A 74-year-old man presented with a left chest wall mass that he had first noted 2 months earlier. His local physician subsequently obtained a bone scan and magnetic resonance imaging. The radiological findings were thought to be suggestive either of a hematoma or of tumor. Fine-needle aspiration was performed. The specimen was composed of spindle-shaped and small blue tumor cells embedded in a myxoid stroma (Figure 1, Diff-Quik, original magnification ×100). A similar appearance was noted on the cell block. A lacelike arrangement of tumor cells with prominent cystic spaces filled with myxoid material was also noted. The tumor cells exhibited slight nuclear pleomorphism, and the nuclear chromatin was evenly distributed. The patient subsequently underwent resection of the left anterior chest wall, including the left lower sternum and lower 6 ribs. Frozen section confirmed the cytological impression, and material was submitted for cytogenetic analysis.
Gross examination of the specimen revealed a 5.6-cm gray-white myxoid tumor with extensive hemorrhage in the soft tissue anterior to the resected ribs. Careful dissection of the plane between the tumor and the ribs showed the tumor to be insinuated between the ribs, but not arising from, distorting, or destroying the ribs themselves. The microscopic appearance was similar to that observed in the cell-block, showing a tumor made up of oval- to spindle-shaped cells lying in nests and strands within a myxoid stroma (Figure 2, hematoxylin-eosin, original magnification ×100). Multiple sections from the ribs were free of tumor. The cells were positive for vimentin, neuron-specific enolase, and synaptophysin but negative for cytokeratin, epithelial membrane antigen, S100, and chromogranin. Cytogenetic analysis revealed a translocation between the long arms of chromosomes 9 and 22, ie, t(9;22)(q22q12), along with separate rearrangements of chromosome 1 (Figure 3).
What is your diagnosis?
Pathologic Diagnosis: Extraskeletal Myxoid Chondrosarcoma
Myxoid chondrosarcomas may be skeletal or extraskeletal.1 The two tumor types differ at the ultrastructural and molecular levels in addition to bone involvement.
First described in 1953 by Stout and Verner,2 extraskeletal myxoid chondrosarcoma (EMC) is an unusual soft tissue sarcoma. In 1972, Enzinger and Shiraki3 enumerated the features of this tumor as a distinct clinicopathologic entity, one with a better prognosis than conventional bone chondrosarcoma. EMC occurs mostly in the deep soft tissues adjacent to the long bones of the extremities, with a predilection for the proximal lower limb.4 It has also been reported in the pelvis, shoulder girdle, chest wall, and back.1,5 The tumor occurs in both sexes, with some series reporting a male preponderance.1,4 The peak incidence is in the fifth to seventh decades, although patients' ages have ranged from 1 to 89 years.1,4–6
The most common presenting complaint is that of a palpable mass. Gross examination usually reveals a lobulated mass with a myxoid appearance and areas of hemorrhage. Histologically, EMC has a very characteristic multinodular architecture, with prominent intralesional hemorrhage. Cells aligned in cords and strands lie in a myxoid stroma. The cells have round to oval nuclei and deeply eosinophilic cytoplasm. Epithelioid cells may be encountered and present a source of diagnostic difficulty.
Immunohistochemically, the tumor cells show variable expression of vimentin, S100, and epithelial membrane antigen and are usually negative for keratins.1,4 Neuron-specific enolase, synaptophysin, and chromogranin are expressed in many cases.7 Our case was immunohistochemically vimentin positive and cytokeratin negative, with expression of the neuroendocrine markers neuron-specific enolase and synaptophysin. On electron microscopy, intracisternal microtubules are the most characteristic feature, although they are inconsistently present.4 The presence of abundant mitochondria is also notable.1,4
The histogenesis of this lesion is disputed. The electron microscopic resemblance to developing chondroblasts indicates that EMC originates in the primitive cartilage-forming mesenchyme.1 Cytogenetic studies show that most cases of EMC harbor the translocation t(9;22) (q22q12). It is now recognized that a t(9;17) translocation may be present in some of the t(9;22)-negative tumors.8 Skeletal myxoid chondrosarcomas consistently lack these cytogenetic abnormalities.1 Indeed, among all chondrosarcomas, specific chromosomal arrangements have been identified only in EMC.9
The differential diagnoses of EMC include skeletal myxoid chondrosarcoma, chordoma, parachordoma,10 mixed myoepithelial tumor,4 and other myxoid soft tissue lesions. Skeletal myxoid chondrosarcoma can closely mimic EMC, but the tumor cells are only rarely clustered in nests or cords. This feature has been asserted as the most apparent light microscopic difference between the two tumors.1 Skeletal myxoid chondrosarcoma originates in bone, lacks intracisternal microtubules ultrastructurally, and has never been shown to harbor the t(9:22) translocation. Chordoma and parachordoma can be differentiated from EMC by the presence of physaliferous cells and epithelial markers, among other features.10 Cytokeratin positivity also helps to distinguish mixed myoepithelial tumor from EMC.4 The location and distinctive morphologic features of EMC usually suffice to distinguish it from other myxoid soft tissue lesions. The morphologic heterogeneity that may be seen in EMC makes the differential diagnosis on cytology or core biopsy specimens particularly difficult. Material collected for cytogenetic analysis at the time of the aspirate/biopsy can be diagnostic and should be a part of the work-up if the preliminary impression is that of a myxoid soft tissue lesion.
EMC is an indolent but unrelenting tumor with a protracted clinical course and a high potential for metastasis, especially to the lungs (ranging from 46% to 90%).1,4 It tends to metastasize more frequently than skeletal myxoid chondrosarcoma, although this high rate of metastasis is not accompanied by decreased survival.1 Recurrences are frequent. The 5-year survival rate is 91% and drops to 78% at 10 years.5 Surgery is the mainstay of treatment. Adjuvant methods, mainly radiotherapy, have been employed. The tumor is unresponsive to chemotherapy.
In summary, EMC is a distinct, uncommon entity that differs from conventional chondrosarcoma at many levels. Correct identification of this lesion requires careful delineation of its gross topography, identification of its distinctive morphological features, and, finally, confirmation of its unique cytogenetic profile.