April 26, 2010


Discussion on Osteosarcoma

By:Muhamad Na’im B. Ab Razak

University Science Malaysia

Osteosarcoma is an ancient disease that is still incompletely understood. The term "sarcoma" was introduced by the English surgeon John Abernathy in 1804 and was derived from Greek roots meaning "fleshy excrescence." In 1805, the French surgeon Alexis Boyer (personal surgeon to Napoleon) first used the term "osteosarcoma." Boyer realized that osteosarcoma is a distinct entity from other bone lesions, such as osteochondroma (exostoses). [Charles T Mehlman]

Osteosarcoma is the most common primary malignant tumor of bone, excluding plasma cell myeloma. Approximately 75% of all osteosarcoma are of the classic or conventional type, and the remaining 25% comprise the osteosarcoma variants [Geoff Hide]. This disease is thought to arise from primitive mesenchymal bone-forming cells, and its histologic hallmark is the production of malignant osteoid. Other cell populations may also be present, as these types of cells may also arise from pluripotential mesenchymal cells, but any area of malignant bone in the lesion establishes the diagnosis as osteosarcoma. [Charles T Mehlman]

Differential diagnosis for osteosarcoma includes 1) traditional differential diagnosis such as; chondroblastoma (Codman's tumor), chondrosarcoma, fibrous dysplasia & osteofibrous dysplasia (ossifying fibroma), aneurysmal bone cyst, telangiectic osteosarcoma,2) nontraditional osteoid-producing entities like dedifferentiated chondrosarcoma, clear cell chondrosarcoma, mesenchymal chondrosarcoma, synovial sarcoma and 3) miscellaneous tumors and condition such as; Ewing Sarcoma, Giant cell tumor of bone, osteoid osteoma & osteoblastoma, fracture, osteomyelitis, inflammatory metachronous hyperostosis, myositis ossificans and bone cyst.

Osteosarcoma can occurs in any bone but most commonly affects the long bone near the metaphyseal growth plate. The most common site is distal femur, proximal tibia and humerus. It may also develop in skull, jaw and pelvis.

Until now, the exact aetiology for osteosarcoma is still unknown. It is believed to be caused by both host and environmental factors Proposed etiology for the development of osteosarcoma includes 1) host factor (age, gender, ethnicity, genetic and familial factor, pre existing bone abnormality), and 2) environmental factors, (ionizing radiation, alkylating agents, perinatal factors, virus and trauma.)

Osteosarcoma has high prevalence based on bimodal age distribution which is during adolescent and in adult older than 65 years old. It is more common in male and higher incidence in African Americans and Hispanic as compared to white population.

In term of genetic role for development of osteosarcoma, there is no doubt about that. However, it is difficult to determine the exact chromosomal aberration characterizing osteosarcoma due to high degree of karyotype complexity in osteosarcoma tumor cells.

Even though extremely rare, there is a reported case of talangiectatic osteosarcoma in two siblings. Pedigree analysis of three generation shows no osteosarcoma being diagnosed before but majority of the family has suffered from various type of carcinoma.

Others rare genetic aetiology for osteosarcoma includes Li–Fraumeni syndrome, Rothmund–Thomson syndrome, and RECQ-helicase disorders (Bloom and Werner Syndromes).

Pre existing bone disorder like Paget's disease, bone changes due to 1) radiation, 2) solitary or multiple osteochondroma, 3) solitary enchondroma or enchondromatosis (Ollier disease), 4) multiple hereditary exostoses, 5) fibrous dysplasia and 6) chronic osteomyelitis play a roles for the development of osteosarcoma. As for the Paget disease itself, around 1% of them will eventually develops osteosarcoma especially in the second bimodal age peak.

Trauma is an important history to be elicited in the suspected case of osteosarcoma. However, there is no exact correlation between osteosarcoma and trauma. Most of the time, it is believed that the association of osteosarcoma and trauma is just an incidental findings. However, it is possible that the trauma cause disruption to the pre existing tumor cells, hence attracting inflammatory agent which therefore increase the transformation of the tumor cell into a malignant type.

Symptoms of osteosarcoma usually presents for weeks or months before the diagnosis is being establish. The most common complaint is pain that is aggravated by activity and become severe at night. The absence of palpable mass does not exclude the diagnosis of osteosarcoma. Pathological fracture is uncommon except for the talangiectatic type. Systemic symptoms are also rare except in the case of metastases.

Radiography is still the best imaging test for suspected bone tumor and most of the time it can give an idea whether it is a benign or malignant tumor. The role of plain X- ray remains limited, but it could give initial idea towards working diagnosis. MRI can be used both for local staging and evaluation of soft tissue component. Pre contrast T1- weighted image show best the intraosseous component while post contrast image used to evaluate soft tissue component and joint invasion. Apart from that, T1- weighted MRI has been shown to be accurate in detecting skip lesion. Lung metastasize is best detected by Chest CT while bone metastasize can be detected with Tc- 9mmethylene diphosphonate (MDP) bone scintigraphy.

