History: 1928 James Ewing described a rare lesion Diaphysis of long bones Childhood Febrile attacks,anorexia, weight loss & anaemia Rapidly involving other parts of skeleton Radiosensitive Histologically –endothelial elements in marrow
Willis – All these tumors were not Ewing’s but Neuroblastomas Reticulum cell sarcomas Metastatic tumors
Ewing’s Sarcoma Epidemiology: 4th. m.c. primary malignancy of bone 2nd. m.c. in age < 30 yrs. Incidence < 1/ million / year 9% of primary malignancies of bonein the Mayo Clinic series.
Age – Wide age range from infants to elderly m.c. 5 – 15 yrs. Male slightly more than females. Very rare in Africans
Location: M.c. in metaphysis of long bones ( often extending intodiaphysis), Flat bones of shoulder and pelvis. Rarely in spine or small hand & footbones. Long bones Tibia > fibula > humerus > femur.
Spread – Whole of the skeleton. Regional lymph nodes.
Clinical features: Pain – Universal complaint Insidious in onset, long standing, intermittentattacks, responding to analgesics. Often H/O preceding trauma. Slow growing tumor in relation to the shaft of long bones.
Delay in diagnosis Av. 34 weeks Patient delay – 15 weeks Physician delay 19 weeks – Importance of Xrays & rpt. Xrays to compare. During attacks of pain tumor size may enlarge visibly.
Other clinical features: Fever, erythema & swelling ~ Osteomyelitis Skin – not involved unless surgical exploration done. Pathological # seldom. Later stage – multiple deposits in skull, ribs, sternum,pelvis & other long bones – cachexia & sec. Anaemia.
Vertebral involvement – severe root pain or paralysis Death – Metastatic involvement of lungs.
MRI: Taken of entire bone involved Extent of diseased bone Soft tissue involvement
Other Investigations: Blood Ix: WBC Leukocytosis, ESR CRP LDH ~ suggestive of infective cause. FNAC – resembles Pus.
Base line X ray & CT chest – m.c. site of metastasis Bone Scan Bone marrow aspiration – routine R/O diffuse systemic disease USG abdomen liver & spleen.
Pathology: Begins in - Marrow (Mid shaft) Gross – Color - Greyish-white Areas of necrosis & hemorrhage with cyst formation. Lamellae destruction.
Medulla Haversian canals Surface. Sub periosteal compensatory layers of new bone aredeposited only to be destroyed Onion Skinappearance.
Histology: Microscopic features – nonspecific. Intensely cellular Cells – Usually one type Blue, Small, round & polyhedral Arrangement – solidcords or sheets.
Intercellular substance – minimal Necrosis Remaining cells arrange around the central bloodvessel – perithelioma. Nuclei – prominent Mitosis - frequent
Rossette arrangement with central fibril(Neuroblastoma) Pseudorosette (without fibril) more common. Despite bone destruction Giant cells/ osteoclasts are not found Nor new bone Except sub periostealdeposits.
Cytogenetics &Immunohistochemistry: To differentiate from other small blue cell tumors. m.c. translocations in >90% cases t(11;22)(q24;q12)diagnostic of Ewing’s. Other diagnostic translocations include t(21;22)(q22;q12) & t(7;22)(p22;p12)
IHC Staining for MIC2 gene products – Specific PAS + usually (high intracellular glycogen). Reticulin – ( c.f. lymphomas)
Histological D/D Lymphomas – PAS -, Reticulin +, Embryonal rhabdomyosarcoma – desmin , myoglobin,muscle specific actins + Hemangeopericytomas – Factor VIII + Small cell metastatic carcinomas & Melanomas –Cytokeratin +
Treatment: Adjunct or Neoadjunct Chemotherapy or both – fordistant metastasis. Local Treatment: (Controversial) Highly radiosensitive Wide resection Decreases local recurrence to <10% Increases overall survival
Large, central, unresectable – Radiation Small, more accessible lesions – Surgery Choice is individual based. Repeat Staging studies after neoadjunct chemotherapy. Repeat X rays - ossification Repeat MRI - soft tissue mass.
At this stage – If Lesions can be resected with wide margins & anacceptable functional deficit – SURGERY. If not – RADIATION. Radiation: Marginal Resection or Contaminated wide resection.
Treatment Plan: After long D/W patients & parents Include expected function after amputation, limbsalvage & radiation Inherent short & long term risks with each option. Disease relapse – and its prognosis.
Survival rates : Long term survival rates reported from most studies –60-70% Before the use of chemotherapy – 10 %
Prognostic factors: Location & Size of primary lesion. Older age of presentation & male gender. Distant metastasis – worst prognostic factor with 20%long term survival even with aggressive therapy andsurgery. Disease relapse Time to relapse
Histological grade is of no significance as ALLEWING’S SARCOMAS ARE CONSIDERED TO BEHIGH GRADE. Fever, anemia, WBC, ESR, LDH indicate extensivedisease so worse prognosis. Aberrant p53 expression & histological response tochemotherapy.