Ewing's Sarcoma

Author: Patrick O'Donnell

Topic updated on 03/10/13 10:10pm

Introduction

A distinctive small round cell sarcoma
Epidemiology
- demographics
  - typically found in patients from 5-25 years of age
  - second most common bone tumor in children
  - uncommon in African Americans and Chinese
- locations
  - ~50% are found in the diaphysis of long bones
    - the most common locations include pelvis, distal femur, proximal tibia, femoral diaphysis, and proximal humerus
Genetics
- t(11:22) translocation
  - found in all cases
  - leads to the formation of a fusion protein (EWS-FLI1)
    - can be identified with PCR and useful to differentiate Ewing sarcoma from other round cell lesions
Prognosis
- survival
  - 60-70% long term survival with isolated extremity disease at presentation and appropriate treatment/tumor response to chemotherapy
  - 40% long term survival with pelvis lesions
  - 15% long term survival if patient presents with metastatic disease
- poor prognostic factors
  - spine and pelvic tumors
  - tumors greater than 100cm3
  - < 90% necrosis with chemotherapy
  - elevated lactic dehydrogenase levels
  - p53 mutation in addition to t(11:22) translocation

Symptoms

Presentation
- pain often accompanied by fever
- often mimics an infection
Physical exam
- swelling and local tenderness

Imaging

Radiographs
- large destructive lesion in the diaphysis or metaphysis with a moth-eaten appearance
- lesion may be purely lytic or have variable amounts of reactive new bone formation
- periosteal reaction may give "onion skin" or "sunburst" appearance
Bone scan
- required as part of staging workup - will show very "hot" lesion
MRI
- necessary to identify soft-tissue extension and marrow involvement
- often shows a large soft tissue component
CT chest
- is required for appropriate staging to look for pulmonary metastasis

Evaluation

Labs
- ESR is elevated
- WBC is elevated
- anemia is common
- lactic dehydrogenase
Bone marrow biopsy
- required as part of workup for Ewing's to rule out metastasis to the marrow

Histology

Gross appearance
- may have liquid consistency mimicking pus
Characteristic findings
- sheets of monotonous small round blue cells
- prominent nuclei and minimal cytoplasm
- may have pseudo-rosettes (circle of cells with necrosis in center)
Immunostaining
- CD99 reactivity

Treatment

Operative
- chemotherapy and limb salvage resection
  - indications
    - standard of care in most patients
  - chemotherapy
    - preoperative chemotherapy given for 8-12 weeks followed by surgical resection and maintenance chemotherapy for 6-12 months
  - irradiation
    - current trend is towards surgical resection and away from irradiation due to long term morbidity associated with radiation
    - situations where radiation may be used
      - non-resectable tumors (eg. large spinal tumors)
      - patients who present with widely metastatic disease

Differentials & Groups

Small-round-cell tumor differential (by age)
- < 5 yrs: neuroblastoma or leukemia
- 5-10 yrs: eosinophilic granuloma
- 5-30 yrs: Ewing's sarcoma
- >30 yrs: lymphoma
- > 50 yrs: myeloma

	Destructive lesion in young patients(1)	Small round cell tumors	Treatment is Wide Resection & Chemotherapy (2)
Ewing's sarcoma	•	•	•
Osteosarcoma	•		•
Lymphoma	•	•
Leukemia	•	•
Eosinophilic granuloma	•	•
Osteomyelitis	•
Desmoplastic fibroma	•
Metastatic disease
Neuroblastoma (soft tissue)		•
Rhabdomyosarcoma (soft tissue)
Secondary sarcoma
Dediff. Chondrosarcoma			•
MFH / fibrosarcomaa
Myeloma		•
ASSUMPTIONS: (1) Younger patient is < 40 yrs; (2) assuming no impending fracture

IBank

	Location	Xray	Xray	CT	B. Scan	MRI	MRI	Histo(1)
Case A	tibia
Case B	femur
Case C	humerus
Case D	pelvis
Case E	pelvis
Case F

(1) - histology does not always correspond to clinical case

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Qbank (8 Questions)

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(OBQ10.171) Each of the following neoplasms demonstrate round cells when examined histologically EXCEPT Topic

Review Topic

1. Embryonal rhabdomyosarcoma
2. Primitive neuroectodermal tumors (PNET)
3. Ewings sarcoma
4. Neuroblastoma
5. Synovial sarcoma

PREFERRED RESPONSE ▶

DISCUSSION: Synovial sarcoma is described histologically as epithelial cells forming glandlike structures alternating with elongated spindle cells in a biphasic pattern.

