Giant-cell tumor of bone

Last updated
Giant-cell tumor of bone
Other namesOsteoclastoma
Giant cell tumour of bone - high mag.jpg
Micrograph of a giant-cell tumor of bone showing the characteristic giant cells, H&E stain
Specialty Oncology, orthopedic surgery  OOjs UI icon edit-ltr-progressive.svg

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 uncommon and occurs in about 2% of all cases. However, if malignant degeneration does occur, it is likely to metastasize to the lungs. Giant-cell tumors are normally benign, [1] with unpredictable behavior. [2] It is a heterogeneous tumor composed of three different cell populations. The giant-cell tumour stromal cells (GCTSC) constitute the neoplastic cells, [3] which are from an osteoblastic origin and are classified based on expression of osteoblast cell markers such as alkaline phosphatase and osteocalcin. 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. [4] [5] [6] In most patients, the tumors are slow to develop, but may recur locally in as many as 50% of cases.

Contents

Signs and symptoms

Distribution of giant-cell tumors of bone 3dee10fb0a8ad6244470738a8cb382 big gallery.jpg
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 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. [7] 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.[ citation needed ]

Diagnosis

High magnification micrograph of giant cells in a giant-cell tumor of bone, H&E stain Giant cell tumour of bone - very high mag.jpg
High magnification micrograph of giant cells in a giant-cell tumor of bone, H&E stain

The diagnosis 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. Soap-bubble appearance is a characteristic feature.[ citation needed ]

Imaging

X-ray of a giant-cell bone tumor in the head of the fourth metacarpal of the left hand Giant cell tumor of bone08.JPG
X-ray of a giant-cell bone tumor in the head of the fourth metacarpal of the left hand

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. [8] Radiologically the tumors may show characteristic 'soap bubble' appearance. [9] 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, [10]

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 or bleeding within tumour. However, axial views of the subarticular bone (bony area adjacent to the articular cartilage) is not accurate due to voxel signal averaging. 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. However, bony cortex destruction is better demonstrated on CT scan. [11]

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 (STIR). The mass enhances after intravenous gadolinium administration. [11]

Differential diagnosis

A number of tumors have giant cells, but are not true benign giant-cell tumors. These include, aneurysmal bone cyst, chondroblastoma, simple bone cyst, osteoid osteoma, osteoblastoma, osteosarcoma, giant-cell reparative granuloma, Giant-cell tumor of the tendon sheath and brown tumor of hyperparathyroidism.[ citation needed ]

Treatment

General treatment regimens have not changed much in the past 30 years, in part due to the lack of randomized clinical trials. [4] Surgery is the treatment of choice if the tumor is determined to be resectable. Curettage is a commonly used technique. [12] 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. [13] 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. [14] 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 zoledronate to be effective in killing osteoclast-like cells. [2] [4] More recently, humanized monoclonal antibodies such as Denosumab 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. [4]

Epidemiology

Giant-cell tumor of the bone accounts for 4-5% of primary bone tumors and about 20% of benign bone tumors. [15] However, significantly higher incidence rates are observed in Asia, where it constitutes about 20% of all primary bone tumors in China. [16] It is slightly more common in females, has a predilection for the epiphyseal/metaphyseal region of long bones, [2] [17] and generally occurs in the third to fourth decade. [14] 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. [2] [4] [17]

See also

Related Research Articles

<span class="mw-page-title-main">Cyst</span> Closed sac growth on the body

A cyst, also traditionally known from Old English as a wen, is a closed sac, having a distinct envelope and division compared with the nearby tissue. Hence, it is a cluster of cells that have grouped together to form a sac ; however, the distinguishing aspect of a cyst is that the cells forming the "shell" of such a sac are distinctly abnormal when compared with all surrounding cells for that given location. A cyst may contain air, fluids, or semi-solid material. A collection of pus is called an abscess, not a cyst. Once formed, a cyst may resolve on its own. When a cyst fails to resolve, it may need to be removed surgically, but that would depend upon its type and location.

Liver tumors are abnormal growth of liver cells on or in the liver. Several distinct types of tumors can develop in the liver because the liver is made up of various cell types. Liver tumors can be classified as benign (non-cancerous) or malignant (cancerous) growths. They may be discovered on medical imaging, and the diagnosis is often confirmed with liver biopsy. Signs and symptoms of liver masses vary from being asymptomatic to patients presenting with an abdominal mass, hepatomegaly, abdominal pain, jaundice, or some other liver dysfunction. Treatment varies and is highly specific to the type of liver tumor.

