AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT Scan
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT Scan
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Background

Ewing sarcoma, a highly malignant primary bone tumor that is derived from red bone marrow, was first described by James Ewing in 1921.¹ This tumor is most frequently observed in children and adolescents aged 4-15 years and rarely develops in adults older than 30 years.² Ewing sarcoma accounts for approximately 5% of biopsy-analyzed bone tumors and approximately 33% of primary bone tumors.² This disease is the second most common malignant bone tumor in young patients, and it is the most lethal bone tumor.³ An association exists between Ewing sarcoma and primitive peripheral neuroectodermal tumor (PNET).^{4, 5} (See also the eMedicine article Ewing Sarcoma and Primitive Neuroectodermal Tumors, as well as the articles New  Standard  of  Care  for Ewing's  Sarcoma and  Treatment Effects in Pediatric Soft Tissue and Bone Tumors, on Medscape.)

For excellent patient education resources, visit eMedicine's Cancer and Tumors Center and Blood and Lymphatic System Center. Also, see eMedicine's patient education articles Cancer: What You Need to Know and Leukemia.)

Pathophysiology

Although the tumor is derived from bone marrow, Ewing sarcoma is histologically related to reticulum cell sarcoma. Most frequently, the tumor is diagnosed as a monostotic lesion in the metaphysis or diaphysis of the long bones of the extremities. The tumor may also occur, although less frequently, in the pelvic area, ribs, and scapulae. In fact, any bone may be involved.

Typically, the periosteal reaction and new bone formation with an onion-skin appearance may suggest the diagnosis of Ewing sarcoma. The radiographic appearance of Ewing sarcoma may vary highly from a lytic one to a dominantly sclerotic one.

Frequency

United States

The frequency of Ewing sarcoma depends on the patient's age. Tumor occurrence ranges from 0.3 cases per 1 million children younger than 3 years to as high as 4.6 cases per 1 million adolescents aged 15-19 years.

International

The annual incidence of Ewing sarcoma is less than 2 cases per 1 million children.

Mortality/Morbidity

• The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) studied 369 patients who were randomized to receive treatments with local therapy and chemotherapy based on 14 courses of vincristine, actinomycin D, cyclophosphamide or ifosfamide, and Adriamycin (doxorubicin) with or without etoposide.⁶ The 3-year, event-free survival rate was 66% in patients with localized tumors, 43% in those with lung metastases at the initial diagnosis, and 29% in those with other metastases. A large tumor volume and/or a tumor primarily localized to the pelvic area were negative prognostic factors.
• In the United States, bone tumors are the third leading cause of mortality in children aged 10-14 years.
• The National Cancer Data Base Report collected data from 1985-2003 for various sarcomas, including Ewing sarcoma.⁷ The relative 5-year survival rate (minimum 5-year follow-up from 1985-1998) was 50.6% for Ewing sarcoma.
• In a small, single-center, retrospective study from the Netherlands, the 5-year overall survival was 58% in adult patients (age >16 y) with either Ewing sarcoma (27 patients) or peripheral primitive neuroectodermal tumors (PNET) (20 patients).⁸

Race

Ewing sarcoma occurs predominantly in whites and, to a lesser extent, in blacks and Asians. This condition is rare in black and Chinese children.

Sex

Males are affected more frequently than females, with a ratio of approximately 1.5:1.

Age

Ewing sarcoma most commonly occurs in children and adolescents aged 4-15 years and rarely develops in adults older than 30 years. Although Ewing sarcoma is uncommon in older individuals, it has been reported in those as old as 60-70 years. Ewing sarcoma is the most lethal and second most common malignant bone tumor in young patients.³

Anatomy

Ewing sarcoma and peripheral neuroepithelioma belong to the Ewing family of tumors (EFTs) and are considered neural tumors.^{3, 9} Ewing sarcoma represents a less differentiated form of the tumors, whereas neuroepithelioma represents a more differentiated form. Unlike neuroblastomas, these neural tumors are not derived from the sympathetic system, and catecholamine metabolites are not excreted in the urine. In vitro, these tumors show neural differentiation and have neural features. Results with neuron-specific enolase and S-100 protein testing are positive. In addition, electron microscopy reveals neural structures such as neurites and dense-core granules. Glycogen granules are present, and alkaline phosphatase is absent.

Clinical Details

Ewing sarcoma is rare; therefore, a screening program is not recommended. The most important and earliest symptom is pain, which is initially intermittent but becomes intense. The pain may radiate to the limbs, particularly with tumors in the vertebral or pelvic region. Neurologic signs such as nerve root signs and cord compression are present in 50% of patients with involvement of the axial skeleton. Rarely, a patient may have a pathologic fracture.

