Osteochondroma

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Osteochondroma
Other namesOsteocartilaginous exostoses
Osteochondroma X-ray.jpg
Lateral radiograph of the knee demonstrating ossification in the peritendinous tissues in a patient with osteochondroma.
Specialty Orthopedics

Osteochondromas are the most common benign tumors of the bones. [1] [2] The tumors take the form of cartilage-capped bony projections or outgrowth on the surface of bones exostoses. [3] [4] It is characterized as a type of overgrowth that can occur in any bone where cartilage forms bone. Tumors most commonly affect long bones about the knee and in the forearm. [1] [3] Additionally, flat bones such as the pelvis and scapula (shoulder blade) may be affected. [5] Hereditary multiple exostoses usually present during childhood. Yet, the vast majority of affected individuals become clinically manifest by the time they reach adolescence. [3] [6] Osteochondromas occur in 3% of the general population and represent 35% of all benign tumors and 8% of all bone tumors. The majority of these tumors are solitary non-hereditary lesions and approximately 15% of osteochondromas occur as hereditary multiple exostoses preferably known as hereditary multiple osteochondromas (HMOs). [4] [7] Osteochondromas do not result from injury and the exact cause remains unknown. Recent research has indicated that multiple osteochondromas is an autosomal dominant inherited disease. Germ line mutations in EXT1 and EXT2 genes located on chromosomes 8 and 11 have been associated with the cause of the disease. [8] The treatment choice for osteochondroma is surgical removal of solitary lesion or partial excision of the outgrowth, when symptoms cause motion limitations or nerve and blood vessel impingements. [4] [7] In hereditary multiple exostoses the indications of surgery are based upon multiple factors that are taken collectively, namely: patient's age, tumor location and number, accompanying symptomatology, esthetic concerns, family history and underlying gene mutation. [1] [3] A variety of surgical procedures have been employed to remedy hereditary multiple exostoses such as osteochondroma excision, bone lengthening, corrective osteotomy and hemiepiphysiodesis. Sometimes a combination of the previous procedures is used. [3] The indicators of surgical success in regard to disease and patient characteristics are greatly disputable. [3] Because most studies of hereditary multiple exostoses are retrospective and of limited sample size with missing data, the best evidence for each of the currently practiced surgical procedures is lacking. [3]

Contents

Signs and symptoms

Limited normal functions and movements are caused by osteochondromas growing slowly and inwardly. The majority of osteochondromas are symptomless and are found incidentally. Each individual with osteochondroma may experience symptoms differently and most of the time individuals will experience no symptoms at all. Some of the most common symptoms are a hard immobile painless palpable mass, adjacent muscle soreness, and pressure or irritation with heavy exercising. [5] Major symptoms arise when complications such as fractures, bone deformity or mechanical joint problems occur. If the occurrence of an osteochondroma is near a nerve or a blood vessel, the affected limb can experience numbness, weakness, loss of pulse or color change. Periodic changes in the blood flow can also take place. Approximately 20% of patients experiencing nerve compression commonly acknowledge vascular compression, arterial thrombosis, aneurysm, and pseudoaneurysm. Formation of pseudoaneurysm and venous thrombosis lead to claudication, pain, acute ischemia, and symptoms of phlebitis. If the tumor is found under a tendon, it can cause pain during movement causing restriction of joint motion. Pain can also occur due to bursal inflammation, swelling or fracture at the base of the tumor stalk. Some of the clinical signs and symptoms of malignant osteochondroma are pain, swelling, and mass enlargement. [4]

