Osteosarcoma is a primary malignant bone or soft tissue tumor arising from osteogenic mesenchymal cells. There are many subtypes of osteosarcoma: typical osteosarcoma, low-grade malignant intramedullary osteosarcoma, osteosarcoma secondary to Paget’s disease, parosteal osteosarcoma, periosteal osteosarcoma, small cell osteosarcoma, soft tissue osteosarcoma, and capillary dilated osteosarcoma. The age of prevalence is 10 to 20 years old, with more males than females. It occurs mostly in the long bone epiphysis of adolescent patients, such as the distal femur, proximal tibia, proximal humerus and distal radius, sometimes with multicentric onset.
Etiology
The cause is unknown, and there are various theories, such as chemical carcinogenesis, viral carcinogenesis, radiation carcinogenesis, etc.
Clinical manifestations
Osteosarcoma has no typical symptoms in the early stage, but only pain near the joints, often intermittent, intensifying after activities, and the pain intensifies after a few weeks and is persistent, local soft tissue masses appear, the masses gradually aggravate, hard to touch, pain is obvious, the increasing masses border is not obvious, local skin temperature increases, superficial venous anger can be seen on the skin surface, some patients may have pathological fractures. When the tumor involves osteochondral bone, swelling of joint cavity may occur. When the tumor progresses significantly, local lymph node enlargement can be palpated. Patients may develop lung metastasis at an early stage, but they may be asymptomatic clinically.
Auxiliary examination
1.X-ray examination. In the early stage, there is dissolution of bone trabeculae in the epiphysis, bone defects may involve the medullary cavity, cancellous bone or bone cortex, and there is consistent density of speckled and massed bone formation, and there may be periosteal reaction, generally in the form of laminae or small radiolucencies. With further development of the lesion, bone destruction occurs in the backbone, and periosteal reaction may appear as Codman’s triangle, often with soft tissue swelling and unshaped scattered tumor bone within the soft tissue mass.
Some osteosarcomas may be sclerotic and are often referred to as sclerosing osteosarcomas, which are generally of the osteoblast type. Osteosarcomas that are purely osteolytic are often referred to as osteolytic osteosarcomas, which are mostly fibroblastic or chondroblastic. In advanced cases, articular cartilage may be involved. Osteosarcoma often metastasizes to the lung and pleura. Chest radiographs show calcification of metastases in the lung and pleural effusion if the pleura is invaded.
2.Radionuclide scan. Typical osteosarcoma shows extensive and high concentration of nuclide, but jumping foci are difficult to identify.
CT can show the specific situation of osteogenesis and destruction, and sometimes can identify the jumping foci. CT examination of osteolytic osteosarcoma can find a small amount of residual bone in the osteolytic area and a small amount of tumor bone in the soft tissue mass; CT examination of osteogenic osteosarcoma can find the erosion and destruction of bone by the tumor in a large amount of dense and elevated tumor bone.
4.MRI examination. Sclerosing osteosarcoma shows low signal on T1-weighted image and T2-weighted image, but the edema or non-sclerotic area around the tumor shows high signal on T2-weighted image. In chondroblastogenic sarcoma, the cartilage component is high signal on T1- and T2-weighted images. Osteosarcoma with a large number of spindle-shaped fibroblasts shows low to moderate signal on T1-weighted image and moderate to high signal on T2-weighted image.
5.Pathological examination
Hard, white tissue, usually with scattered fish-like or hemorrhagic areas, is seen by the naked eye. When the tumor is marked preoperatively with tetracycline, it is easier to determine the intramedullary extent, satellite nodes, jumping foci, epiphyseal invasion, and joint invasion. Satellite foci are small and usually need to be visualized below the scope. Isolated satellite foci can be seen within the reaction zone of either low- or highly malignant sarcomas. Satellite foci are not true metastases, but are tiny lesions that invade directly outside the tumor envelope. Sometimes, when it is large enough, it can be seen directly on the gross specimen and on x-ray.
What is seen microscopically Typical osteosarcoma has highly malignant cytologic changes with tumorigenic bone formation. The tumorigenic bone is immature, irregular in shape, and not aligned in the direction of stress. Areas of cartilage and/or fibrous differentiation are often seen.
[Differential diagnosis
1. Chondrosarcoma develops at an older age, preferably in the flat bone or long bone epiphysis, with irregular osteolytic destruction, unclear borders, mostly calcified shadows within, and surrounded by soft tissue masses. Microscopically, chondrocytes are lobulated, with a uniform distribution of cells and hypertrophic nuclei, often with binucleated cells, and occasionally with irregularly shaped giant chondrocytes. The main points of differentiation between the two are the older age of chondrosarcoma, the absence of tumor bone in the lesion, the presence of calcified shadows, the rare periosteal reaction, and the absence of tumor bone in the tumor on pathological examination.
Fibrosarcoma is more frequent in 30-50 years old, and the X-ray of fibrosarcoma in bone shows a penetrating eccentric destruction area with reduced density, without tumor bone and calcification.
Treatment idea]
Ninety percent of the cases are stage II-B tumors, another 5% are stage II-A tumors, and 5% are stage III tumors. For typical osteosarcoma, if its preoperative chemotherapy is effective, extensive bulky resection is feasible. However, if chemotherapy is ineffective, radical resection or amputation should be performed. Distant metastases from osteosarcoma are mostly located in the lungs and, to a lesser extent, in the bone. While distant soft tissue metastases are mostly neglected, lung metastases are often treated by surgical resection.
Treatment methods
1.Non-surgical treatment
(1) Chemotherapy: The current chemotherapy for osteosarcoma is called neoadjuvant chemotherapy, and the principles include three parts.
(1) Emphasize the importance of preoperative chemotherapy ;
②The resected tumor should be examined for necrosis rate;
(3) The postoperative chemotherapy plan is decided according to the tumor necrosis rate. The current trend is to use very strong pre-surgical chemotherapy in combination with high doses of methotrexate, cisplatin, isocyclophosphamide and adriamycin.
After a short course of chemotherapy for approximately 2 months, surgery can be performed when liver and kidney function is not significantly abnormal and platelets and neutrophils have returned to normal levels. In the few cases where chemotherapy cannot be completed before surgery due to very bulky and rapidly growing tumors, amputation should be performed without delay.
After surgical resection, at least one section of the entire tumor specimen should be examined histologically. When the necrosis of tumor cells reaches 90%, it means that the tumor has good sensitivity to chemotherapy, so the same drugs should be used continuously.
The commonly used drugs are methotrexate (MTX), adriamycin (ADM), cisplatin (CDP), vincristine (VCR), isocyclophosphamide (IFO) and so on. All antineoplastic drugs have toxic effects on the body, and the main toxic reactions are liver function damage, digestive system reaction, oral mucosal ulcer, bone marrow suppression, etc.
At present, although it is not possible to achieve uniformity in chemotherapy regimens, some principles have gradually been agreed upon. The aim of chemotherapy is to improve the long-term survival of patients and to reduce the incidence of fatal distant metastases. Therefore, the main target of chemotherapy is distant micro-metastases rather than local primary foci, and the concept of simply pursuing resection rate is wrong.