Ewing's sarcoma 1

Ewing's sarcoma

Ewing sarcomasClassification and external resources

Micrograph of metastatic Ewing sarcoma (right of image) in normal lung (left of image). PAS stain.

ICD-10 C41.9 [1]

ICD-9 170.9 [2]

ICD-O: M9260/3 [3]

OMIM 133450 [4]

DiseasesDB 4604 [5]

MedlinePlus 001302 [6]

eMedicine ped/2589 [7]

MeSH D012512 [8]

Ewing's sarcoma is a malignant small, round, blue cell tumour. It is a rare disease in which cancer cells are found inthe bone or in soft tissue. The most common areas in which it occurs are the pelvis, the femur, the humerus, the ribsand clavicle (collar bone).Because a common genetic locus is responsible for a large percentage of Ewing's sarcoma and primitiveneuroectodermal tumors, these are sometimes grouped together in a category known as the Ewing family of tumors.[]

The diseases are, however, considered to be different: peripheral primitive neuroectodermal tumours are generallynot associated with bones, while Ewing sarcomas are most commonly related to bone.Ewing's sarcoma occurs most frequently in teenagers and young adults, with a male/female ratio of 1.6:1.[]

Although usually classified as a bone tumour, Ewing's sarcoma can have characteristics of both mesodermal andectodermal origin, making it difficult to classify.[]

James Ewing (1866–1943) first described the tumour, establishing that the disease was separate from lymphoma andother types of cancer known at that time.[9][10]

Ewing's sarcoma 2

CausesGenetic exchange between chromosomes can cause cells to become cancerous. Most cases of Ewing's sarcoma(85%) are the result of a translocation between chromosomes 11 and 22, which fuses the EWS gene of chromosome22 to the FLI1 gene of chromosome 11.[]

EWS/FLI functions as the master regulator.[]

Other translocations are at t(21;22)[] and t(7;22).[]

Signs symptoms include: intermittent fevers, anemia, leukocytosis, increased sedimentation rate, and othersymptoms of inflammatory systemic illness.[]

According to The Bone Cancer Research Trust (BCRT), the most common symptoms are: localized pain, swelling,and sporadic bone pain with variable intensity. The swelling is most likely to be visible if the sarcoma is located on abone near the surface of the body, but when it occurs in other places deeper in the body, like on the pelvis, it may notbe visible.[11]

Clinical findings

Distribution of Ewing's sarcoma. Most frequentlocations are the large long bones and the pelvis.

Ewing's sarcoma is more common in males and usually presents inchildhood or early adulthood, with a peak between 10 and 20 years ofage. It can occur anywhere in the body, but most commonly in thepelvis and proximal long tubular bones, especially around the growthplates. The diaphyses of the femur are the most common sites,followed by the tibia and the humerus. Thirty percent are overtlymetastatic at presentation. Patients usually experience extreme bonepain.

Ewing's sarcoma cells are positive for CD99 and MIC2,[] and negativefor CD45.[]

Ewing's sarcoma 3

Imaging findings

X-Ray of a child withEwing sarcoma of the tibia.

Magnetic resonance imaging slice showingEwing's sarcoma of the left hip (white area shown

right).

On conventional radiographs, the most common osseous presentationis a permeative lytic lesion with periosteal reaction. The classicdescription of lamellated or "onion skin" type periosteal reaction isoften associated with this lesion. Plain films add valuable informationin the initial evaluation or screening. The wide zone of transition (e.g.permeative) is the most useful plain film characteristic indifferentiation of benign versus aggressive or malignant lytic lesions.

MRI should be routinely used in the work-up of malignant tumours.MRI will show the full bony and soft tissue extent and relate thetumour to other nearby anatomic structures (e.g. vessels). Gadoliniumcontrast is not necessary as it does not give additional information overnoncontrast studies, though some current researchers argue thatdynamic, contrast enhanced MRI may help determine the amount ofnecrosis within the tumour, thus help in determining response totreatment prior to surgery.

CT can also be used to define the extraosseous extent of the tumour,especially in the skull, spine, ribs and pelvis. Both CT and MRI can beused to follow response to radiation and/or chemotherapy.

Bone scintigraphy can also be used to follow tumour response totherapy.

