single arm study demonstrated the feasibility and dosimetric advantages (superior cardiac sparing and superior dose coverage of lung volumes) of cardiac sparing whole lung irradiation using VMAT technique. There were no significant severe RT related toxicities and the survival rates were similar to those seen in previous studies. Further studies with greater sample size and longer follow-up will be required to establish the long-term efficacy and safety of this irradiation technique.

18F-fluorodeoxyglucose positron emission tomography / computed tomography in primary Ewing sarcoma of the lung

Introduction. Ewing sarcoma is rare in medical practice, and evaluating positron emission tomography / computed tomography (PET/CT) imaging of soft tissue Ewing sarcoma is a challenge. Primary Ewing sarcoma of the lung is an infrequent diagnosis. Case outline. A 22-year-old female patient was sent for PET/CT examination to the Center for Nuclear Medicine with Positron Emission Tomography, of the University Medical Center of Serbia, with a referral diagnosis of primary Ewing sarcoma of the right lung. In parallel to tumor visualization, the PET/CT imaging showed a radiological entity named ?kissing sign,? due to an enlarged beaver tail liver. Conclusion. According to the concept of functional mimicry and tissue specificity of molecular markers, a better understanding of the molecular mechanisms of soft tissue Ewing sarcoma is the challenge. These observations can be the platform for further investigation of new therapeutic regimens.

18F]FDG PET/CT quantitative parameters for the prediction of histological response to induction chemotherapy and clinical outcome in patients with localised bone and soft-tissue Ewing sarcoma

The application of [18F]FDG PET/CT in predicting histologic response to induction chemotherapy in patients with Ewing sarcoma (EWS) has been proposed using the values of pre-post treatment SUVmax as a referral parameter, although with heterogeneous results. The aim of this retrospective study was to evaluate the diagnostic accuracy of [18F]FDG PET/CT volumetric parameters (metabolic tumour volume (MTV) and total lesion glycolysis (TLG)) as compared to SUVmax to predict response to chemotherapy and clinical outcome in patients with localised EWS of bone and soft-tissue. Twenty-eight patients with non-metastatic EWS of bone (n = 20) and soft tissues (n = 8) who underwent a [18F]FDG PET/CT scan before (PET1) and after induction chemotherapy (PET2) were enclosed in the analysis. Values of PET metrics (SUVmax, MTV, TLG) at diagnosis and after neoadjuvant chemotherapy as well as the percentage change between PET1 and PET2 (ΔSUV, ΔMTV and ΔTLG) were correlated to histological response and to progression-free survival (PFS). ΔTLG (cut-off: -60%) is the best predictor for histologic response with 100% sensitivity and 77.8% specificity. MTV1 > 33.4 cm3 and TLG1 > 112 were also associated with a favourable histologic response (sensitivity 80% and specificity 77.8% for both). On multivariate analysis, SUV2 (> 3.3) and ΔTLG (< -18%) were independent predictors of worse PFS. [18F]FDG PET/CT could accurately predict histologic response to neoadjuvant chemotherapy in patients with EWS, also showing a possible prognostic value for future disease relapse. • The variation of the PET parameter tumour lesion glycolysis (TLG) can predict the histologic response to induction chemotherapy (sensitivity 100%, specificity 77.8%), in patients with Ewing sarcoma. • The percentage variation of TLG and the value of the SUVmax at PET scan after chemotherapy show a prognostic role for future disease relapse. The combination of both the parameters identifies three prognostic classes of patients with low, intermediate and high risk of disease relapse.

