Ewing's sarcoma

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Ewing's sarcoma_table_infobox_0

Ewing's sarcomaEwing's sarcoma_header_cell_0_0_0
Other namesEwing's sarcoma_header_cell_0_1_0 Ewing sarcoma, peripheral primitive neuroectodermal tumor, Askin tumor, and Ewing sarcoma family of tumorsEwing's sarcoma_cell_0_1_1
PronunciationEwing's sarcoma_header_cell_0_2_0 Ewing's sarcoma_cell_0_2_1
SpecialtyEwing's sarcoma_header_cell_0_3_0 OncologyEwing's sarcoma_cell_0_3_1
SymptomsEwing's sarcoma_header_cell_0_4_0 Swell and pain near the tumorEwing's sarcoma_cell_0_4_1
ComplicationsEwing's sarcoma_header_cell_0_5_0 Pleural effusion, paraplegiaEwing's sarcoma_cell_0_5_1
Usual onsetEwing's sarcoma_header_cell_0_6_0 10 to 20 years oldEwing's sarcoma_cell_0_6_1
CausesEwing's sarcoma_header_cell_0_7_0 UnknownEwing's sarcoma_cell_0_7_1
Diagnostic methodEwing's sarcoma_header_cell_0_8_0 Tissue biopsyEwing's sarcoma_cell_0_8_1
Differential diagnosisEwing's sarcoma_header_cell_0_9_0 Osteosarcoma, neuroblastoma, osteomyelitis, eosinophilic granulomaEwing's sarcoma_cell_0_9_1
TreatmentEwing's sarcoma_header_cell_0_10_0 Chemotherapy, radiation therapy, surgery, stem cell transplantEwing's sarcoma_cell_0_10_1
PrognosisEwing's sarcoma_header_cell_0_11_0 Five year survival ~ 70%Ewing's sarcoma_cell_0_11_1
FrequencyEwing's sarcoma_header_cell_0_12_0 1 per million people (US)Ewing's sarcoma_cell_0_12_1

Ewing's sarcoma is a type of cancer that may be a bone sarcoma or a soft-tissue sarcoma. Ewing's sarcoma_sentence_0

Symptoms may include swelling and pain at the site of the tumor, fever, and a bone fracture. Ewing's sarcoma_sentence_1

The most common areas where it begins are the legs, pelvis, and chest wall. Ewing's sarcoma_sentence_2

In about 25% of cases, the cancer has already spread to other parts of the body at the time of diagnosis. Ewing's sarcoma_sentence_3

Complications may include a pleural effusion or paraplegia. Ewing's sarcoma_sentence_4

The cause of Ewing's sarcoma is unknown. Ewing's sarcoma_sentence_5

Most cases appear to occur randomly. Ewing's sarcoma_sentence_6

It is sometimes grouped together with primitive neuroectodermal tumors, in a category known as the Ewing family of tumors. Ewing's sarcoma_sentence_7

The underlying mechanism often involves a genetic change known as a reciprocal translocation. Ewing's sarcoma_sentence_8

Diagnosis is based on biopsy of the tumor. Ewing's sarcoma_sentence_9

Treatment often includes chemotherapy, radiation therapy, surgery, and stem cell transplant. Ewing's sarcoma_sentence_10

Targeted therapy and immunotherapy are being studied. Ewing's sarcoma_sentence_11

Five year survival is about 70%. Ewing's sarcoma_sentence_12

A number of factors, however, affect this estimate. Ewing's sarcoma_sentence_13

James Ewing in 1920 established that the tumor is a distinct type of cancer. Ewing's sarcoma_sentence_14

It affects about one in a million people per year in the United States. Ewing's sarcoma_sentence_15

Ewing's sarcoma occurs most often in teenagers and young adults and represents 2% of childhood cancers. Ewing's sarcoma_sentence_16

Caucasians are affected more often than African Americans or Asians. Ewing's sarcoma_sentence_17

Males are affected more often than females. Ewing's sarcoma_sentence_18

Signs and symptoms Ewing's sarcoma_section_0

Ewing's sarcoma is more common in males (1.6 male:1 female) and usually presents in childhood or early adulthood, with a peak between 10 and 20 years of age. Ewing's sarcoma_sentence_19

It can occur anywhere in the body, but most commonly in the pelvis and proximal long tubular bones, especially around the growth plates. Ewing's sarcoma_sentence_20

The diaphyses of the femur are the most common sites, followed by the tibia and the humerus. Ewing's sarcoma_sentence_21

