Article

Osteosarcoma Anatomic and Histologic Variants

Department of Pathology, University of Alabama at Birmingham and the Birmingham Veterans Affairs Medical Center 35233, USA.
American Journal of Clinical Pathology (Impact Factor: 2.51). 05/2006; 125(4):555-81. DOI: 10.1309/UC6K-QHLD-9LV2-KENN
Source: PubMed

ABSTRACT

Osteosarcoma is the most common primary tumor of bone, yet its absolute incidence among malignant tumors is low. Within its strict histologic definition, osteosarcoma comprises a family of lesions with considerable diversity in histologic features and grade. Its prognosis is dependent not only on these parameters, but also on its anatomic site. It may occur inside the bones (in the intramedullary or intracortical compartment), on the surfaces of bones, and in extraosseous sites. Information of diagnostic or prognostic significance has not been elucidated from studies of its cytogenetics. This review summarizes the anatomic and histologic variations of osteosarcoma and offers a schema for its subclassification.

Download full-text

Full-text

Available from: Gene P Siegal
    • "Given its diverse histological classification, it is therefore, hypothesized that osteosarcoma originates from a multipotent cell (Klein and Siegal, 2006; Mohseny et al., 2009). Although surgery and neo-adjuvant chemotherapy have improved outcome remarkably, the main clinical problem of this tumor is its unpredictable recurrence or metastasis, which is likely the result of a few resistant tumor cells. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Osteosarcoma is a bone tumor displaying significant cellular and histological heterogeneity and a complex genetic phenotype. Although multiple studies strongly suggest the presence of cancer stem cells in osteosarcoma a consensus on their characterization is still missing. We used a combination of functional assays (sphere-forming, Aldefluor and side-population) for identification of cancer stem cell populations in osteosarcoma cell lines. Expression of stemness-related transcription factors, quiescent nature, in vivo tumorigenicity and Wnt/β-catenin activation were evaluated. We show that different cancer stem cell populations may co-exist in osteosarcoma cell lines exhibiting distinct functional properties. Osteosarcoma spheres are slowly-proliferating populations, overexpress SOX2 and KLF4 stemness-related genes and have enhanced tumorigenic potential. Additionally, spheres show specific activation of Wnt/β-catenin signaling as evidenced by increased nuclear β-catenin, TCF/LEF activity and AXIN2 expression, in a subset of the cell lines. Aldefluor-positive populations were detected in all osteosarcoma cell lines and overexpress SOX2, but not KLF4. The side-population phenotype is correlated with ABCG2 drug-efflux transporter expression. Distinct functional methods seem to identify cancer stem cells with dissimilar characteristics. Intrinsic heterogeneity may exist within osteosarcoma cancer stem cells and can have implications on the design of targeted therapies aiming to eradicate these cells within tumors.
    No preview · Article · Sep 2015 · Journal of Cellular Physiology
  • Source
    • "It demonstrates locally invasive growth with a high rate of recurrence but no metastatic potential (Harrington, Accurso et al. 2011). On the other hand, osteosarcoma is the commonest, non-hematopoietic, malignant primary tumor of bone (Klein and Siegal 2006). It occurs most frequently in young adults and adolescents(Dai, Huang et al. 2015). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and Aims: A group of osteogenic bone tumors can be diagnostically challenging at the histopathological level. These include aggressive osteoblastoma and osteoblastoma-like osteosarcoma. This study aimed at assessing the utility of Ki-67 labeling index in the differentiation between these types of neoplasms. Methods: A total of 39 patients were enrolled in this study, including 9 osteoblastomas (6 conventional and 3 aggressive types) and 30 osteosarcomas (20 high grade and 10 low grade). Immunohistochemical staining using Ki-67 antibody was done. Ki-67 labeling index was calculated and statistically compared between the different groups of tumors. Results: There was gradual significant increase (p<0.05) in Ki-67 labeling index from osteoblastomas, through low grade osteosarcomas, to high grade osteosarcomas. There was also significant difference (p<0.001) in proliferation index between aggressive osteoblastoma and low-grade osteosarcoma. Conclusion: Our results suggest that estimation of the proliferation index may help in the distinction between aggressive osteoblastomas and osteoblastoma-like osteosarcoma. However, careful interpretation of the clinical, radiological and histopathological features remains essential to reach proper diagnosis.
    Full-text · Article · Jul 2015
  • Source
    • "Osteosarcoma (OS) is the most common primary malignant tumor of the bone. This neoplasm is defined histologically by osteoid deposition by the malignant mesenchymal cells [1]. In OS, current evidence supports an osteoblastic population as the cell of origin [2], although the distinct histological subtypes (e.g. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Receptor activator of nuclear factor kappa-B ligand (RANKL) is an essential mediator of osteoclast formation, function and survival. In patients with solid tumor metastasis to the bone, targeting the bone microenvironment by inhibition of RANKL using denosumab, a fully human monoclonal antibody (mAb) specific to RANKL, has been demonstrated to prevent tumor-induced osteolysis and subsequent skeletal complications. Recently, a prominent functional role for the RANKL pathway has emerged in the primary bone tumor giant cell tumor of bone (GCTB). Expression of both RANKL and RANK is extremely high in GCTB tumors and denosumab treatment was associated with tumor regression and reduced tumor-associated bone lysis in GCTB patients. In order to address the potential role of the RANKL pathway in another primary bone tumor, this study assessed human RANKL and RANK expression in human primary osteosarcoma (OS) using specific mAbs, validated and optimized for immunohistochemistry (IHC) or flow cytometry.
    Full-text · Article · Jul 2015 · Journal of Bone Oncology
Show more