Osteosarcoma (osteosarcoma) is a malignant osteogenic tumor characterized histologically by direct osteogenesis or production of bone matrix by tumor cells. Osteosarcoma is the most malignant, most prevalent, and most representative malignant bone tumor in orthopedics. Osteosarcoma is a large family, which can be generally divided into two categories: central and superficial, each of which is divided into many subtypes, each with different clinical, imaging, histological and biological behavioral characteristics. Among them, conventional central osteosarcoma (conventional
central
The most common and earliest recognized type of osteosarcoma is osteosarcoma, which is customarily referred to as osteosarcoma in clinical practice and in the literature, and can be subdivided into osteoblast, chondroblast, and fibroblast osteosarcomas according to their histological characteristics, while other pressure types must be named with their respective subtypes. WHO osteosarcoma typing
General osteosarcoma (osteoblast type, chondroblast type, fibroblast type) Capillary-dilated osteosarcoma (telangiectatic)
osteosarcoma) small round-cell osteosarcoma
low-grade central osteosarcoma (low-grade central osteosarcoma)
surface
osteosarcoma)
parosteal osteosarcoma
periosteal osteosarcoma
osteosarcoma)
high-grade surface osteosarcoma
Secondary osteosarcoma
Secondary to Paget’s disease and osteoblastoma
Age of onset
Although osteosarcoma can occur at any age, including infants, children, and the elderly, it usually occurs in the 10-30 year old age group and is more common in males than females, with a ratio of nearly 2:1.
Site of disease
Eighty percent of cases occur in the tubular bones of the extremities, especially the femur (40%), tibia (16%), and humerus (15%); the most common sites are the distal femur and proximal tibia, followed by the proximal humerus. It occurs in the knee in 50% to 75% of cases. Osteosarcoma is uncommon in the fibula, hip, mandible, maxilla, and spine. Rare sites include the skull, ribs, scapula, clavicle, patella, sternum, radius, ulna, and the small bones of the hands and feet. The preferred site is the epiphysis of the long tuberosity. It occurs in the diaphysis in 2% to 11% of cases.
Clinical manifestations
The main symptom is pain, which starts mildly, intermittently, and does not affect activity, and can worsen to unbearable persistent pain within a few weeks, often worsening at night and affecting sleep. Local swelling occurs, often developing into a visible mass by the time of consultation. The surface skin is congested, warm, and the veins are angry. The nearby joints tend to show varying degrees of flexion deformity and restricted movement. Pathological fractures may occur under minor external forces in cases of severe bone destruction.
Pulmonary metastasis may occur with chest pain, cough, hemoptysis, dyspnea, etc.
Laboratory tests
Serum alkaline phosphatase (ALP) is elevated in most cases. After effective chemotherapy or surgical removal of the primary tumor, ALP can be reduced to normal. If it is elevated, it indicates the possibility of recurrence or metastasis.
Imaging
Radiographs The early radiographic manifestations of osteosarcoma are ill-defined bone destruction in the epiphysis of the long tubular bone, under the bone cortex on one side, blurred surrounding bone trabeculae or increased bone density, and causing subperiosteal reactive osteogenesis. In fact, early lesions are rarely clinically visible pathologically, and imaging changes are evident by the time the patient is seen. The x-ray presentation of osteosarcoma is highly variable and depends primarily on the amount of tumor osteogenesis.
In osteogenic tumors, bone destruction is not obvious, and the lesions appear as cloudy high-density shadow, Codman’s triangle or daylight radiolucent periosteal reaction, and soft tissue mass shadow; in osteolytic tumors, bone destruction in the epiphysis is obvious, and the boundary of bone destruction is unclear, and the tumor penetrates the bone cortex and enters the soft tissue to form soft tissue mass;
Osteogenic and osteolytic tumors are the most common and typical radiographic manifestations, which show a large amount of high-density tumor bone in epiphyseal bone destruction, tumor penetrating the bone cortex to form soft tissue masses, tumor bone lifting the periosteum to form Codman’s triangle, and tumor bone in soft tissue arranged in a needle-like pattern to form a sun-burst image.
CT examination CT examination can help to determine the extent of tumor lesions in bone and soft tissue.
MRI
MRI plays a very important role in the diagnosis and treatment of osteosarcoma. It is significantly better than CT in determining the extent of tumor lesions within the bone and the size of soft tissue masses, as well as the relationship with surrounding blood vessels and nerves.
Currently, MRI is a mandatory preoperative test for limb preservation treatment of osteosarcoma. MRI can help physicians determine whether limb preservation is possible and the level of osteotomy for limb preservation treatment. In order to achieve extensive resection, osteotomy at 5CM from the lesion margin is currently advocated. Osteosarcoma appears as a low signal intensity image on T1-weighted images.
