Category Archives: Soft tissue pathology

EWSR1 rearrangements were first identified in Ewing sarcoma, but EWSR1-rearranged neoplasms now includes many tumour subtypes.

EWSR1 gene is located in chromosome 22q12.

Here is a compilation of tumors associated with EWSR1 rearrangement. This includes latest updates from the WHO 2020 5th edition of soft tissue and bone tumors.

TUMORS ASSOCIATED WITH EWSR1-REARRANGEMENT

1. Ewings sarcoma
2. Desmoplastic small round cell tumor (DSRCT)
3. Extraskeletal myxoid chondrosarcoma (EMC)
4. Angiomatoid fibrous histiocytoma (AFH)
5. Clear cell sarcoma (CCS)
6. Primary pulmonary myxoid sarcoma (PPMS)
7. Salivary gland hyalinizing clear cell carcinomas
8. Undifferentiated round cell sarcomas with EWSR-non ETS fusion- NEW ENTITY
9. EWSR1 – SMAD3 fibroblastic tumor PROVISIONAL ENTITY
10. Myxoid liposarcoma (MLPS)
11. Clear cell sarcoma of the gastrointestinal tract (CCSGT)
12. Mesothelioma

AN EASY WAY TO REMEMBER

1.Ewings sarcoma

Common EWSR1 fusion transcripts associated with Ewing’s sarcoma.

• t(11;22)(q24;q12)of FLI1-EWSR1 genes
• t(21;22)(q12q12)of ERG-EWSR1 genes

2.Desmoplastic small round cell tumor (DSRCT)

• Has pathogenic balanced translocation t(11;22)(p13;q12) of the EWSR1 gene to the Wilms tumor (WT1 gene)

3.Extraskeletal myxoid chondrosarcoma (EMC)

• t(9;22)(q22-31;q11-12): CHN-EWS fusion gene, is consistent marker for extraskeletal myxoid chondrosarcoma

4.Angiomatoid fibrous histIocytoma (AFH)

• t(12;22)(q13;q12) creating ATF1-EWSR1 gene
• t(2;22)(q33;q12) creating CREB1-EWSR1 gene 

However, the most common rearrangement in angiomatoid fibrous histoocytoma is t(12;16)(q13;p11) creating ATF1-FUS fusion.

5.Clear cell sarcoma (CCS)

• t(12;22)(q13;q12): ATF1 and EWSR1

6.Primary pulmonary myxoid sarcoma (PPMS)

• EWSR1 rearrangement is seen in 85% cases. Fusion partner is usually ATF1 same as AFH and CSS.

7.Salivary gland hyalinizing clear cell carcinomas

• > 80% of cases have EWSR1-ATF1 fusion

8.Undifferentiated round cell sarcomas with EWSR-non ETS fusion- NEW ENTITY

• EWSR1-NFATC2
• EWSR1-PATZ1

Both have distinct morphologic features.- CHECK BELOW

9.EWSR1 – SMAD3 fibroblastic tumor PROVISIONAL ENTITY

• EWSR1-SMAD1 fusion

HERE IS A QUICK SUMMARY

10.Myxoid liposarcoma (MLPS)

• t(12;22)(q13;p11) – EWSR1-DDIT3 -rare

Most common translocation associated with t(12;16)(q13;p11) – FUS-DDIT3 is seen in 90%

11.Clear cell sarcoma of the gastrointestinal tract (CCSGT)

• EWSR1-CREB fusion

12.Mesothelioma

• EWSR1-YY1 appears to be uncommon

Did we miss out anything? Leave a reply.

Ref: WHO 5th edition soft tissue and bone tumors 2020