Mechanism

Osteochondromas are long and slender, pedunculated on a stalk often taking the shape of a cauliflower. The cartilage cap is covered by fibrous perichondrium and continues with the periosteum of the underlying bone. The cartilage cap is less than 2 cm thick and the thickness decreases with age. A cap more than 2 cm thick, indicates malignant transformation of a tumor. The cartilage cap merges with the epiphyseal area of the long bones called spongiosa. In the spongiosa, the chondrocytes are arranged in accordance with the epiphyseal growth plate. The spongiosa of the stalk continues with the underlying cancellous bone. Fractures within the stalk causes fibroblastic proliferation and formation of a new bone. Development of bursa takes place over the osteochondroma, which is attached to the perichondrium of the cap. Inflammation of the bone is indicated by the bursal wall lined by the synovium. As a result, patients may have swelling and pain for years related to the location and site of the lesion indicative of mechanical obstruction, nerve impingement, pseudoaneurysm of the overlying vessel, fracture at the stalk of the lesion, or formation of bursa over the osteochondroma. [7] Heparan sulphate (HS) are glycosaminoglycans which are involved in the formation of proteoglycans. The biosynthesis of HS takes place in the Golgi apparatus and endoplasmic reticulum, where glycosaminoglycans chains are maintained by type II glycosyltransferases encoded by EXOSTOSIN genes EXT1 and EXT2 . Decreased levels of HS leads to mutations in EXT1 or EXT2 causing skeletal abnormality. [9] The underlying mechanism for solitary and multiple osteochondromas have been associated with genetic alterations in EXT1 or EXT2 genes located on chromosomes 8 and 11. Approximately 65% of osteochondromas arise in the EXT1 gene loci on chromosome 8 and 35% arise in EXT2 gene loci on chromosome 11. About 70–75% of multiple osteochondromas are caused by point mutations, often involving deletion of single or multiple axons as found in 10% of all hereditary cases. In about 10–15% of all cases no genomic alterations are detected. The mechanism behind the formation of multiple osteochondroma is large genomic deletions of EXT1 and EXT2 genes. The identified mechanism behind solitary osteochondromas is the homozygous deletions of the EXT1 gene. [6] However, the exact cause of osteochondroma is unknown. [5] Additionally, the molecular basis of genetics and clinical variability of multiple osteochondroma as well as the underlying causes for the malignant transformation and the onset of osteochondroma in EXT negative patients is also currently unknown. [10]

Diagnosis

Osteochondromas are often asymptomatic and may not cause any kind of discomfort. They are often found accidentally when an X-ray is done for an unrelated reason. [11]

Tests for osteochondroma can also identify diseases such as secondary peripheral chondrosarcoma and multiple osteochondromatosis. In large, secondary chondrosarcoma arises at the site of osteochondroma due to increased thickness of the cartilage cap indicating potential malignant transformation. The symptoms of multiple osteochondromatosis are similar to solitary osteochondroma, but they are often more severe. Painless bumps can arise at the site of tumor and pain and other discomforts can also take place if pressure is put on the soft tissues, nerves, or blood vessels. [4] [11] Dysplasia Epiphysealis Hemimelica (DEH) or Trevor's disease and metachondromatosis (MC) are considered differential diagnosis of both solitary and hereditary osteochondromas. DEH is described as a type of over growth at one or more epiphyses. Similar to osteochondroma, DEH is diagnosed prior to 15 years of age and the growth of lesions end at puberty, when the growth plates close. Metachondromatosis is a rare disorder that exhibit symptoms of both multiple osteochondromas and enchondromas in children and is also inherited in autosomal dominant mode. [13]

A type that contains fat is known as an osteolipochondroma (osteo, bone, lipos, fat, + chondros, cartilage, oma, tumor). [14]

Treatment

Surgical extraction of osteochondromas is sometimes beneficial. Shown is an osteochondroma surgically extracted from a ten-year-old patient. The bone is the cylindrical stalk at the bottom, about 1/2 inch long, the two diagonal growths are cartilage. This morphology is typical of a tibial bone spur. Surgically-extracted Tibial Osteochondroma Bone Spur.jpg
Surgical extraction of osteochondromas is sometimes beneficial. Shown is an osteochondroma surgically extracted from a ten-year-old patient. The bone is the cylindrical stalk at the bottom, about 1/2 inch long, the two diagonal growths are cartilage. This morphology is typical of a tibial bone spur.

