Neurosurgery notes/Tumours/Mesenchymal non meningothelial tumours/Soft tissue tumors/Ewing sarcoma

Ewing sarcoma

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Soft tissue tumors

General

Immunophenotype
  • Positive
    • Synaptophysin, neuronspecific enolase, cytokeratin (focally seen 20%), cytoplasmic CD99
    • By RT-PCR of EWSR1-FLI1 or EWSR1-ERG or CIC-DUX4 and BCOR-CCNB3 intrachromosomal inversion fusion transcript
    • By FISH for EWSR1 gene rearrangement
Differential diagnosis
  • Negative

General

  • Ewing sarcoma of the nervous system is an extraosseous small round cell sarcoma.
  • Involves the CNS either as a primary dural neoplasm or by direct extension from contiguous bone or soft tissue (e.g. skull, vertebra, or paraspinal soft tissue)
  • It contains a fusion between one FET family gene, usually EWSR1, and one ETS family gene, most often FLI1.

Diagnostic criteria

  • Essential criteria
    • A small round cell morphology and diffuse membranous expression of CD99. AND
    • The presence of a FET-ETS fusion is also an essential diagnostic requirement.
      • Definitive diagnosis generally requires molecular confirmation of the FET::ETS-type gene fusion.
  • Desirable
    • criteria include the expression of NKX2-2 and PAX7.

Epidemiology

  • Ewing sarcoma is most commonly found in children and young adults.
  • Older patients more frequently present with extraosseous disease, including within the nervous system.
  • Presentation in individuals over 50 years of age is rare.

WHO grade

  • Ewing sarcoma is assigned a CNS WHO grade of 4.

Histopathology

  • Macroscopic
    • These tumours typically appear soft, grey, and fleshy.
    • Foci of necrosis and haemorrhage are frequently observed on the cut surface.
    • In the cauda equina, nerve roots may be found entrapped within the tumour mass.
  • Microscopic
      • The tumour consists predominantly of sheets of monomorphic, primitive-appearing small round cells.
      • Neoplastic cells exhibit brisk mitotic activity and have delicate chromatin.
      • The cytoplasm is scant and clear or amphophilic, often being rich in glycogen and PAS-positive.
      • The tumour is reticulin-rich and may show evidence of neuronal differentiation, such as Homer Wright rosettes with central neuropil.
      • Rare cases may show ganglion cell differentiation.
      Ewing sarcoma / peripheral primitive neuroectodermal tumour. (A) Invasion of nerve roots. (B) Diffuse membrane immunoreactivity for CD99. (C) FISH results positive for EWSR1 (EWS) gene rearrangement, with split of paired red and green signals (white lines).
      Ewing sarcoma / peripheral primitive neuroectodermal tumour. (A) Invasion of nerve roots. (B) Diffuse membrane immunoreactivity for CD99. (C) FISH results positive for EWSR1 (EWS) gene rearrangement, with split of paired red and green signals (white lines).
       
  • Immunophenotype
    • Positive
      • Diffuse membranous pattern: CD99
      • Nuclear expression of PAX7 and NKX2-2.
    • Lineage markers are generally negative, though neuronal markers such as synaptophysin or NeuN may be positive depending on the level of differentiation.

Pathogenesis

  • These tumours uniformly harbour an oncogenic gene fusion between a member of the FET RNA-binding protein family and an ETS transcription factor family member.
  • The FET family member is usually EWSR1 and rarely FUS.
  • The t(11;22)(q24;q12) translocation, resulting in the EWSR1::FLI1 fusion protein, is present in roughly 85 per cent of all cases.
  • Additional mutations in STAG2, CDKN2A, or TP53 may occur and are sometimes associated with a worse prognosis.

Localisation

  • Roughly 12 per cent of Ewing sarcomas are extraosseous, with a small subset involving the craniospinal axis.
  • Most craniospinal cases are meningeal, paraspinal, or peripheral nerve-associated masses, including those involving the cauda equina.
  • The tumour can also involve the nervous system through direct extension from adjacent bone primaries.

Clinical features

  • Signs and symptoms depend on the tumour location and are typically caused by mass effect.
  • Presentations include localised pain, cranial or radicular neuropathies, bone fractures, and fever.
  • Fever is more frequent in patients presenting with metastatic disease.

Radiological features

  • Imaging is necessary to define the site of origin, the extent of local disease, and metastatic spread.
  • Radiological findings do not otherwise provide specific diagnostic information for this entity.
Postcontrast T1-weighted MRI of a dural-based Ewing sarcoma / peripheral primitive neuroectodermal tumour mimicking meningioma.
Postcontrast T1-weighted MRI of a dural-based Ewing sarcoma / peripheral primitive neuroectodermal tumour mimicking meningioma.

Management

  • Standard treatment involves induction chemotherapy.
  • This is followed by surgical resection and radiation therapy.

Prognosis

  • Metastatic disease at the time of presentation is the strongest negative predictor of outcome.
  • The 5-year overall survival rate for patients with localised disease is estimated to be between 70 and 80 per cent.
  • For patients with disseminated disease, the survival rate decreases to approximately 30 per cent.
  • A favourable prognosis is associated with a complete response to induction chemotherapy, defined as zero per cent viable tumour in the post-therapy specimen.

Differential

  • Meningioma
  • Solitary fibrous tumour/Haemangiopericytoma (+ for CD99)