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Ewing sarcoma family of tumors

Tuesday 2 November 2004

Primitive neuroectodermal tumor/Ewing sarcoma, PNET/ES, - Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET), ES/PNET group tumors, ES/PNET tumors, EFTs, Ewing family of tumors

Digital cases (Digital slides)

- HPC:31 : Ewing sarcoma
- HPC:132 : Ewing sarcoma
- HPC:182 : Ewing sarcoma
- HPC:376 : EWSR1-FLI1+ bone-forming Ewing sarcoma (EWSR1-FLI1+ small cell osteosarcoma)

Definition: Ewing sarcoma/peripheral primitive neuro-ectodermal tumor (PNET) is a round-cell sarcoma that may show varying degrees of neuro-ectodermal differentiation.

These tumors are identified by a characteristic round-cell morphology and immunohistochemical profile, as well as by specific translocations involving the EWS gene on chromosome 22 and the 3’ portion of the E26 transformation-specific family of transcription factors.

These translocations result in fusion proteins that act as aberrant transcription factors. The majority of Ewing sarcoma cases are characterized by a balanced t(11;22).

Specific chromosomal abnormalities often correlate with distinct morphologic or phenotypic subtypes of tumors and play an important role in prognosis.

As neuroblastic tumors (neuroblastoma), Ewing sarcoma and primitive neuroectodermal tumors (PNETs) are closely related neoplasms supposedly derived from the neural crest.


- Ewing sarcoma
- pPNET (peripheral primitive neuroectodermal tumors)


- "adamantinoma-like" variant
- spindled variant
- sclerosing variant
- clear cell variant
- anaplastic variant
- neuroendocrine variant


- bones
- extra-osseous ES/PNET tumors

Cytogenetics and molecular biology

- 22q12 reaarangements (EWS or EWSR1)

  • t(11;22)(q24;q12) (EWSR1/FLI1 fusion gene) (90-95%)
  • t(21;22)(q22;q12) (EWSR1/ERG fusion gene) (5-10%)
  • t(2;22)(q33;q12) (EWSR1/FEV fusion gene)
  • t(2;11;22)(q33;q24;q12)
  • t(7;22)(p22;q12) (EWSR1/ETV1 fusion gene)
  • t(17;22)(q21;q12) (EWSR1/ETV4 fusion gene)

- other 22q12 rearrangements

  • der(22)r(20;22) with amplification of the proximal region of the EWSR1 gene (17175374)

- t(16;21)(p11;q22) (FUS/ERG fusion gene) (1290763)
- variant translocations involving a third chromosome: 4q21, 5q31, 6p21, 7q12, 10p11.2, 12q14, 14q11, 18p23

- chromosomal insertions

  • 22q12 insertion in Chr.21 or Chr.11
  • 21q21-q22 insertion in 22q12 (15899394)

- secondary chromosomal changes (50%)

  • 8+
  • 12+
  • unbalanced tranlocations involving Chr.1 or Chr.16
  • 1p- 1p deletion

FISH and RT-PCR are ancillary techniques possessing high sensitivity in the diagnosis of ESFT; nevertheless, FISH is more specific than RT-PCR in the diagnosis of formalin-fixed paraffin-embedded tissue. Both methods in combination displayed the highest sensitivity and specificity.

The combination of histopathologic, IHC, and molecular findings is the method of choice for the diagnosis of ESFT, as well as for the differential diagnosis with other SRCTs.


- Molecular diagnosis of Ewing sarcoma family of tumors: a comparative analysis of 560 cases with FISH and RT-PCR. Machado I, Noguera R, Pellin A, Lopez-Guerrero JA, Piqueras M, Navarro S, Llombart-Bosch A. Diagn Mol Pathol. 2009 Dec;18(4):189-99. PMID: 19861898

- A novel t(4;22)(q31;q12) produces an EWSR1-SMARCA5 fusion in extraskeletal Ewing sarcoma/primitive neuroectodermal tumor. Sumegi J, Nishio J, Nelson M, Frayer RW, Perry D, Bridge JA. Mod Pathol. 2011 Mar;24(3):333-42. PMID: 21113140 [Free]

- Aurias A, Rimbaut C, Buffe D, Zucker JM, Mazabraud A. Translocation involving chromosome 22 in Ewing’s sarcoma. A cytogenetic study of four fresh tumors. Cancer Genet Cytogenet. 1984 May;12(1):21-5. PMID: 6713357

- Turc-Carel C, Philip I, Berger MP, Philip T, Lenoir GM. Chromosome study of Ewing’s sarcoma (ES) cell lines. Consistency of a reciprocal translocation t(11;22)(q24;q12). Cancer Genet Cytogenet. 1984 May;12(1):1-19. PMID: 6713356

- Turc-Carel C, Philip I, Berger MP, Philip T, Lenoir G. [Chromosomal translocation (11; 22) in cell lines of Ewing’s sarcoma] C R Seances Acad Sci III. 1983;296(23):1101-3. PMID: 6416622