Ewing Sarcoma/PNET of Soft Tissue

Ewing Sarcoma/PNET of Soft Tissue

Cyril Fisher, MD, DSc, FRCPath

Ewing sarcoma and PNET are usually extremely cellular, with a dense, solid to sheet-like distribution of cells. A delicate vascularity is noted, but overall this is a solid population of cells.

This is a very cellular tumor arranged in a diffuse sheetlike pattern image. Geographic areas of coagulative necrosis are easily identified image . There is often perivascular viable tumor.



  • Ewing sarcoma (ES)

  • Primitive neuroectodermal tumor (PNET)


  • Family of small round cell translocation-associated sarcomas occurring in bone or soft tissue

    • Extraskeletal ES

    • Small cell tumor of thoracopulmonary region (Askin tumor)

    • PNET of soft tissue

      • Same morphologic spectrum as ES

      • Additionally shows neural differentiation

  • Several translocations known

    • Similar changes in all types and sites



  • Incidence

    • Rare

  • Age

    • Mostly children and young adults

    • Sporadic cases at any age

  • Gender

    • Slight male predominance

  • Ethnicity

    • More common in Caucasians

    • Very rare in Africans and African-Americans


  • Lung, mediastinum, paravertebral region

  • Retroperitoneum, abdominal cavity

  • Limbs (deep soft tissue), skin (rare)

    • Primary bone tumor can extend and present in soft tissue

  • Rarely in viscera (kidney, uterus, pancreas, larynx)


  • Painful or painless mass

  • Systemic symptoms

    • Fever, anemia, leukocytosis


  • Options, risks, complications

    • Chemotherapy is treatment of choice

    • Surgical excision of residual masses

    • Irradiation in selected cases

  • Drugs

    • Multiagent

      • At least 3 of vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide

    • Potential biologic therapies

      • Anti-CD99 antibodies

      • Small interfering RNA against EWSR1-FLI1 gene product

      • Trastuzumab (against EGFR2), figitumumab (against IGF-1R)


  • 5-year survival: 65-90%

    • 25% in those presenting with metastatic disease

  • Locally infiltrative

  • Metastasizes to bone, lungs

  • Presence of EWSR1-FLI1 rearrangement is prognostically favorable

  • Cutaneous and subcutaneous tumors have improved prognosis


General Features

  • Pale friable tumor

  • Hemorrhage and necrosis

  • Can be cystic


  • Variable, up to 20 cm


Histologic Features

  • Sheets of closely packed uniform cells

  • Sometimes divided into lobules

    • Pseudoalveolar pattern

  • Round uniform nuclei

  • Dispersed fine chromatin, inconspicuous nucleoli

  • Scanty cytoplasm

    • Can be clear due to glycogen

  • Cells rarely spindled focally

  • Homer-Wright rosette formation in PNET

    • Central fibrillary core without lumen

  • Minimal intercellular collagen or reticulin

  • Rare myxoid change

    • Stromal microcysts sometimes present

  • Necrosis frequent

    • Perivascular preservation

  • Rare morphologic variants

    • Atypical (large cell) variant

      • Larger, vesicular nuclei

      • Irregular nuclear outline

      • Conspicuous nucleoli

      • Pleomorphism, spindling

    • Adamantinoma-like variant occurs mostly in bone

    • Sclerosing and clear cell variants described



  • PAS

    • Reactivity: Positive for glycogen

    • Staining pattern

      • Cytoplasmic

      • Staining is abolished by pretreatment with diastase

  • Reticulin

    • Reactivity: Negative

    • Staining pattern

      • Minimal or no intercellular reticulin except around blood vessels

In Situ Hybridization

  • FISH with break-apart probe for EWSR1 gene (at 22q12) shows rearrangement

Molecular Genetics

  • Several balanced translocations and fusions involving EWSR1 and ETS family genes

    • t(11;22)(q24;q12), EWSR1-FLI fusion (90% of cases)

    • t(21;22)(q12;q12), EWSR1-ERG fusion (5-10% of cases)

    • t(2;22)(q33;q12), EWSR1-FEV fusion (< 1% of cases)

    • t(7;22)(p22;q12), EWSR1-ETV1 (< 1% of cases)

    • t(17;22)(q12;q12), EWSR1-E1AF (< 1% of cases)

  • Rarely others in occasional cases

  • Genetic changes do not correlate with site or morphology

Jul 9, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Ewing Sarcoma/PNET of Soft Tissue
Premium Wordpress Themes by UFO Themes
%d bloggers like this: