1. In the name of GOD

2. Case presentation
Dr Azar baradaran
Resident:Dr behnaz sabaghi

3. 19 years boy without past history presents with fatigue,loss of energy and severe bone pain.

4. Radiologic study show multiple blastic lesion in bones.
In lab data patient had increased ESR.

8. Panel 1

9. LCA

10. CK

11. CD138

12. CD20

13. CD10

14. CD99

15. S100

16. CK7

17. Ki67

18. PLAP

19. TTF1

20. CDX2

21. Chromogranin

22. Step 2

23. Vim

24. Melan A

26. PAS

27. PAS+diastase

28. Ewing sarcoma/PNET

29. Clinical features =================================
Usually ages 5-20 years.
May present with pain, fever, weight loss, leukocytosis and increased erythrocyte sedimentation rate mimicking osteomyelitis.

30. Sites: marrow of femur, tibia, humerus, fibula, pelvis, ribs, vertebra, mandible, clavicle; may permeate cortex and invade soft tissue.

31. Cortical thickening and widening of the medullary canal.
Radiographic changes ==========================================================
Cortical thickening and widening of the medullary canal.
With progression of the lesion,reactive periosteal bone may be deposited in layers parallel to the cortex(onion-skin apearance) or at right angles to it (sun-ray appearance)

32. Typical ill-defined quality, with extensive involvement of medulla and cortex associated with elevation of periosteum

33. Microscopic feature:
Solid sheets of cells divided into irregular masses by fibrous strands.Individual cells are small and uniform.The nuclei are round,small nucleoli,and variable but usually brisk mitotic activity.
Well-developed vascular network.
Necrosis is common.
May have Homer-Wright rosettes (central fibrillary space) or pseudorosettes (cells arrange themselves around vessels).

34. Positive stains
CD99 (O13, MIC2), usually PAS+ diastase sensitive (glycogen), NSE, Leu7/CD57, FLI1 protein, vimentin.
Variable low molecular weight keratin, variable synaptophysin.

35. Negative stains
S100, CD45/LCA, muscle markers, vascular markers.

36. Molecular description
t(11,22)(q24;q12) or t(21;22)(q22;q12) in 95%.
Fusion of the EWS(Ewing sarcoma) gene at 22q12 with the FLI1 or ERG gene.

37. Electron microscopy description ===================================================== Undifferentiated tumor cells with multiple small foci of cytoplasmic glycogen are joined by two rudimentary cell junction.

38. Spread and metastases The lung and pleura.
Other bones(particulary the skull).
CNS.
Regional lymph node(rarely).
About 25% of the patients have multiple bone and/or visceral lesion at the time of presentation.

39. Preoperative chemotherapy, surgery, radiation therapy.
Treatment:
Preoperative chemotherapy, surgery, radiation therapy.

40. Poor prognostic factors
Extraosseous location.
Soft tissue extension.
Metastases.
Surgical margins.
Grossly viable tumor post chemotherapy.
possibly filigree pattern.
Neural differentiation.

41. Type of gene fusion(expect of EWS-FLI1 type fusion)
Overexpression of TP53.
MYC.
Deletion of INK4a.
Aneuploidy.

42. Differential diagnosis:
Lymphoblastic lymphoma.
Desmoplastic small cell tumor.
Embryonal/alveolar rhabdomyosarcoma.

43. Desmoplastic small round cell tumor
High grade malignant neoplasm, usually of peritoneum or other serosal surfaces, rarely in bone or soft tissue.

44. LYMPHOMA
LCA+,TDT+, older patients, polymorphic infiltrate.

45. Embryonal/alveolar rhabdomyosarcoma
Loss of cellular cohesion so cells appear to float in alveolar spaces.
Posive for actin,desmin,myoD1.