Giant cell tumor of bone is a relatively common type of bone tumor, accounting for 5%-8% of all bone tumors. In the 1940s, Jaffe proposed the pathological classification of giant cell tumor of bone, which was divided into three grades according to the proportion of cellular components in the tumor tissue, the presence or absence of pathological nuclear division, the presence or absence of intercellular molting, and the presence or absence of sarcomatous components, among which grades I and II were benign and grade III was malignant. However, in the course of long-term clinical practice, it was found that this simple histological grading often failed to make an accurate judgment on the prognosis.
The WHO 2002 classification of bone tumors divides giant cell tumors into two categories: one is the common giant cell tumor (GCT), which is a benign tumor with local aggressiveness and consists of lamellar arrangement of tumor mononuclear cells and interspersed osteoblast-like giant cells. The other type is called “malignancy in giant cell tumor”, or “giant cell tumor malignancy”, and is divided into two categories: primary and secondary. Primary malignancy in giant cell tumor is extremely rare and refers to a large benign giant cell tumor seen adjacent to a large highly malignant sarcoma in the initial lesion, which is clearly distinguishable. Secondary malignant giant cell tumor of bone refers to the appearance of a highly malignant sarcoma at the same site several years after treatment for giant cell tumor of bone. It can occur after radiotherapy or without a trigger. Whether primary or secondary malignant giant cell tumors, their malignant component is a highly malignant spindle cell sarcoma, usually a malignant fibrous histiocytic, common osteosarcoma or fibrosarcoma.
I. Clinical characteristics
1.Age
The peak age of onset of giant cell tumor of bone is 20 to 45 years old, and it is rare before puberty, i.e., before epiphyseal closure and after 50 years old.
2. Gender
Females are slightly more common than males.
3.Site
Giant cell tumors of bone mostly occur at the ends of long bones, especially at the distal femur, proximal tibia, distal radius and proximal humerus. A few involve the pelvis, sacrum or other vertebrae. Giant cell tumors of multicentric origin are rare and most often involve small tubular bones and short bones at the ends of the limbs. Tumors originating in soft tissues with characteristics of giant cell tumors are rare.
4.Symptoms and signs
The main symptom is pain, often sore, vague or dull, which is the main reason for patients to visit the doctor. In some cases, there is local swelling, which is mostly caused by bone swelling. The local mass is more pronounced when the lesion penetrates the bone cortex and invades the soft tissue. Pressure pain and increased skin temperature are common. When the tumor is adjacent to a joint, it often causes joint dysfunction and joint effusion. A few patients are seen for pathological fractures, which can cause more severe pain and dysfunction. Tumors in the spine and sacrum often show symptoms of nerve compression.
Imaging performance
1.X-ray characteristics
X ray of lesions occurring in long bones usually shows expansive, eccentric osteolytic destruction, sometimes with soap bubble-like changes. There is usually no periosteal reaction to osteogenesis. The lesion mainly involves the epiphysis and adjacent metaphysis, often extending to the subchondral region, and sometimes to the joints. In rare cases, the lesions are confined to the epiphysis, which occurs in adolescents with developing epiphyseal plates, and lesions in the diaphysis are usually less common.
Campanacci classifies giant cell tumors of bone into 3 grades according to their imaging characteristics: grade I is a stationary lesion located in the bone with a clear border and a peripheral sclerotic rim; grade II is an active lesion with a clear border, thinning and swelling of the bone cortex and no peripheral sclerotic rim; grade III is an aggressive tumor that penetrates the bone cortex and forms a soft tissue mass with an indistinct border. There is no good correspondence between the above grading system and histological changes.
2.CT and MRI performance
CT examination can provide a more accurate assessment of tumor destruction or penetration of the bone cortex and invasion of the joint, while MRI imaging is of great value in evaluating the extent of tumor expansion in the bone and the extent of soft tissue and intra-articular involvement. Giant cell tumors in bone typically show low to moderate signal on T1-weighted images and moderate to high signal on T2-weighted images, and often produce low signal changes in both MRI presentations due to the presence of large amounts of iron-containing heme within the lesion.
Pathological changes
1. Gross
The lesion is a well-defined area of eccentric bone destruction, often surrounded by a thin incomplete reactive bone shell, which rarely penetrates the articular cartilage, although the lesion often erodes. The lesion tissue is soft and brownish-red in texture, but yellow areas due to yellow tumor-like changes may be present, and tough white areas are fibrotic. Sometimes blood-filled cystic areas can be seen, and when such changes are extensive, they can be easily confused with aneurysmal bone cysts.
