Askin Tumor Research Articles

Thoracoabdominal peripheral primitive neuroectodermal tumors in childhood: radiological features

Peripheral primitive neuroectodermal tumors (PNET) are extremely uncommon, malignant neoplasms affecting mostly children and young adults. We retrospectively reviewed the clinical data and radiological studies of four such cases. All cases were pathologically proven. Plain films, US, and CT scans were used. The youngest child had a huge pelvic tumor and two adolescents each had a chest wall (Askin) tumor. The fourth patient had a most unusual location of the PNET in the anterior mediastinum. The CT findings are emphasized. We emphasize that the markedly abnormal CT findings are not specific for PNET.

Primary Neoplasm of the Chest Wall: Surgical Management

From January 1986 to December 1997, 17 patients (12 males and 5 females) aged 13 to 70 years were treated for primary neoplasms of the chest wall. There were 4 cases of fibrous dysplasia, 3 each of chondrosarcoma and Askin's tumor, 2 of plasmacytoma, and 1 each of fibrosarcoma, Ewing's sarcoma, synovial sarcoma, osteosarcoma, and enchondroma. All patients, except the case of Ewing's sarcoma, underwent wide excision or debulking for unresectable tumor, and reconstruction of the chest wall. Preoperative neoadjuvant chemotherapy was given to 1 patient with osteosarcoma, radiotherapy and chemotherapy were given to 2 others. In 8 patients, the skeletal defect was reconstructed with prosthetic material. Soft tissue reconstructive procedures with various myocutaneous flaps were performed in 6 patients. None of the patients required mechanical ventilation postoperatively. There were 2 early deaths. During follow-up of 3 months to 10 years, all patients with benign tumors were free of recurrence, 2 with Askin's tumors and 1 with osteosarcoma died. Prefabricated acrylic ribs are recommended for skeletal support during chest wall reconstruction.

Fine Needle Aspiration Cytology of the Ewing’s Sarcoma Family of Tumors

To study the cytomorphologic features of the Ewing's sarcoma (ES) family of tumors. During a period of eight years (1990-1997), 123 soft tissue tumors and 65 bone tumors were evaluated by fine needle aspiration cytology (FNAC); 14 cases were diagnosed as in the ES family of tumors. The ages of the patients ranged from 8 to 30 years. All the cases were histologically confirmed. Of 14 cases of the ES family of tumors, 7 were ES, 3 extraosseous ES (EOE), 2 peripheral primitive neuroectodermal tumor (PPNET) and 2 Askin tumor. Cytologically, smears from all the cases showed round tumor cells with a high nuclear/cytoplasmic ratio. On detailed examination, subtle differentiating features were observed. The cells in ES had finer nuclear chromatin in comparison to those of PPNET and Askin tumor, and punched-out clear cytoplasmic vacuoles were present. PPNET showed nuclear molding, unipolar cytoplasmic tags and Homer-Wright rosettes. Histologically, all cases of ES and EOE and one case of Askin tumor showed periodic acid-Schiff-positive inclusions. FNAC features coupled with clinical findings enable a rapid diagnosis of the ES family of tumors, from which treatment modalities can be determined.

Apoptotic responsiveness of the Ewing's sarcoma family of tumours to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL).

