Giant cell tumor of bone
Encyclopedia
Giant-cell tumor of the bone (GCTOB) is a relatively uncommon tumor
of the bone. It is characterized by the presence of multinucleated giant cells (osteoclast
-like cells). Malignancy in giant cell tumor is not common. However, if malignant degeneration does occur it is likely to metastasize to the lungs. Giant cell tumors are normally benign
, with unpredictable behavior. It is a heterogeneous tumor composed of three different cell populations. The giant-cell tumour stromal cells (GCTSC) constitute the neoplastic cells, which are from an osteoblastic origin and are classified based on expression of osteoblast cell markers such as alkaline phosphatase and ostocalsin. In contrast, the mononuclear histiocytic cells (MNHC) and multinucleated giant cell (MNGC) fractions are secondarily recruited and comprise the non-neoplastic cell population. They are derived from an osteoclast-monocyte lineage determined primarily by expression of CD68
, a marker for monocytic precursor cells. In most patients, the tumors are slow to develop, but may recur locally in as many as 50% of cases.
at the site of the tumor.
The symptoms may including muscular aches and pains in arms, legs and abdominal pain.
Patients may also experience nerve pain which feels like an electric shock.
On x-ray, giant-cell tumors (GCTs) are lytic/lucent lesions that have a epiphyseal location and grow to the articular surface of the involved bone. Radiologically the tumors may show characteristic 'soap bubble' appearance. They are distinguishable from other bony tumors in that GCTs usually have a non-sclerotic and sharply defined border. 5% of giant-cell tumors metastatise, usually to lung, which may be benign metastasis, when the diagnosis of giant-cell tumor is suspected, a chest x-ray or CT
may be needed. MRI can be used to assess intramedullary and soft tissue extension.
of giant cell tumors is based on biopsy
findings. The key histomorphologic feature is, as the name of the entity suggests, (multinucleated) giant cells with up to a hundred nuclei that have prominent nucleoli. Surrounding mononuclear and small multinucleated cells have nuclei similar to those in the giant cells; this distinguishes the lesion from other osteogenic lesions which commonly have (benign) osteoclast
-type giant cells.
is a commonly used technique. The situation is complicated in a patient with a pathological fracture. It may be best to immobilize the affected limb and wait for the fracture to heal before performing surgery.
Patients with tumors that are not amenable to surgery are treated with radiation therapy. However caution is employed since a majority of recurrent tumors with transformations to the malignant sarcoma phenotype have been in patients receiving radiotherapy for their primary benign lesion. Pharmacotherapy for GCTOB, includes bisphosphonates such as Zoledronate
, which are thought to induce apoptosis
in the MNGC fraction, preventing tumor-induced osteolysis. Indeed in-vitro studies have shown Zolidronate to be effective in killing osteoclast-like cells. More recently, humanized monoclonal antibodies
such as Denosumab
targeting the RANK ligand (RANKL) have been employed in treatment of GCTOB in a phase II study. This is based on the notion that increased expression of RANK-ligands by stromal cells plays a role in tumor pathogenesis.
, chondroblastoma
, simple bone cyst
, osteoid osteoma
, osteoblastoma
, osteosarcoma
, giant-cell reparative granuloma, and brown tumor
of hyperparathyroidism.
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
of the bone. It is characterized by the presence of multinucleated giant cells (osteoclast
Osteoclast
An osteoclast is a type of bone cell that removes bone tissue by removing its mineralized matrix and breaking up the organic bone . This process is known as bone resorption. Osteoclasts were discovered by Kolliker in 1873...
-like cells). Malignancy in giant cell tumor is not common. However, if malignant degeneration does occur it is likely to metastasize to the lungs. Giant cell tumors are normally benign
Benign
A benign tumor is a tumor that lacks the ability to metastasize. Common examples of benign tumors include moles and uterine fibroids.The term "benign" implies a mild and nonprogressive disease. Indeed, many kinds of benign tumors are harmless to human health...
, with unpredictable behavior. It is a heterogeneous tumor composed of three different cell populations. The giant-cell tumour stromal cells (GCTSC) constitute the neoplastic cells, which are from an osteoblastic origin and are classified based on expression of osteoblast cell markers such as alkaline phosphatase and ostocalsin. In contrast, the mononuclear histiocytic cells (MNHC) and multinucleated giant cell (MNGC) fractions are secondarily recruited and comprise the non-neoplastic cell population. They are derived from an osteoclast-monocyte lineage determined primarily by expression of CD68
CD68
CD68 is a glycoprotein which binds to low density lipoprotein.It is expressed on monocytes/macrophages.The mouse equivalent is called "macrosialin".-Use in pathology:...
, a marker for monocytic precursor cells. In most patients, the tumors are slow to develop, but may recur locally in as many as 50% of cases.
Epidemiology
Giant-cell tumor of the bone accounts for 4-5% of primary bone tumors and ~20% of benign bone tumors. However, significantly higher incidence rates are observed in Asia, where it constitutes about 20% of all primary bone tumors in China. It is slightly more common in females, has a predilection for the epiphyseal/metaphyseal region of long bones, and generally occurs in the third to fourth decade. Although classified as a benign tumor, GCTOB has been observed to metastesize to the lungs in up to 5% of cases, and in rare instances (1-3%) can transform to the malignant sarcoma phenotype with equal disease outcome.Clinical Presentation
Patients usually present with pain and limited range of motion caused by tumor's proximity to the joint space. There may be swelling as well, if the tumor has been growing for a long time. Some patients may be asymptomatic until they develop a pathologic fracturePathologic fracture
A pathologic fracture is a broken bone caused by disease leading to weakness of the bone. This process is most commonly due to osteoporosis, but may also be due to other pathologies such as: cancer, infection, inherited bone disorders,or a bone cyst...
at the site of the tumor.