In the group of malignant small round cell tumours which includeEwing's sarcoma, bone lymphoma and small cell osteosarcoma, thecortex may appear almost normal radiographically, while there ispermeative growth throughout the Haversian channels. These tumoursmay be accompanied by a large soft tissue mass while there is almostno visible bone destruction. The radiographs frequently do not shownany signs of cortical destruction.Radiographically Ewing's Sarcoma presents as "Moth-eaten"destructive radiolucencies of the medulla and erosion of the cortexwith expansion.A grouping of three unrelated teenagers in Wake Forest NC havediagnosed with Ewing's sarcoma. All three children were diagnosed in2011 and all attended the same temporary classroom together while the school underwent renovation. A fourthteenager living nearby was diagnosed in 2009. The odds of this grouping are considered significant. [12]

Ewing's sarcoma 4

Clinical differential diagnosisOther entities that may have a similar clinical presentation include osteomyelitis, osteosarcoma (especiallytelangiectatic osteosarcoma) and eosinophilic granuloma. Soft tissue neoplasms such as pleomorphicundifferentiated sarcoma (malignant fibrous histiocytoma) that erode into adjacent bone may also have a similarappearance.

Diagnosis

Micrograph of a metastatic Ewing's sarcoma withthe characteristic cytoplasmic clearing on H&E

staining, which was showing to be PAS positive.

The definitive diagnosis is based on histomorphologic findings,immunohistochemistry and molecular pathology.

Ewing's sarcoma is a small round cell tumor, that typically has a clearcytoplasm on H&E staining, due to glycogen. The presence of theglycogen can be demonstrated with positive PAS staining and negativePAS diastase staining. The characteristic immunostain is CD99 whichdiffusely marks the cell membrane. Morphologic andimmunohistochemical findings are corroborated with an associatedchromosomal translocation, of which there are several. The mostcommon translocation, present in approximately 90% of Ewingsarcoma cases, is t(11;22)(q24;q12).[13][]

The pathologic differential diagnosis is the grouping of Small, round, blue cell tumours, which includes lymphoma,alveolar rhabdomyosarcoma and desmoplastic small round cell tumor, among others.

EpidemiologyEwing's sarcomas represent 16% of primary bone sarcomas.[]

Ewing's sarcoma in the United States is most common in the second decade of life,[] with a rate of 0.3 cases permillion in children under 3 years of age, and as high as 4.6 cases per million in adolescents aged 15–19 years.Internationally the annual incidence rate averages less than 2 cases per million children.[14] In the United Kingdoman average of six children per year are diagnosed, mainly males in early stages of puberty. Due to the prevalence ofdiagnosis during teenage years, there may possibly be a link between the onset of puberty and the early stages of thisdisease, although no research is currently being conducted to confirm this hypothesis.

TreatmentAlmost all patients require multidrug chemotherapy (often including ifosfamide and etoposide)[] as well as localdisease control with surgery and/or radiation.[] An aggressive approach is necessary because almost all patients withapparently localized disease at the time of diagnosis actually have asymptomatic metastatic disease.Treatment often consists of neo-adjuvant chemotherapy, which may include vincristine, doxorubicin, andcyclophosphamide with ifosfamide and etoposide.[] After about three months of chemotherapy, the remaining tumoris surgically resected, radiated, or both.[] The surgical resection may involve limb salvage or amputation. Completeexcision at the time of biopsy may be performed if malignancy is confirmed at the time it is examined.Treatment lengths vary depending on location and stage of the disease at diagnosis. Radical chemotherapy may be as short as 6 treatments at 3 week cycles, however most patients will undergo chemotherapy for 6–12 months and radiation therapy for 5–8 weeks.[citation needed] Radiotherapy has been used for localised disease. The tumor has a unique property of being highly sensitive to radiation, sometimes acknowledged by the phrase "melting like snow". But the main drawback is that it recurs dramatically after sometime.[citation needed] Antisense oligodeoxynucleotides have been proposed as possible treatment by down-regulating the expression of the oncogenic fusion protein

Ewing's sarcoma 5

associated with the development of Ewing's sarcoma resulting from the EWS-ETS gene translocation.[15][] Inaddition, the synthetic retinoid derivative fenretinide (4-hydroxy(phenyl)retinamide) has been reported to inducehigh levels of cell death in Ewing sarcoma cell lines in vitro and to delay growth of Ewing sarcoma xenografts invivo mouse models.[16][17]

Fertility preservationIn women, chemotherapy may damage the ovaries and cause infertility. To avail for future pregnancies, the womanmay preserve oocytes or ovarian tissue by oocyte cryopreservation or ovarian tissue cryopreservation prior to startingchemotherapy. However, the latter may reseed the cancer upon reinsertion of the ovarian tissue.[] If it is performed,the ovarian tissue should be examined for traces of malignancy at both the pathological and molecular levels prior tothe grafting of the cryopreserved tissue.[]

PrognosisStaging attempts to distinguish patients with localized from those with metastatic disease.[] Most commonly,metastases occur in the chest, bone and/or bone marrow. Less common sites include the central nervous system andlymph nodes.Five-year survival for localized disease is 70% to 80% when treated with chemotherapy.[] Long term survival formetastatic disease may be less than 10%. However, some sources state it is 25-30%.[18]

Research, information and supportIn the UK and Ireland The Bone Cancer Research Trust (BCRT) funds research and provides information on Ewingsarcoma and other bone cancers. This includes information for teenagers who have this condition.

