Osteosarcoma is a malignant bone tumor characterized by the direct formation of bone or bone-like tissue by tumor cells, with the highest incidence of malignant bone tumors. Osteosarcoma can be divided into primary and secondary types. Primary osteosarcoma can be divided into intraosseous osteosarcoma occurring in bone and extraosseous osteosarcoma occurring in soft tissue, the latter is rare; secondary osteosarcoma is osteosarcoma occurring secondary to some bone tumor, bone disease or certain lesions after radiotherapy, which is rare in clinical practice. In addition to the most common common type (or classic) osteosarcoma, the former includes subtypes such as capillary dilated osteosarcoma, intramedullary highly differentiated osteosarcoma, and small (round) cell osteosarcoma. surface osteosarcoma). According to the histological characteristics of the tumor, it can be divided into osteoblast type, chondroblast type, fibroblast type osteosarcoma and other types. The general term osteosarcoma refers to the common type (classic) osteosarcoma. Kwon
I. Clinical characteristics
Age
Osteosarcoma occurs in adolescents between 10 and 20 years old, but rarely before 10 years old and after 30 years old.
Sex
There are more male patients than female patients, and the ratio is about 3:2.
Location
Osteosarcoma is most common in the long bones of the extremities and the pelvis, with the distal femur, proximal tibia and proximal humerus accounting for 3/4 of all osteosarcomas.
Symptoms and signs
The earliest clinical symptom is localized pain, which is mild at the beginning, gradually worsens and becomes apparent at night, and is easily attributed to injury and ignored by the patient. It is easily attributed to injury and ignored by patients. Subsequently, soft tissue swelling or lump with pressure pain appears, and some patients have limitation of joint movement. Increased skin temperature and subcutaneous venous anger may be seen locally in the tumor. In a few patients, pathological fracture may appear earlier due to rapid progression of the lesion.
Laboratory tests
Serum alkaline phosphatase may be normal in early stage of osteosarcoma, sclerosing osteosarcoma, parosteal osteosarcoma and low-grade malignant osteosarcoma, and may exceed the normal value by more than 10 times when the tumor is huge and metastases are present. After high-dose chemotherapy or surgery, alkaline phosphatase mostly decreases, and then increases again when the tumor recurs or metastasizes. Therefore, alkaline phosphatase can be used as a sensitive indicator to judge the efficacy of chemotherapy and to monitor whether the tumor has recurrence or metastasis.
Imaging characteristics
Osteosarcoma is characterized by a variety of radiographic manifestations: sclerosing osteosarcoma, which is mainly osteogenic; osteolytic osteosarcoma, which is characterized by simple bone destruction; and mixed osteosarcoma, which is characterized by a mixture of bone destruction and osteogenic areas. Most of the lesions have indistinct borders, and periosteal reactions are seen as Codman’s triangle or sunburst periosteal reactions. Soft tissue masses can be seen when the tumor penetrates the bone cortex.
CT and MRI are not specific, but can clarify the extent of tumor invasion and adjacent relationship, especially MRI can show the extent of tumor invasion in the intramedullary and surrounding soft tissues, which can help determine the level of osteotomy and surgical plan.
DSA examination can understand the blood supply of the tumor and its relationship with the main blood vessels, which is important for the formulation of surgical plan. interventional treatment and placement of arterial perfusion chemotherapy device can also be performed after DSA examination.
ECT is an important tool for early detection of osteosarcoma and its distant metastases, and is also valuable for the evaluation of chemotherapy efficacy of osteosarcoma.
Pathological changes
General
The tumor is located in the epiphysis of long bones with unclear boundary, and the cross-section is diverse: the area with abundant tumor cells is grayish red, grayish white, soft and fish-like; accompanied by dark red and grayish yellow hemorrhagic necrotic area, grayish white brittle chondrogenic area and gravel-like or hard ivory-like osteogenic area. When the tumor penetrates the bone cortex, it may form a fish-like soft tissue mass.
Microscopy
The formation of bone or bone-like tissue by interstitial tumor cells is necessary for the diagnosis of osteosarcoma. Osteosarcoma cells are pleomorphic and heterogeneous, showing shuttle, ovoid or irregular shape, abundant cytoplasm, eosinophilic, variable size of nuclei, coarse or massive chromatin, and easy to see nuclear schizophrenia and pathological nuclear schizophrenia. The tumor cells produce bone like tissue or bone tissue in varying numbers and morphology. Ordinary osteosarcoma is divided into osteoblast type, chondroblast type and fibroblast type according to the main cellular components of mesenchymal lesions.
Differential diagnosis
1.Osteoblastoma
Osteoblastoma is easily confused with osteoblastoma in terms of histomorphology. Osteoblastoma is a well-defined cystic osteolytic destruction with clinical and X-ray features of benign tumor.
