Article

Reappraisal of mesenchymal chondrosarcoma: novel morphologic observations of the hyaline cartilage and endochondral ossification and β-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: 2.81). 02/2010; 41(5):653-62. DOI: 10.1016/j.humpath.2009.11.006
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
77 Views
  • [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 · 0.62 Impact Factor
  • Source
    [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: La conducta médica inicial ante el hallazgo de un tumor óseo primario es fundamental, pues permite definir la mejor estrategia diagnóstica y terapéutica. Desde luego, la asistencia médica ha de ser multidisciplinaria. Esto conduce a la elección del método de biopsia diagnóstica y a la vía de acceso más adecuada. En el menor tiempo posible, la biopsia se enviará en «estado fresco» al patólogo, quien ha de repartir el material (fijación, congelación, etc.) según la cantidad, la calidad o los presuntos diagnósticos. Se conocen unas 50 formas de tumores óseos primarios, distribuidas en 12 clases principales. Algunas de estas formas, sobre todo los condrosarcomas, cuentan con una clasificación histopronóstica específica.
    02/2013; 46(1):1–15. DOI:10.1016/S1286-935X(13)64175-1