Ewing's sarcoma primarily occurs in patients that are less than 20 years of age and is the 2nd most common bone tumor in children. The etiology of Ewing's sarcoma is a 11:22 chromosomal translocation that produces the EWS/FLI1 fusion gene, which can be detected by polymerase chain reaction(PCR). Radiographic features of Ewings include a lytic, permeative lesion with layers of periosteal reaction creating an "onion skin" appearance. Gross pathology often appears similar to pus and histology includes sheets of round cells with large nuclei and small amounts of cytoplasm. Immunohistochemical staining is positive for CD99. Treatment consistently includes neoadjuvant multiagent chemotherapy followed by either surgical resection or radiation.

Neuroblastoma, primitive neuroectodermal tumors (PNET), Ewing's sarcoma, and embryonal rhabdomyosarcoma are all described in the AAOS Comprehensive Orthopaedic Review textbook as having round cell components. Other processes that are often described as having round cells include eosinophilic granuloma, lymphoma, myeloma, and round cell liposarcoma.

REFERENCES:

1. Patterson FR, Basra SK. Ewing's sarcoma. In: Schwartz HS, ed. Orthopaedic Knowledge Update: Musculoskeletal Tumors 2. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2007:175-183.

2. Damron TA. Orthopaedic Surgery Essentials, Oncology and Basic Science. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:187-191.

Question Authors:

Michael Hughes MD, Ben Taylor MD,

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(OBQ10.194) A 15-year-old cross country runner complains of vague shin pain. A radiograph of the tibia is seen in Figure A. A biopsy is performed and is shown in Figure B. Which of the following chromosomal translocations is most likely associated with this condition? Topic

Review Topic

FIGURES: A

1. t(10;20)
2. t(11;22)
3. t(X;18)
4. t(9;22)
5. t(2;13)

PREFERRED RESPONSE ▶

DISCUSSION: The clinical presentation, images, and biopsy are consistent with Ewings sarcoma. Ewings sarcoma is a pediatric round cell bone tumor resulting from a translocation of chromosomes 11 and 22 which leads to the formation of a fusion protein (EWS-FLI 1). Radiographs demonstrate a lytic lesion with periosteal reaction (“onion skin” type). An MRI is useful to evaluate soft-tissue involvement (see Illustration A). 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. Histologically, uniform sheets of small round blue cells are seen with round or oval nuclei of uniform size as demonstrated in Figure B.

Incorrect Answers:

Synovial sarcoma is associated with t(X;18).
Extraskeletal myxoid Chondrosarcoma is associated with t(9;22).
Rhabdomyosarcoma is associated with t(2;13).

Illustrations: A

REFERENCES:

1. Thacker MM. Musculoskeletal oncology. In: Fischgrund JS, ed. Orthopaedic Knowledge Update 9. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2008:197-219.

2. Montag A. Management of surgical specimens. In: Simon MA, Springfield D, eds. Surgery for Bone and Soft Tissue Tumors. Philadelphia, PA: Lippincott-Raven; 1998:67-75.

Question Authors:

Jan Szatkowski MD,

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(OBQ08.53) For which of the following patients would a bone marrow biopsy be indicated during tumor staging? Topic

Review Topic

1. 15-year-old girl with bone forming distal femoral lesion on radiographs
2. 7-year-old boy with lipomatous lesion in his proximal thigh
3. 3-year-old boy with renal mass
4. 5-year-old girl with lytic diaphyseal femur lesion positive for the EWS-FLI1 transgene
5. 12-year-old boy with shepard's crook deformity of his proximal femur and deactivating mutation in the G-beta subunit of the G-protein coupled receptor.

PREFERRED RESPONSE ▶

DISCUSSION: Bone marrow biopsy for musculoskeletal sarcomas is only routinely done for Ewing’s sarcoma.

Ewing’s sarcoma falls in the group of small round blue cell tumors, and while there is argument regarding the cell origin for Ewing’s, most agree that the cell of origin develops in the bone marrow. In addition to the normal tumor staging, Ewing’s sarcoma requires a bone marrow biopsy at a distant site to ensure no marrow metastasis - which would change the patient’s prognosis.

Carvajal discusses the neuroectodermal family of tumors, including Ewing's sarcoma, and specifically discuss hematopoetic development/transformation, diagnosis, treatment, and outcomes.