The only blood tests with prognostic significance are lactic dehydrogenase (LDH) and alkaline phosphatase (ALP). Patients with an elevated ALP at diagnosis are more likely to have pulmonary metastases. In patients without metastases, those with an elevated LDH are less likely to do well than are those with a normal LDH. [Charles T Mehlman,] Others lab investigations are particularly being carrying out to assess organ function before administering chemotherapy and to monitor function post- chemotherapy.

Biopsy should never being done before radiological and lab investigation being performed. It is done prior starting the chemotherapy. These procedures should be carried out in strict aseptic technique.

Previously, the mainstay treatment for osteosarcoma is the amputation of the affected site which is not really proven benefit as the survival rate is only 10-20%. [R. Nagarajan] Limb sparing technique with oncological intervention has become the mainstay treatment for osteosarcoma. However, there is little debate for the advantage of this treatment as a modality of choice in osteosarcoma involving the upper extremity. For the osteosarcoma of the lower limb, limb salvage is the preferred method except that it will give less benefit in term of functional outcome or would compromise the curative intent of the surgery.

Amputations tend to have fewer complications and are typically related to stump healing/pain and phantom pain. [R. Nagarajan]

The current limb sparing technique that has been used includes endoprosthetic implants, allograft bone, composite endoprosthetic implants, expanding endoprostheses, arthrodesis, and rotationplasty. The selection of the procedures depends on the site of the tumor, age of the patient, patient prognosis, and orthopedic surgeon expertise [R. Nagarajan]

Various chemotherapeutic agents have been used in treating osteosarcoma including cisplatin doxorubicin, highdose methotrexate, cyclophosphamide, etoposide, and ifosfamide and all of them have been shown to be effective.

Another issue to deal with is the complications seen with chemotherapy administration, which has acute (e.g., nausea, hair loss, neutropenia, missing school/work, etc.) and long-term effects (e.g., cardiomyopathy, infertility, second malignancy, etc.) [R. Nagarajan].

The role of radiotherapy in the management of osteosarcoma remains controversy but can be attempted where amputation is not possible. However, if it is used together with chemotherapy and tumor resection, it will yield high curative rate.

Current study in evaluating the mode of treatment for osteosarcoma is to see the efficacy of immunotherapy. The term “immunotherapy” broadly refers to any attempt to modulate the immune response for therapeutic gain. This can refer to “active immunotherapy,” such as vaccination, or “adoptive immunotherapy,” such as the infusion of cytotoxic lymphocytes or pre-formed antibodies. In the context of cancer treatment, immunotherapy can also refer to the use of cytokines or other immunomodulatory agents to affect the treatment of malignant disease [David M. Loeb]. These treatments hold promise for treating osteosarcoma but yet with many challenge remains particularly in identifying appropriate targets and optimizing the timing of these treatments

Apart from that complication, issues confining to the quality of life of the patient suffered from osteosarcoma or complication of treatment should be addressed by the treating physicians. According to R. Nagarajan three aspect should be look for which include functional limitations (an impairment of physical, mental, or emotional performance) ,disability (limited ability or inability to perform actions, tasks, or activities required for self-care, home management, work, school, or leisure) , and personal identity (body image and self-concept)

The overall 5-year survival rate for patients diagnosed between 1974 and 1994 was 63% (59% for males, 70% for females). [Charles T Mehlman]. Currently, it is believed that the survival rate is much more higher compared to this figure.


1) Charles T Mehlman & Timothy P Cripe, "Osteosarcoma", http://emedicine.medscape.com/article/1256857-overview, accessed on 24 April 2010, 2.50 PM

2) Geetika Khanna, "Imaging of Pediatric Bone Tumors: Osteosarcoma and Ewing Sarcoma", L.S. Medina et al. (eds.), Evidence-Based Imaging in Pediatrics, Springer Science + Business Media, LLC 2010.

3) Geoff Hide, "Osteosarcoma, Variants", http://emedicine.medscape.com/article/394057-overview, accessed on 24 April 2010, 2.30 PM

4) N. Jaffe et al. (eds.), "Pediatric and Adolescent Osteosarcoma", Cancer Treatment and Research 152, Springer Science + Business Media, LLC 2009

5) Rajaram Nagarajan, "Quality of Life (QOL) in Patients with Osteosarcoma", Treatment of Bone and Soft Tissue Sarcomas. Recent Results in Cancer Research 179, Springer-Verlag Berlin Heidelberg 2009

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