giant-cell tumor of bone
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Giant-cell tumor of the bone (GCTOB) is a relatively uncommon
bone tumor A bone tumor is an abnormal growth of tissue in bone, traditionally classified as noncancerous (benign) or cancerous (malignant). Cancerous bone tumors usually originate from a cancer in another part of the body such as from lung, breast, th ...
characterized by the presence of multinucleated giant cells (
osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and bone remodeling, remodeling of bones of the vertebrate, vertebral skeleton. The osteoclast disassembles and digests th ...
-like cells).
Malignancy Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not ...
in giant-cell tumor is uncommon and occurs in about 2% of all cases. However, if malignant degeneration does occur, it is likely to
metastasize Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...
to the lungs. Giant-cell tumors are normally
benign Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...
, with unpredictable behavior. It is a heterogeneous tumor composed of different cell populations. The giant-cell tumour stromal cells (GCTSC) constitute the neoplastic cells, which are from a mesenchymal stem cell origin and are classified based on expression of osteoblast cell markers such as
alkaline phosphatase The enzyme alkaline phosphatase (ALP, alkaline phenyl phosphatase, also abbreviated PhoA) is a phosphatase with the physiological role of dephosphorylating compounds. The enzyme is found across a multitude of organisms, prokaryotes and eukaryo ...
and
osteocalcin Osteocalcin, also known as bone gamma-carboxyglutamic acid-containing protein (BGLAP), is a small (49-amino-acid) noncollagenous protein hormone found in bone and dentin, first identified as a calcium-binding protein. Because osteocalcin has ...
. In contrast, the mononuclear osteoclast precursor cells giving rise to multinucleated giant cells (MNGC) are secondarily recruited and comprise the non-neoplastic cell population. They are derived from an hematopoietic
monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also ...
/ macrophage lineage determined primarily by expression of ''
CD68 CD68 ( Cluster of Differentiation 68) is a protein highly expressed by cells in the monocyte lineage (e.g., monocytic phagocytes, osteoclasts), by circulating macrophages, and by tissue macrophages (e.g., Kupffer cells, microglia). Structure and ...
'', 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.


Signs and symptoms

Distribution of giant-cell tumors of bone Patients usually present with pain and limited range of motion caused by tumor's proximity to the joint space. Swelling may occur, as well, if the tumor has been growing for a long time. Some patients may be asymptomatic until they develop a
pathologic fracture A pathologic fracture is a bone fracture caused by weakness of the bone structure that leads to decrease mechanical resistance to normal mechanical loads. This process is most commonly due to osteoporosis, but may also be due to other pathologies ...
at the site of the tumor. They usually originate from the epiphysis of long bones, but in rare cases, they may arise from anterior arc of the ribs. The symptoms may include muscular aches and pains in arms or legs and abdominal pain. Patients may also experience nerve pain which feels like an electric shock due to weight bearing.


Diagnosis

The
diagnosis Diagnosis (: diagnoses) is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in a lot of different academic discipline, disciplines, with variations in the use of logic, analytics, and experience, to determine " ...
of giant-cell tumors is based on
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, an interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves the extraction of sampling (medicine), sample ...
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 An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and bone remodeling, remodeling of bones of the vertebrate, vertebral skeleton. The osteoclast disassembles and digests th ...
-type giant cells. Soap-bubble appearance is a characteristic feature.