S2027 Ewing's Sarcoma: A Difficult Diagnosis to Swallow

INTRODUCTION: Ewing sarcoma family of tumors (EFT) compromises of a spectrum of similar histological undifferentiated cells. EFT includes Ewings Sarcoma (ES) and Primitive Neuroectodermal Tumor (PNET). These tumors are rare and aggressive with a tendency of early metastatic spread. Peak incidence are between ages of 10-15 years of age; however, 30% can occur in adults over the age of 20. EFT affect mainly Caucasians and are extremely uncommon in other races. Most common origin occurs from the bone of the extremities and axial skeleton. These tumors are not commonly found in the gastrointestinal tract. Our case demonstrates a rare presentation of metastatic Ewing Sarcoma found during evaluation for dysphagia. CASE DESCRIPTION/METHODS: 69 year old female who is a daily smoker with history of large cell lymphoma (previously treated with Adriamycin) and Barrett's esophagus presented with dysphagia. Labs were relevant for iron deficiency anemia. EGD revealed a fungating mass in an area of Barretts esophagus. The mass was not bleeding, non obstructing and partially circumferential. Biopsies from the mass revealed Ewing sarcoma (ES) based on histological stains. Microscopically the cells were arranged in cords suggestive of a neuroectodermal tumor. Fluorescent in situ hybridization (FISH) testing was negative for EWSR fusion protein. Cells were strongly positive for CD-99 and weakly positive for FLI1 also highly suggestive of ES. Further imaging revealed metastatic disease to the liver. Liver lesions were also biopsied confirming diagnosis of extra-skeletal Ewings Sarcoma. DISCUSSION: Soft tissue Ewing Sarcoma patients are older and more likely to be female. These tumors do express high levels of cell surface glycoproteins such as CD99, MIC2, and p30. MIC2 expression is a sensitive diagnostic marker for ES however it lacks specificity. Typically ES can be diagnosed with immunohistochemical stains for CD99 in the right clinical setting. However, if the presentation is atypical, such as in our case, further confirmatory testing with Next Generation Sequencing to detect translocation or point mutations are needed. Because of the vast differentials molecular genetics plays a large role in diagnosis. Translocations in EWSR1 gene on chromosome 22q12 are found in 85% of cases and can be detected using FISH analysis. This case illustrates the importance of timely establishment of type of esophageal cancer in order to obtain prompt molecular genetic assessments in order to confirm histological diagnosis.Figure 1.: Lower esophageal fungating, non obstructing, partially circumferential mass found on EGD.Figure 2.: The cells are small to medium sized, and are arranged in cords, interspersed with smooth muscle fibers suggestive of a neuroectodermal tumor.Figure 3.: Immunohistochemical stain positive for CD99 (cell surface glycoprotein) found in Ewings Sarcoma.

Abstract 1181: Associations of socioeconomic status and race/ethnicity with metastasis at sarcoma diagnosis