The symptoms may including muscular aches and pains in arms, legs and abdominal pain.
Patients may also experience nerve pain which feels like an electric shock.
Imaging
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
may be needed. MRI can be used to assess intramedullary and soft tissue extension.
Diagnosis
The diagnosisDiagnosis
Diagnosis is the identification of the nature and cause of anything. Diagnosis is used in many different disciplines with variations in the use of logics, analytics, and experience to determine the cause and effect relationships...
of giant cell tumors is based on biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
findings. The key histomorphologic feature is, as the name of the entity suggests, (multinucleated) giant cells with up to a hundred nuclei that have prominent nucleoli. Surrounding mononuclear and small multinucleated cells have nuclei similar to those in the giant cells; this distinguishes the lesion from other osteogenic lesions which commonly have (benign) osteoclast
Osteoclast
An osteoclast is a type of bone cell that removes bone tissue by removing its mineralized matrix and breaking up the organic bone . This process is known as bone resorption. Osteoclasts were discovered by Kolliker in 1873...
-type giant cells.
Treatment
General treatment regimens have not changed much in the past 30 years, in part due to the lack of randomized clinical trials Surgery is the treatment of choice if the tumor is determined to be resectable. CurettageCurettage
Curettage, in medical procedures, is the use of a curette to remove tissue by scraping or scooping.Curettages are also a declining method of abortion. It has been replaced by vacuum aspiration over the last decade....
is a commonly used technique. The situation is complicated in a patient with a pathological fracture. It may be best to immobilize the affected limb and wait for the fracture to heal before performing surgery.
Patients with tumors that are not amenable to surgery are treated with radiation therapy. However caution is employed since a majority of recurrent tumors with transformations to the malignant sarcoma phenotype have been in patients receiving radiotherapy for their primary benign lesion. Pharmacotherapy for GCTOB, includes bisphosphonates such as Zoledronate
Zoledronate
Zoledronic acid or zoledronate is a bisphosphonate. Zometa is used to prevent skeletal fractures in patients with cancers such as multiple myeloma and prostate cancer, as well as for treating osteoporosis...
, which are thought to induce apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
in the MNGC fraction, preventing tumor-induced osteolysis. Indeed in-vitro studies have shown Zolidronate to be effective in killing osteoclast-like cells. More recently, humanized monoclonal antibodies
Monoclonal antibodies
Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....
such as Denosumab
Denosumab
Denosumab is a fully human monoclonal antibody for the treatment of osteoporosis, treatment induced bone loss, bone metastases, rheumatoid arthritis, multiple myeloma and giant cell tumor of bone. It was developed by the company Amgen....
targeting the RANK ligand (RANKL) have been employed in treatment of GCTOB in a phase II study. This is based on the notion that increased expression of RANK-ligands by stromal cells plays a role in tumor pathogenesis.
Other bone tumors with giant cells
A number of tumors have giant cells, but are not true benign giant-cell tumors. These include, aneurysmal bone cystAneurysmal bone cyst
Aneurysmal bone cyst is a benign osteolytic bone neoplasm characterized by blood filled spaces separated by fibrous septa. The term aneurysmal is mainly derived from its macroscopic appearance.- Causes :...
, chondroblastoma
Chondroblastoma
Chondroblastoma is a rare bone tumor, usually benign with a slow-growing nature.In children, it is the most common epiphyseal tumor.-Presentation:...
, simple bone cyst
Bone cyst
A bone cyst or geode is a type of cyst that can present itself in the jaw, or on other locations in the body.Types include:* Simple bone cyst* Aneurysmal bone cyst* Traumatic bone cyst- History :...
, osteoid osteoma
Osteoid osteoma
An osteoid osteoma is a benign bone tumor which arises from osteoblasts and originally thought to be a smaller version of an osteoblastoma. Osteoid osteomas tend to be less than 1.5 cm in size. The tumor can be in any bone in the body but are most common in long bones, such as the femur and tibia....
, osteoblastoma
Osteoblastoma
Osteoblastoma is an uncommon osteoid tissue-forming primary neoplasm of the bone.It has clinical and histologic manifestations similar to those of osteoid osteoma; therefore, some consider the two tumors to be variants of the same disease, with osteoblastoma representing a giant osteoid osteoma...
, osteosarcoma
Osteosarcoma
Osteosarcoma is an aggressive cancerous neoplasm arising from primitive transformed cells of mesenchymal origin that exhibit osteoblastic differentiation and produce malignant osteoid...
, giant-cell reparative granuloma, and brown tumor
Brown tumor
Brown tumors are tumors of bone that arise in settings of excess osteoclast activity, such as hyperparathyroidism, and consist of fibrous tissue, woven bone and supporting vasculature, but no matrix. They are radiolucent on x-ray...
of hyperparathyroidism.