Extraskeletal Myxoid Chondrosarcoma [EMC]: A Review Tom Corbett

1. Extraskeletal Myxoid Chondrosarcoma [EMC]: A ReviewTom Corbett

2. Reason for review: • patient was seen with an EMC. • chondrosarcomas are known to be both radiation and chemo-resistant. • myxoid tumors are known to be very radiation sensitive. • given a combination of myxoid and chondrosarcoma in the same specimen it wasn’t clear if radiation or chemotherapy would be appropriate for this patient • consequently a literature search was undertaken. • Also presented is the importance of consultation with the surgeon in defining radiation volumes.

3. Background • first described in 1972. • is a rare multinodular growth of primitive chondroid cells in an abundant myxoid matrix. • previously called chordoid sarcoma as it resembles chordoma. • estimated to account for 2.5% of all soft tissue sarcomas. • ultrastructural studies have shown markers of neuroendocrine differentiation • iInitially thought to be a low-grade sarcoma, studies with longer follow-up have shown a high potential for local recurrence and metastasis.

4. Radiographically • characterized on MRI by multilobular soft-tissue mass often invading extracompartmental, bony, and vascular structures. • peripheral enhancement has been reported more commonly in tumors with the EWS-NR4A3 variant. • tumors show intermediate to high signal intensity relative to muscle on T1-weighted images. • signal intensity on T2-weighted MR is heterogeneous. • mild to moderate enhancement is seen with gadolinium infusion.

5. Genetics • chromosomal translocation t(9;22)(q22;q12.2) • results in a fusion gene EWSR1-NR4A3 (previously called CHN, TEC or NOR1). • reported in ~75% of cases. • an alternate fusion is t(9;17)(q22;q11.2) • Results in the fusion gene RBP56-NR4A3. • The chromosomal translocations result in fusion gene products responsible for alterations in cellular growth and differentiation.

6. Treatment • Surgery with complete resection is the mainstay of surgery. • Adjuvant radiation has been utilized but details and indications are unclear. • One report where pre-operative radiation was utilized indicated the percent necrosis at time of surgery was 20% - 50%.

7. Chemotherapy • adriamycin, cisplatin, ifosfamide and dacarbazine – all reported very low response rates • Novel agents that modulate the pathways involving the EWSR1-NR4A3 fusion gene may be active. • SGK1, a serine-threonine kinase which is upregulated in these tumors. • PGA2, a prostaglandin that transactivates the EWSR1-NR4A3 fusion protein • Six-3, a cofactor that activates the CHN gene.

8. Outcomes • Inadequate initial surgery is associated with decreased recurrence-free survival. • Other purported prognostic factors are tumor size, Ki-67 >25% and high mitotic activity (>2 mitoses per 10 hpf). • Age has variably been reported to be significant. • Gender, tumor depth and site of tumor and histologic grade were not found to be associated with disease-free, metastasis-free, recurrence-free, or overall survival.

9. FIG. 20 . The estimated probability of developing local recurrence in EMC.

10. FIG. 21 . The estimated probability of developing metastasis in EMC.

11. FIG. 22 . The estimated probability of survival in EMC.

12. Initial – based on post-op CT only E:\abdo1.GIF

13. Initial – based on post-op CT only

14. Original – based on pre-op CT, discussion with surgeon • E:\abdo1.GIF

15. Comparison – post-op CT alone versus pre-op and surgeon input