Ewing’s Sarcoma

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James Ewing originally described it in 1921. Ewing first described the tumour as an

"endothelioma of bone" believing that it arose from the blood vessels of bone tissue.

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History of Ewing’s Sarcoma

History of Ewing’s Sarcoma

• He later recognised that the histopathologic features were more complex and went on to describe it as a "endothelial myeloma"

• He described the histopathology as "broad sheets of small polyhedral cells with pale cytoplasm, small hyperchromatic nuclei, well-defined cell borders and complete absence of inter-cellular material"

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• Ewing's sarcoma is an unusual disease comprising about 4-6% of all primary bone tumors.

• Although it has been reported as occurring at all ages, by far the majority develops within the first two decades of life. In the second decade, it is the most common primary neoplasm of bone after osteosarcoma.

• The usual site of occurrence is in the diaphysis of long bones, less often in ribs, pelvis and vertebrae.

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Epidemiology

Epidemiology

• Involvement of the head and neck in Ewing's sarcoma is very unusual, accounting for approximately 1% to 4% of cases.

• Males are affected somewhat more commonly than females; the ratio is 3:2.

• Unlike osteosarcoma, Ewing's sarcoma has a predilection for whites; blacks and Asians are uncommonly affected.

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Cell of origin is unknown.

Previously a diagnosis of exclusion.

Reciprocal translocation.

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Pathology…

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Gross: soft, tan, gray tissue

Micro: nests of small round cells

No osteoid or chondroid production

Surface cell glycoprotein

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EZRIN Membrane-cytoskeleton linker protein

Initially identified as a determinant of cell shape

Plays a critical role in cell motility and attachment

Activatation initiated by threonine phosphorylation at position 567

Subsequent tyrosine phosphorylation allows for interaction with signal transduction pathways

Band 4.1 homology a-helixN C

Y143 T567Y353

F-actinBinding

1. Ezrin is highly and ubiquitously expressed in Ewing’s sarcoma.

2. Expression of a Ezrin containing a non-phosphorylatable mutation at threonine 567 functions as dominant negative.

3. These dominant negative effects are observed on AKT, as well as 4EBP1 genes.

Lymphoma Osteomyelitis Osteogenic Sarcoma Metastatic neuroblastoma

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Differential Diagnosis

Symptoms of Ewing's sarcoma vary from person to person and depending on the location and size of the cancer.

The most common symptoms are pain and swelling or tenderness in the affected area.

Pain may become very intense when the tumour is located near important nerves, like in the sacrum, pelvis or spine.

Swelling is often seen, especially when the log bones of the arms or legs are affected.

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What are the symptoms of Ewing's sarcoma ?

Local warmth, inflammation

Pleural effusions

Neurological signs if spinal involvement

ESR, LDH, anemia, leukocytosis

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Other features include

Includes:◦ Ewing tumor of bone.

◦ Extra osseous Ewing.

◦ PNET (PRIMITIVE NEURO-EPITHELIAL TUMOUR)

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Ewing Sarcoma Family of Tumors (ESFTs)

Expression of CD99 surface protein.

More than 90% of ESFTs have an 11,22 translocation.

PNETs are distinguished from other types of

Ewing sarcoma by evidence of neural differentiation.

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Diagnosing of ESFT

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Primary tumor sites in a series of 900 people with Ewing’s

At present, there is no formal staging system for Ewing's sarcoma/primitive neuroepithelial tumor.

Patients are grouped depending on whether cancer is found in only one part of the body (localized disease) or whether cancer has spread from one part of the body to another (metastatic disease).

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Staging of Ewing’s Sarcoma

Staging of Ewing’s Sarcoma• Localized

The cancer cells have not been shown to have spread beyond the bone in which the cancer began or are found only in the bone and nearby tissues.

Metastatic The cancer cells have spread from the bone in which the cancer began to other parts of the body. The cancer most often spreads to the lung, other bones, and bone marrow .Spread of cancer to the lymph nodes or the central nervous system (brain and spinal cord) is less common.

Recurrent Recurrent disease means that the cancer has come back (recurred) after it has been treated. It may come back in the tissues where it first started or it may come back in another part of the body.

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• Localized Ewing's sarcoma/primitive neuroepithelial tumorTreatment for localized Ewing's sarcoma/primitive neuroepithelial tumor depends on where the cancer is found in the body. If the cancer is in the bone below the elbow or knee or in the jaw, skull, face, shoulder blade, collar bone, or segments of the spinal column, treatment may be one of the following:

1. Combination chemotherapy

2. Surgery and combination chemotherapy.

3. Radiation therapy and combination chemotherapy.

4. A clinical trial of chemotherapy and new ways of giving radiation therapy.

5. A clinical trial of chemotherapy followed by surgery, with or without radiation therapy.

6. Clinical trials are also evaluating new doses and combinations of chemotherapy.

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Treatment of Ewing’s Sarcoma

Metastatic Ewing's sarcoma/primitive neuroepithelial tumorTreatment may be one of the following:

1. Combination chemotherapy.

2. Radiation therapy plus combination chemotherapy.

3. Combination chemotherapy plus surgery to remove cancer that has spread to the lungs.

4. Clinical trials are evaluating new doses and combinations of chemotherapy with or without radiation treatment.

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Treatment cont….

Location

Tumor Size

Metastases at diagnosis

Response to chemotherapy

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PROGNOSIS

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SOME X-RAYS……

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Findings:

1. An expansile lytic lesion of distal the 5th metatarsal.

2. Cortical thinning.

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DR.KIRAN KAILAS25

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DR.KIRAN KAILAS28

DR.KIRAN KAILAS29

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Thank you…