Osteochondromas are benign lesions and do not affect life expectancy. [13] Complete excision of osteochondroma is curative and the reoccurrences take place when the removal of tumor is incomplete. Multiple reoccurrences in a well-excised lesion indicate that it may be malignant. [4] The risk of malignant transformation takes place in 1–5% of individuals. [13] If any symptoms of cancerous tumor takes place, then the patient should be evaluated by a bone specialist. [11] No treatment is necessary for Solitary osteochondromas that are asymptomatic. Treatments for solitary osteochondroma are careful observation over time and taking regular x-rays to monitor any changes in the tumor. [11] If the lesion is causing pain with activity, nerve or vessel impingement, or if the bone growth has fully matured and the presence of a large cartilage cap is prominent, then it is advised that the tumor be surgically removed. [15] [16]

Osteochondromas have a low rate of malignancy (<1%) and resection of the tumor is suggested if symptoms such as pain, limitation of movement, or impingement on nerves or vessels occur. Resection of the tumor also takes place when the tumor increases in size and progresses towards malignancy. During surgical resection, the entire lesion along with the cartilaginous cap should be removed to minimize any chances of reoccurrences. [7] Surgical treatment becomes the sole treatment of choice if common complications such as fractures, symptoms of peripheral nerves such as paresthesia, paraplegia, peroneal neuropathy, and upper limb neuropathy take place. A prophylactic resection is suggested if the lesion lies next to a vessel.[ citation needed ]

Depending on the size and location of the tumor, the time it takes to return to normal daily activities varies between individuals. Limitation on some activities is advised if pain or discomfort persists after surgical excision. [11]

Research

Research done using Zebrafish dackel (dak) have shown that in EXT2-/- Zebrafish, chondrocytes fail to undergo terminal differentiation and bone formation fails to progress from pre-osteoblasts stage to osteoblasts. Instead, abnormal lipid deposition and premature adipocyte differentiation takes place. The expression of xbp1, master regulator of osterix gets reduced, suggesting that unfolded proteins responses may play a role in pathogenesis of multiple osteochondroma. The research concludes that heparan sulphates are required for terminal differentiation and formation of scaffold that is needed for bone development. At least one copy of EXT2 gene is needed for proper bone development and to maintain the balance between bone and fat cell lineages. Due to homozygous loss of EXT2 function, leads to imbalance between cartilage, bone, and fat cell lineages. These observations in null zebrafish points toward the musculoskeletal defects observed in patients with multiple osteochondroma. Due to the findings of bone-fat imbalance in Zebra fish model, future studies should address status of lipid composition in patients with multiple osteochondroma. [9] Research conducted using sequencing methods has identified a novel frame shift mutation at the glycosyltransferase domain (c.1457insG) located at codon 486 of exon 6 of the EXT1 gene, that causes multiple osteochondromas. This study was conducted in two multiple osteochondroma (MO) patients from the Chinese descent (same family) and the results were validated with four other members of the same MO family and 200 unrelated healthy subjects. The results of the mutations were validated using two different sequencing methods (Exome and Sanger). The results of immunohistochemistry and multiple sequence alignment supports the cause of MO being a mutation in EXT1 gene. However, the exact molecular mechanism of multiple osteochondroma remains unclear. The EXT1 gene encodes the endoplasmic reticulum-resident type II transmembrane glycosyltransferase, which catalyzes polymerization of heparin sulfate chain at the endoplasmic reticulum and the Golgi apparatus. Heparin sulfate regulates signal transduction during chondrocyte differentiation, ossification, and apoptosis. Malfunction in heparin sulfate synthesis causes chondrocytes to rapidly differentiate. Based on these results future studies should elucidate the underlying molecular mechanism of the glycosyltransferase domain of the EXT1 and its involvement in the development of multiple osteochondromas. [8] Osteochondromas are associated with secondary peripheral chondrosarcomas, but the pathogenesis of the malignant bone tumor remains unknown. Research has demonstrated that chondrocytes with dysfunctional EXT1 is present in solitary osteochondromas, but the EXT1 is functional in sporadic (solitary) secondary peripheral chondrosarcomas. Research indicates that osteochondromas creates a special niche in which wild type cells are mixed in with EXT functional cells. Then these EXT functional cells undergo other mutations, that give rise to secondary peripheral chondrosarcoma, indicating the involvement of an alternative mechanism for the pathogenesis of secondary peripheral chondrosarcoma. Future studies should address the contributing gene that causes the formation of peripheral chondrosarcoma. It should also illustrate what causes chondrocytes functional with EXT1 and EXT2 within the osteochondroma to become more susceptible to mutations leading to malignancy. [6]