Abstract Background: Sarcomas comprise a group rare and heterogeneous neoplasms. As sarcomas have few early recognizable signs, they often have an extended delay between symptom onset and diagnosis. Approximately 10% - 30% of sarcoma cases present with metastasis at diagnosis. However, the extent to which a delayed diagnosis increases the likelihood of presenting with metastasis remains unclear. To expand this under-researched area of study, we sought to determine whether socioeconomic status (SES) or race/ethnicity were independently associated with metastasis at diagnosis of sarcoma by individual subtype. Methods: The influence of small-area SES and race/ethnicity on metastasis at diagnosis of sarcoma across all ages was evaluated using data from the SEER program (years of diagnosis: 2001 – 2015). Small-area SES was evaluated from a composite index measured at the census-tract level. Odds ratios (OR) for presenting with metastasis and 95% confidence intervals (CI) were estimated from logistic regression models that included SES as an ordinal variable, race/ethnicity, age, sex and year of diagnosis. Analyses were stratified by age groups (pediatric; &amp;lt; 20 years, adult: 20 – 65 years, older adult: 65 + years) and reported for any subtype with more than 100 metastatic cases within each age group category. A secondary analysis of adult cases evaluated the influence of insurance status (uninsured, Medicaid insured, privately insured) on metastasis using logistic regression, adjusted for small-area SES, race/ethnicity, sex, age, and year; this analysis was restricted to the years of available data, 2007 – 2015. Results: A total of 55,635 first primary sarcoma cases were identified. A higher SES was associated with a lower odds of metastasis for pediatric osteosarcoma (ordinal OR: 0.90, 95% CI: 0.85, 0.99; p-trend: 0.02), liposarcoma in adults (ordinal OR: 0.85, 95% CI: 0.78, 0.94; p-trend: 0.001) and unclassified sarcomas in adults (ordinal OR: 0.91, 95% CI: 0.84, 0.98; p-trend: 0.01) and older adults (ordinal OR: 0.91, 95% CI: 0.83, 0.99; p-trend: 0.03); the odds of metastasis in the remaining subtypes evaluated were not associated with SES. We also observed the odds of metastasis to be higher in minority populations compared to non-Hispanic (NH)-white cases for several subtypes, including leiomyosarcoma in NH-black (OR: 1.80, 95% CI: 1.51, 2.14), Asian pacific islander and American Indian or Alaskan native (API/AIAN) (OR: 1.45, 95% CI: 1.17, 1.79), and Hispanic (OR: 1.32, 95% CI: 1.10, 1.57) adult cases, as well as Ewing sarcoma of soft tissue in Hispanic adult cases (OR: 1.81, 95% CI: 1.07, 1.34). Having Medicaid or no insurance was a strong predictor of presenting with metastasis for all subtypes evaluated, except Ewing sarcoma of bone (significant ORs ranged from 1.38 to 2.27), and attenuated the associations with SES. The increased odds of metastasis among NH-Black cases with leiomyosarcoma and unclassified sarcomas, however, remained statistically significant. (Leiomyosarcoma OR: 1.88, 95% CI: 1.52, 2.33; unclassified sarcomas OR: 1.62, 95% CI: 1.11, 2.35). Conclusion: Small-area SES was not associated with metastasis at diagnosis of most sarcomas. However, based on our analysis of insurance status, delayed access to care may still be an important predictor advanced stage. Biological factors may also play a role in the racial disparities for sarcoma stage observed in adults. Citation Format: Brandon J. Diessner, Logan G. Spector, Jenny N. Poynter. Associations of socioeconomic status and race/ethnicity with metastasis at sarcoma diagnosis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1181.

Small round cell tumor of cervical region: a case report with unusual site &amp; course

Ewing’s sarcoma belongs to a spectrum of neoplastic diseases known as Ewing’s family of tumors. Ewing sarcoma can arise in either bone or soft tissue. Small round cell tumors comprise a heterogeneous group of neoplasms that predominate in childhood and adolescence, share similar morphological features, consisting of dense cellular proliferation of small round cells with primitive appearance. Ewing sarcoma is the second most common malignant bone tumour in children and young adults, although, rarely, it may be of extraskeletal origin. Extra-osseous tumor with metastatic or recurrent disease has a worse outcome; 5-year overall survival remains about 25 %. A female patient presented in surgical OPD for the first time at the age of 12 years with swelling in right supraclavicular region. The swelling was excised & a provisional diagnosis of small round cell tumor was given & patient was lost to follow up. Swelling recurred at the age of 23 years & was gradually increasing in size, measuring 20 x 20 x 20 cm. Radiologically, lesion was suggestive of sarcoma / lymphoma. Patient was operated & histopathological diagnosis of malignant round cell tumor was given with differential diagnosis of Ewing’s sarcoma, PNET, lymphoma. Patient had third recurrence of swelling at the age of 28 years at same site. On IHC, diagnosis of Soft Tissue Ewing sarcoma was given. Inspite of recurrence & huge size of tumor, patient was otherwise asymptomatic. Ours is a rare case of more than 16 years of survival inspite of recurrence. Immunochemistry is mandatory for diagnosis of Extraskeletal Ewing sarcoma in younger age group patients. Regular follow up of such patients is essential for timely detection & complete treatment of recurrent tumors.