Occasionally, the clinical picture may be similar to that of acute or chronic osteomyelitis and include remittent fever, mild anemia, leukocytosis, and an elevated erythrocyte sedimentation rate (ESR). Increased serum lactic dehydrogenase (LDH) levels and weight loss may also be observed. Symptoms usually last a few weeks to a few months. Eventually, most patients have a large palpable mass, which grows rapidly, with a tense and tender local swelling. (See also the eMedicine article Osteomyelitis, Chronic [in the Radiology section] and Osteomyelitis [in the Emergency Medicine section], as well as Chronic Osteomyelitis From Staphylococcus Aureus, on Medscape.)

Patients with Ewing sarcoma usually are assigned to 1 of 2 groups, and the tumor is classified as either localized or metastatic disease. The prognosis is highly affected by the group to which the patient is assigned. Some prognostic factors may be used to subdivide the local disease classification into a high-risk group and a low-risk group.¹⁰

A European study of 359 patients with nonmetastatic Ewing sarcoma revealed that the following factors are associated with a poor prognosis¹¹:

• Male sex
• Age older than 12 years
• Anemia
• Elevated LDH levels
• Radiation therapy only for local control
• Poor chemotherapeutic course

Preferred Examination

No single morphologic or functional imaging method provides findings for a specific diagnosis of Ewing sarcoma, but the results do contribute to tumor staging. Therefore, obtaining a histologic specimen of the lesion in all patients is essential in planning therapy. Because the clinical symptoms of Ewing sarcoma are nonspecific and because they frequently suggest osteomyelitis, an initial conventional radiographic and/or magnetic resonance imaging (MRI) examination is performed.^{12, 13} These studies may reveal the classic signs of Ewing sarcoma. Although plain radiographs may show typical signs of Ewing sarcoma, MRI provides more accurate information about tumor size. MRI is also superior to computed tomography (CT) scanning in delineating the extent of the neoplasms and their relation to the surrounding structures.^{14, 15}

Limitations of Techniques

The radiographic appearance of Ewing sarcoma may mimic that of osteomyelitis, as well as those of other malignant tumors, such as leukemia. The appearance of Ewing sarcoma may vary from that of pure lysis to sclerosis. MRI findings alone may not be conclusive for a malignant lesion, but MRIs help to show the full extent of tumor spread. (See also the eMedicine articles Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, and Chronic Lymphocytic Leukemia, as well as Risk Factors for Acute Leukemia in Children: A Review and ASCO 2007: Hematologic Malignancies, on Medscape.)

DIFFERENTIALS

Section 3 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT Scan
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Other Problems to Be Considered

Osteomyelitis – Especially in the long bones, particularly when the lesion is in the metaphysis
 
Round-cell tumors – Metastatic neuroblastoma, leukemia (See also Metastatic Neuroblastoma at Medscape.)
 
Osteosarcomas – Bone-forming tumors, usually located in metaphysis of long bones; more homogeneous, cloudlike, osteoid formation  (See also Osteosarcoma and Low-Grade Central Osteosarcoma [in the Orthopedic Surgery section], Osteosarcoma [in the Pediatrics section], and Osteosarcoma, Classic [in the Radiology section], as well as Prognostic Significance of Drug-regulated Genes in High-grade Osteosarcoma, Intensified Chemotherapy Does Not Improve Osteosarcoma Survival, and Osteosarcoma Recurrence Rare, and Sometimes Treatable, on Medscape.)
 
Osteolytic osteosarcoma and fibrosarcoma – Difficult to differentiate between these 2 entities, because of lytic lesions, periosteal reaction
 
Myeloma – Frequently has multiple lytic areas, patients much older than those with Ewing sarcoma (See also the eMedicine articles Multiple Myeloma and Myeloma [in the Radiology section] and Multiple Myeloma [in the Hematology section].) 
 
Lymphoma – May cause bone destruction or bone sclerosis; extent and type of bone involvement not predictable; usually, no major periosteal reaction in the primary lymphoma in the bone marrow; lytic, poorly defined, or predominantly osteoblastic secondary malignant lesions (See also the eMedicine article Lymphoma, Bone.)
 
Eosinophilic granules and osteomyelitis – Consider these within benign lesions. Both have a less aggressive appearance than that of Ewing sarcoma; thus, the margins of these 2 may be better defined, and the periosteal reaction may have sharper borders.
 