Related Research Articles

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

A sarcoma is a malignant tumor, a type of cancer that arises from cells of mesenchymal origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or other structural tissues, and sarcomas can arise in any of these types of tissues. As a result, there are many subtypes of sarcoma, which are classified based on the specific tissue and type of cell from which the tumor originates. Sarcomas are primary connective tissue tumors, meaning that they arise in connective tissues. This is in contrast to secondary connective tissue tumors, which occur when a cancer from elsewhere in the body spreads to the connective tissue. Sarcomas are one of five different types of cancer, classified by the cell type from which they originate. The word sarcoma is derived from the Greek σάρκωμα sarkōma 'fleshy excrescence or substance', itself from σάρξsarx meaning 'flesh'.

<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">Osteosarcoma</span> Cancerous tumour in a bone

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 mesenchymal origin and that exhibits osteoblastic differentiation and produces malignant osteoid.

<span class="mw-page-title-main">Hereditary multiple exostoses</span> Rare skeletal disorder

Hereditary multiple osteochondromas (HMO), also known as hereditary multiple exostoses, is a disorder characterized by the development of multiple benign osteocartilaginous masses (exostoses) in relation to the ends of long bones of the lower limbs such as the femurs and tibias and of the upper limbs such as the humeri and forearm bones. They are also known as osteochondromas. Additional sites of occurrence include on flat bones such as the pelvic bone and scapula. The distribution and number of these exostoses show a wide diversity among affected individuals. Exostoses usually present during childhood. The vast majority of affected individuals become clinically manifest by the time they reach adolescence. A small percentage of affected individuals are at risk for development of sarcomas as a result of malignant transformation. The incidence of hereditary multiple exostoses is around 1 in 50,000 individuals. Hereditary multiple osteochondromas is the preferred term used by the World Health Organization.

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

Chondrosarcoma is a bone sarcoma, a primary cancer composed of cells derived from transformed cells that produce cartilage. A chondrosarcoma is a member of a category of tumors of bone and soft tissue known as sarcomas. About 30% of bone sarcomas are chondrosarcomas. It is resistant to chemotherapy and radiotherapy. Unlike other primary bone sarcomas that mainly affect children and adolescents, a chondrosarcoma can present at any age. It more often affects the axial skeleton than the appendicular skeleton.

<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">Neurofibromatosis type I</span> Type of neurofibromatosis disease

Neurofibromatosis type I (NF-1), or von Recklinghausen syndrome, is a complex multi-system human disorder caused by the mutation of Neurofibromin 1, a gene on chromosome 17 that is responsible for production of a protein (neurofibromin) which is needed for normal function in many human cell types. NF-1 causes tumors along the nervous system which can grow anywhere on the body. NF-1 is one of the most common genetic disorders and is not limited to any person's race or sex. NF-1 is an autosomal dominant disorder, which means that mutation or deletion of one copy of the NF-1 gene is sufficient for the development of NF-1, although presentation varies widely and is often different even between relatives affected by NF-1.

<span class="mw-page-title-main">Exostosis</span> Formation of new bone on the surface of a bone

An exostosis, also known as a bone spur, is the formation of new bone on the surface of a bone. Exostoses can cause chronic pain ranging from mild to debilitatingly severe, depending on the shape, size, and location of the lesion. It is most commonly found in places like the ribs, where small bone growths form, but sometimes larger growths can grow on places like the ankles, knees, shoulders, elbows and hips. Very rarely are they on the skull.

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

Enchondroma is a type of benign bone tumor belonging to the group of cartilage tumors. There may be no symptoms, or it may present typically in the short tubular bones of the hands with a swelling, pain or pathological fracture.

<span class="mw-page-title-main">Hamartoma</span> Tumour-like overgrowth due to a systemic genetic condition

A hamartoma is a mostly benign, local malformation of cells that resembles a neoplasm of local tissue but is usually due to an overgrowth of multiple aberrant cells, with a basis in a systemic genetic condition, rather than a growth descended from a single mutated cell (monoclonality), as would typically define a benign neoplasm/tumor. Despite this, many hamartomas are found to have clonal chromosomal aberrations that are acquired through somatic mutations, and on this basis the term hamartoma is sometimes considered synonymous with neoplasm. Hamartomas are by definition benign, slow-growing or self-limiting, though the underlying condition may still predispose the individual towards malignancies.