Incorrect Answers:
Patient’s with osteosarcomas, lipomas, Wilm’s tumor, and fibrous dysplasia do not require a bone marrow biopsy.

REFERENCES:

1. Carvajal R, Meyers P. Ewing's sarcoma and primitive neuroectodermal family of tumors. Hematol Oncol Clin North Am. 2005 Jun;19(3):501-25, vi-vii. Review. PMID:15939194 (Link to Abstract)

2. AAOS Comprehensive Review p 429-432.

Question Authors:

Patrick O'Donnell MD/PhD, Patrick McCulloch MD,

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(OBQ06.65) An 8-year-old girl comes to the office with increasing thigh pain mostly at night. Radiograph and biopsy specimen are shown in Figures A and B. The patients WBC and ESR are both elevated. What is the most likely diagnosis? Topic

Review Topic

FIGURES: A

1. Ewing's sarcoma
2. Osteosarcoma
3. Osteomyelitis
4. Giant cell tumor
5. Chondrosarcoma

PREFERRED RESPONSE ▶

DISCUSSION: This patients history, radiograph, and biopsy are consistent with Ewing’s sarcoma. Specifically the radiograph shows an infiltrative, non-geographic lesion with periosteal reaction and "onion-skinning." The pathology slide shows a diffuse sheet of small round blue cells lining the bone trabeculae-diagnostic of Ewing's sarcoma. Current treatment for Ewing's sarcoma include neoadjuvant chemotherapy, surgical resection, and adjuvant chemotherapy. Only in "unresectable" tumors, or situations where resection would be associated with poor functional outcome would Ewing's be treated with chemotherapy and radiotherapy without surgical excision. While Ewing's sarcoma is very radiation sensitive, the worry with radiation therapy in young patients is the increased lifetime risk of radiation induced sarcomas and the other complications of radiotherapy including fibrosis, fracture, and wound problems.

The article by Krasin et al looked at 79 patients who received different chemotherapy protocols and received either low dose <40Gy or high dose >40Gy radiotherapy. Local failure at 10yrs was 19% when tumors <8cm were treated with <40Gy and no failures were seen with >40Gy.

REFERENCES:

1. Krasin MJ, Rodriguez-Galindo C, Billups CA, Davidoff AM, Neel MD, Merchant TE, Kun LE. Definitive irradiation in multidisciplinary management of localized Ewing sarcoma family of tumors in pediatric patients: Outcome and prognostic factors. Int J Radiat Oncol Biol Phys 2004;60:830-838. PMID:15465200 (Link to Abstract)

Question Authors:

Patrick O'Donnell MD/PhD,

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(OBQ06.161) A 13-year old female complains of constant, dull right knee pain for the past several months. The pain is worse at night and with walking. She denies weight loss or fatigue. An AP and lateral radiograph are shown in Figures A and B, respectively. She was found to have a bony lesion in the distal femur which was biopsied at an outside institution which is shown in Figure C. What is the genetic translocation with this type of condition? Topic

Review Topic

FIGURES: A

1. t (9; 22)
2. t (11;22)
3. t (12;16)
4. t (X;18)
5. t (12;22)

PREFERRED RESPONSE ▶

DISCUSSION: Ewings sarcoma is a pediatric round cell tumor occurring in the bone consisting of round blue cells resulting from translocation of chromosomes 11 and 22. Figures A and B display the most common finding of a lesion with periosteal reaction (“onion skin” type). A MRI is essential to elucidate soft-tissue involvement 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. Histologically, uniform sheets of small round blue cells are seen with round or oval nuclei of uniform size with poor delineation of cytoplasm.

Maheshwari et al review the Ewing Sarcoma Family of Tumors (ESFT), and discuss their genetics, evaluation, and treatment. The common translocation in this family of tumors results in the EWS-ETS fusion protein (between the EWS gene on chromosome 22 and an ETS-type gene on chromosome 11).

Incorrect Answers:
Answer 1: t(9; 22) is found with chondrosarcoma and leads to the fusion protein EWS-CHN.
Answer 3: t(12;16) is found with myxoid liposarcoma and leads to the chimeric oncoprotein TLS-CHOP
Answer 4: t(X;18) is found with synovial sarcoma and leads to the fusion protein SYT-SSX1.
Answer 5: t (12;22)) is found with clear cell sarcoma and leads to the fusion protein EWS-ATF1.

