Reappraisal of mesenchymal chondrosarcoma: Novel morphologic observations of the hyaline cartilage and endochondral ossification and beta-catenin, Sox9 and osteocalcin immunostaining of 22 cases

Department of Orthopedic and Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
Human pathology (Impact Factor: 2.77). 02/2010; 41(5):653-62. DOI: 10.1016/j.humpath.2009.11.006
Source: PubMed


Mesenchymal chondrosarcoma, a rare malignant round cell and hyaline cartilage tumor, is most commonly intraosseous but can occur in extraskeletal sites. We intensively observed the morphology and applied Sox9 (master regulator of chondrogenesis), beta-catenin (involved in bone formation, thought to inhibit chondrogenesis in a Sox9-dependent manner), and osteocalcin (a marker for osteoblastic phenotype) to 22 central nervous system and musculoskeletal mesenchymal chondrosarcoma. Cases of mesenchymal chondrosarcoma were retrieved and reviewed from our files. Immunohistochemistry and follow-up were obtained on mesenchymal chondrosarcoma and tumor controls. Twenty-two mesenchymal chondrosarcomas included 5 central nervous system (all female; mean age, 30.2; mean size, 7.8 cm; in frontal lobe [n = 4] and spinal cord [n = 1]) and 17 musculoskeletal (female-male ratio, 11:6; mean age, 31.1; mean size, 6.2 cm; 3 each of humerus and vertebrae; 2 each of pelvis, rib, tibia, neck soft tissue; one each of femur, unspecified bone, and elbow soft tissue). The hyaline cartilage in most tumors revealed a consistent linear progression of chondrocyte morphology, from resting to proliferating to hypertrophic chondrocytes. Sixty-seven percent of cases demonstrated cell death and acquired osteoblastic phenotype, cells positive for osteocalcin at the site of endochondral ossification. Small round cells of mesenchymal chondrosarcoma were negative for osteocalcin. SOX9 was positive in both components of 21 of 22 cases of mesenchymal chondrosarcoma. beta-Catenin highlighted rare nuclei at the interface between round cells and hyaline cartilage in 35% cases. Control skull and central nervous system cases were compared, including chondrosarcomas and small cell osteosarcoma, the latter positive for osteocalcin in small cells. Mesenchymal chondrosarcoma demonstrates centrally located hyaline cartilage with a linear progression of chondrocytes from resting to proliferative to hypertrophic, which undergoes endochondral ossification, recapitulating growth plate cartilage and suggesting that this component of mesenchymal chondrosarcoma may be a differentiated (benign or metaplastic) component of a malignant metastasizing tumor. This hyaline cartilage component is morphologically different from cartilage of control chondrosarcoma. Mesenchymal chondrosarcoma can be separated from small cell osteosarcoma, using Sox 9 for cartilage and osteocalcin for osteoblastic phenotype. Rare nuclear beta-catenin expression at the interface between hyaline cartilage and small round cells potentially implicates the APC/Wnt pathway during endochondral ossification in morphologically benign hyaline cartilage component of mesenchymal chondrosarcoma.

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    • "Translocations upstream of the coding sequence suggested that the altered expression of Sox9 is capable of severely impacting chondrogenesis and thus lead to abnormal skeletal development. As a transcriptional activator, the Sox9 gene is able to co-regulate the proliferation and differentiation of the chondrocytes together with other signal pathways through direct or indirect means.1011 This can be achieved through the combination with the chondrocytes-specific enhancer type II collagen gene (Col2al) and L-Sox5, Sox6. "
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    • "The undifferentiated small cell component of mesenchymal CHSs is consistently positive for CD99 and may stain for vimentin and Leu7 while negative for osteocalcin, actin, cytokeratin, and epithelial membrane antigen (EMA) (Figure 13). SOX9 is almost invariably positive in both components [63, 64]. "
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