“A 60 year-old Woman with a Mass
in Her Right Thigh”
California Tumor Tissue Registry’s
Case of the Month
CTTR COTM Vol 13:6
www.cttr.org
March, 2011
A 60 year-old woman presented with a progressively enlarging, deeply-seated mass in
her right thigh. A 4.5 x 3.5 x 3.0 cm, well-circumscribed, nodular, soft tissue mass was
excised.
Microscopically, the tumor was composed of small eosinophilic cells with round to oval
nuclei arranged in strands and cords separated by an abundant myxoid matrix (Fig.
1)(Fig. 2). There were varying degrees of cellularity, ranging from areas with high
cellularity and a vaguely storiform pattern to paucicellular areas with stellate, tissue
culture-like cells embedded in a thick myxoid background (Fig. 3). Focal bands of
mature collagen were seen, at times, associated with copious hemorrhage and
hemosiderin deposition (Fig. 5). Mitotic figures were difficult to identify.
Immunohistochemical staining was performed to exclude other possible mimicking
lesions. The tumor did not stain for S100 protein, cytokeratins, or desmin; ruling out a
tumor of melanocytic/neural, epithelial, or myogenic derivation, respectively.
Diagnosis: “Extraskeletal Myxoid Chondrosarcoma”
Brian Willis PSF and Donald Chase MD
Department of Pathology, Loma Linda University and Medical Center, Loma
Linda, California
California Tumor Tissue Registry, Loma Linda, California
Extraskeletal myxoid chondrosarcoma (EMC) is a rare morphologically unique malignant
soft tissue sarcoma characterized by cords and strands of chondroblast-like cells
deposited in an abundant myxoid matrix. Although the nomenclature suggests
cartilaginous differentiation, this tumor is currently classified as a tumor of uncertain
differentiation due to the lack of convincing evidence that the cells represent actual
chondroblasts.
EMC usually arises in the deep tissues of the proximal extremities and limb girdles of
adults, primarily during the fifth and six decades, with only a few rare cases encountered
in children and adolescents. Men are affected nearly twice as often as women. It has a
predilection to develop in the thigh or popliteal fossa, similar to myxoid liposarcoma;
however, rare examples of other unusual locations have been reported. Clinical
symptoms are non-specific, with most patients presenting with a slowly growing deepseated mass that may cause pain and tenderness. Radiographic findings are not
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distinctive; however, it should be noted that because a morphologically identical tumor
may occur in bone and correlation with MRI or CT findings are necessary to establish
soft tissue origin.
Grossly, conventional EMC is a circumscribed multinodular mass surrounded by a dense
fibrous pseudocapsule. Sectioning reveals a gelatinous tan-brown surface divided into
lobules by thick fibrous septa, frequently with large amounts of hemorrhage. Most
tumors are 4-7 cm in greatest diameter at the time of resection, however, tumor sizes
ranging from 1.1 to 25.0 cm have been reported.
Histologically, the tumor consists of nodules of uniform elongated cells in anastamosing
cords and strands embedded in an abundant myxoid matrix separated by dense fibrous
septa. These cells have small hyperchromatic nuclei with a rim of deeply eosinophilic
cytoplasm which may resemble chondroblasts; however, unlike osseous
chondrosarcomas there is no differentiation towards cartilage producing cells, and
distinct chondrocytes in lacunae are never encountered. Other less common patterns that
have been reported include a pseudoacinar pattern and a “cellular variant” with sheets of
epithelioid cells with vesicular nuclei reminiscent of Ewings sarcoma. Mitotic figures are
rare in most cases, but may be more abundant in undifferentiated cellular forms of the
tumor.
Immunohistochemical findings are essentially non-contributory, with positivity for
vimentin being the only consistent marker. Varying results have been obtained using S100 protein, with reports ranging from about 18-40% positivity. In addition, scattered,
focal reactivity to keratins and EMA, as well as synaptophysin and neuron-specific
enolase have been reported in some cases.
The ultrastructural features are consistent mesenchymal origin, and in some cases feature
intracisternal microtubules, a distinct finding that is also present in cases of myxoid
chondrosarcoma of the bone. The cytoplasm and rough endoplasmic reticulum contain
inclusions of granular material identical to that found in the extra cellular matrix.
EMC is characterized by several distinct cytogenetic findings. The most common and
unique clonal abnormality is a balanced translocation t(9;22)(q22;q12) which results in
the fusion of the EWS gene on 22q12 with the NR4A3 gene on 9q22. A second less
common, but equally specific, translocation t(9;17)(q22;q12) fuses NR4A2 with RBP56.
While the molecular consequence of these translocations has yet to be fully elucidated, it
appears that the RBP56 and EWS fusion proteins have almost identical oncogenic
potential. In a recent study, Filion and colleagues demonstrated that the EWS/NR4A3
fusion protein upregulates the nuclear PPARG gene.
The differential diagnosis of extraskeletal myxoid chondrosarcoma includes:
 Chondroid syringoma
 Parachordoma
Chondroid syringoma is a benign tumor of the skin and subcutaneous tissue that
typically occurs in the head and neck. This tumor is of epithelial derivation but features
large areas of myxoid stroma with chondrocyte-like cells. It is distinguished from EMC
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by the presence of duct like structures lined with a two cell layer that stain strongly
positive for cytokeratins.
Parachordoma is an unusual entity of uncertain type that may represent a part of a
morphologic spectrum that includes myoepithelioma of soft tissue and mixed tumor.
This tumor may form lobules with nests of spindled cord-like cells in a myxoid matrix,
mimicking the some of the histological findings of EMC; however, it is distinguished by
its consistent co-expression of S-100 protein and cytokeratins. Further cytogenetic
studies to demonstrate the characteristic t(9,22) translocations of EMC may be of value in
particularly difficult cases.
Extraskeletal myxoid chondrosarcoma is a slow-growing tumor that is prone to late local
recurrence and may eventually metastasize. While a possibly aggressive clinical course
may be suggested by the findings of high grade or cellular variants, the results of large
studies fail to correlate cellularity with prognosis. It is therefore, most prudent to treat all
suspected cases of extraskeletal myxoid chondrosarcoma with radical local excision with
or without adjuvant high-dose radiation to prevent the possibility of future local
recurrence.
Suggested Reading:
1. Enzinger FM, Shiraki M. Extraskeletal myxoid chondrosarcoma. An analysis of
34 cases. Hum Pathol 1972; 3: 421-435
2. Meis-Kindblom JM, Bergh P, Gunterberg B, Kindblom LG. Extraskeletal
myxoid chondrosarcoma: a reappraisal of its morphologic spectrum and
prognostic factors based on 117 cases. Am J Surg Phathol 1999; 23: 636-650
3. Subramanian S, West R B, Marinelli RJ, et al. The gene expression profile of
extraskeletal myxoid chondrosarcoma. J Pathol 2005; 206: 433-444
4. Fletcher CD M, Powell G, Mckee PH. Extraskeletal myxoid chondrosarcoma: a
histochemical and immunohistochemical study. Histopathology 1986; 10: 489499
5. Drilon AD, Popat S, Bhuchar G, et al. Extraskeletal myxoid chondrosarcoma: a
retrospective review from 2 referral centers emphasizing long-term outcomes with
surgery and chemotherapy. Cancer 2008; 113(12): 3364-3371
6. Filion C, Motoi T, Olshen AB, et al. The EWSR1/NR4A3 fusion protein of
extraskeletal myxoid chondrosarcoma activates the PPARG nuclear receptor
gene. J Pathol. 2009; 217(1): 83-93
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