We investigated the cytotoxic responsiveness of 40 cell lines derived from representatives of the Ewing's sarcoma family of tumours (ESFT), i.e., Ewing's sarcoma (ES), peripheral primitive neuroectodermal tumour (pPNET) and Askin tumour (AT), to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Incubation with TRAIL at 100 ng/ml induced cell death at 24 hr in 19 of 26 ES, 11 of 12 pPNET and 2 of 2 AT cell lines. Half-maximal cell death concentrations (IC(50) values) varied from 0.1 to 20 ng/ml. TRAIL displayed potent cytotoxic activity against freshly derived ESFT cell isolates. Cytotoxicity was associated with phosphatidylserine expression and internucleosomal DNA fragmentation, features characteristic of apoptosis. The apoptotic programme in the sensitive ESFT VH-64 cell line revealed TRAIL-induced activation of FLICE/MACH1 (caspase-8) and CPP32/Yama/apopain (caspase-3) and processing of the prototype caspase substrate poly(ADP-ribose) polymerase. In addition, TRAIL provoked a collapse of the mitochondrial transmembrane potential (DeltaPsi(m)), parallelled by a reduction in ATP levels and release of cytochrome c from mitochondria into the cytosol. Inhibition of caspase-8 and caspase-3 by zIETDfmk and zDEVDfmk, respectively, substantially prevented TRAIL-induced apoptosis. However, zIETDfmk, but not zDEVDfmk, reduced TRAIL-mediated DeltaPsi(m) dissipation, indicating that TRAIL causes mitochondrial dysfunction through caspase-8 acting upstream of mitochondria. While macromolecule synthesis inhibitors (actinomycin D, cycloheximide) augmented susceptibility to TRAIL in TRAIL-responsive cell lines, these agents did not render TRAIL-resistant cell lines susceptible to TRAIL. However, the proteasome inhibitor MG132 sensitised to TRAIL in resistant cell lines. Collectively, these results show that TRAIL initiates effective death in the vast majority (80%) of cell lines derived from ESFT. Since TRAIL provoked cell death in ESFT ex vivo, this cytokine may be a promising drug for the treatment of ESFT in vivo.

Neurogenic tumours of the mediastinum: a report of 60 cases.

To analyze retrospectively 60 patients (13 infants and children, 47 adults--21 men and 39 women) with mediastinal neurogenic tumours admitted to Atatürk Centre for Chest Disease and Chest Surgery, Ankara, Turkey between 1988 and 1999. This comprised 21.2% of 283 patients who had surgical operations for all mediastinal masses during the same period. The patients ranged from four to 67 years of age. Thirteen patients were younger than 15 years and 47 were 15 years of age or older. Medical records were reviewed for demographic data, clinical presentation, diagnostic investigations, operative procedures, and tumour location and invasion. Postoperative morbidity and mortality were noted as well as long term follow-up. The clinical investigations included chest x-ray and computed tomography of the thorax in all patients, and spinal magnetic resonance imaging and bronchoscopical examination in some. Clinical variables were compared. The tumours had the following characteristics: 42 (70%) were nerve sheath tumours; 15 (25%) were autonomic ganglion tumours; two (3.6%) were paragangliomas; and one (1.4%) was a malignant peripheral neuroectodermal tumour (Askin's tumour). Nerve cell tumours comprised the majority of tumours in infants and children (nine of 13, 69%), whereas the nerve sheath tumours were most frequent in adults (39 of 47, 83%). There were 48 benign and 12 (20%) malignant tumours when all age groups were considered; the malignancy rate was 61.5% (eight of 13) in children and 8.5% (four of 47, P<0.05) in adults. All patients were operated via a posterolateral thoracotomy. Surgical resection of the tumour was complete in 56 of 60 patients (93.3%). Resection of malignant tumours was grossly incomplete in four cases (four of 12, 33.3%). All benign tumours were totally excised. There were two major complications (respiratory failure and pulmonary emboli) and 14 minor complications in the perioperative period. The mean follow-up period was five years and seven months. Tumours recurred in 5.3% (three of 56) of patients who had a complete resection initially. There were no late deaths related to benign tumours. Complete resection of tumours can be performed safely by a thoracotomy approach and is important for achieving satisfactory long term survival in most mediastinal neurogenic tumours.