Cutaneous Ewing's sarcoma of scalp with lung metastases in an elderly female: A rare case report

Ewing's sarcoma (ES) is a primitive neuroectodermal tumor. It is usually a primary bone tumor but rarely occurs in the skin and subcutaneous tissues (primary cutaneous ES [PCES]). It usually involves the deep subcutaneous tissue or muscles and rarely occurs as primary skin cancer. Most patients are white, women, and in the second decade of life. The diagnosis is made by aspiration cytology, histochemical stains, immunohistochemistry, electron microscopy, cytogenetics, and molecular genetics of translocations. Due to their rarity and morphological similarity to other cutaneous tumors, ESs are subject to being clinically and pathologically underdiagnosed. Cutaneous ES has a better prognosis than primary bone or soft-tissue ES, with a survival rate of 91% in 10 years and the presence of metastasis being rare. At present, no specific treatment guidelines inform the management of cutaneous Ewing tumor. The treatment modalities are extrapolated based on the management of bone ES while includes neoadjuvant chemotherapy, surgery, adjuvant chemotherapy (±radiotherapy), and autologous bone marrow transplantation in high-risk patients. Standard first-line treatment for patients with these tumors includes chemotherapy with a five-drug regimen of vincristine, doxorubicin (Adriamycin®), and cyclophosphamide, alternating with ifosfamide and etoposide. We report a rare case in a 60-year-old female diagnosed as PCES with lung metastases, treated by palliative chemotherapy.

Primary Cutaneous Ewing Sarcoma: Case Report and Review of Literature

Ewing sarcoma (ES) is a primitive neuroectodermal tumor. It’s usually a primary bone tumor but rarely occurs in the skin and subcutaneous tissues. Current literature reports only a few isolated cases or small series. To date, less than 100 cases have been reported. The diagnosis is made by aspiration cytology, histochemical stains, immunohistochemistry, electron microscopy, cytogenetics and molecular genetics of translocations. Cutaneous ES has better prognosis than primary bone or soft tissue ES with a survival rate of 91% in 10 years. The presence of metastasis is really rare. Currently, no specific recommendations to primitively cutaneous Ewing tumors, these latter are treated as bone Ewing's sarcomas: neoadjuvant chemotherapy, surgery, adjuvant chemotherapy (+/− radiotherapy), and autologous bone marrow transplantation in high risk patients. We report a new case in a 20-yearold female with a lesion in the left elbow.

Primary soft tissue Ewing’s sarcoma of the maxillary sinus in elderly patients: presentation, management and prognosis

Nonosseous or soft tissue Ewing's sarcoma is a rare form of Ewing's sarcoma/primitive neuroectodermal tumour that seldom affects the head and neck region. Involvement of the nose and paranasal sinuses is extremely uncommon, with only eight of such patients being reported to date, mostly affecting adolescents and young adults. To our knowledge, this study is the first comprehensive report of primary soft tissue Ewing's sarcoma involving the paranasal sinuses in an elderly patient who successfully completed treatment. We herein discuss the pathogenesis, management and factors affecting the prognosis of this rare group of tumours involving the nose and paranasal sinuses, in relation to the available literature.

A t(17;22)(q21;q12) with partial ETV4 deletion in a soft tissue Ewing sarcoma

Cytogenetic analysis of a lumbar soft tissue Ewing sarcoma (ES) in a 7-month-old female child showed a t(17;22)(q21;q12), a rare translocation leading to an EWSR1-ETV4 chimeric transcript. These findings were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) techniques. The breakpoints were characterized by direct sequencing of the chimeric fusion gene. Tumor genotyping using the Affymetrix Genome-Wide Human single nucleotide polymorphism (SNP) array 6.0 Genechip identified deletions of both chromosomal regions involved in the translocation, resulting in partial deletion of ETV4, but an uninvolved EWSR1 gene. The creation of a fusion between EWSR1 and an ETS family gene consecutive to a chromosomal translocation is characteristic of the Ewing family of tumors (EFT). This is the first report of a deletion involving the two breakpoints in an EWS-ETS translocation. To date, only two cases of t(17;22)(q21;q12) in Ewing sarcoma have been reported, with no associated deletion. Interestingly, both cases had also occurred in soft tissue tumors, which are less common than their bone-involving counterparts.