Thirty percent are overtly metastatic at presentation. Ewing's sarcoma_sentence_22

People usually experience extreme bone pain. Ewing's sarcoma_sentence_23

Rarely, it can develop in the vagina. Ewing's sarcoma_sentence_24

Signs and symptoms include intermittent fevers, anemia, leukocytosis, increased sedimentation rate, and other symptoms of inflammatory systemic illness. Ewing's sarcoma_sentence_25

According to the Bone Cancer Research Trust (BCRT), the most common symptoms are localized pain, swelling, and sporadic bone pain with variable intensity. Ewing's sarcoma_sentence_26

The swelling is most likely to be visible if the sarcoma is located on a bone near the surface of the body, but when it occurs in other places deeper in the body, like on the pelvis, it may not be visible. Ewing's sarcoma_sentence_27

Genetics Ewing's sarcoma_section_1

Genetic exchange between chromosomes can cause cells to become cancerous. Ewing's sarcoma_sentence_28

Most cases of Ewing's sarcoma (85%) are the result of a translocation between chromosomes 11 and 22, which fuses the EWSR1 gene of chromosome 22 to the FLI1 gene of chromosome 11. Ewing's sarcoma_sentence_29

A genome-wide association study (GWAS) identified three susceptibility loci located on chromosomes 1, 10 and 15. Ewing's sarcoma_sentence_30

A continuative study discovered that the Ewing's sarcoma susceptibility gene EGR2, which is located within the chromosome 10 susceptibility locus, is regulated by the EWSR1-FLI1 fusion oncogene via a GGAA-microsatellite. Ewing's sarcoma_sentence_31

EWS/FLI functions as the master regulator. Ewing's sarcoma_sentence_32

Other translocations are at t(21;22) and t(7;22). Ewing's sarcoma_sentence_33

Ewing's sarcoma cells are positive for CD99 and MIC2, and negative for CD45. Ewing's sarcoma_sentence_34

Diagnosis Ewing's sarcoma_section_2

The definitive diagnosis is based on histomorphologic findings, immunohistochemistry and molecular pathology. Ewing's sarcoma_sentence_35

Ewing's sarcoma is a small-blue-round-cell tumor that typically has a clear cytoplasm on H&E staining, due to glycogen. Ewing's sarcoma_sentence_36

The presence of the glycogen can be demonstrated with positive PAS staining and negative PAS diastase staining. Ewing's sarcoma_sentence_37

The characteristic immunostain is CD99, which diffusely marks the cell membrane. Ewing's sarcoma_sentence_38

However, as CD99 is not specific for Ewing's sarcoma, several auxiliary immunohistochemical markers can be employed to support the histological diagnosis. Ewing's sarcoma_sentence_39

Morphologic and immunohistochemical findings are corroborated with an associated chromosomal translocation, of which several occur. Ewing's sarcoma_sentence_40

The most common translocation, present in about 90% of Ewing sarcoma cases, is t(11;22)(q24;q12), which generates an aberrant transcription factor through fusion of the EWSR1 gene with the FLI1 gene. Ewing's sarcoma_sentence_41

The pathologic differential diagnosis is the grouping of small-blue-round-cell tumors, which includes lymphoma, alveolar rhabdomyosarcoma, and desmoplastic small round cell tumor, among others. Ewing's sarcoma_sentence_42

Medical imaging Ewing's sarcoma_section_3

Differential diagnosis Ewing's sarcoma_section_4

Other entities with similar clinical presentations include osteomyelitis, osteosarcoma (especially telangiectatic osteosarcoma), and eosinophilic granuloma. Ewing's sarcoma_sentence_43

Soft-tissue neoplasms such as pleomorphic undifferentiated sarcoma (malignant fibrous histiocytoma) that erode into adjacent bone may also have a similar appearance. Ewing's sarcoma_sentence_44

Accumulating evidence suggests that EWSR1-NFATc2 positive sarcomas, which were previously considered to possibly belong to the Ewing family of tumors, differ from Ewing's sarcoma in their genetics, transcriptomes, epigentic and epidemiological profiles, indicating that they might represent a distinct tumor entity. Ewing's sarcoma_sentence_45

Treatment Ewing's sarcoma_section_5

Almost all people receive multidrug chemotherapy (most often vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide), as well as local disease control with surgery and/or radiation. Ewing's sarcoma_sentence_46

An aggressive approach is necessary because almost all people with apparently localized disease at the time of diagnosis actually have asymptomatic metastatic disease. Ewing's sarcoma_sentence_47