Extraosseous Ewing sarcoma – Rare occurrence but has been reported (eg, adrenal masses); early metastases is possible; metastatic spread to lung or bone is common and present in as many as 26% of patients; occurrence of metastases not related to tumor size or location
 
PNETs – These tumors are similar to Ewing sarcoma, and the 2 entities may be difficult to histologically differentiate from one another. Many Ewing sarcomas and PNET tumors can be differentiated from other similar tumors, such as rhabdomyosarcoma, by the presence of the cell-surface glycoprotein p30/32 MIC2. This protein is produced from the MIC2 gene on the short arms of the X and Y chromosomes. (See also the eMedicine article Rhabdomyosarcoma, as well as Rhabdomyosarcoma, on Medscape.)

RADIOGRAPH

Section 4 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT Scan
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

Both long and flat bones are affected in Ewing sarcoma because no bone is immune to tumor development. In the long bones, the tumor is almost always metaphyseal or diaphyseal. Most commonly, radiographs show a long, permeative lytic lesion in the metadiaphysis and diaphysis of the bone, with a prominent soft-tissue mass extending from the bone.

Sclerotic lesions are less common but may occur in approximately 25% of cases. Plain radiographs of the long bones may show a lesion with poorly defined margins that is destroying the bone. The lesion may invade the cortical bone, although Ewing sarcoma may also traverse the haversian system and cause a large soft-tissue mass outside the bone despite the absence of cortical destruction. This phenomenon is noted in approximately 50% of patients with Ewing sarcoma. A periosteal reaction is usually present, and it often has an onion-skin or sunburst pattern, which indicates an aggressive process.

In some patients, Codman triangles may be present at the margins of the lesion. These result from the elevation of the periosteum and central destruction of the periosteal reaction caused by the tumor. In rare cases, a lesion is not visible on plain radiographs.

Degree of Confidence

Ewing sarcoma is vascular, and the extent of spread through the medullary cavity is usually greater than that indicated on plain radiographs. Therefore, MRI is recommended in addition to conventional radiography as the preferred imaging means for staging the tumor. MRI provides information about the true extent of the lesion, as well as the involvement of critical adjacent structures.

False Positives/Negatives

The typical periosteal reaction of Ewing sarcoma may be difficult to differentiate from infection or other malignant tumors of bone. Osteomyelitis is the most common differential diagnosis. Occasionally, a sclerotic Ewing sarcoma may be mistaken for an osteosarcoma, whereas a telangiectatic osteosarcoma may be mistaken for a Ewing sarcoma.

Benign, solitary bone lesions usually do not cause false-positive or false-negative results. Vertebral manifestations of Ewing sarcoma may mimic those of hemangiomas. Other malignant tumors such as chondrosarcoma, fibrosarcoma, and soft-tissue sarcomas must be included in the differential diagnosis, although these usually occur in patients older than those with Ewing sarcoma. (See also the eMedicine articles Telangiectatic Osteosarcoma, Fibrosarcoma, and Hemangioma [in the Orthopedic Surgery section], Chondrosarcoma [in the Radiology section], and Nonrhabdomyosarcoma Soft Tissue Sarcomas [in the Pediatrics section].)

CT SCAN

Section 5 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT Scan
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

CT scanning helps to define the bone destruction that is associated with Ewing sarcoma. Tumor size can be evaluated with contrast-enhanced CT scanning, which may be used in follow-up evaluation during chemotherapy. However, the preferred method for staging and following up Ewing sarcoma is still MRI.

Degree of Confidence

Although CT scanning provides accurate information about tumor size, differentiating Ewing sarcoma from acute osteomyelitis, fibrosarcoma, osteosarcoma, and other conditions is difficult with this modality.

False Positives/Negatives

A low rate of false-negative results is reported for both CT scan and MRI studies, which have an accuracy of approximately 90%.¹⁵ However, differentiation of Ewing sarcoma from other bone tumors, as well as osteomyelitis and other conditions, may be difficult with CT scanning, and false-positive results may occur.

MRI

Section 6 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT Scan
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

MRI is essential to elucidate soft-tissue involvement (see Image 5) because the tumor has low signal intensity on T1-weighted images compared with the normal high signal intensity of the bone marrow. On T2-weighted images, the tumor is hyperintense compared with muscle. These images should be obtained with fat saturation, if possible. Otherwise a short-tau (τ) inversion recovery (STIR) sequence is recommended as a substitute.