Soft-Tissue Ewing Sarcoma in a Low-incidence Population: Comparison to Skeletal Ewing Sarcoma for Clinical Characteristics and Treatment Outcome

Due to the low incidence, treatments for Korean soft tissue Ewing sarcoma patients have been heterogeneous, and reported data are limited. In this study, we retrospectively analyzed soft tissue Ewing cases treated at our institution. We analyzed the clinicopathologic characteristics and treatment outcome of soft tissue Ewing sarcoma patients and compared with those of skeletal cases. Twenty-seven soft tissue Ewing sarcoma cases were evaluated. Patients with soft tissue Ewing sarcoma were older than patients with skeletal tumors (P = 0.03), and tended to have metastasis at diagnosis (P = 0.12). However, sex ratios, pathologies, tumor volumes, and histologic response to preoperative chemotherapy were not different in the two groups. The 5-year overall survival (49.0%) and event-free survival (45.6%) of soft tissue Ewing sarcoma patients were similar to those of skeletal tumor patients (51.8% and 46.0%, respectively). Presence of metastasis at diagnosis and poor histologic response to preoperative chemotherapy were associated with an adverse outcome for both groups. Similar to skeletal tumors, central tumor location, pathology and tumor volume tended to be related to the survival of soft tissue Ewing sarcoma. However, age and the use of a modality other than surgery to achieve local control did not influence the survival of soft tissue Ewing sarcoma patients. Our data could provide a basis to design a collaborative or multinational study targeting Ewing sarcoma family tumors.

Radiation Therapy for Non-Rhabdomyosarcoma Soft Tissue Sarcomas in Adolescents and Young Adults

Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) are less responsive to radiotherapy than the more common pediatric soft tissue sarcomas, rhabdomyosarcoma and Ewing sarcoma of soft tissue. However, radiation therapy does play an important role in the treatment of NRSTS, including synovial sarcoma. Little data exists regarding the behavior or treatment of these tumors in adolescents and young adults compared to older populations. Limb-preservation with adjuvant radiation thereby is standard. There is a greater incentive to reduce long-term complications of radiation in younger patients and thus smaller margins, lower doses, and conformal techniques should be considered. Results of anticipated cooperative group studies promise to guide future therapy for the various types of NRSTS.

Identification of Various Exon Combinations of theews/fli1Translocation: An Optimized RT-PCR Method for Paraffin Embedded Tissue

Chromosomal translocations t(11;22) (q24;q12) are characteristic of about 80-90 % of Ewing's sarcoma family of tumors [bone and soft tissue Ewing's sarcoma and peripheral neuroectodermal tumors (PNET)]. They generate ews/fli1 rearrangements showing great diversity in breakpoint exon combination. In about 5 % of Ewing's tumors, ews is fused to the erg gene at 21q22. The various chimeric proteins encoded may function as aberrant oncogenic transcription factors. These specific translocations can be used for exact molecular diagnosis in these poorly differentiated small round-cell tumors. Moreover, the prognostic relevance of different translocational variants has been previously suggested. Furthermore, the sensitive molecular detection of minimal metastatic and residual disease and its clinical significance can be evaluated. To address these questions more definitively in the large number of patients registered in multicenter studies, it is often necessary to access archival paraffin-embedded tumor tissue if no fresh or frozen tumor material is available for analysis by RT (reverse transcription)-PCR. Specific problems arise from formalin-fixed and paraffin-embedded tissue due to the degradation of RNA and insufficient extraction efficiency. Therefore, primer distance and product size are limited for successful PCR amplification. This conflicts with the requirement for identification of various possible exon combinations by PCR simultaneously using one single primer pair with larger distance.We examined paraffin embedded soft part tumor tissue samples from 47 Ewing's tumor patients. Patients were treated according to either CWS (Cooperative Weichteilsarkomstudie, CWS-91 or CWS-96) or Euro-E.W.I.N.G. 99 therapy protocols.We established a novel RT-PCR method, using 3 different exon specific sets of PCR primer pairs, selected according to the coding ews and fli1 nucleotide sequences (NCBI database), suitable for RT-PCR identification of variant ews/fli1 fusion transcripts in RNA isolated from formalin-fixed, paraffin-embedded tissue. For use in combination with ews -primer, an erg specific primer was selected to alternatively test for ews/erg fusion transcripts. As positive control for the integrity of isolated mRNA, we used the ubiquitously expressed gapdh transcript for RT-PCR amplification in each sample.In 31 cases (= 66 %) of 47 paraffin samples of Ewing's tumors analysed, gapdh control indicated adequate quality of RNA. In 16 cases no gapdh control fragment was amplifiable, nevertheless in 2 of these 16 samples distinct ews fusion products could be detected. In 23 cases we identified ews fusion transcripts. Thereof in 65 % ews exon 7 being fused to fli1 exon 6 (fusion type I), in 22 % to fli1 exon 5 (fusion type II). In 4 % each ews exon 10 being juxtaposed to fli1 either exon 6 or exon 5, respectively. An ews/erg fusion was detected in 4 % ( ews exon 7 fused to erg exon 6). In 10 samples, a gapdh fragment was amplified, but no ews/fli1 or - erg fusion transcript could be identified. The reference pathological review (I. L., Kiel, Germany) disproved the primary histopathology in 5 cases.Using our different sets of exon specific primer pairs, it was possible to detect 4 different breakpoints of ews/fli1 fusion transcripts and the ews/erg fusion by RT-PCR in RNA isolates from formalin-fixed, paraffin-embedded Ewing's tumor tissue. This method can be a very useful alternative in clinical situations (to ensure diagnosis and perform minimal metastatic and residual disease investigations) and in order to assess prognostic significance of translocation subtypes when no fresh tumor tissue is available.