Malignant chest wall tumors in children and young adults

Purpose: Primary chest wall malignancies, which occur infrequently in children, can pose complex technical challenges to the surgeon. This study was undertaken to evaluate the pathology, treatment approaches, role of surgical resection and reconstruction, and outcomes of patients with these tumors. Methods: This is a retrospective review of all patients with malignant primary chest wall tumors treated at our institution between February 1983 and July 1998. Results: Nineteen cases were identified: malignant small round cell type (MSRCT, also called Ewing's sarcoma, primitive neuroectodermal tumor [PNET], and Askin's tumor; n = 8), rhabdomyosarcoma (RMS; n = 6), and other tumors (n = 5). Three patients underwent “upfront” complete resections. Sixteen patients underwent initial biopsy, followed by chemo-or radiotherapy. Nine of these 16 survived to undergo delayed chest wall resections. Six of the 12 “resected” patients required en bloc resection of adjacent muscles or organs; 7 required complex chest wall reconstruction. Eight of 19 patients (42%) have survived (median follow-up of survivors, 4 years), all with no evidence of disease; the remaining 11 patients died of progressive disease. Local invasion did not alter chance of survival. Two of the 10 patients with metastases at diagnosis (20%) survived. Six of the 9 patients (67%) with localized disease survived. All five patients with tumor types other than MSRCT or RMS, metastatic or not at diagnosis, are alive with no evidence of disease. There were no local recurrences. Conclusion: Surgical resection, with en bloc removal of involved structures and chest wall reconstruction, provides excellent local control of malignant chest wall tumors.

Malignant small cell (Askin) tumor of the thoracopulmonary region originating from the phrenic nerve

Malignant small cell (Askin) tumor of the thoracopulmonary region originating from the phrenic nerve

Malignant Bone Tumors of the Chest

Malignant bone tumors constitute only 0.2% of all tumors. Bone sarcomas occur at a rate approximately one tenth that of sarcomas of the soft tissue. Malignant bone tumors of the chest wall and sternum are even more rare because most bone tumors occur in the long bones or joints. Because of the relative paucity of experience treating these malignancies, progress in successful therapies has been limited. Chondrosarcomas remain the most common bony malignant chest wall lesions and are discussed elsewhere in this issue. Other lesions in descending order of incidence include Ewing's sarcoma, osteosarcoma, malignant fibrous histiocytoma, solitary plasmacytoma, and Askin tumors. This article reviews these remaining five malignant bony chest wall tumors, along with their symptoms, presentations, and current approaches to therapy.

Diagnosis and Classification of the Small Round-Cell Tumors of Childhood

The small-round-cell tumors of childhood include neuroblastoma, the Ewing family of tumors, rhabdomyosarcoma, lymphoma, and desmoplastic small-round-cell tumor. Although classical histological features are generally highly suggestive of tumor type, on occasion these tumors may be indistinguishable by light microscopy, making a definitive diagnosis difficult. Accurate diagnosis of pediatric small-round-cell tumors has become increasingly crucial, as disparate approaches to therapy are used for distinct tumor types. In addition, because for many pediatric cancers, therapy is also tailored according to patient risk, it has become important to further classify tumors biologically, using cytogenetic or molecular studies to identify chromosome translocations, gene amplification, gene expression patterns, and/or mutations. In this issue of The American Journal of Pathology, Gilbert and colleagues used a reverse transcriptase polymerase chain reaction (RT-PCR) assay to analyze the expression of two genes involved in the catecholamine biosynthetic pathway, tyrosine hydoxylase and dopa decarboxylase, in 84 pediatric malignancies. 1 Their studies demonstrate that the expression of these two genes is highly specific for neuroblastoma. Of the 29 non-neuroblastoma tumor samples examined, only pheochromocytomas expressed clearly detectable levels of the genes. These results suggest that analysis of tyrosine hydoxylase and dopa decarboxylase expression may help distinguish neuroblastoma from other small-round-cell childhood tumors. Despite recent advances in immunohistochemistry and molecular pathology, some cases of small-round-cell tumors of childhood remain diagnostically problematic. Thus, additional diagnostic tools, such as the ones described by Gilbert and co-workers, are needed to ensure that every child with a small-round-cell tumor is diagnosed correctly. The value and limitations of current immunohistochemical, cytogenetic, and molecular studies as diagnostic aids for the small-round-cell tumors of childhood are highlighted below.

