A molecularly-confirmed extraskeletal myxoid chondrosarcoma with dual gene rearrangements, EWSR1::NR4A3 and HAPLN1::EDIL3 fusion

Background

Extraskeletal myxoid chondrosarcoma (EMC) is a rare mesenchymal neoplasm with uncertain origin that is commonly seen in the lower extremities. Due to lack of specific clinical presentation, radio-pathologic and immunohistochemical (IHC) findings, the diagnosis of EMC is challenging.

Case report

Here we report a 60-year-old female presenting with a slow-growing tender mass on the right medial knee over the last 10 years. Histological evaluation of the resected specimen showed a subcutaneous multi-lobular lesion composed of uniform bland small oval to spindle shaped cells interconnected to arrange in cords and clusters in abundant myxoid matrix. Necrosis was identified in 10 % of the specimen. IHC staining showed that the tumor cells were weak and patchy positive for INSM1 and NSE and rarely positive for EMA. DNA and RNA next-generation sequencing reveal a dual gene rearrangement, including EWSR1::NR4A3 and HAPLN1::EDIL3 fusion. The combination of histopathologic and molecular findings supports the diagnosis of EMC.

Conclusion

This is the first reported case, to the best of our knowledge, of EMC with dual gene fusions. Although diagnostic and prognostic significance of HAPLN1::EDIL3 fusion and coexistence of HAPLN1::EDIL3 fusion and EWSR1::NR4A3 fusion in EMC remains unknown at this time, our hope that this case will be helpful to broaden the spectrum of known gene fusion variants in EMC, and augment the awareness and interest of researcher in investigating the impact of individual HAPLN1::EDIL3 fusion and dual gene rearrangement of HAPLN1::EDIL3 fusion and EWSR1::NR4A3 fusion on clinical behavior of EMC.