2.Microscopic
The characteristic histological changes are round, ovoid, polygonal or spindle-shaped mononuclear stromal cells and osteoblast-like giant cells evenly distributed among them. These giant cells can be very large in size, and the number of nuclei can reach 50-100. The nuclei of stromal cells are similar to the nuclei of giant cells in morphology, with loose chromatin, one to two small nucleoli, indistinct cytoplasmic boundaries, and small amounts of collagen between cells.
It is now largely accepted that the large characteristic osteoblast-like giant cells are not tumor cells, and the mononuclear stromal cells, which are tumorigenic components, are thought to be derived from primitive mesenchymal stromal cells, which are less abundant in tumor tissues and express RANKL to stimulate the transformation and maturation of osteoblast precursor cells into osteoblasts. The expression of RANKL stimulates the transformation and maturation of osteoclast precursor cells into osteoblasts.
Based on these basic features, giant cell tumors of bone can be classified into various types. In some cases, the monocytes tend to be more spindle-shaped and can be arranged in a spoke-like structure. Often, a small number of foamy cells may be present, and in a few cases, the presence of a large number of foamy cells produces fibrous histiocytoma-like changes. In approximately 10% of cases with secondary aneurysmal bone cysts, areas of fibrosis may be present. Small focal areas of new bone formation may be present in the tumor, especially in cases where pathologic fractures or bone biopsies have occurred. When the lesion extends into the soft tissues or metastasizes into the lung tissue, the histologic features are identical to those of the primary focus and a peripheral reactive bone shell can often be seen. In 1/3 of cases, a striking feature is the presence of intravascular tumor thrombi, especially in the peripheral part of the tumor, but of no particular prognostic value. Tumor necrosis is also common in larger lesions.
Differential diagnosis
Although multinucleated giant cells are one of the major components of giant cell tumors of bone and are named as such, the presence of multinucleated giant cells should not be used to diagnose giant cell tumors of bone, as many other bone tumors and tumor-like lesions can contain multinucleated giant cells. A combination of clinical, radiologic, and pathologic approaches is the correct way to make the diagnosis. Lesions that are easily confused with giant cell tumor of bone include aneurysmal bone cyst, osteoblastoma, chondroblastoma, mucinous fibroma of cartilage, and non-ossifying fibroma, etc. The combination of clinical, radiological and pathological methods should be insisted to differentiate them.
V. Treatment and prognosis
Surgery is the main treatment method for giant cell tumor of bone. The method of scraping the lesion and bone grafting can be used for both grade I and grade II imaging. The use of autologous bone or allogeneic bone to fill the bone defect is a common method. If the bone defect is too large, a combination of autologous bone and allogeneic bone can be used. In this case, the autologous cancellous bone should be placed in the subchondral area of the articular cartilage, and the allograft bone should be placed relatively far away from the articular cartilage. The main advantage of filling the defect with bone cement is that it allows for early weight-bearing activity. However, when the tumor has reached the articular cartilage, it is not advisable to place the cement in direct contact with the articular cartilage, but rather to place approximately 2 cm of autologous cancellous bone under the articular cartilage, followed by a thin layer of gelatin sponge, and finally the cement.
The recurrence rate of previous lesion scraping can be as high as 50%. In the past 10 years or so, some scholars have used expanded scraping to treat Campanacci grade I and II giant cell tumors of bone with good results. Expanded scraping is the application of a high-speed electric grinding drill to remove the bone from the cavity of the tumor, followed by high-pressure flushing and chemical inactivation agents to treat the bone cavity, so that the application of scraping can achieve similar results as marginal resection. Clinical applications have initially demonstrated that extended curettage is an effective treatment that maximizes limb preservation while reducing tumor recurrence rates.
For Campanacci grade III giant cell tumor of bone and all malignant giant cell tumors of bone, extensive or marginal block resection of the tumor segment, artificial prosthesis or allograft hemiarthroplasty should be used. In a few cases where the tumor has extensively invaded soft tissues and important nerves and blood vessels, amputation should be performed.
The lung metastases of giant cell tumor should be surgically removed in time after the diagnosis, and most cases can be cured.
The majority of cases can be cured. Giant cell tumor of bone is not sensitive to chemotherapy, and radiotherapy can cause malignant transformation of giant cell tumor of bone, so it should be used with caution.
The most common postoperative complication of giant cell tumor of bone is local recurrence, and the recurrence rate can be as high as 50%. The incidence of pulmonary metastases from common giant cell tumor of bone are 1% to 3%. Pulmonary metastases remain histologically common giant cell tumor manifestations without pathological nuclear division, intercellular changes, or sarcomatous components, and most metastases can be cured after resection, but there are still a few cases of death due to uncontrollable disease. Malignant giant cell tumor of bone has a high mortality rate, similar to that of common osteosarcoma.