Diagnostic imaging of primitive neuroectodermal tumour of the chest wall (Askin tumour).

To describe the radiological features of primitive neuroectodermal tumour (PNET) of the chest wall (Askin tumour) at diagnosis and to analyse the radiological changes occurring as a consequence of treatment and during follow-up. Nine children with histologically proven PNET were studied. At diagnosis, all patients underwent chest X-ray (CXR), chest CT and bone scintigraphy; three patients also had MR and three had US. During treatment and follow-up, CT was performed in all patients. CT demonstrated a solid heterogeneous chest wall mass in all children at diagnosis and six had a rib lesion. Small nodular densities in the extra-pleural fat were identified in three patients at diagnosis. US, performed in three patients, excluded tumour infiltration of the lung or diaphragm, which had been suspected on CT. On MR, the lesions showed high signal intensity in T1-weighted/proton-density images and intermediate/high signal intensity in T2-weighted images compared with muscle. Minimal chest wall involvement was demonstrated in one case by MRI. Extensive necrosis of tumour mass with pseudo-cystic appearance was documented in the five patients who underwent chemotherapy. Macroscopically complete resection was performed in five patients but there was early local recurrence after surgery in two, identified by CT in one and by MR in the other. PNET of the chest wall should be considered in a child with a chest wall mass. CT is valuable for evaluating tumour extension at diagnosis, the effects of chemotherapy and assessing tumour recurrence after surgery. However, CT can overestimate pleural, lung or diaphragmatic infiltration, which are better evaluated by US. MR was superior to CT in the evaluation of tumour extension in one of three patients and may be considered complementary to CT, particularly in very large chest wall tumours.

Askin Tumor and Acute Myeloid Leukemia in a Patient with Constitutional Partial Y Disomy

We report the case of a young adult male carrying a constitutional unbalanced t(Y;13)(q11-12;p13) leading to a partial Y disomy, and presenting successively, in a 39-month interval, with an Askin tumor and a t(8;21) acute myeloid leukemia. The origin of the two neoplasias in this patient is discussed.

Diagnosis in oncology. Askin tumor.

Diagnosis in oncology. Askin tumor.

Molecular Diagnosis of Ewing Tumors

Most Ewing tumors (ET), including Ewing sarcomas, peripheral primitive neuroectodermal tumors (PNET), and Askin's tumors, can be defined according to the specific chromosomal translocations t(11;22)(q24;q12) (EWS-FLI-1) or t(21;22)(q21;q12) (EWS-ERG). Detection of the chimeric RNA transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) has greatly facilitated the diagnosis of ET. Because of variable chromosomal breakpoint locations, however, the EWS gene fusions with FLI-1 and ERG genes are highly heterogenous, resulting in different sizes of the amplification products. To improve the diagnostic usefulness of the RT-PCR assay, we have developed an assay to detect chimeric mRNA transcripts by nested RT-PCR, followed by digestion of the PCR fragments with three different restriction endonucleases. This allows confirmation of the specificity of the PCR product and provides a rapid method to determine the combination of exons present in a transcript. In the 12 Ewing tumors tested, five different exon combinations were detected. In nine repeat biopsies of four patients, the case-specific translocation remained unchanged. One additional central PNET had no ET-specific translocation. In conclusion, the suggested combination of RT-PCR and restriction analysis of the PCR products allows a rapid and specific determination of ET-specific translocations.

Evaluation of mutant frequencies at the hprt and the T-cell receptor loci in pediatric cancer patients before treatment