The surgical resection may involve limb salvage or amputation. Ewing's sarcoma_sentence_48

Complete excision at the time of biopsy may be performed if malignancy is confirmed at the time it is examined. Ewing's sarcoma_sentence_49

Treatment lengths vary depending on location and stage of the disease at diagnosis. Ewing's sarcoma_sentence_50

Radical chemotherapy may be as short as six treatments at three-week cycles, but most people undergo chemotherapy for 6–12 months and radiation therapy for 5–8 weeks. Ewing's sarcoma_sentence_51

Radiotherapy has been used for localized disease. Ewing's sarcoma_sentence_52

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 some time. Ewing's sarcoma_sentence_53

Antisense oligodeoxynucleotides have been proposed as possible treatment by down-regulating the expression of the oncogenic fusion protein associated with the development of Ewing's sarcoma resulting from the EWS-ETS gene translocation. Ewing's sarcoma_sentence_54

In addition, the synthetic retinoid derivative fenretinide (4-hydroxy(phenyl)retinamide) has been reported to induce high levels of cell death in Ewing's sarcoma cell lines in vitro and to delay growth of xenografts in in vivo mouse models. Ewing's sarcoma_sentence_55

In most pediatric cancers including sarcoma, proton beam radiation (also known as proton therapy) delivers an equally effective dose to the tumor with less damage to the surrounding normal tissue compared to photon radiation. Ewing's sarcoma_sentence_56

Prognosis Ewing's sarcoma_section_6

Staging attempts to distinguish people with localized from those with metastatic disease. Ewing's sarcoma_sentence_57

Most often, metastases locate to the lungs, bone and/or bone marrow. Ewing's sarcoma_sentence_58

Less common sites include the central nervous system and lymph nodes. Ewing's sarcoma_sentence_59

Five-year survival for localized disease is greater than 70% after therapy. Ewing's sarcoma_sentence_60

Prior to the use of multi-drug chemotherapy, long-term survival was less than 10%. Ewing's sarcoma_sentence_61

The development of multi-disciplinary therapy with chemotherapy, irradiation, and surgery has increased current long-term survival rates in most clinical centers to greater than 50%. Ewing's sarcoma_sentence_62

However, some sources state it is 25–30%. Ewing's sarcoma_sentence_63

Retrospective research showed that two chemokine receptors, CXCR4 and CXCR7, can be used as molecular prognosis factors. Ewing's sarcoma_sentence_64

People who express low levels of both chemokine receptors have the highest odds of long-term survival with >90% survival at five years post-diagnosis versus <30% survival at five years for patients with very high expression levels of both receptors. Ewing's sarcoma_sentence_65

A recent study also suggested a role for SOX2 as an independent prognostic biomarker that can be used to identify patients at high risk for tumor relapse. Ewing's sarcoma_sentence_66

Epidemiology Ewing's sarcoma_section_7

Ewing's sarcomas represent 16% of primary bone sarcomas. Ewing's sarcoma_sentence_67

In the United States, they are most common in the second decade of life, with a rate of 0.3 cases per million in children under 3 years of age, and as high as 4.6 cases per million in adolescents aged 15–19 years. Ewing's sarcoma_sentence_68

Internationally, the annual incidence rate averages less than 2 cases per million children. Ewing's sarcoma_sentence_69

In the United Kingdom, an average of six children per year are diagnosed, mainly males in early stages of puberty. Ewing's sarcoma_sentence_70

Due to the prevalence of diagnosis during teenage years, a link may exist between the onset of puberty and the early stages of this disease, although no research confirms this hypothesis. Ewing's sarcoma_sentence_71

A grouping of three unrelated teenagers in Wake Forest, North Carolina, have been diagnosed with Ewing's sarcoma. Ewing's sarcoma_sentence_72

All three children were diagnosed in 2011 and all attended the same temporary classroom together while the school underwent renovation. Ewing's sarcoma_sentence_73

A fourth teenager living nearby was diagnosed in 2009. Ewing's sarcoma_sentence_74

The odds of this grouping are considered significant. Ewing's sarcoma_sentence_75

Ewing's sarcoma occurs about 10- to 20-fold more commonly in people of European descent as compared to people from African descent. Ewing's sarcoma_sentence_76

Ewing's sarcoma is the second most common bone cancer in children and adolescents, with poor prognosis and outcome in ~70% of initial diagnoses and 10–15% of relapses. Ewing's sarcoma_sentence_77

Credits to the contents of this page go to the authors of the corresponding Wikipedia page: en.wikipedia.org/wiki/Ewing's sarcoma.