Extraskeletal Myxoid Chondrosarcoma [EMC]: A Review Tom Corbett

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.

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.

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.

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.

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%.

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.

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.

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

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

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

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

Initial – based on post-op CT only

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

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