<span class="mw-page-title-main">Bone tumor</span> Medical condition

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, thyroid, kidney and prostate. There may be a lump, pain, or neurological signs from pressure. A bone tumor might present with a pathologic fracture. Other symptoms may include fatigue, fever, weight loss, anemia and nausea. Sometimes there are no symptoms and the tumour is found when investigating another problem.

<span class="mw-page-title-main">Gastrointestinal stromal tumor</span> Human disease (cancer)

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs arise in the smooth muscle pacemaker interstitial cell of Cajal, or similar cells. They are defined as tumors whose behavior is driven by mutations in the KIT gene (85%), PDGFRA gene (10%), or BRAF kinase (rare). 95% of GISTs stain positively for KIT (CD117). Most (66%) occur in the stomach and gastric GISTs have a lower malignant potential than tumors found elsewhere in the GI tract.

<span class="mw-page-title-main">Brenner tumour</span> Medical condition

Brenner tumours are an uncommon subtype of the surface epithelial-stromal tumour group of ovarian neoplasms. The majority are benign, but some can be malignant.

<span class="mw-page-title-main">Surface epithelial-stromal tumor</span> Medical condition

Surface epithelial-stromal tumors are a class of ovarian neoplasms that may be benign or malignant. Neoplasms in this group are thought to be derived from the ovarian surface epithelium or from ectopic endometrial or fallopian tube (tubal) tissue. Tumors of this type are also called ovarian adenocarcinoma. This group of tumors accounts for 90% to 95% of all cases of ovarian cancer; however is mainly only found in postmenopausal women with the exception of the United States where 7% of cases occur in women under the age of 40. Serum CA-125 is often elevated but is only 50% accurate so it is not a useful tumor marker to assess the progress of treatment. 75% of women with epithelial ovarian cancer are found within the advanced-stages; however younger patients are more likely to have better prognoses than older patients.

<span class="mw-page-title-main">Benign tumor</span> Mass of cells which cannot spread throughout the body

A benign tumor is a mass of cells (tumor) that does not invade neighboring tissue or metastasize. Compared to malignant (cancerous) tumors, benign tumors generally have a slower growth rate. Benign tumors have relatively well differentiated cells. They are often surrounded by an outer surface or stay contained within the epithelium. Common examples of benign tumors include moles and uterine fibroids.

<span class="mw-page-title-main">Ameloblastoma</span> Medical condition

Ameloblastoma is a rare, benign or cancerous tumor of odontogenic epithelium much more commonly appearing in the lower jaw than the upper jaw. It was recognized in 1827 by Cusack. This type of odontogenic neoplasm was designated as an adamantinoma in 1885 by the French physician Louis-Charles Malassez. It was finally renamed to the modern name ameloblastoma in 1930 by Ivey and Churchill.

<span class="mw-page-title-main">Aneurysmal bone cyst</span> Medical condition

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 pain and swelling in the affected bone. Pressure on neighbouring tissues may cause compression effects such as neurological symptoms.

<span class="mw-page-title-main">Central giant-cell granuloma</span> Medical condition

Central giant-cell granuloma (CGCG) is a localised benign condition of the jaws. It is twice as common in females and is more likely to occur before age 30. Central giant-cell granulomas are more common in the anterior mandible, often crossing the midline and causing painless swellings.

<span class="mw-page-title-main">Odontogenic keratocyst</span> Medical condition

An odontogenic keratocyst is a rare and benign but locally aggressive developmental cyst. It most often affects the posterior mandible and most commonly presents in the third decade of life. Odontogenic keratocysts make up around 19% of jaw cysts.

<span class="mw-page-title-main">Chondroblastoma</span> Medical condition

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 centers, originating from the epiphyseal plate or some remnant of it.

<span class="mw-page-title-main">Brown tumor</span> Medical condition

The brown tumor is a bone lesion that arises in settings of excess osteoclast activity, such as hyperparathyroidism. They are a form of osteitis fibrosa cystica. It is not a neoplasm, but rather simply a mass. It most commonly affects the maxilla and mandible, though any bone may be affected. Brown tumours are radiolucent on x-ray.