Osteosarcoma appears as a low signal intensity image on T1-weighted images and as a uniform or heterogeneous high signal intensity effect on T2-weighted images.
DSA examination
DSA examination can help doctors to understand the blood supply of the tumor and its relationship with the major blood vessels, which is important for the development of surgical plan. DSA examination can be followed by embolization of the blood vessels supplying the tumor or arterial perfusion chemotherapy. Since DSA is an interventional method with impairment, MRA
can replace DSA in some cases.
ECT
ECT is an important test for early detection of osteosarcoma and its distant metastases, and is also valuable for assessing the efficacy of chemotherapy for osteosarcoma.
Pathological examination
A trocar aspiration biopsy or excisional biopsy is an essential test to further confirm the diagnosis histologically and to stage the disease. Adequate amount of tumor tissue should be obtained for histopathological and immunohistochemical examination during biopsy. At present, the diagnostic accuracy of trocar needle aspiration biopsy is over 95% in larger bone tumor treatment centers in China, but due to the limited amount of tissue obtained and the fact that the tissue obtained by aspiration may not be the most active part of the tumor and is not representative.
Therefore, puncture biopsy still has some limitations, and sometimes puncture biopsy may not yield accurate diagnosis and need to be re-punctured or incisional biopsy may be required. The disadvantage of incisional biopsy is that there is a surgical incision and the surgical operation may lead to the spread of tumor, which may also bring trouble to the surgical incision for limb preservation treatment, therefore, the incision for incisional biopsy should be chosen to be able to be removed during the re-operation.
Osteosarcoma is a large tumor with an average diameter of 5cm or more. The tumor often invades soft tissues, and because the tumor contains cartilage, fibrous tissue and bone tissue components, the cut surface can be magenta or grayish white brittle fish-like; because there may be a large number of cartilage components the tumor cut surface can be gray to blue-gray; necrosis, hemorrhage and cystic changes can be seen in the tumor cut surface.
Microscopically, osteosarcoma is traditionally classified into three types according to the main differentiation characteristics of tumor cells, namely osteoblast type, chondroblast type and fibroblast type. About 50% of the osteoblast type produces tumor bone and bone-like tissue, 25% of the tumors differentiate mainly toward cartilage and become chondroblast type osteosarcoma, and the remaining 25% of the tumors differentiate toward fibrous tissue and become fibroblast type osteosarcoma.
Recently, other tissue types of osteosarcoma have also been reported, such as chondroblastoma-like osteosarcoma, osteoblast-like osteosarcoma, cartilage mucinous fibroma-like osteosarcoma, fibrous histiocytic osteosarcoma, and osteosarcoma with clear cell components. Microscopically, tumor cells with highly malignant cytological manifestations are seen surrounded by irregularly shaped immature bone or bone stroma that does not follow the direction of stress.
Treatment
Prior to the 1970s, the treatment of primary malignant bone tumors was mainly amputation, and for osteosarcoma, despite amputation, the 5-year survival rate was only about 20%. For osteosarcoma, chemotherapy is no longer an adjuvant treatment, but a major life-saving measure. By the late 1970s, chemotherapy has been standardized, emphasizing following the principles of combination drug use, neoadjuvant chemotherapy and dose intensity.
Through a combination of chemotherapy and surgical treatment, the 5-year survival rate of patients with osteosarcoma has reached about 75%, and the tumor-free survival rate has increased to about 60%. The drugs commonly used in chemotherapy for osteosarcoma are: methotrexate (MTX), adriamycin (ADM), cisplatin (CDP), carboplatin (carboplatin), cyclophosphamide (cyclophosphamide), isocyclophosphamide ( ifosfamide,
IFO), vincristine, and others. Chemotherapy is composed of different regimens of the above mentioned drugs. The route of administration is mainly intravenous, but arterial perfusion therapy is also possible. Failure of chemotherapy is due to multidrug resistance, and there is no effective way to overcome it.
Neoadjuvant chemotherapy: After the diagnosis of malignant bone tumor, preoperative chemotherapy for 6-8 weeks, followed by tumor resection and postoperative chemotherapy for 4-6 months is called neoadjuvant chemotherapy, which has become the standard of care for osteosarcoma, Ewing sarcoma, and malignant fibrous histiocytoma.
Preoperative chemotherapy has the following advantages.
(1) Killing microscopic metastatic lesions that may exist at a distant site as early as possible to improve the cure rate;
(2) Chemotherapy causes necrosis and shrinkage of the primary tumor, decreases edema around the tumor, eliminates possible satellite foci and jumping foci, and improves the safety of limb preservation treatment;
③ Chemotherapy provides time for custom-made artificial prosthesis; ④ By analyzing the necrosis rate of postoperative tumor tissues, the sensitivity of chemotherapy is determined and postoperative chemotherapy is guided.