REFERENCES:

1. Maheshwari AV, Cheng EY. Ewing sarcoma family of tumors. J Am Acad Orthop Surg. 2010 Feb;18(2):94-107. PMID:20118326 (Link to Abstract)

Question Authors:

Derek Moore, Ben Taylor MD, John Badylak MD,

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(OBQ06.214) After tumor staging, what is the most appropriate treatment for a 17-year-old male with stage IIb Ewing's sarcoma in his proximal tibia? Topic

Review Topic

1. Neoadjuvant radiotherapy, marginal surgical resection, adjuvant chemotherapy
2. Neoadjuvant chemotherapy, marginal surgical resection, adjuvant radiotherapy
3. Neoadjuvant chemotherapy, wide surgical resection, adjuvant chemotherapy
4. Wide surgical excision and reconstruction
5. Radiotherapy and chemotherapy without surgery

PREFERRED RESPONSE ▶

DISCUSSION: The treatment for a 17-year-old male with Ewing's sarcoma in his proximal tibia is neoadjuvant chemotherapy, wide surgical resection, and adjuvant chemotherapy.

While non-resectable Ewing's sarcoma may be treated with radiotherapy and chemotherapy (answer 5), a tumor confined to the proximal tibia is considered resectable and as such wide excision and reconstruction is the treatment of choice.

Sluga et al review their series of patients with Ewing's sarcoma which suggest that neoadjuvant chemotherapy followed by wide surgical resection is the treatment which affords the best long term survival. With appropriate treatment, including adjuvant therapy and negative margin resection, the 5-year overall survival for Ewing's sarcoma approaches 60%.

In a similiar fashion, Toni et al review their series of patients treated for Ewing's sarcoma. Of their cohort, they treated almost half (47%) with radiotherapy alone and saw a significantly higher rate of local recurrence (24%). Whether this is due to the tumor biology, difficulty of achieving adequate radiation doses, or some other factor, they suggest that Ewing's sarcoma should be treated with surgical excision when at all possible.

Illustration A displays the MSTS (Enneking) Staging System.

Illustrations: A

REFERENCES:

1. Sluga M, Windhager R, Lang S, Heinzl H, Krepler P, Mittermayer F, Dominkus M, Zoubek A, Kotz R. The role of surgery and resection margins in the treatment of Ewing's sarcoma. Clin Orthop Relat Res. 2001 Nov;(392):394-9. PMID:11716413 (Link to Abstract)

2. Toni A, Neff JR, Sudanese A, Ciaroni D, Bacci G, Picci P, Barbieri E, Campanacci M, Giunti A. The role of surgical therapy in patients with nonmetastatic Ewing's sarcoma of the limbs. Clin Orthop Relat Res. 1993 Jan;(286):225-40. PMID:8425351 (Link to Abstract)

Question Authors:

Patrick O'Donnell MD/PhD, Michael Hughes MD, Ben Taylor MD,

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(OBQ06.239) Which of the following tests is required for a standard work-up of Ewing's sarcoma that is not routinely obtained for staging of osteosarcoma? Topic

Review Topic

1. MRI
2. CT scan
3. Bone scan
4. Protein electrophoresis
5. Bone marrow biopsy

PREFERRED RESPONSE ▶

DISCUSSION: Bone marrow biopsy is a routine part of the staging workup for Ewing’s sarcoma, and is not routinely obtained for staging of osteosarcoma.

Ewing’s is a small round cell (blue cell) tumor that occurs most commonly in children and young adults. Clinical presentations of these tumors frequently mimic infection with low grade fever, elevated white counts and high markers of inflammation. The radiographic appearance will show a large lytic lesion in the metaphysis or diaphysis. Reactive periosteum may be lifted off the bone in multiple layers, termed “onion skinning” which is characteristic but uncommon. Bone marrow biopsy is done because Ewing's sarcoma can metastasize via the marrow.

Carvajal et al report the Ewing's sarcoma family of tumors (EFT) includes ES of bone (ESB), extraosseous ES (EES), peripheral primitive neuroectodermal tumor of bone (pPNET), and malignant small-cell tumor of the thoracopulmonary region, or Askin's tumor, all of which are now known to be neoplasms of neuroectodermal origin.

REFERENCES:

1. Menendez LR (ed): Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 21-27.

2. Gorlick RG Toretsky JA, Marina N, et al: Bone tumors. In Kufe DW, Pollock RE, Weichselbaum RR, et al (eds): Cancer Medicine 6. Hamilton, BC, Decker, 2003, pp 2388-2392.

