(Author, Department, University,
Corresponding Address and email)
Osteosarcoma, also known as osteogenic sarcoma, is a bone tumor commonly found in the childhood and adolescence. It has been commonly reported in patients in the age range of 15 to 19 years. Incidence of the disease is almost similar for both males and females. This disease develops in bone-generating mesenchymal cells (Huether & McCance, 2013).
Causes of Osteosarcoma
Rapid local growth can result in osteosarcoma and can increase the chances of mutation. Ionizing radiation, even in low doses, can become the cause of rapid local growth. It has been reported that even therapeutic radiations for other forms of cancer can result in osteosarcoma. The latent period after exposure to the radiation can range from 5 years to 40 years. It has also been found to be associated to retinoblastoma, which is a genetically induced eye tumor (Huether & McCance, 2013). Research shows that some agents can result in osteosarcoma by changing the genetic make-up. These agents may include chemical agents such as beryllium, and viruses as, for example, Finkel-Biskis-Jinkins (FBJ) virus having the src oncogene (Dai, Ma, He, & Jha, 2011).
Studies show that there is a deletion of hereditary material on the long arm of chromosome, 13, leading to the recognition of a tumor-suppressor gene as being a component of the mechanism behind the development of tumor. The oncogene src has also been found to be linked to the development of osteosarcoma (Huether & McCance, 2013).
Pathophysiology of Osteosarcoma
Most commonly, osteosarcoma occurs in the metaphyses of long bones near areas of active physeal growth. The tumor occurs primarily at the distal femur, proximal humerus, or proximal tibia. Production of osteoid cells is an important feature of osteosarcoma as it is a tumor of mesenchymal cells (Huether & McCance, 2013). Studies show that mutations in some tumor suppressor pathways including p53 and Rb tumor suppressor pathways can result in the development of osteosarcoma pathogenesis (D Lamplot et al., 2013).
Diagnosis of Osteosarcoma
Early signs and symptoms of the bone cancer may help in the diagnosis of the disease as told by physician. Physician and physician assistant noted that early signs and symptoms of the disease might include swelling in the bone as well as pain (Huether & McCance, 2013). Usually, this pain cannot be treated with over-the-counter medicines. Moreover, the pain may come and go, and can be severe at night. Bone fractures without any apparent reasons can also be an important sign of bone cancer. Some less severe signs and symptoms may also develop such as fever, fatigue, anemia, and/or weight loss. Physician told that these signs and symptoms could occur due to the presence of some other less serious problems (Centers for Disease Control and Prevention, n.d.).
Diagnosis of osteosarcoma usually starts with a complete medical history and physical examination. A blood test for an enzyme, alkaline phosphatase is also used for the diagnosis of osteosarcoma. This enzyme is commonly found in the blood of growing children, in broken bones when they are mending, or during production of diseased or cancerous bone tissue (Centers for Disease Control and Prevention, n.d.).
The conventionally used plain radiograph helps in making the diagnosis of the disease by showing features such as sun burst appearance, new formation of bones in soft tissues with a particular pattern of damage to the already existing bones, and Codman’s triangle (as shown in Figure 1 in Appendix). An X-ray scan along with some other scanning procedures such as Positron Emission Tomography (PET) scan, computerized tomography (CT) scan, magnetic resonance imaging (MRI), or bone scan, and a needle or surgical biopsy, are used in the diagnosis of cancer. X-ray can help in finding metastasis in the form of nodules or cannon ball appearance in the lungs. PET scan also helps in the diagnosis of metastases and/or local recurrence of the disease after resection. In case of thorax, CT scan is found to be of more help. MRI of the lesion delineates the extent of the cancer into the soft tissues, the joint, the medullary canal, and the skin lesions. Tc99 bone scan finds the osseous metastases (Kundu, 2014).
