Giant cell tumor of bone (GCT) is one of the common primary bone tumors, accounting for approximately 15% of all benign bone tumors, and the incidence of GCT is higher in China than in Western countries. X-ray, pathology-specific presence and differentiation from other benign lesions.
Giant cell tumor of bone is an aggressive bone tumor with stromal cells and multinucleated giant cells as the main structures, which is considered by most scholars to be potentially malignant and cannot be treated in the same way as a benign tumor. According to statistics, 20% of bone giant cell tumors are malignant, and 8% of them are primary malignant giant cell tumor of bone (PMGCT).
(I) Clinical manifestations
1. Symptoms and signs
Giant cell tumor of bone occurs in young adults whose epiphyseal plates have fused, and the age of onset is mostly between 20 and 40 years old. The incidence is slightly higher in women than in men. The early symptoms of giant cell tumor are atypical, and patients tend to feel pain, which is sore or dull in nature but not severe. There may be mild local swelling, mostly as a result of bony swelling. Local masses are more pronounced when the lesion breaks through the bone cortex and invades the soft tissue.
Pressure pain and elevated skin temperature are prevalent. In slow-growing cases, a ping-pong ball-like bone shell may appear when the finger is pressed, and in cases of hemorrhagic necrosis, it may rapidly increase in size and become cystic or fluctuate. If the tumor destroys the joint, it may produce corresponding joint dysfunction, such as limitation of joint flexion and extension; tumor in trunk bone may also produce corresponding symptoms, such as presacral mass may compress sacral plexus and cause severe pain, and compress rectum and cause difficulty in defecation. Compared with benign giant cell tumor of bone, malignant giant cell tumor of bone grows rapidly, the mass increases rapidly, the local pain is progressively aggravated, the nature of pain develops from intermittent to persistent, and signs such as venous dilatation can be seen, accompanied by different degrees of systemic symptoms.
2.Site of origin
The primary site of giant cell tumor of bone almost always occurs in the epiphysis after the epiphyseal growth plate is completely fused, and gradually invades the epiphysis as the lesion expands. The diagnosis of giant cell tumor cannot be established if the lesion is limited to the epiphysis but not the epiphysis. 90% of giant cell tumors invade the long bones, with the lower femur and upper tibia being the most frequent sites; the other sites are the distal radius, fibula, proximal femur and proximal humerus in that order. About 10% of giant cell tumors occur in non-long tubular bones such as the hand, spine, and pelvis.
Figure 1 Giant cell tumor of bone in the distal femur.
(II) Imaging examination
The typical radiographic findings are osteolytic lesions invading the epiphysis, eccentric, distended, and without sclerotic margins; no reactive new bone production, thinning of the bone cortex in the lesion, and soap bubble-like changes (Figure 1); and often pathological fractures, caused by osteolytic destruction, usually without displacement. According to the campanacci grading system of imaging [4] it can be classified into three grades.
Grade I : shows intraosseous lesions with clear soap bubble-like signs or capsules within the lesion and no soft tissue mass shadow.
Grade II : still intraosseous lesion, but thin bone shell, partial blurring of soap bubble-like intervals within the lesion, and lysis and fracture.
Grade III: Malignant giant cell tumor of bone, typically showing tumor spread to extraosseous soft tissue, with large osteolytic destruction in the lesion, sometimes residual soap bubble-like interval, and common shell-breaking sign and soft tissue block shadow with blurred margin.
Figure 2 CT and MRI images of a giant cell tumor of the proximal tibia showing destruction of the bone cortex and invasion of the tumor into the joint cavity.
CT examinations are more useful than X-rays in determining the boundaries of the tumor and are helpful in clarifying the relationship between the tumor and the articular cartilage and joint cavity and the extent of tumor invasion of the surrounding soft tissues. The advantage of MRI images for this disease is that they can clearly show the presence of the lesion and the involvement of the bone marrow and joint cavity. MRI is also significantly better than other imaging methods in terms of the display of the surrounding soft tissue masses and the relationship with the peripheral nerves and blood vessels (Figure 2).
Figure 3 Giant cell tumor of bone with active cell growth.
Figure 4 Pathological grading of giant cell tumor of bone Grade II.
(III) Pathologic histological examination
1. Visual observation
Compared with other substantial tumors, the tumor tissue of giant cell tumor of bone is rich in circulation, soft and brittle. The tumor tissue is reddish-brown and resembles granulation tissue, easily bleeding, with fibrous mechanized area and bleeding area. When the bone cortex becomes thin, the tumor expands through the cortex to the soft tissue.
2.Microscopic view
It is composed of multinucleated giant cells and stromal cells, and the multinucleated giant cells are distributed among the stromal cells (Figure 3). Multinucleated giant cells can be formed by the fusion of mononuclear stromal cells, with the number of nuclei ranging from a few to hundreds, and have the characteristics of macrophages and osteoblasts. Stromal cells can be divided into two types: one similar to fibroblasts and one similar to histiocytes. It is generally believed that multinucleated giant cells do not have tumor cell characteristics, while fibroblast-type stromal cells are the main tumor component.