On T1-weighted images, the tumor has low signal with heterogeneous gadolinium enhancement, whereas signal intensity on T2-weighted images varies after contrast enhancement. The use of gadolinium-based contrast agents does not add significant value to the MRI evaluation of Ewing sarcoma.

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving  or  straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

After treatment, osteosarcomas and Ewing sarcomas may have the reduced signal intensity similar to that of the bone marrow, which may be isointense with muscle. These tumors may also have a well-defined margin. However, the changes in signal intensity reflect changes in the bone marrow structure and nonspecific changes such as fibrosis. The change in signal intensity is helpful in noting a therapeutic effect, but it sometimes causes difficulties in detecting residual tumor tissue.¹⁶

Erlemann et al evaluated the value of MRI for treatment follow-up and noted that static MRI has little value in assessing the response to treatment.¹³ The authors reported that on T2-weighted images, a reduction in the signal intensity of soft-tissue masses indicated a response with a sufficient degree of accuracy (71%) but low sensitivity. An increase in signal intensity after the administration of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) indicated zones of viable tissue, with low specificity. Erlemann et al found that dynamic MRI, on the other hand, proved to have a high degree of accuracy (85.7%) relative to scintigraphy.

Degree of Confidence

The accuracy of MRI—that is, the positive predictive value plus the negative predictive value—has been reported to be 90.3% in one study.¹⁵ In most patients, MRI seems to provide more specific information than CT scanning. Hence, MRI is the test of choice for staging in cases of suspected Ewing sarcoma.

False Positives/Negatives

CT scanning and MRI are problematic in the differentiation among osteosarcomas, fibrosarcomas, and other malignant tumors, as well as osteomyelitis. However, Ewing sarcoma occurs in patients of a particular age group, and its diagnosis is usually apparent. Differentiating Ewing sarcoma from closely related diseases such as neuroblastoma and PNET tumors may be difficult.

ULTRASOUND

Section 7 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT Scan
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

Ultrasonography (US) is not routinely used to stage the primary tumor in Ewing sarcoma. However, US can help delineate the extraosseous part of the tumor, particularly in follow-up care during treatment. In addition, US may be used to guide a biopsy of a lesion and to help exclude metastases in the liver.

Degree of Confidence

In the pelvic and abdominal area, US may be used to delineate extraosseous soft-tissue masses. US findings, however, are not specific for the diagnosis of Ewing sarcoma.

False Positives/Negatives

Although US may help delineate the size of an extraosseous mass in the abdomen, the differential diagnosis of soft-tissue masses in the abdominal area include those with a variety of histologic features.

NUCLEAR MEDICINE

Section 8 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT Scan
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

With static bone scintigraphy, the primary tumor of Ewing sarcoma is usually depicted as a focal area of increased radionuclide activity. Whole-body bone scans can provide information about the primary lesion and depict skip lesions. Also, bone scintigraphy can be used to localize distant metastases during tumor staging. Three-phase dynamic bone scintigraphy (TPBS) can help in the assessment of treatment effects, with a reported accuracy of 88%.¹⁷ In cases that respond to treatment, a reduction of both flow and tracer uptake can be observed.

In addition to technetium-99m (^99mTc), other tracers, such as thallium-201 (²⁰¹Tl), are used to assess the therapeutic response. However, ²⁰¹Tl may cause an overestimation of tumor viability. Gallium-67 (⁶⁷Ga) scanning was introduced for use in monitoring therapeutic responses; however, positron emission tomography (PET) scanning with fluorodeoxyglucose (FDG) is currently used instead (see Images 6-7).^{18, 19}

FDG is used as a marker of tumor viability, and it may help to detect lesions that are not depicted on conventional bone scans. In addition, PET scanning is the most sensitive modality for therapeutic follow-up, and this modality can reveal early changes in tumor metabolism, which is an indicator of the therapeutic effect.²⁰ The area of necrosis is correlated with the change in FDG uptake, and a poor response is associated with a decrease in FDG accumulation (ie, tumor-nontumor ratios) of less than 30%. Bone marrow scanning is of limited use because of the availability of MRI.

PET scanning with FDG can be recommended as the most sensitive method for the detection of early changes in tumor metabolism as a result of therapeutic effects. Some preliminary results in bone tumors suggest that FDG kinetics are modulated by the expression of chemoresistant genes MDR1 and MRP. A low FDG uptake is more frequently observed in resistant tumors.¹⁹

Degree of Confidence

Bone scans typically indicate changes in osteoid formation, and as such, the findings are nonspecific. As a result, false-positive findings caused by a number of diseases may suggest the presence of metastases or a tumor at the primary site. False-negative results are uncommon. Compared with conventional scintigraphy, PET scanning with FDG is more sensitive and provides a higher spatial resolution. However, high FDG uptake is also observed in other bone tumors and inflammatory processes such as osteomyelitis.