Primary Ewing's sarcoma of the vertebral column.

To determine the demographics, imaging findings, clinical symptoms, and prognosis of primary vertebral Ewing's sarcoma (PVES). A retrospective review of medical records and radiological studies of patients diagnosed with PVES from 1936 through 2001 in our institution and Department of Pathology consultation files was undertaken. Metastatic and soft tissue Ewing's sarcoma cases were excluded. From a total of 1,277 cases of Ewing's sarcoma, 125 (9.8%) had a primary vertebral origin. There were 48 females and 76 males. Patient ages ranged from 4 to 54 (mean 19.3, standard deviation 10.7, median 16) years. Vertebral column distribution was four cervical (3.2%), 13 thoracic (10.5%), 31 lumbar (25%), and 67 sacrum (53.2%). More than one vertebral segment was involved in ten cases (8%). Satisfactory imaging studies were available in 51 patients: 49 radiographs, 27 computerized tomography (CT), and 23 magnetic resonance imaging (MRI) studies. The majority of tumors were lytic (93%). Three cases were mixed lytic and sclerotic (6%) and one sclerotic. In the nonsacral spine, the majority of lesions (12/20) involved the posterior elements with extension into the vertebral body. Five cases were centered in the vertebral body with extension into the posterior elements. Two cases were limited to the posterior elements, and one case solely involved the vertebral body. Ala was the most frequently affected site in the sacrum (18/26). Spinal canal invasion was frequent (91%). Detailed clinical information was available in 53 patients. Duration of symptoms ranged from 1 to 30 (mean 7) months. Local pain was the first symptom and seen in all cases. Neurological deficits were present in 21 (40%) cases. All patients received radiation in various dosages; 70% additionally received chemotherapy. Twenty-five patients had surgery, and two patients received bone marrow transplantation. Forty-five patients had follow-up; the five-year disease-free survival probability is 0.53. Disease-free survival probabilities are 0.60 for sacral tumors and 0.45 for nonsacral tumors. PVES is an uncommon tumor, usually seen in the second decade of life (mean age 19.3 years) with a male predilection (62%). An aggressive osteolytic lesion, particularly in the sacrum, should raise suspicion for this tumor in adolescents. Prognosis was similar in sacral and nonsacral tumors.

Adult soft tissue Ewing sarcoma or primitive neuroectodermal tumors: predictors of survival?

