1. Extraskeletal Myxoid Chondrosarcoma
An overview from a clinical and basic science perspective
1. Clinical case and overview
Robert Maki, Memorial Sloan-Kettering Cancer Center, New York, NY

2. Case presentation
64 M with a two-year history of a >10 cm para-testicular perineal mass causing discomfort when sitting
Hypertension only pertinent medical history, no significant family, social history.
Exam, ultrasound → Complex cystic and solid mass.
01 / 2000: Resected with radical orchiectomy with portions of left corpus cavernosum and pubis (15 cm tumor, 1300 gram specimen).

3. Case, continued.
Dx: EMC, t(9;22) positive, margins grossly positive, with lung metastases noted
04/2000: Local tumor recurred, complicated by cutaneous fistula to urethra that slowly healed
Mass grew further, mostly in perineum

4. CT 1/19/2000

5. 4/12/00 CT of recurrence site

6. EMC
4/26/00

7. CT 8/16/00

8. Case, continued.
9/00-11/00: doxorubicin 75 mg/m2 x 3 cycles – no change
Declined further systemic therapy
Later agreed to thalidomide up to 300 mg a day but he had no benefit
Asymptomatic despite increasing size of lung metastases for the remainder of his life

9. 2/20/01

10. 5/31/02

11. Patient history, conclusion
07/02: Motor vehicle accident: found with CNS lesions, (largest 4.1 cm parietal mass): biopsy = glioblastoma multiforme
Therapy: whole brain XRT, glucocorticoids; patient declined an operation
Died of GBM 03/03

12. EMC: Extraskeletal Myxoid Chondrosarcoma
Rare, perhaps 1-2% of sarcomas
First described in 1953 by Stout and Verner, more clearly defined by Enzinger and Shiraki in 1972
M : F ~ 2 : 1, peak incidence ~ age 50
Thigh and popliteal fossa most common sites (like myxoid liposarcoma)
Somewhat similar to myxoid liposarcoma microscopically
Prolonged course with local recurrences and late metastases

13. EMC
Largest study 117 pts, 6-89 yrs old (median 52), median size 7 cm (1-25 cm)
80% proximal extremities, limb girdles
99 cases with follow up, median 9 yrs
48 NED, 23 AWD, 18 DOD
Local recurrence in 48% (40/83), mets in 46% (35/76 patients)
Grading not of prognostic value in this series
Microscopically identical tumor appears in bone, but in bone it has no specific translocation and lower risk of metastasis
Meis-Kindblom JM et al. Am J Surg Path 1999; 23:636
Antonescu C et al. Cancer 1998; 83:1504

14. Extraskeletal myxoid (chondrosarcoma)?
Not chondroid at all:
Cells most frequently do not show chondroid differentiation
Cells are S100 negative, typically
EM: cells not particularly chondrocytic, but more primitive
Collagen expression
Little collagen II, no collagen X, like chondrocytes have
More typically collagens I, III, VI positive, like fibroblasts
May represent a primitive mesenchymal precursor
Rules out relationship to mesenchymal chondrosarcoma, standard chondrosarcoma, and chordoma
Aigner T et al. Mod Pathol 2004; 17: 214

15. 3 typical microscopic views of EMC
Meis-Kindblom JM et al Am J Surg Path 1999; 23:636

16. Differential pathologic diagnosis
mixed myoepithelial tumors
chondroid lipoma
myxoid liposarcoma
myxofibrosarcoma
fibromyxoid sarcoma
myxoid variants of ossifying fibromyxoid tumor
of soft parts
myxoid sclerosing epithelioid fibrosarcoma

17. Local and metastatic risk, overall survival
Local recurrence risk
Risk of metastases
60% Overall Survival
at 15 years,
?disease specific
Overall survival
Meis-Kindblom JM et al. Am J Surg Path 1999; 23:636

18. Therapy Surgery, ?radiation Chemotherapy appears entirely ineffective
MD Anderson experience: 11 cases, 30 yrs
10 cm median size, 10/11 received chemotherapy, median 4 cycles
Doxorubicin-based
Dacarbazine-based
Three received ifosfamide, no response
One patient in Winnipeg, MB received IFN-alfa-2b with a response
Patel SR et al. Am J Clin Oncol 1995; 18:161
Rubinger M et al. Chest 1995; 108:281

19. EMC typical translocation t(9;22)

20. EMC translocation t(9;22) EWS-TEC
TEC also called NR4A3, NOR1, MINOR, CHN
Seen in 75% of EMC
Fusion protein links trans-activation domain of EWS to entire TEC protein, an orphan nuclear steroid/thyroid receptor gene superfamily member
Less common: t(9;17)(q22;q11) TAF2N-TEC (15%), rare t(9;15) TCF12-TEC.

21. EMC Therapy
Given the lack of viable options, one hopes that understanding of the molecular events associated with EMC will lead to better therapy