Reappraisal of mesenchymal chondrosarcoma: Novel morphologic observations of the hyaline cartilage and endochondral ossification and b-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.

8 Reads
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sox9 is an operon that positively regulates the transcription of type II collagen. The generation of type II collagen plays a critical role in the healing process of the bone-tendon junction (BTJ). Sox9 was injected into an established bone-tendon healing model in order to observe its effect on the healing by determining the biomechanical properties of the BTJ. In addition, the recombinant adenovirus Sox9 was used to transduce the animal model samples and in vivo observations of the effect of the adenovirus-mediated Sox9 transduction as well as its promotion of the healing properties were made. Sox9 was not only able to promote the healing, but also increased the biomechanical strength. The recombinant Sox9 delivered by adenoviral vector can be expressed at a high level in the damaged tissues of the bone-tendon junction, which can stimulate the production of type II collagen and improve the healing of the BTJ. Based on the results of this study, we considered that gene therapy may be applicable in the healing process of the bone-tendon junction.
    Indian Journal of Orthopaedics 03/2014; 48(1):88-95. DOI:10.4103/0019-5413.125521 · 0.64 Impact Factor
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Chondrosarcoma (CHS) is a malignant cartilage-forming tumor and usually occurs within the medullary canal of long bones and pelvic bones. Based on the morphologic feature alone, a correct diangosis of CHS may be difficult, Therefore, correlation of radiological and clinicopathological features is mandatory in the diagnosis of CHS. The prognosis of CHS is closely related to histologic grading, however, histologic grading may be subjective with high inter-observer variability. In this paper, we present histologic grading system and clinicopathological and radiological findings of conventional CHS. Subtypes of CHSs, such as dedifferentiated, mesenchymal, and clear cell CHSs are also presented. In addition, we introduce updated cytogenetic and molecular genetic findings to expand our understanding of CHS biology. New markers of cell differentiation, proliferation, and cell signaling might offer important therapeutic and prognostic information in near future.
    Sarcoma 02/2011; 2011(1357-714X):405437. DOI:10.1155/2011/405437
  • [Show abstract] [Hide abstract]
    ABSTRACT: Several malignant tumours occurring in the sinonasal tract may present with an undifferentiated morphology. Overall, these lesions pose significant diagnostic difficulties for the surgical pathologist, especially in limited biopsy material, but their correct classification is becoming increasingly important for an appropriate treatment strategy. This review deals with the criteria for differential diagnosis of these neoplasms, with emphasis on recent advances in immunohistochemistry and molecular biology, as well as with previous progress in electron microscopy. Through careful microscopic examination of haematoxylin and eosin-stained sections, in the light of clinical information and imaging data, a list of differential diagnoses can be made and an appropriate panel of antibodies can be chosen to further categorize the tumour. An initial panel including cytokeratins, synaptophysin, S100 protein, desmin and CD45 may allow the classification of most lesions or may help to narrow the list of differential diagnoses. Further refinement can be obtained through second-line markers, including in-situ hybridization for Epstein-Barr virus, other neuroendocrine markers, melanocytic markers, myogenin, CD99, other lymphocyte markers, and CD138 and light chains. Finally, molecular analysis can further assist in the recognition of specific entities such as nuclear protein in testis midline carcinoma, Ewing's sarcoma/peripheral neuroectodermal tumour, alveolar rhadbomyosarcoma, and poorly differentiated synovial sarcoma.
    Histopathology 04/2011; 59(6):1034-45. DOI:10.1111/j.1365-2559.2011.03813.x · 3.45 Impact Factor
Show more