References[1] http:/ / apps. who. int/ classifications/ icd10/ browse/ 2010/ en#/ C41. 9[2] http:/ / www. icd9data. com/ getICD9Code. ashx?icd9=170. 9[3] http:/ / www. progenetix. net/ progenetix/ I92603/[4] http:/ / omim. org/ entry/ 133450[5] http:/ / www. diseasesdatabase. com/ ddb4604. htm[6] http:/ / www. nlm. nih. gov/ medlineplus/ ency/ article/ 001302. htm[7] http:/ / www. emedicine. com/ ped/ topic2589. htm[8] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2013/ MB_cgi?field=uid& term=D012512[12] http:/ / www. wral. com/ three-wake-students-battle-rare-cancer-cluster-or-coincidence-/ 12389860/

• 20. Bone Tumors - Differential diagnosis (http:/ / www. radiologyassistant. nl/ en/ 494e15cbf0d8d). Henk Jan vander Woude and Robin Smithuis.Radiology department of the Onze Lieve Vrouwe Gasthuis, Amsterdam and theRijnland hospital,Leiderdorp,the Netherlands.

External links• Cancer.Net: Ewing Family of Tumors, Childhood (http:/ / www. cancer. net/ patient/ Cancer+ Types/ Ewings+

Family+ of+ Tumors+ -+ Childhood)• Ewing family of tumors (http:/ / www. cancer. gov/ dictionary?CdrID=322134) entry in the public domain NCI

Dictionary of Cancer Terms

Article Sources and Contributors 6

Article Sources and ContributorsEwing's sarcoma  Source: http://en.wikipedia.org/w/index.php?oldid=553868057  Contributors: Ahnine, Anthonyhcole, Anupam, Arcadian, ArchonMeld, Baggy75, Bdkelly78, BennyK95,Biruitorul, Bobo192, Body Soul Mind, Bonnie13J, Brim, Brownsteve, Catoosaflash, Cireshoe, CommonsDelinker, Crzrussian, Davemcarlson, Dayleeds, Deepika.nagireddy, Dl2000, Drchazz,Ebyabe, Eitakitiki, Emma20001, Eumolpo, Favonian, Gabbe, Gj1lc47188, Graham87, HLD75, Headbomb, Helena Manana, Hovea, Hu12, I dream of horses, IceCreamAntisocial, Immunize,InvictaHOG, Isoxyl, Jetman, Jfdwolff, John254, Kats, Kauczuk, Keilana, LanceBarber, Ligulem, Lspector, MER-C, Madhero88, Medical geneticist, Mikael Häggström, Mike Rosoft, Mmmzeta0,Moink, Mrich, Nephron, Ngebendi, Nlu, Optigan13, Patho, Purgatory Fubar, RDBrown, Rajking, Red, Reinyday, Rich Farmbrough, Rjwilmsi, Rytyho usa, SolomonHume, Stevenfruitsmaak,Stewartadcock, Tassedethe, Tedder, TenPoundHammer, Uncle Dick, UrsusArctosL71, WhatamIdoing, WikHead, WolfmanSF, Woohookitty, Worc63, Wouterstomp, Wtmitchell, Zigger, 135anonymous edits

Image Sources, Licenses and ContributorsFile:Ewing sarcoma - PAS - very high mag.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Ewing_sarcoma_-_PAS_-_very_high_mag.jpg  License: Creative CommonsAttribution-Sharealike 3.0  Contributors: Nephronimage:636039cfb96dc46674512d89a8229c big gallery.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:636039cfb96dc46674512d89a8229c_big_gallery.jpg  License: unknown Contributors: User:Frank GaillardImage:Ewing sarcoma tibia child.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Ewing_sarcoma_tibia_child.jpg  License: GNU Free Documentation License  Contributors:Michael Richardson, M.D. on Oct 25th, 2004; Upload by Christaras AImage:Ewing's sarcoma MRI nci-vol-1832-300.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Ewing's_sarcoma_MRI_nci-vol-1832-300.jpg  License: Public Domain Contributors: Unknown photographer/artistImage:Ewing sarcoma - intermed mag.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Ewing_sarcoma_-_intermed_mag.jpg  License: Creative Commons Attribution-Sharealike 3.0 Contributors: Nephron

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