For the pathological grading of giant cell tumors of bone, the grading criteria proposed by Jaffe et al [1] in 1940 were mainly based on the number of giant cells and the degree of differentiation of mesenchymal cells: degree I, about half of the giant cell tumors belong to this category, is apparently benign, with many giant cells and few cell divisions, noting that all tumors need to be degree I to be judged as degree I. Degree II, malignant or benign is not easily distinguished. There are more stromal cells and fewer giant cells than in grade I (Figure 4). Grade III, also known as malignant giant cell tumor, has more stromal cells, larger nuclei, and a sarcoma-like morphology, with more cell divisions and fewer and smaller giant cells and fewer nuclei. It has been pointed out [5] that the grading of cytology only reflects the general rule, and distant metastasis occurs in individual clinical cases of grade I, while grade III sometimes has a less poor prognosis, which indicates that the understanding of the properties of giant cell tumor of bone should be considered in combination with clinical and X-ray manifestations.
(IV) Diagnosis and differential diagnosis
The diagnosis of giant cell tumor of bone needs to be made based on a combination of clinical, imaging and pathological aspects. Among them, X-ray provides important clues for the diagnosis of giant cell tumor of bone, and pathological confirmation is required for the final diagnosis. Giant cell tumors of bone are sometimes highly variable and should be clinically differentiated from the following lesions.
1. Aneurysmal bone cysts: Patients are mostly adolescents, most often between the ages of 10 and 20, and about three-quarters of patients develop before the age of 20, whereas giant cell tumors of bone rarely develop before the age of 20. X-rays generally show eccentric osteolysis at the cancellous bone of the epiphysis, and the osteolysis may extend to thin the bone cortex, balloon-like expansion or multi-cystic bone destruction. The cystic cavity is filled with blood, and in resting aneurysmal bone cysts the cavity is large and contains blood clots and serous fluid. When the diagnosis cannot be clearly made by frozen section, the diagnosis can only be confirmed by wax film.
2. Brown tumor: It is a localized bone destruction caused by hyperparathyroidism, mostly seen in adults aged 30 to 50. In addition to local swelling and pain, there are also symptoms of general weakness, such as mental depression, lethargy, decreased muscle tone and weakness, anorexia, peptic ulcer, abdominal pain, vomiting, irritability, polyuria, kidney stones, renal insufficiency, etc. It is mainly due to elevated serum calcium and is easily misdiagnosed. X-rays show extensive osteoporosis or limited osteolytic destruction, which may be central or eccentric, thinning or even disappearance of bone cortex, moderate expansion of the involved bone, no invasion of soft tissue and no periosteal reaction.
3, isolated bone cyst: mostly occurs in children or adolescents, symptoms are light; lesion site in the epiphysis eccentric, most common in the proximal humerus. x-ray shows the bone stem or bone end is transparent lesion, cortical mild expansion, clear boundary; capsule filled with fluid, large specimens are easy to distinguish from bone giant cell tumor.
Fibrosarcoma: The age of onset is older than that of giant cell tumor of bone, only osteolysis without expansion. The tumor is tough and biopsy can help to differentiate the diagnosis.
Sometimes, it should be distinguished from fibrous heteroplasia, chondroblastoma and osteosarcoma.
Figure 5 a b is after lesion scraping plus bone grafting, c d is six months postoperative review.
(E) Treatment and prognosis
Surgery is the most effective treatment for giant cell tumor of bone, but giant cell tumor of bone is prone to recurrence after surgery. According to the degree of anatomical structure and functional destruction of bone and joint, surgery is divided into three levels: intra-lesion scraping, segmental resection and amputation. Intra-lesion scraping includes scraping bone grafting and scraping bone cement filling; lumpectomy includes simple lumpectomy, lumpectomy autologous bone grafting, lumpectomy allogeneic bone grafting, lumpectomy inactivated replantation, joint fusion and artificial joint replacement.
The principle of surgery is to completely remove the tumor while preserving the normal structure and function of the bone and joint as much as possible. Because the cell proliferation rate of giant cell tumor of bone is not high and it is not sensitive to chemotherapy, the efficacy is often unsatisfactory, and chemotherapy is only used to control the tumor development before surgery for patients with lung metastasis. Radiation therapy is also only applicable to patients whose tumors are not surgically resectable due to their special growth sites, and the sensitivity of this tumor to radiation therapy is also very low, and the malignancy rate of radiation therapy is high. Most of the cases can be cured with timely and appropriate treatment, and the joint function can be preserved satisfactorily.
