Ewing Sarcoma/PNET of Soft Tissue



Ewing Sarcoma/PNET of Soft Tissue


Cyril Fisher, MD, DSc, FRCPath





Key Facts


Terminology



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


  • Additionally, PNET shows neural differentiation


Clinical Issues



  • Mostly children and young adults


  • Painful or painless mass


  • 5-year survival: 65-90%



    • 25% in those presenting with metastatic disease


Microscopic Pathology



  • Sheets of closely packed uniform cells


  • Round uniform nuclei



    • Scanty cytoplasm, sometimes clear


  • Homer-Wright rosette formation in PNET


  • Atypical (large cell) variant



    • Conspicuous nucleoli


Ancillary Tests



  • PAS stains glycogen in cytoplasm


  • Several translocations involving EWSR1 and ETS family genes



    • Most common are EWSR1-FLI1 (90%) and EWSR1-ERG (8-10%)


Top Differential Diagnoses



  • Alveolar rhabdomyosarcoma


  • Poorly differentiated synovial sarcoma


  • Desmoplastic small round cell tumor


  • Neuroblastoma


  • Small cell carcinoma


  • Extraskeletal mesenchymal chondrosarcoma


  • Lymphoma






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.


TERMINOLOGY


Abbreviations



  • Ewing sarcoma (ES)


  • Primitive neuroectodermal tumor (PNET)


Definitions



  • 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


CLINICAL ISSUES


Epidemiology



  • 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


Site



  • 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)


Presentation



  • Painful or painless mass


  • Systemic symptoms



    • Fever, anemia, leukocytosis


Treatment



  • 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)


Prognosis



  • 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


MACROSCOPIC FEATURES


General Features



  • Pale friable tumor


  • Hemorrhage and necrosis


  • Can be cystic


Size



  • Variable, up to 20 cm



MICROSCOPIC PATHOLOGY


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


ANCILLARY TESTS


Histochemistry



  • 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

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Jul 9, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Ewing Sarcoma/PNET of Soft Tissue

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