Ewing sarcoma (ES) is the second most common primary osseous malignancy in childhood and adolescence. The improvement in survival is primarily associated with the combination of surgery and chemotherapy. Little is known about the outcome of adults with soft tissue ES or primitive neuroectodermal tumors (PNET). Certain prognostic factors from soft tissue sarcomas (tumor size, tumor location, margin status, and initial presentation) in adults (>16 years) with ES/PNET will help to identify factors associated with outcome. Between July 1, 1982, and June 30, 2000, we identified 59 adult patients with primary soft tissue ES/PNET. Clinicopathologic factors were correlated with the end points studied: patient factors, tumor factors, pathologic factors, status of surgical margins, adjuvant chemotherapy, and radiation therapy. There were 41 male and 18 female patients, with a median age of 27 years (range, 16-72 years). Median tumor size was 8 cm, with all lesions being high grade. The most common site was the trunk (n = 22), with an even distribution of retroperitoneal, pelvis, buttock, and lower extremity (all n = 5). The median follow-up was 29 months (range, 6-222 months), with local recurrence identified in 13 patients (22%), with a median time to recurrence of 15 months (range, 5-200 months). Overall 5-year survival was 60%. Initial presentation was the only predictor of long-term survival, with primary tumor-only presentation having a 5-year survival of 60% (median not reached) compared with primary tumor plus metastatic disease having a 5-year survival of 33% (median, 17 months) (P =.02). Initial presentation of disease represents the only predictor of survival identified in this small group of adult patients with ES/PNET.

Ewing's Sarcoma of the Nose

Ewing's sarcoma is a bone tumor that rarely arises in the head and neck region. Head and neck tumors account for only 2% to 3% of all Ewing's sarcomas. There is an extremely rare subgroup of Ewing's tumors, that are histologically indistinguishable, which are not metastatic and arise in soft tissue rather than bone. Two Ewing's sarcomas of the nose are described. One case is the first reported nasal Ewing's soft tissue sarcoma. The other case is the more traditional type involving bone of the nose and extending into ethmoid sinuses and intracranially.

Soft tissue Ewing's sarcoma: Characterization in established cultures and xenografts with evidence of a neuroectodermic phenotype

This study characterizes the histogenesis of soft tissue Ewing's sarcoma (StEs) based upon an analysis of three tumors. Long-term cultured cell lines and nude mice xenografts were established from original neoplasms or from their metastases. Histologically they revealed a small round cell pattern without signs of differentiation. Several ultrastructural features of neural type were found; the same were also seen on culture cell lines. Moreover, immunohistochemical study for neural markers revealed the presence of HNK-1, NSE, LIRC-LON 36, S-100 protein, glial fibrillary acidic protein, neurofilaments (70 kilodaltons), and chromogranin; some of these markers were present only in the transplants. Cytokeratin was also seen. The translocation t(11;22)(q24;q12) was found in all three neoplasms together with other chromosomal abnormalities. N-myc RNA gave negative results whereas c-myc RNA was expressed. Therefore it may be postulated that StEs displays neuroectodermal features somewhat similar to those seen in peripheral neuroepithelioma as well as in atypical Ewing's sarcoma of bone.

Extraosseous Ewing's sarcoma versus primitiverhabdomyosarcoma: Diagnostic criteria and clinical correlation

A light and electron microscopic study of 51 cases of Ewing's sarcoma of bone (ESB) and 33 soft tissue sarcomas (carrying a variety of light microscopic diagnoses, including primitive rhabdomyosarcoma) in children and young adults was performed to clarify the similarities and differences among these tumors. Ultrastructural criteria were developed to evaluate the neoplasms. Remarkable ultrastructural uniformity was found in the cases of ESB. In contrast, the soft tissue sarcomas could be divided into two distinct groups on the basis of the ultrastructural criteria: those closely resembling primitive areas of otherwise differentiated rhabdomyosarcomas, and those indistinguishable from ESB. It is proposed that the diagnosis of soft tissue Ewing's sarcoma be reserved for lesions identical to ESB by both light and electron microscopy. The first group of sarcomas may be histogenetically related to rhabdomyosarcoma and should be distinguished from extraosseous Ewing's sarcoma, as their clinical behavior appears to be quite different.