3. Carvajal R, Meyers P. Ewing's sarcoma and primitive neuroectodermal family of tumors. Hematol Oncol Clin North Am. 2005 Jun;19(3):501-25, vi-vii. Review. PubMed PMID: 15939194. PMID:15939194 (Link to Abstract)

Question Authors:

Greg Galano MD, Derek Moore, Michael Hughes MD,

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(OBQ04.116) What is the appropriate treatment for a 10-year-old boy with Ewing's sarcoma isolated to the proximal femur? Topic

Review Topic

1. Neoadjuvant chemotherapy and surgical excision
2. Neoadjuvant chemotherapy, surgical excision, and radiation therapy
3. Neoadjuvant chemotherapy, surgical excision, and adjuvant chemotherapy
4. Neoadjuvant radiation therapy and surgical excision
5. Surgical excision and hormonal therapy

PREFERRED RESPONSE ▶

DISCUSSION: Ewing's sarcoma is a malignant small round blue cell neoplasm which has a predilection for long tubular bones, pelvis, and ribs. The radiographic appearance of "onion-skinning" seen in illustrations A and B is due to the body's periosteal reaction. Illustration C shows the large soft tissue extra-osseous mass characteristic for Ewing's sarcoma. Finally, Illustration D shows the histology where the multiple small round blue neoplastic cells are seen. Ewing's sarcoma is most commonly treated with neoadjuvant chemotherapy, surgical excision, and adjuvant chemotherapy - in particular for tumors located in bones which can be easily resected and reconstructed. For large tumors in areas which either cannot be completely excised or where excision is associated with significant morbidity, some centers consider chemotherapy and radiation therapy without surgical excision. There is a current trend towards surgical resection and away from irradiation for Ewing's sarcoma even though it is radiosensitive, because of the risk of secondary malignancy and growth disturbance due to radiation.
Pierz et al review many of the common bone tumors including Ewing's sarcoma and discuss the relevant diagnostic factors as well as specific treatment protocols for each tumor.

Illustrations: A

REFERENCES:

1. Mirra, JM. Ewing’s Sarcoma, in Bone Tumors: clinical, radiographic, and pathologic correlations. Lea and Febiger, 1989, pp 1087-1119

2. Pierz KA, Womer RB, Dormans JP. Pediatric bone tumors: osteosarcoma ewing's sarcoma, and chondrosarcoma associated with multiple hereditary osteochondromatosis. J Pediatr Orthop. 2001 May-Jun;21(3):412-8. Review. PMID:11371830 (Link to Abstract)

Question Authors:

Patrick O'Donnell MD/PhD, Eric Shirley MD, John Badylak MD,

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Videos

	Total Scapula Prosthesis Ewings Sarcoma - Dr. Wittig - Part 4 Pathology - Surgical Techniques - Ewing's Sarcoma Total Scapula Prosthesis Ewing's Sarcoma Part 4 - Specimen and Reconstruction	8/18/2012 52 views 5
	Total Scapula Prosthesis Ewings Sarcoma - Dr. Wittig - Part 3 Pathology - Surgical Techniques - Ewing's Sarcoma Total Scapula Prosthesis Ewing's Sarcoma Part 3 - Completion of Resection	8/18/2012 29 views 5
	Total Scapula Prosthesis Ewings Sarcoma - Dr. Wittig - Part 2 Pathology - Surgical Techniques - Ewing's Sarcoma Detachment of Periscapular Muscles	8/18/2012 36 views 5
	Total Scapula Prosthesis Ewings Sarcoma - Dr. Wittig - Part I Pathology - Surgical Techniques - Ewing's Sarcoma Incision and Exposure of Scapula and Surrounding Muscles	8/18/2012 34 views 0

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	The role of surgery and resection margins in the treatment of Ewing's sarcoma. Sluga M, Windhager R, Lang S, Heinzl H, Krepler P, Mittermayer F, Dominkus M, Zoubek A, Kotz R Clin. Orthop. Relat. Res.. 2001 Nov;(392):394-9. PMID: 11716413 (Link to Pubmed) Pathology - Journal Club - Ewing's Sarcoma	5/16/2013 14 responses 0
	Tested Article: The Role of Surgery and Resection Margins in the Treatment of Ewing's sarcoma. Sluga M, Windhager R, Lang S, Heinzl H, Krepler P, Mittermayer F, Dominkus... Pathology - Journal Club - Ewing's Sarcoma	3/7/2013 1 responses 0