1. Lesion scraping and bone grafting (Attachment 5): Preoperative balloon tourniquet is tied to avoid blood expulsion operation, and firstly, the tumor is scraped thoroughly by opening the window. Make a longitudinal arc incision centered on the tumor site, with both ends exceeding the upper and lower poles of the tumor. After dissecting the deep fascia, the periosteum is incised in the direction of the incision and subperiosteal dissection is performed. The junction between the normal bone and the tumor is found, and the hole is drilled continuously with a bone drill, and then a window is opened along the bone hole with a bone knife or bone chisel (usually the area with severe bone destruction and non-weight-bearing bone area). The size of the window depends on the extent of tumor invasion, and it is appropriate to scrape away the tumor under direct vision. After the lesion is fully exposed, the tumor tissue in the bone cavity is first scraped off with a scraper, and then the bone wall, interval, sclerotic bone and its residual lesion are removed from the upper wall, inner wall and lower wall in three directions with a bone knife until the normal bone is exposed, and if necessary, a thin layer of cancellous bone can be removed to reduce the retention of tumor cells around the tumor. In the process of excision and scraping, care should be taken not to damage the articular cartilage and strive to preserve the normal articular surface.
The correct use of adjuvant methods combined with modern extensive scraping techniques is an important tool to reduce the recurrence rate. The inactivating agents used clinically are: carbolic acid, liquid nitrogen, 95% alcohol, zinc chloride, phenol, hydrogen phosphate, hydrogen peroxide, etc. Recently, argon electric knife cautery and microwave irradiation have also been put into use.
Finally, the residual bone graft is used to fill the lesion with autologous and/or allogeneic bone and compress it in order to restore the strength of the subchondral bone of the joint in as short a time as possible. If the lesion is small, autologous bone grafting can solve the problem; if the bone defect is too large for autologous bone to meet the filling needs, combined autologous and allogeneic bone implantation can be used, in which case the autologous bone should be placed directly in the subchondral area of the articulation, and the allogeneic bone should be placed in the area that is not important for bone repair. Regular postoperative film review should be taken to determine the weight-bearing time according to the bone repair situation.
2. Focal scraping and bone grafting + bone cement filling (Attachment 6): The surgical opening and inactivation methods are the same as focal scraping and bone grafting, with the difference that the residual cavity is repaired with bone grafting + bone cement filling. It is mainly used in cases where the residual cavity is large and the scraped edge reveals part of the articular cartilage, mostly in the lower femur and upper tibia with osteomegaloblastic tumors. In order to maintain the stability of the articular surface and the survival of the articular cartilage, autologous iliac bone is taken and approximately 10 mm thick cancellous bone is implanted on the exposed cartilage surface before cement filling. Bone cement (methyl methacrylate) can be used as a bone filler, a support, and an aid in tumor killing by the toxicity of its monomer and the heat generated during polymerization. It has been reported [9] that the recurrence rate is significantly reduced after lesion scraping with bone cement filling of the residual cavity, and Figure 7 shows a 5-year follow-up X-ray after scraping with bone cement filling of a giant cell tumor of the distal femur, with no tumor recurrence.
Figure 6 a shows a giant cell tumor of the distal femur, and b shows the lesion after scraping and cement filling.
Figure 7 X-rays of the distal femoral giant cell tumor 5 years after scraping and cement filling.
3. Segmental resection + arthroplasty (Figure 8): For giant cell tumor that invades most of the bone ends and the joint surface has collapsed, or the pathology has been changed by fibrosarcoma, segmental resection plus arthroplasty can be used. Other indications include.
①The systemic condition and local soft tissue conditions allow, the main nerves and blood vessels are not involved, extensive resection can be achieved, and the expected local recurrence rate is not higher than that of amputation;
②No metastatic lesions or metastatic lesions can be cured;
③The patient has a strong desire for limb preservation and financial ability;
④Postoperative function is better than that of prosthesis.
Contraindications for surgery are.
①Tumor invasion is extensive, and important nerves and blood vessels are involved and cannot be completely removed;
②Local and systemic infection;
③Poor systemic condition or local skin and soft tissue conditions, which may make it difficult to tolerate the surgery or may lead to difficulty in closing the incision and skin and soft tissue necrosis after surgery;
(iv) Advanced tumor, short life expectancy and no strong desire for limb preservation.
Figure 8 a b shows a giant cell tumor of the proximal tibia, c shows a one-week X-ray after resection of the tumor segment + artificial prosthesis replacement, and d shows a one-year postoperative review X-ray.
Bone tumor prosthesis replacement is different from general artificial joint replacement in that the design, material properties and fixation techniques of the tumor prosthesis are more demanding. The postoperative complications of prosthesis replacement mainly include recurrence, infection, prosthesis loosening and prosthesis fracture. Infection is the most serious of the postoperative complications, often leading to catastrophic consequences, and should be prevented.
Figure 9 a b shows the pathological fracture of the distal bone giant cell tumor of the flexural bone. c d shows the review X-ray one and a half years after the resection and inactivation of the lumpectomy, the osteotomy healed and the tumor did not recur.
4.Inactivation and replantation of lumpectomy + bone cement filling (Figure 9): After lumpectomy, the tumor tissue in the bone shell was scraped away, and the bone shell was placed in 95% alcohol and inactivated for 40 minutes and then replanted, and the residual defect was filled with bone cement.