<span class="mw-page-title-main">USP6</span> Protein-coding gene in the species Homo sapiens

Ubiquitin carboxyl-terminal hydrolase 6 (USB6), also termed TRE17 and Tre-2, is a deubiquitinating enzyme that in humans is encoded by the hominid USP6 gene located at band 13.2 on the short arm of chromosome 17. Deubiquitinating enzymes (DUBs) are enzymes that act within cells to remove ubiquitins from various functionally important proteins. Ubiquitin enzymes add ubiquitin to these proteins and thereby regulate their cellular location, alter their activity, and/or promote their degradation. By deubiquitinating these proteins, DUBs counter the effects of the ubiquinating enzymes and contribute to regulating the actions of the targeted proteins. In normal adult tissues, USP6 is highly expressed in testicle tissue, modestly expressed in ovarian tissue, and absent or minimally expressed in other tissues. It is also highly expressed in fetal brain tissue. The specific functions of USP6 are poorly defined primarily because its presence is restricted to primates: there are no available animal models to determine the effects of its deletion, although some studies suggest that UPSP6 contributes to normal brain development. In all events, USP6 has gained wide interest because of its abnormally increased expression by the neoplastic cells in various tumors derived from mesenchymal tissue.

<span class="mw-page-title-main">Salivary gland tumour</span> Medical condition

Salivary gland tumours, also known as mucous gland adenomas or neoplasms, are tumours that form in the tissues of salivary glands. The salivary glands are classified as major or minor. The major salivary glands consist of the parotid, submandibular, and sublingual glands. The minor salivary glands consist of 800 to 1000 small mucus-secreting glands located throughout the lining of the oral cavity. Patients with these types of tumours may be asymptomatic.

<span class="mw-page-title-main">Bone cyst</span> Medical condition

A bone cyst or geode is a cyst that forms in bone.

<span class="mw-page-title-main">Non-ossifying fibroma</span> Medical condition

A non-ossifying fibroma (NOF) is a benign bone tumor of the osteoclastic giant cell-rich tumor type. It generally occurs in the metaphysis of long bones in children and adolescents. Typically, there are no symptoms unless there is a fracture. It can occur as part of a syndrome such as when multiple non-ossifying fibromas occur in neurofibromatosis, or Jaffe–Campanacci syndrome in combination with cafe-au-lait spots, mental retardation, hypogonadism, eye and cardiovascular abnormalities.

Odontogenic cyst are a group of jaw cysts that are formed from tissues involved in odontogenesis. Odontogenic cysts are closed sacs, and have a distinct membrane derived from rests of odontogenic epithelium. It may contain air, fluids, or semi-solid material. Intra-bony cysts are most common in the jaws, because the mandible and maxilla are the only bones with epithelial components. That odontogenic epithelium is critical in normal tooth development. However, epithelial rests may be the origin for the cyst lining later. Not all oral cysts are odontogenic cysts. For example, mucous cyst of the oral mucosa and nasolabial duct cyst are not of odontogenic origin.

<span class="mw-page-title-main">Unicameral bone cyst</span> Medical condition

A unicameral bone cyst, also known as a simple bone cyst, is a cavity filled with a yellow-colored fluid. It is considered to be benign since it does not spread beyond the bone. Unicameral bone cysts can be classified into two categories: active and latent. An active cyst is adjacent to the epiphyseal plate and tends to grow until it fills the entire diaphysis, the shaft, of the bone; depending on the invasiveness of the cyst, it can cause a pathological fracture or even destroy the epiphyseal plate leading to the permanent shortening of the bone.

<span class="mw-page-title-main">Proliferative fasciitis and proliferative myositis</span> Medical condition

Proliferative fasciitis and proliferative myositis (PF/PM) are rare benign soft tissue lesions that increase in size over several weeks and often regress over the ensuing 1–3 months. The lesions in PF/PM are typically obvious tumors or swellings. Historically, many studies had grouped the two descriptive forms of PF/PM as similar disorders with the exception that proliferative fasciitis occurs in subcutaneous tissues while proliferative myositis occurs in muscle tissues. In 2020, the World Health Organization agreed with this view and defined these lesions as virtually identical disorders termed proliferative fasciitis/proliferative myositis or proliferative fasciitis and proliferative myositis. The Organization also classified them as one of the various forms of the fibroblastic and myofibroblastic tumors.

