ewingssarcoma-140706052648-phpapp01 (1).pptx

EWING SARCOMA

1. EWING S SARCOMA Dr.Hemanth Kumar Ortho pg 5-10-17

2. Introduction Its a small round cell tumour arising in the bones, rarely in soft tissues of children and adolescents. Third most common non hematologic primary malignancy of bone. 2 nd most common in patients younger than 30 years( after osteosarcoma)

3. Hi s t o r y First reported by James Ewing in 1921 – proposed endothelial origin Angervall & Enzinger reported 1 st case of soft tissue Ewings sarcoma in 1975 Jaffe et al described small round cell tumor of bone and called PNET( primitive neuroectodermal tumor) of bone

4. Etiology Neuroectodermal in origin 90% have t(11;22) (q24;q12 ) translocation

5. The protein includes an N-terminal transcriptional activation domain and a C- terminal RNA-binding domain. Chromosomal translocations result in the production of chimeric proteins that are involved in tumorigenesis. Mutations in EWS-ETS gene, specifically at t(11;22)(q24;q12) cause Ewing sarcoma as well as neuroectodermal and various other tumors.

6. Incidence Incidence: one per 1 million per year. 9% of primary malignancies of bone

7. A g e Wide range but most common is 5-25 years Peak incidence 2 nd decade The age of the patient is important diagnostically When confronted with patients older than 30yrs elimination of small-cell carcinoma and large-cell lymphoma, to be done Less than 5yrs- metastatic neuroblastoma or acute leukemia to be ruled out

8. S e x M: F - 1.3-1.5 : 1 Caucasians > Asians Africans and African-Americans rarely suffer. Race

9. Skeletal distribution Any bone can be the site Lower half > upper half Most common diaphysis > metaphysis of long bones. Rare in epiphysis

10. Pelvis- 26% Femur-20% Tibia-10% Fibula-8% Humerus-6% Spine -6% Chest wall-16% Ribs-10% Scapula -4%

11. M e t a st asis High potential of metastasis To lungs & bones > 10% patients presents with bone metastasis - initial diagnosis Metastasis to lymph nodes are rare

12. Extra skeletal Ewings sarcoma occurs in patients between 10-30yrs Most common sites - chest wall, para- vertebral muscles, extremities, buttocks and retro-peritoneal space Rapid growth and distant metastasis is present

13. Association with Retinoblastoma Few Patients with Retinoblastoma also developed Ewings Sarcoma, it can be due to chromosomal error.

14. Clinical presentation Symptoms Local pain- universal complaint- intermittent, mild at first increase in severity with time worse at night Pain may be accompanied by paresthesia in pelvic or vertebral tumors Conservative treatment of pain can delay the diagnosis for weeks to months

15. Swelling- rapidly growing and painful, tense, elastic, hard with local raise of temperature. Not palpable if it is deep seated. Periods of remission can be present Few cases present with pathological fractures Weight loss, fatigue, intermittent pyrexia

16. Signs Palpable tender mass with prominent veins Fever, erythema and swelling Joints and neurological manifestation, joint effusion with limited mobility Paralysis and root pain if spine involved

17. Investigations Hb% reduced Increased ESR, CRP & TC Leucocytosis Aspirate may grossly resemble pus

18. Plain Radiography Presents as extensive diaphyseal lesion At midshaft of the long bone, the cortex displays increased density, extending externally as periosteal new bone, forming multiple thin parallel layers giving ‘onion peel appearence’

19. Periosteal reactions may also have codmans triangle- lifting of periosteum from the bone. Ewing sarcoma appears as ill defined, permeative, focally moth eaten, destructive intramedullary lesion accompanied by a periosteal reaction(onion skin) Lesion may have both lytic and sclerotic regions Extraosseous component is radiolucent with the same density of soft tissue.

20. Isotope scans Technetium-99 whole-body radionucleotide bone scan to identify skeletal metastasis Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) increases the sensitivity of detection of metastasis. Will show other clinically unsuspected sites

21. Angiogram Shows hypervascular reaction & intrinsic neoplastic vasculature quite well Early arterial phase shows the reactive and a capsular vessel as well as extent of the soft tissue mass

22. CT scanning Shows details of radiolucent portion of the lesion and areas of cortical destruction Does not outline the soft tissue extent

23. MRI scanning Most precise in defining the local extent of the tumor Evaluate the extent of soft tissue masses For staging and surgical planning To assess the response to neoadjuvant chemotherapy or irradiation

24. Differential diagnosis Chronic osteomyelitis Metastatic neuroblastom a Lymphosarcoma . Reticulum cell sarcoma

25. Ewings sarcoma Chronic osteomyelitis Most common in diaphysis Most common in metaphysis Very Aggressive Not aggressive Onion peel Moth eaten and osteoporotic and areas of sclerosis More of small round cell Shows granulocytes Soft tissue mass commonly accompanies the lesion Ulceration and sinuses of the skin

26. Histopathology Gross appearence Soft, gray white, occasionally shiny Areas of haemorrhage and necrosis Cortex may be partially or completely destroyed & periosteum may be reflected

27. Histological features Composed of homogeneous population of small round cells, with high nuclear to cytoplasmic ratios, scanty cytoplasm, which is pale, vacuolated and charecterised by faded boundaries.

28. The cytoplasm of the tumor cells contain glycogen demonstrated by PAS stain and this differentiates from Reticulum cell sarcoma and lymphomas which are PAS negative and reticulin positive(doesn't have glycogen)

29. Bio p s y FNAC Trocar puncture biopsy CT guided biopsy Open biopsy The definitive diagnostic method is biopsy. Although sampling can be done by FNAC or core needle. It is most adequately achieved by incisional biopsy.

30. Staging for Ewings sarcoma Based on histological grade of the tumor, local extent, presence or absence of the metastasis

31. Prognostic factors Unfavourable –distant metastasis Even with aggressive treatment, long term survival is 20% in distant metastasis Bone or bone marrow metastasis at the time of initial diagnosis have worse prognosis than with isolated pulmonary metastasis Age older than 10 years Size larger than 200 ml More central lesions (as in the pelvis or spine) Poor response to chemotherapy Histological grade - no prognostic significance- high grade Fever, anemia, and elevation of the number and values of WBC, ESR, and LDH have been reported to indicate more extensive disease and a poorer prognosis.

32. T r e a tme n t Goal - make patient free from disease Minimize pain and preserve function Includes neoadjuvant and adjuvant chemotherapy Radiation therapy Surgery

33. Prior to multi agent chemotherapy, long term survival was less than 10% now increased to 60%- 70% Drugs effective are Doxorubicin(DXR), Cyclophosphamide(CPA), Vincristine(VCR), Actinomycin-D(ACT), Ifosfamide(IFM) and Etopside(VP16), G-CSF Not advisible in 1 st trimester of pregnancy- congenital anomalies in fetus Less hazardous in 2 nd trimester and least in 3 rd trimester

34. Radiotherapy Goal- deliver maximum dose of radiation to tumor cells, and minimize toxicity- linear accelerators used Highly radio sensitive & radiocurable 25 fractions over 5 weeks( 5 fractions per week)

35. Surgical management Indications Expendable site Lesion near major epiphysis Failed radiation therapy Large lesion with irreparable pathological fracture

36. Surgery/Radiation Individual basis If possible to resect with wide margin resection without irradiation is the treatment of choice If surgical margins are uncertain pre operative radiotherapy to be added If surgical margins are found inadequate after surgery, postoperative radiotherapy may be added

37. References Campbell's Operative Orthopaedics, 12 th edition Orthopaedics & trauma- GS Kulkarni