False Positives/Negatives

Other malignant and benign bone lesions may mimic Ewing sarcoma on bone scans.

ANGIOGRAPHY

Section 9 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT Scan
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

Angiography is not a standard imaging modality that is used for tumor staging. However, tumor vascularity during chemotherapy can be evaluated with magnetic resonance angiography.

False Positives/Negatives

Angiographic findings in Ewing sarcoma are not pathognomonic and can occur in a variety of tumors.

INTERVENTION

Section 10 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT Scan
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Medical/Legal Pitfalls

• Because of the limited prognosis for Ewing sarcoma, a high diagnostic accuracy is important with the morphologic imaging methods, functional procedures, and histologic analyses.
• In particular, differentiating Ewing sarcoma from osteomyelitis usually requires histologic confirmation.
• Tumor spread must be recognized, and methods such as PET scanning with FDG and/or bone scanning can help in detecting metastases.
• Furthermore, monitoring of therapeutic responses requires both morphologic imaging (to trace the tumor volume) and quantitative functional studies (to assess tumor vitality).

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT Scan
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Media file 1:  Radiograph of Ewing sarcoma of the os naviculare, a rare location for the tumor. This image depicts a significant periosteal reaction.
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Media type:  X-RAY

Media file 2:  Fusion magnetic resonance imaging (MRI) and positron emission tomography scan studies obtained with fluorodeoxyglucose (FDG) in a patient with a Ewing sarcoma of the left tibia. This image demonstrates the tumor is primarily confined to the bone, with a small periosteal fraction. The MRI findings matched those of the PET images obtained with FDG scanning. (See also Image 3.)
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Media type:  Nuclear Image

Media file 3:  Positron emission tomogram obtained with fluorodeoxyglucose (FDG) scanning at the level of the magnetic resonance image in Image 2. This image shows high FDG accumulation in the lesion, which indicates high tumor viability. Moderate FDG accumulation in the periosteum and soft tissue resulted from tumor involvement.
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Media type:  Nuclear Image

Media file 4:  Radiograph from an 11-year-old boy with a large Ewing sarcoma in the right pelvic area. Destruction of the bone structure resulted from tumor involvement. (See also Images 5-6.)
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Media type:  X-RAY

Media file 5:  Magnetic resonance images from an 11-year-old boy with a right pelvic Ewing sarcoma (same patient as in Images 4 and 6). The tumor in the right iliac bone has the typical hyperintense appearance and extends to the hip. Significant involvement of the soft-tissue structures is depicted.
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Media type:  MRI

Media file 6:  Cross-sectional positron emission tomograms obtained after the administration of fluorodeoxyglucose (FDG). The images correspond to the magnetic resonance image in Image 5. These tomograms depict increased metabolic activity in the tumor, as well as in the surrounding soft-tissue area.
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Media type:  Nuclear Image

Media file 7:  Cross-sectional fusion magnetic resonance image (MRI) and positron emission tomographic image of a Ewing sarcoma. The highest metabolic activities match the MRI findings. Note the soft-tissue involvement resulting from the large tumor.
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Media type:  Nuclear Image

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT Scan
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