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ABOS II: Ewing's Tumor

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Evidence & References Show References

Level of Evidence 4 (Case Series)

Krasin MJ, Rodriguez-Galindo C, Billups CA, Davidoff AM, Neel MD, Merchant TE, Kun LE. Definitive irradiation in multidisciplinary management of localized Ewing sarcoma family of tumors in pediatric patients: Outcome and prognostic factors. Int J Radiat Oncol Biol Phys 2004;60:830-838. PMID:15465200 (Link to Abstract)
Sluga M, Windhager R, Lang S, Heinzl H, Krepler P, Mittermayer F, Dominkus M, Zoubek A, Kotz R. The role of surgery and resection margins in the treatment of Ewing's sarcoma. Clin Orthop Relat Res. 2001 Nov;(392):394-9. PMID:11716413 (Link to Abstract)
Toni A, Neff JR, Sudanese A, Ciaroni D, Bacci G, Picci P, Barbieri E, Campanacci M, Giunti A. The role of surgical therapy in patients with nonmetastatic Ewing's sarcoma of the limbs. Clin Orthop Relat Res. 1993 Jan;(286):225-40. PMID:8425351 (Link to Abstract)

Level of Evidence 5 and Other Journal Articles (includes Case Reports, Expert Opinions, Personal Observations, and Biomechanic Studies)

Maheshwari AV, Cheng EY. Ewing sarcoma family of tumors. J Am Acad Orthop Surg. 2010 Feb;18(2):94-107. PMID:20118326 (Link to Abstract)
Pierz KA, Womer RB, Dormans JP. Pediatric bone tumors: osteosarcoma ewing's sarcoma, and chondrosarcoma associated with multiple hereditary osteochondromatosis. J Pediatr Orthop. 2001 May-Jun;21(3):412-8. Review. PMID:11371830 (Link to Abstract)

Textbooks

Review of Orthopaedics, 6th Edition, Mark D. Miller MD, Stephen R. Thompson MBBS MEd FRCSC, Jennifer Hart MPAS PA-C ATC, an imprint of Elsevier, Philadelphia, Copyright 2012
AAOS Comprehensive Orthopaedic Review, Jay R. Leiberman. Published by American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2009
Orthopaedic Knowledge Update 10, John M Flyn. Published by American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2011
Hoppenfeld SP. Surgical Exposures in Orthopaedics: The Anatomic Approach. Lipponcott, Williams, and Wilkins, Philadelphia, PA, Copyright 2009
Orthopaedic In-training Examination (OITE) Questions 2004-2012, American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2004-2012
Self-Assessment Examination (SAE) Questions 2004-2012, American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2004-2012
Damron TA. Orthopaedic Surgery Essentials, Oncology and Basic Science. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:187-191.
Mirra, JM. Ewing’s Sarcoma, in Bone Tumors: clinical, radiographic, and pathologic correlations. Lea and Febiger, 1989, pp 1087-1119
Patterson FR, Basra SK. Ewing's sarcoma. In: Schwartz HS, ed. Orthopaedic Knowledge Update: Musculoskeletal Tumors 2. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2007:175-183.

Undefined

AAOS Comprehensive Review p 429-432.
Carvajal R, Meyers P. Ewing's sarcoma and primitive neuroectodermal family of tumors. Hematol Oncol Clin North Am. 2005 Jun;19(3):501-25, vi-vii. Review. PubMed PMID: 15939194. PMID:15939194 (Link to Abstract)
Carvajal R, Meyers P. Ewing's sarcoma and primitive neuroectodermal family of tumors. Hematol Oncol Clin North Am. 2005 Jun;19(3):501-25, vi-vii. Review. PMID:15939194 (Link to Abstract)
Gorlick RG Toretsky JA, Marina N, et al: Bone tumors. In Kufe DW, Pollock RE, Weichselbaum RR, et al (eds): Cancer Medicine 6. Hamilton, BC, Decker, 2003, pp 2388-2392.
Menendez LR (ed): Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 21-27.
Montag A. Management of surgical specimens. In: Simon MA, Springfield D, eds. Surgery for Bone and Soft Tissue Tumors. Philadelphia, PA: Lippincott-Raven; 1998:67-75.
Thacker MM. Musculoskeletal oncology. In: Fischgrund JS, ed. Orthopaedic Knowledge Update 9. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2008:197-219.

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Ewing's Sarcoma

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