Definition/General
Introduction:
Ewing sarcoma is a malignant small round cell tumor
Shows neuroectodermal differentiation
Represents 6-8% of primary bone tumors
FNAC shows uniform small round cells.
Origin:
Arises from primitive neuroectodermal cells
Neural crest origin
Can occur in bone or soft tissue
Extraosseous Ewing sarcoma (soft tissue)
Shows variable neural differentiation.
Classification:
WHO classification: Ewing sarcoma family
Includes: Ewing sarcoma
Peripheral PNET
Extraosseous Ewing sarcoma
Atypical Ewing sarcoma.
Epidemiology:
Peak incidence 2nd decade
Male predominance (1.5:1)
Caucasian predominance
Rare in African-Americans
Children and young adults.
Clinical Features
Presentation:
Rapidly enlarging mass
Pain (80% cases)
Soft tissue swelling
Fever (25%)
Weight loss
Pathological fracture (bone lesions).
Symptoms:
Localized pain
Swelling
Limitation of movement
Systemic symptoms (fever, malaise)
Rapid growth
Mass effect.
Risk Factors:
Caucasian race
Age 5-25 years
Male gender
No known environmental factors
Possible genetic predisposition.
Screening:
Clinical examination
Imaging (X-ray, MRI)
FNAC/Biopsy
Molecular studies
Staging workup
Bone marrow evaluation.
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Gross Description
Appearance:
Gray-white, soft mass
Areas of necrosis
Hemorrhage common
Poorly circumscribed
Infiltrative margins
Soft consistency.
Characteristics:
Fleshy appearance
Tan-gray color
Necrosis and hemorrhage
Cystic areas
Soft to firm
Friable.
Size Location:
Chest wall (common extraosseous site)
Extremities
Paravertebral region
Retroperitoneum
Size: Variable 5-20 cm
Large at presentation.
Multifocality:
Usually solitary
Metastases at diagnosis (25%)
Lung metastases most common
Bone metastases
Bone marrow involvement.
Microscopic Description
Histological Features:
FNAC shows uniform small round cells
High nuclear-cytoplasmic ratio
Round to oval nuclei
Fine chromatin
Scanty cytoplasm
High mitotic activity.
Cellular Characteristics:
Monotonous small cells
Round nuclei
Fine, evenly distributed chromatin
Small nucleoli
Scanty, clear cytoplasm
Fragile cells.
Architectural Patterns:
Loose cellular cohesion
Individual cells predominant
Occasional rosettes
Streaming pattern
Clean background
Crush artifact common.
Grading Criteria:
High-grade by definition
Uniform morphology
High mitotic rate
Extensive necrosis
Rapid growth
Metastatic potential.
Immunohistochemistry
Positive Markers:
CD99 - positive (membranous, characteristic)
FLI1 - positive (nuclear)
ERG - positive
CD117 - positive
Vimentin - positive
NSE - positive.
Negative Markers:
Desmin - negative
MyoD1 - negative
Cytokeratin - negative
S-100 - negative
CD45 - negative
Synaptophysin - usually negative.
Diagnostic Utility:
CD99 essential (membranous pattern)
FLI1 confirms diagnosis
Differentiates from other small round cell tumors
Ki-67 high (>50%)
Molecular confirmation required.
Molecular Subtypes:
All types: CD99+, FLI1+
EWSR1 rearrangement in 85%
FUS rearrangement in 10%
Neural markers variable in PNET.
Molecular/Genetic
Genetic Mutations:
t(11;22)(q24;q12) - most common (85%)
EWSR1-FLI1 fusion
t(21;22)(q22;q12) - EWSR1-ERG (10%)
FUS-ERG fusion (5%)
Other rare translocations.
Molecular Markers:
EWSR1 rearrangement
ETS transcription factors
FLI1 overexpression
CD99 overexpression
Simple karyotype
Low mutational burden.
Prognostic Significance:
Fusion type affects prognosis
EWS-FLI1 type 1: Better prognosis
Metastatic disease: Poor prognosis
Age >10 years: Worse outcome
Tumor size important.
Therapeutic Targets:
Multimodal therapy
Chemotherapy (vincristine, doxorubicin, cyclophosphamide)
Radiotherapy
Surgery
IGF-1R inhibitors
Immunotherapy trials.
Differential Diagnosis
Similar Entities:
Lymphoma
Rhabdomyosarcoma
Neuroblastoma
Small cell carcinoma
Synovial sarcoma
Desmoplastic small round cell tumor.
Distinguishing Features:
Ewing sarcoma: CD99+, FLI1+, t(11;22)
Lymphoma: CD45+, B/T cell markers
Rhabdomyosarcoma: MyoD1+, myogenin+
Neuroblastoma: Synaptophysin+, catecholamines
Small cell carcinoma: TTF1+, adult age.
Diagnostic Challenges:
Distinguishing from other small round cell tumors
CD99 not specific
Crush artifacts
Limited tissue in FNAC
Molecular confirmation essential.
Rare Variants:
Large cell variant
Clear cell variant
Spindle cell variant
Sclerosing variant.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Fine needle aspiration from [site], [size] cm soft tissue mass
Clinical History
[age]/[sex] with [duration] history of rapidly growing, painful mass at [site]
Microscopic Examination
Highly cellular smears showing uniform small round cells with high N:C ratio, round nuclei, fine chromatin, and scanty cytoplasm. High mitotic activity noted.
Immunocytochemistry
CD99: Positive (membranous), FLI1: Positive (nuclear), Desmin: Negative, MyoD1: Negative
Molecular Studies
EWSR1 rearrangement: [Positive/Pending], Fusion type: [EWSR1-FLI1/EWSR1-ERG]
Cytological Diagnosis
Cytological and molecular features consistent with EWING SARCOMA
Comments
Molecular confirmation essential for diagnosis. Urgent multidisciplinary pediatric oncology evaluation required. High-grade malignancy with metastatic potential.