Mutant frequencies (Mfs) at the two genetic loci, the hypoxanthine phosphoribosyl transferase (hprt) gene and the T-cell receptor (TCR) gene were evaluated in pediatric cancer patients before starting chemotherapy or radiotherapy. The study population consisted of 27 patients with various solid tumors (mean age±SD; 5.5±5.1 years, range; 0.2–14.5 years), 5 patients with acute leukemia (10.3±6.1, 1.3–17.0 years), and 26 healthy controls (11.6±4.0, 4.4–22.2 years). Although the age distributions were different, the mean Mf values of the hprt and the TCR loci were comparable among these three groups. On an individual basis taking the age factor into consideration, the hprt-Mfs of 3 patients with solid tumors, i.e., two patients with Hodgkin's disease and one patient with Askin tumor, were found to be well above the 95% confidence limit. There were no patients with a TCR-Mf exceeding the 95% confidence limit. These data suggest the possibility that some patients with solid tumors may be predisposed to mutational susceptibility before treatment. The assay of the hprt-Mf appears more sensitive than the TCR-Mf assay in distinguishing these patients.

559 - Radiotherapy in treatment of Ewing's sarcoma of the chest wall (Askin tumors)

559 - Radiotherapy in treatment of Ewing's sarcoma of the chest wall (Askin tumors)

Surgical treatment of primary malignant chest wall tumours.

Primary malignant tumours of the bony chest wall are uncommon and data concerning treatment and results are sparse. To assess the results of surgical resection and chest wall reconstruction we reviewed our experience with primary malignant chest wall tumours treated since 1958. Of the 49 lesions, 42 were found in the ribs and the remaining 7 in the sternum. These included chondrosarcomas [22], solitary plasmacytoma [18], Ewing's tumours [7], Askin's tumour [1] and Desmoid tumour [1]. Skeletal reconstruction was performed in 36 of the 49 patients. Marlex mesh alone was used in 17 patients. Since 1972, a sandwich of two layers of Marlex mesh with a filler of methyl methacrylate was utilised [19] successfully, producing better functional and cosmetic results. Primary soft tissue closure was possible in all but 8 cases in whom latissimus dorsi myocutaneous flaps were used. Bilaterally, partially transposed pectoralis major muscle was used to cover upper sternal defects in 4 cases. All but 1 patient had an uneventful post-operative recovery none requiring ventilatory support. Overall survival at 5 and 10 years was 68%. The differential figures for 10-year survival were for chondrosarcoma 67%, Ewing's sarcoma 43%, and solitary plasmacytoma 59%. These were the results of radical en-bloc excisions. The patient with Desmoid tumour is alive at 5 years, following incomplete initial resection and the patient with Askin's tumour survived for 3 years. Radical en-bloc excision remains the treatment of choice in all primary malignant chest wall neoplasms except large solitary plasmacytomas where incisional biopsy followed by irradiation appears to be the method of preference. In Ewing's and Askin's tumours, additional chemotherapy and radiotherapy have to be used. The extent of surgical excision should only be limited by the amount of tissue necessary to remove for adequate malignant tissue clearance, since even large defects can be reconstructed with little functional disturbance.

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.

Preresection Chemotherapy Improves Survival for Children With Askin Tumors

To test whether patients with Askin tumor treated with aggressive neoadjuvant chemotherapy have a better clinical outcome. Retrospective case series. Pediatric referral center. All children diagnosed with malignant small-cell tumors of the chest wall (Askin tumor) and treated from 1975 to September 1987 (phase 1, n = 6) and from September 1987 to the present (phase 2, n = 9). Survival as a function of extent of disease and response to therapy as measured by tumor volume, survival, and recurrence. All phase 2 patients had significant reduction of tumor volume and improved survival by Kaplan-Meier estimates compared with phase 1 patients. No phase 1 patients are still alive. Patients with Askin tumor treated with aggressive preresection chemotherapy have smaller tumors to resect and improved survival.

A Long Way from Definition of the Molecular Basis to Benefit in the Clinical Management of Ewing Tumours

Recently, the Ewing family of tumours (ET). previously classified by clinical appearance and histology as Ewing’s sarcoma (ES), Askin tumour, peripheral primitive neuroectodermal tumour (pPNET) or neu

311The role of radiotherapy in the multimodal treatment of Ewing's sarcoma of the chest walk (Askin tumors)

311The role of radiotherapy in the multimodal treatment of Ewing's sarcoma of the chest walk (Askin tumors)