References

  1. ↑ Pai SB, Lalitha RM, Prasad K, Rao SG, Harish K (September 2005). "Giant cell tumor of the temporal bone—a case report". BMC Ear Nose Throat Disord. 5: 8. doi: 10.1186/1472-6815-5-8 . PMC   1253509 . PMID   16162299.
  2. 1 2 3 4 Werner M (2006). "Giant cell tumour of bone: morphological, biological and histogenetical aspects". Int Orthop. 30 (6): 484–489. doi:10.1007/s00264-006-0215-7. PMC   3172738 . PMID   17013643.
  3. ↑ Huang , Xu J, Wood DJ, Zheng MH (2000). "Gene Expression of Osteoprotegerin Ligand, Osteoprotegerin, and REceptor Activator of NF-kB in Giant Cell Tumor of Bone". American Journal of Pathology. 156 (3): 761–767. doi:10.1016/s0002-9440(10)64942-5. PMC   1876848 . PMID   10702390.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. 1 2 3 4 5 Thomas DM, Skubitz T (2009). "Giant-cell tumour of bone". Current Opinion in Oncology. 21 (4): 338–344. doi:10.1097/CCO.0b013e32832c951d. PMID   19444102. S2CID   41807503.
  5. ↑ Werner M (2006). "Giant-cell tumour of bone: morphological, biological and histogenetical aspects". Int Orthop. 30 (6): 484–489. doi:10.1007/s00264-006-0215-7. PMC   3172738 . PMID   17013643.
  6. ↑ Wuelling M, Delling G, Kaiser E (2003). "The Origin of the Neoplastic Stromal Cell in Giant Cell Tumor of Bone". Human Pathology. 34 (10): 983–993. doi:10.1053/S0046-8177(03)00413-1. PMID   14608531.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ↑ Dehghan A, Moaddab AH, Eskandarlou M, Moeeni A. Anterior chest wall giant cell tumor. Gen Thorac Cardiovasc Surg. 2010 Jan;58(1):39-41.
  8. ↑ Murphey M, Nomikos G, Flemming D, Gannon F, Temple H, Kransdorf M (2001). "From the archives of AFIP. Imaging of giant cell tumor and giant cell reparative granuloma of bone: radiologic-pathologic correlation". Radiographics. 21 (5): 1283–309. doi: 10.1148/radiographics.21.5.g01se251283 . PMID   11553835.
  9. ↑ essentials of skeletal radiology . Lippincott Williams & Wilkins. 2005. pp.  1–. ISBN   978-0-7817-3946-7. GGKEY:29STUY0DQ70. Retrieved 21 June 2010.
  10. ↑ "Giant-cell tumor of bone - Wheeless' Textbook of Orthopaedics". 22 July 2020.
  11. 1 2 Chakarun, Corey J.; Forrester, Deborah M.; Gottsegen, Christopher J.; Patel, Dakshesh B.; White, Eric A.; Matcuk, George R. (January 2013). "Giant Cell Tumor of Bone: Review, Mimics, and New Developments in Treatment". RadioGraphics. 33 (1): 197–211. doi:10.1148/rg.331125089. ISSN   0271-5333. PMID   23322837.
  12. ↑ Balke M, Schremper L, Gebert C, et al. (March 2008). "Giant cell tumor of bone: treatment and outcome of 214 cases". J. Cancer Res. Clin. Oncol. 134 (9): 969–78. doi:10.1007/s00432-008-0370-x. PMID   18322700. S2CID   2971150.
  13. ↑ Mendenhall W, Zlotecki R, Scarborough M, Gibbs C, Mendenhall N (2006). "Giant cell tumor of bone". Am J Clin Oncol. 29 (1): 96–9. doi:10.1097/01.coc.0000195089.11620.b7. PMID   16462511. S2CID   31907929.
  14. 1 2 Mendenhall WM, Zlotecki RA, Scarborough MT, Gibbs PC, Mendenhall NP (2006). "Giant Cell Tumor of Bone". American Journal of Clinical Oncology. 29 (1): 96–99. doi:10.1097/01.coc.0000195089.11620.b7. PMID   16462511. S2CID   31907929.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ↑ Gamberi G, Serra M, Ragazzini P, Magagnoli G, Pazzaglia L, Ponticelli F, Ferrari C, Zanasi M, Bertoni F, Picci P, Benassi M (2003). "Identification of markers of possible prognostic value in 57 giant-cell tumors of bone". Oncol Rep. 10 (2): 351–6. doi:10.3892/or.10.2.351. PMID   12579271.
  16. ↑ Thomas D. M., Skubitz T. (2009). "Giant-cell tumour of bone". Current Opinion in Oncology. 21 (4): 338–344. doi:10.1097/cco.0b013e32832c951d. PMID   19444102. S2CID   41807503.
  17. 1 2 Dickson B. C., Li S.-Q., Wunder J. S., Ferguson P. C., Eslami B., Werier J. A.; et al. (2008). "Giant-cell tumor of bone express p63". Modern Pathology. 21 (4): 369–375. doi: 10.1038/modpathol.2008.29 . PMID   18311114.{{cite journal}}: CS1 maint: multiple names: authors list (link)
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.