Ewings Tumor

History:1928 James Ewing described a rare lesion

Diaphysis of long bonesChildhoodFebrile attacks,anorexia, weight loss &

anaemiaRapidly involving other parts of skeletonRadiosensitive Histologically –endothelial elements in marrow

Willis – All these tumors were not Ewing’s butNeuroblastomasReticulum cell sarcomasMetastatic tumors

Ewing’s SarcomaEpidemiology:

4th. m.c. primary malignancy of bone2nd. m.c. in age < 30 yrs.Incidence < 1/ million / year9% of primary malignancies of

bone in 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 into diaphysis),

Flat bones of shoulder and pelvis.Rarely in spine or small hand &

foot bones.Long bones

Tibia > fibula > humerus > femur.

Spread –Whole of the skeleton.Regional lymph nodes.

Clinical features:Pain – Universal complaint

Insidious in onset, long standing, intermittent attacks, responding to analgesics.

Often H/O preceding trauma.Slow growing tumor

in relation to the shaft of long bones.

Delay in diagnosis Av. 34 weeksPatient delay – 15 weeksPhysician delay 19 weeks – Importance of

Xrays & rpt. X rays to compare.During attacks of pain tumor size may

enlarge visibly.

Other clinical features:Fever, erythema & swelling ~ OsteomyelitisSkin – 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.

Radiological appearance:X-rays:

Classically Destructive lesions,

diaphysis long bones, onion peel appearance.

Reality Metaphysis long bones frequently

extending into diaphysis.

Diffuse rarefaction towards center of shaft extending to considerable area peripherally.

Flat bones:Non-specific destructive lesions & large

adjacent soft tissue mass.

Early stage:Condensation

LaterReactive irritation – Onion skin layers

Last stageGross tumor formation, destruction of

bone, pathological #s.

MRI:Taken of entire bone involvedExtent of diseased boneSoft 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 ScanBone marrow aspiration – routine

R/O diffuse systemic diseaseUSG abdomen

liver & spleen.

Pathology:Begins in - Marrow (Mid shaft)Gross –

Color - Greyish-whiteAreas of necrosis & hemorrhage with cyst

formation.Lamellae destruction.

Medulla Haversian canals Surface.Sub periosteal compensatory layers of new

bone are deposited only to be destroyed Onion Skin appearance.

Histology:Microscopic features –

non specific.Intensely cellularCells –

Usually one typeBlue,Small, round &

polyhedralArrangement –

solid cords or sheets.

Intercellular substance – minimalNecrosisRemaining cells arrange around the central

blood vessel – perithelioma.Nuclei – prominentMitosis - frequent

Rossette arrangement with central fibril (Neuroblastoma)

Pseudorosette (without fibril) more common.

Despite bone destructionGiant cells/ osteoclasts are not found

Nor new boneExcept sub periosteal

deposits.

Vessels & lymphatics Tumor emboli tumor spread.

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)

IHCStaining for MIC2 gene products – SpecificPAS + usually (high intracellular glycogen).Reticulin – ( c.f. lymphomas)

Histological D/DLymphomas – PAS -, Reticulin +, Embryonal rhabdomyosarcoma – desmin ,

myoglobin, muscle specific actins +Hemangeopericytomas – Factor VIII +Small cell metastatic carcinomas & Melanomas

– Cytokeratin +

Other D/D:Chronic OsteomyelitisMetastatic NeuroblastomaHistiocytosisRarely Osteolytic Osteosarcoma

Treatment:Adjunct or Neoadjunct Chemotherapy or both

– for distant metastasis.Local Treatment: (Controversial)Highly radiosensitiveWide resection

Decreases local recurrence to <10%Increases overall survival

Large, central, unresectable – RadiationSmall, more accessible lesions – SurgeryChoice is individual based.Repeat Staging studies

after neoadjunct chemotherapy.Repeat X rays - ossificationRepeat MRI - soft tissue mass.

At this stage – If Lesions can be resected with wide margins &

an acceptable functional deficit – SURGERY.If not – RADIATION.

Radiation:Marginal Resection orContaminated wide resection.

Treatment Plan:After long D/W patients & parentsInclude expected function after amputation,

limb salvage & radiationInherent 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 and surgery.

Disease relapseTime to relapse

Histological grade is of no significance as ALL EWING’S SARCOMAS ARE CONSIDERED TO BE HIGH GRADE.

Fever, anemia, WBC, ESR, LDH indicate extensive disease so worse prognosis.

Aberrant p53 expression & histological response to chemotherapy.