2.Special type of fracture
Osteoblastoma is easily mistaken for osteosarcoma on X-ray when it is formed in certain areas such as occult fatigue fracture of tibia or pathological fracture secondary to some benign lesions. In this case, we should take a detailed medical history and follow the principle of careful diagnosis by combining clinical, imaging and pathology to avoid irreparable damage.
3.Chondrosarcoma
Adolescent patients with chondrosarcoma have rapid disease development and severe pain, which need to be distinguished from osteosarcoma. Osteosarcoma can be seen microscopically as direct osteogenesis of tumor chondroblasts or spindle cells, while chondrosarcoma shows intrachondral ossification.
4.Osteogenic metastatic cancer
Bone metastases from prostate cancer and breast cancer are often accompanied by osteogenesis, which can be easily mistaken as osteosarcoma on X-ray. With detailed medical history, complete relevant examinations, combined with consideration of patient’s gender, age and location, a clear diagnosis can be made.
V. Treatment and prognosis
The currently accepted treatment plan for osteosarcoma is a comprehensive treatment based on high-dose chemotherapy and surgery. After preoperative high-dose chemotherapy, the tumor can be widely resected and artificial bone joint replacement or large allograft bone joint transplantation can be used for limb preservation treatment. After surgery, high-dose chemotherapy is continued to control lung metastases and reduce the local recurrence rate.
Since high-dose chemotherapy was introduced, the prognosis of osteosarcoma has been greatly improved, and the five-year survival rate of osteosarcoma patients with standardized treatment has reached 70 to 80%, and 90% of patients can save their limbs. After lung metastasis of osteosarcoma occurs, metastasectomy on the basis of high-dose chemotherapy can still achieve certain efficacy, and the five-year survival rate can reach about 30%.
Special types of osteosarcoma
1. Telangiectatic osteosarcoma (capillary dilatation osteosarcoma)
Telangiectatic osteosarcoma is rare, accounting for less than 5% of osteosarcomas. The age of predilection is 10-30 years old, and it is more common in males, and the site of onset is mainly located in the femur and tibia. Early symptoms are mainly painful, and pathological fractures may occur with the expansion of the lesion, which may result in inflammatory-like changes due to the spread of blood from the tumor to the subcutaneous fascial space. After biopsy of the lesion, there may be prolonged bleeding from the wound.
CT and MRI may show features of bleeding in the lesion, and soft tissue masses may appear when the lesion penetrates the bone cortex.
Pathological changes: The tumor area is seen as a dark red blood-filled cavity with irregular border like jagged or thorny, and the bone cortex may be completely destroyed and disappeared.
The bone cortex can be completely destroyed and disappeared, and the remaining bone cortex at the edge is like a porous sponge. Microscopically, a large number of blood-containing sinus-like and “ribbon-like” structures can be seen, which can be easily mistaken for aneurysmal bone cysts. The tumor cells are obviously heterogeneous, and pathological nuclear division is common. Benign multinucleated giant cells can be seen scattered in the luminal wall tissue.
This disease should be distinguished from aneurysmal bone cysts and giant cell tumor cystic lesions of bone.
The treatment of this disease is the same as that of the common type of osteosarcoma. The disease progresses rapidly and the prognosis is worse than that of common osteosarcoma.
2.Intraosseous well-differentiated osteosarcoma
Intraosseous well-differentiated osteosarcoma, also known as central low-grade osteosarcoma, is less common and accounts for about 1% of osteosarcomas. The age of onset is older than that of ordinary osteosarcoma, and it is more common in women. The histological features and biological behavior are similar to those of parosteal osteosarcoma, but the lesion occurs in the marrow cavity of long bones and may break through the bone cortex and grow outward as the disease progresses, and compress or encircle major nerves and blood vessels.
Treatment is mainly surgical, and extensive resection of the tumor segment and appropriate bone reconstruction should be performed. It is easy to recur after local excision, but rarely metastasizes and has a better prognosis than common osteosarcoma.
3.Small-cell osteosarcoma
Small-cell osteosarcoma, also known as round-cell osteosarcoma, is a rare type of highly malignant osteosarcoma with tumor cells similar to the small round cells of Ewing sarcoma. The age of the disease is 10 to 20 years old.
Radiographic manifestations: worm-like osteolytic lesions located in the epiphysis, more than half of them have periosteal reaction and soft tissue masses.
Pathologic changes: It consists of dense, diffuse, low-differentiated or undifferentiated small round cells, which often have polymorphic, large chromatin-containing nuclei with obvious nucleoli and common nuclear schizophrenia, and darkly stained cytoplasm, usually without cytoplasmic glycogen. There is a small amount of fine-needle and reticulated bone-like tissue between the cells, which is the basis for differentiation from Ewing sarcoma.