Bone biopsy is considered as a definitive method for the determination of malignancy of the cancer (Kundu, 2014). There can be an open or closed biopsy. Open biopsy is performed through a little incision. Although it has an advantage of taking adequate amount of sample for analysis, but it is a time consuming process requiring more expertise. On the other hand, closed biopsy is performed as a fine needle aspiration cytology and core needle biopsy. Research shows that percutaneous core needle biopsy is one of the safest and accurate methods of diagnosis of bone tumors. This process is done through a small stab utilizing the Jamshidi needle and obtaining multiple cores from the main part of the tumor (Kundu, 2014) Research shows that a diagnosis made with core needle biopsy shows a sensitivity of about 93%, and specificity of 100%. Moreover, positive predictor value of the diagnostic method is 100%. This method also showed no complications in patients (Taupin, Decouvelaere, Vaz, & Thiesse, 2016). Figure 2 in appendix shows the Core Needle Biopsy.
Treatment and Prognosis
Osteosarcoma has a poor prognosis secondary to a high grade at presentation. It has also been found that Rb and/or p16INK4A alterations can be related to poor osteosarcoma prognosis. Therefore, research on these tumor suppressor agents and their related pathways could improve prognosis. Moreover, studies on Runx2 pathway could also help in improving the prognosis (D Lamplot et al., 2013).
Although osteosarcoma may show high level of resistance to chemotherapy (D Lamplot et al., 2013), but there are three options of treatment, which can be used either alone or in combination. Usually, the therapeutic strategy is considered by looking at the type, location, and stage of the cancer. Moreover, rate of the growth of tumor is also considered in selecting a therapeutic strategy. These therapeutic strategies may include (Centers for Disease Control and Prevention, n.d.):
Chemotherapy such as high doses of methotrexate or the use of trastuzumab,
Surgery in which a surgeon removes either a cancerous portion or the entire limb, and
Radiotherapy
Research shows that cytotoxic chemotherapy can improve therapeutic outcomes from less than 20% to more than 65%. Moreover, limb-salvage surgery can help most of the patients of osteosarcoma (D Lamplot et al., 2013). Some of the therapeutic agents used in the treatment of osteosarcoma include insulin-like growth factor (IGF) inhibitors such as Ganitumab; mammalian target of rapamycin (mTOR) targeting agents such as Rapamycin, and vascular endothelial growth factor (VEGF) inhibitors such as AZD2171 (D Lamplot et al., 2013). Radiotherapy such as High-dose photon irradiation (50–70 Gy) is also used, especially in situations when lesions are present at inaccessible sites. Researchers are also working on the use of autologous stem cells for the treatment of osteosarcoma, and it is thought that combination of stem cell therapy with chemotherapy could be an important therapeutic strategy in the future (Dai et al. 2011).
References
Centers for Disease Control and Prevention. (n.d.). Questions and Answers about Bone Cancer. Retrieved from http://www.cdc.gov/nceh/radiation/phase2/mbone.pdf
Dai, X., Ma, W., He, X., & Jha, R. K. (2011). Review of therapeutic strategies for osteosarcoma, chondrosarcoma, and Ewing’s sarcoma. Medical Science Monitor, 17(8), RA177-RA190.
D Lamplot, J., Denduluri, S., Qin, J., Li, R., Liu, X., Zhang, H., . . . Shui, W. (2013). The Current and Future Therapies for Human Osteosarcoma. Current Cancer Therapy Reviews, 9(1), 55-77.
Huether, S. E., & McCance, K. L. (2013). Understanding Pathophysiology: Elsevier Health Sciences.
Kundu, Z. S. (2014). Classification, imaging, biopsy and staging of osteosarcoma. Indian J Orthop, 48(3), 238.
Taupin, T., Decouvelaere, A. V., Vaz, G., & Thiesse, P. (2016). Accuracy of core needle biopsy for the diagnosis of osteosarcoma: A retrospective analysis of 73patients. Diagn Interv Imaging, 97(3), 327-331. doi: 10.1016/j.diii.2015.09.013
Appendix
Figure 1: Frontal Codman Triangle Description (Source : Radiopaedia.org)
Figure 2: Core needle biopsy: (a) Jamshidi needle along with trochar as well as stylet. (b) Biopsy obtained through stab incision. (c) Five proper cores taken (Source: Kundu, 2014)
