Ewing sarcoma

[7][4] Ewing 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.

[14][10] The resultant chromosomal translocation causes the EWS trans-activation domain (which is usually silent in the wild type) to become very active, this leads to the translation of a new EWS-FLI1 fusion protein.

This phase transition property allows the fusion protein to access and activate micro-satellite regions of the genome that would otherwise be inaccessible.

This fusion protein can convert usually silent chromatin regions into fully active enhancers leading to oncogenesis of the cells.

The fusion protein does this by recruiting enzymes that affect DNA methylation, histone acetylation and direct inhibition of non-coding microRNA.

EWS-FLI1 reduces DNA methylation (which occurs mostly in areas corresponding to transcription enhancers), leading to increased gene expression.

MiRNA-145 normally activates RNA-induced silencing complexes (RISCs) to inhibit or degrade mRNA that is involved in cell pluripotency.

[10] The proliferative reaction of bone can also create delicate laminations constituting the periosteal layers and giving the radiographic appearance of an onion peel.

The wide zone of transition (e.g. permeative) is the most useful plain film characteristic in differentiation of benign versus aggressive or malignant lytic lesions.

It will show the full bony and soft tissue extent and relate the tumor to other nearby anatomic structures (e.g. vessels).

[27] Computed axial tomography (CT) can also be used to define the extraosseous extent of the tumor, especially in the skull, spine, ribs, and pelvis.

Radiographically, Ewing sarcoma presents as "moth-eaten" destructive radiolucencies of the medulla and erosion of the cortex with expansion.

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

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

[28][29][30][31] Almost all people receive multidrug chemotherapy (most often vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide),[32] as well as local disease control with surgery and/or radiation.

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.

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

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%.

[43] 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.

[46] In the United Kingdom, an average of six children per year are diagnosed; mainly males in early stages of puberty.

With occurrences primarily arising in older children and teenagers, one causal theory is puberty, e.g. its rapid growth spurts making bone tissue more cancer susceptible during development years.

[47] A grouping of three unrelated teenagers in Wake Forest, North Carolina, have been diagnosed with Ewing sarcoma.

[49][10] Ewing 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.

Distribution of Ewing sarcoma: The most frequent locations are the large long bones and the pelvis.
Micrograph of a metastatic Ewing sarcoma with the characteristic cytoplasmic clearing on H&E staining, which was showing to be PAS positive
X-ray of a child with Ewing sarcoma of the tibia
Magnetic resonance imaging slice showing Ewing sarcoma of the left hip (white area shown right)