Small cell osteosarcoma has a poorer prognosis than common osteosarcoma, and death usually occurs within one year after diagnosis.
4.Parosteal osteosarcoma (parosteal osteosarcoma)
Parosteal osteosarcoma, also known as Juxtacortical osteosarcoma, is a classic type of superficial osteosarcoma, which is slow growing, less malignant and has a better prognosis.
The age of onset of parosteal osteosarcoma is higher than that of the common type of osteosarcoma, with symptoms appearing between 15 and 40 years of age. There are slightly more women than men. It is most common in the long epiphysis of the extremities, most often behind the distal femur, followed by the proximal humerus, tibiofibula and ulnar radius, and occasionally in the pelvis.
The disease develops slowly, with mild symptoms and a long course. Its first symptom is a localized mass, or in the distal femur, a mass in the N fossa. Local pain is insignificant with mild pressure pain. The tumor is bony and hard, with an irregular surface shape, and the base is fixed in the bone cortex, with limited movement. When the tumor is adjacent to a joint, joint movement may be limited. The patient’s general condition is good and alkaline phosphatase is not high.
The x-ray presentation of parosteal osteosarcoma is very typical: the tumor is located on the side of the long bone epiphysis, encircling the bone stem, with lobulated or irregular hyperdense shadow and clear margins. There are scattered translucent areas of different sizes in the dense image, and there may be narrow translucent lines between the tumor and the bone cortex. In advanced stage, it may destroy the bone cortex and enter the medullary cavity.
The pathologic changes of parosteal osteosarcoma are consistent with the radiographic presentation, showing a large lobulated or irregular mass with a hard texture and a pseudofibrous envelope. The surface is grayish or yellowish white, with a hard bone like center and base, and a slightly soft margin. Microscopically, the tumor is composed of spindle-shaped tumor cells and mature bone trabeculae, and the anisotropy of spindle cells is not obvious.
Parosteal osteosarcoma needs to be differentiated from osteomyositis, lobulated osteochondroma and paracortical chondrosarcoma.
Treatment of parosteal osteosarcoma is mainly surgical, and chemotherapy and radiotherapy are usually not required. Extensive resection can achieve satisfactory results, and bone grafting can be given to the bone defect after resection. If resection is not complete, the recurrence rate is high. In a few cases of recurrent recurrence, high malignancy, extensive lesions or involvement of major blood vessels and nerves, amputation is required.
Parosteal osteosarcoma is less malignant than common osteosarcoma and has a better prognosis, with more than 80% of patients being cured.
5.Periosteal osteosarcoma (Periosteal osteosarcoma)
Periosteal osteosarcoma is a malignant osteogenic tumor that occurs in the periosteum of the long bone stem and grows outward. It is slightly more common in women than men, and the peak age of onset is 10 to 20 years. The preferred site is the long bone stem, especially the middle tibia as the typical site; followed by the femur, humerus, fibula and iliac bone. The tumor can be seen as an exophytic mass of the long bone stem with a small size, a few of them can destroy the bone cortex, and generally do not involve the medullary cavity. x-ray examination shows a pyknotic thickening of the periosteum and erosion of the bone cortex from the outside, and there may be pin-like bone. The histological manifestation is chondroblastic osteosarcoma, which should be distinguished from periosteal chondrosarcoma.
The treatment of periosteal osteosarcoma is extensive resection of the tumor segment, and chemotherapy is usually not required. The prognosis is better than that of common osteosarcoma and worse than that of parosteal osteosarcoma.
6.High-grade surface osteosarcoma (High-grade surface osteosarcoma)
High-grade surface osteosarcoma occurs on the surface of bone, but has similar histological characteristics and biological behavior as ordinary osteosarcoma. x-ray examination shows that the tumor is located on the surface of bone, the density is not uniform, irregular destruction of bone cortex and involvement of marrow cavity can be seen, and periosteal reaction can be seen. The histology of the tumor is osteoblast type osteosarcoma with obvious cell anisotropy. The treatment of this type of osteosarcoma is the same as that of ordinary osteosarcoma, and the prognosis is poor.
VII. Typical cases
1. Case 1: Male 22-year-old giant pelvic osteosarcoma with extensive tumor resection and artificial hemipelvic prosthesis replacement after high-dose chemotherapy.
Preoperative radiograph
Preoperative MRI
Postoperative X-ray
2. Case 2: Female 25 years old, osteosarcoma of the left lower femur with pathological fracture, extensive resection of the tumor after high-dose chemotherapy and custom-made artificial joint replacement.
Pre-operative X-ray
Postoperative X-ray