Imaging

On X-ray, giant-cell tumors (GCTs) are lytic/lucent lesions that have an 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 nonsclerotic and sharply defined border. About 5% of giant-cell tumors metastasize, usually to a lung, which may be benign metastasis. Plain radiograph is still the main method of diagnosing giant cell tumour. But MRI and CT scans are useful for staging and surgical planning. CT is more superior than plain radiograph in delineating the tumour outline, its extension into structures outside the bone, determining the involvement of bony cortex and tumour recurrence. CT scans show features such as thin and expanded bony cortex, with or without bony matrix calcifications, and fluid levels due to
aneurysmal bone cyst Aneurysmal bone cyst (ABC) is a non-cancerous bone tumor composed of multiple varying sizes of spaces in a bone which are filled with blood. The term is a misnomer, as the lesion is neither an aneurysm nor a cyst. It generally presents with ...
or bleeding within tumour. However, axial views of the subarticular bone (bony area adjacent to the articular cartilage) is not accurate due to
voxel In computing, a voxel is a representation of a value on a three-dimensional regular grid, akin to the two-dimensional pixel. Voxels are frequently used in the Data visualization, visualization and analysis of medical imaging, medical and scient ...
signal averaging Signal averaging is a signal processing technique applied in the time domain, intended to increase the strength of a signal relative to noise that is obscuring it. By averaging a set of replicate measurements, the signal-to-noise ratio (SNR) will ...
. MRI is superior than CT on delineating the tumour because of its better contrast resolution and imaging in multiple planes. MRI is also useful in determining the extension outside the bone and evaluating the involvement articular surface, skip lesions within bony matrix, and
medullary cavity The medullary cavity (''medulla'', innermost part) is the central cavity of bone shafts where red bone marrow and/or yellow bone marrow (adipose tissue) is stored; hence, the medullary cavity is also known as the marrow cavity. Located in the ma ...
. However, bony cortex destruction is better demonstrated on CT scan. On MRI, the mass generates intermediate to reduced signal intensity on T1-weighted images, and increased signal intensity on fluid sensitive MRI images such as
short tau inversion recovery Inversion recovery is a magnetic resonance imaging sequence that provides high contrast between tissue and lesion. It can be used to provide high T1 weighted image, high T2 weighted image, and to suppress the signals from fat, blood, or cerebros ...
(STIR). The mass enhances after intravenous
gadolinium Gadolinium is a chemical element; it has Symbol (chemistry), symbol Gd and atomic number 64. It is a silvery-white metal when oxidation is removed. Gadolinium is a malleable and ductile rare-earth element. It reacts with atmospheric oxygen or moi ...
administration.


Differential diagnosis

A number of tumors have giant cells, but are not true benign giant-cell tumors. These include
aneurysmal bone cyst Aneurysmal bone cyst (ABC) is a non-cancerous bone tumor composed of multiple varying sizes of spaces in a bone which are filled with blood. The term is a misnomer, as the lesion is neither an aneurysm nor a cyst. It generally presents with ...
,
chondroblastoma Chondroblastoma is a rare, benign, locally aggressive bone tumor that typically affects the epiphyses or apophyses of long bones. It is thought to arise from an outgrowth of immature cartilage cells ( chondroblasts) from secondary ossification ...
, simple bone cyst,
osteoid osteoma An osteoid osteoma is a benign (non-cancerous) bone tumor that arises from osteoblasts and some components of osteoclasts. It was originally thought to be a smaller version of an osteoblastoma. Osteoid osteomas tend to be less than 1.5 cm ...
,
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, wi ...
,
osteosarcoma An osteosarcoma (OS) or osteogenic sarcoma (OGS) is a cancerous tumor in a bone. Specifically, it is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchyme, mesenchymal origin (and thus a sarcoma) and that exhi ...
, giant-cell reparative granuloma, Giant-cell tumor of the tendon sheath and brown tumor of hyperparathyroidism.


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.
Curettage Curettage ( or ), in medical procedures, is the use of a curette (French, meaning "scoop" Mosby's Medical, Nursing & Allied Health Dictionary, Fourth Edition, Mosby-Year Book 1994, p. 422) to remove tissue by scraping or scooping. Curettages ...
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 Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed to treat osteoporosis. Evidence shows that they reduce the risk of fracture in p ...
such as Zoledronate, which are thought to induce
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
in the MNGC fraction, preventing tumor-induced osteolysis. Indeed, ''in vitro'' studies have shown zoledronate to be effective in killing osteoclast-like cells. More recently, humanized
monoclonal antibodies A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a Lineage (evolution), cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Mon ...
such as
Denosumab Denosumab, sold under the brand name Prolia among others, is a human monoclonal antibody used for the treatment of osteoporosis, treatment-induced bone loss, metastasis, metastases to bone, and giant cell tumor of bone. The most common side ef ...
targeting the RANK ligand 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.


Epidemiology

Giant-cell tumor of the bone accounts for 4-5% of primary bone tumors and about 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 metastasize 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.


See also

*
Large cell Large cell is a term used in oncology. It does not refer to a particular type of cell; rather it refers to cells that are larger than would be normally expected for that type. It is frequently used when describing lymphoma and lung cancer. It was ...
*
Aneurysmal bone cyst Aneurysmal bone cyst (ABC) is a non-cancerous bone tumor composed of multiple varying sizes of spaces in a bone which are filled with blood. The term is a misnomer, as the lesion is neither an aneurysm nor a cyst. It generally presents with ...


References


External links

{{DEFAULTSORT:Giant Cell Tumor Of Bone Osseous and chondromatous neoplasia