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2. Rogers LF. Bone tumors and related conditions. In: Juhl JH, Crummy AB, Paul L, eds. Paul and Juhl's Essentials of Radiologic Imaging. 5^th ed. Philadelphia, Pa: Lippincott-Raven; 1987:85-384.
3. Riggi N, Stamenkovic I. The biology of Ewing sarcoma. Cancer Lett. Aug 28 2007;254(1):1-10. [Medline].
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5. Dehner LP. Peripheral and central primitive neuroectodermal tumors. A nosologic concept seeking a consensus. Arch Pathol Lab Med. Nov 1986;110(11):997-1005. [Medline].
6. Paulussen M, Ahrens S, Braun-Munzinger G, et al. [EICESS 92 (European Intergroup Cooperative Ewing's Sarcoma Study)-- preliminary results] [German]. Klin Padiatr. Jul-Aug 1999;211(4):276-83. [Medline].
7. Damron TA, Ward WG, Stewart A. Osteosarcoma, chondrosarcoma, and Ewing's sarcoma: National Cancer Data Base Report. Clin Orthop Relat Res. Jun 2007;459:40-7. [Medline].
8. Smorenburg CH, van Groeningen CJ, Meijer OW, Visser M, Boven E. Ewing's sarcoma and primitive neuroectodermal tumour in adults: single-centre experience in The Netherlands. Neth J Med. Apr 2007;65(4):132-6. [Medline]. [Full Text].
9. Iwamoto Y. Diagnosis and treatment of Ewing's sarcoma. Jpn J Clin Oncol. Feb 2007;37(2):79-89. [Medline]. [Full Text].
10. Bacci G, Balladelli A, Forni C, et al. Ewing's sarcoma family tumours: Differences in clinicopathological characteristics at presentation between localised and metastatic tumours. J Bone Joint Surg Br. Sep 2007;89(9):1229-33. [Medline].
11. Bacci G, Ferrari S, Bertoni F, et al. Prognostic factors in nonmetastatic Ewing's sarcoma of bone treated with adjuvant chemotherapy: analysis of 359 patients at the Istituto Ortopedico Rizzoli. J Clin Oncol. Jan 2000;18(1):4-11. [Medline]. [Full Text].
12. O'Sullivan P, O'Dwyer H, Flint J, Munk PL, Muller NL. Malignant chest wall neoplasms of bone and cartilage: a pictorial review of CT and MR findings. Br J Radiol. Aug 2007;80(956):678-84. [Medline].
13. Erlemann R, Sciuk J, Bosse A, et al. Response of osteosarcoma and Ewing sarcoma to preoperative chemotherapy: assessment with dynamic and static MR imaging and skeletal scintigraphy. Radiology. Jun 1990;175(3):791-6. [Medline]. [Full Text].
14. Zhang WD, Xie CM, Mo YX, Li JY. [CT and MRI features of peripheral primitive neuroectodermal tumor] [Chinese]. Ai Zheng. Jun 2007;26(6):643-6. [Medline].
15. San-Julian M, Aquerreta JD, Benito A, Cañadell J. Indications for epiphyseal preservation in metaphyseal malignant bone tumors of children: relationship between image methods and histological findings. J Pediatr Orthop. Jul-Aug 1999;19(4):543-8. [Medline].
16. Hayashida Y, Yakushiji T, Awai K, et al. Monitoring therapeutic responses of primary bone tumors by diffusion-weighted image: initial results. Eur Radiol. Dec 2006;16(12):2637-43. [Medline].
17. Ozcan Z, Burak Z, Kumanlioglu K, et al. Assessment of chemotherapy-induced changes in bone sarcomas: clinical experience with 99Tcm-MDP three-phase dynamic bone scintigraphy. Nucl Med Commun. Jan 1999;20(1):41-8. [Medline].
18. Shulkin BL, Mitchell DS, Ungar DR, et al. Neoplasms in a pediatric population: 2-[F-18]-fluoro-2-deoxy-D-glucose PET studies. Radiology. Feb 1995;194(2):495-500. [Medline]. [Full Text].
19. Strauss LG, Koomaegi R, Dimitrakopoulou-Strauss A. Dynamic positron emission tomography (PET) with 18F-deoxyglucose (FDG) in bone tumors: correlation of quantitative PET and gene expression [abstract]. J Nucl Med. 2001;42:33P.
20. Arush MW, Israel O, Postovsky S, et al. Positron emission tomography/computed tomography with (18)fluoro-deoxyglucose in the detection of local recurrence and distant metastases of pediatric sarcoma. Pediatr Blood Cancer. Dec 2007;49(7):901-5. [Medline].
21. Lopes SL, Almeida SM, Costa AL, Zanardi VA, Cendes F. Imaging findings of Ewing's sarcoma in the mandible. J Oral Sci. Jun 2007;49(2):167-71. [Medline]. [Full Text].
22. Miser JS, Goldsby RE, Chen Z, et al. Treatment of metastatic Ewing sarcoma/primitive neuroectodermal tumor of bone: evaluation of increasing the dose intensity of chemotherapy. Report from the Children's Oncology Group. Pediatr Blood Cancer. Dec 2007;49(7):894-900. [Medline].
23. Rodríguez-Galindo C, Liu T, Krasin MJ, et al. Analysis of prognostic factors in ewing sarcoma family of tumors: review of St. Jude Children's Research Hospital studies. Cancer. Jul 15 2007;110(2):375-84. [Medline].

Article Last Updated: Nov 2, 2007