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

Metachondromatosis is an autosomal dominant, incompletely penetrant genetic disease affecting the growth of bones, leading to exostoses primarily in the hands and feet as well as enchondromas of long bone metaphyses and iliac crests. This syndrome affects mainly tubular bones, though it can also involve the vertebrae, small joints, and flat bones. The disease is thought to affect exon 4 of the PTPN11 gene. Metachondromatosis is believed to be caused by an 11 base pair deletion resulting in a frameshift and nonsense mutation. The disease was discovered and named in 1971 by Pierre Maroteaux, a French physician, when he observed two families with skeletal radiologic features with exostoses and Ollier disease. The observation of one family with five affected people led to the identification of the disease as autosomal dominant. There have been less than 40 cases of the disease reported to date.

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

A neurofibroma is a benign nerve-sheath tumor in the peripheral nervous system. In 90% of cases, they are found as stand-alone tumors, while the remainder are found in persons with neurofibromatosis type I (NF1), an autosomal-dominant genetically inherited disease. They can result in a range of symptoms from physical disfiguration and pain to cognitive disability.

<span class="mw-page-title-main">Chondroblast</span> Mesenchymal progenitor cell that forms a chondrocyte

Chondroblasts, or perichondrial cells, is the name given to mesenchymal progenitor cells in situ which, from endochondral ossification, will form chondrocytes in the growing cartilage matrix. Another name for them is subchondral cortico-spongious progenitors. They have euchromatic nuclei and stain by basic dyes.

<span class="mw-page-title-main">Schwannomatosis</span> Rare genetic disorder

Schwannomatosis is an extremely rare genetic disorder closely related to the more-common disorder neurofibromatosis (NF). Originally described in Japanese patients, it consists of multiple cutaneous schwannomas, central nervous system tumors, and other neurological complications, excluding hallmark signs of NF. The exact frequency of schwannomatosis cases is unknown, although some populations have noted frequencies as few as 1 case per 1.7 million people.

<span class="mw-page-title-main">Epiphyseal plate</span> Cartilage plate in the neck of a long bone

The epiphyseal plate is a hyaline cartilage plate in the metaphysis at each end of a long bone. It is the part of a long bone where new bone growth takes place; that is, the whole bone is alive, with maintenance remodeling throughout its existing bone tissue, but the growth plate is the place where the long bone grows longer.

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

Ollier disease is a rare sporadic nonhereditary skeletal disorder in which typically benign cartilaginous tumors (enchondromas) develop near the growth plate cartilage. This is caused by cartilage rests that grow and reside within the metaphysis or diaphysis and eventually mineralize over time to form multiple enchondromas. Key signs of the disorder include asymmetry and shortening of the limb as well as an increased thickness of the bone margin. These symptoms are typically first visible during early childhood with the mean age of diagnosis being 13 years of age. Many patients with Ollier disease are prone to develop other malignancies including bone sarcomas that necessitate treatment and the removal of malignant bone neoplasm. Cases in patients with Ollier disease has shown a link to IDH1, IDH2, and PTH1R gene mutations. Currently, there are no forms of treatment for the underlying condition of Ollier disease but complications such as fractures, deformities, malignancies that arise from it can be treated through surgical procedures. The prevalence of this condition is estimated at around 1 in 100,000. It is unclear whether the men or women are more affected by this disorder due to conflicting case studies.

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

A buccal exostosis is an exostosis on the buccal surface of the alveolar ridge of the maxilla or mandible. More commonly seen in the maxilla than the mandible, buccal exostoses are considered to be site specific. Existing as asymptomatic bony nodules, buccal exostoses don’t usually present until adult life, and some consider buccal exostoses to be a variation of normal anatomy rather than disease. Bone is thought to become hyperplastic, consisting of mature cortical and trabecular bone with a smooth outer surface. They are less common when compared with mandibular tori.

<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">EXT1</span> Protein-coding gene in the species Homo sapiens

Exostosin-1 is a protein that in humans is encoded by the EXT1 gene.

<span class="mw-page-title-main">EXT2 (gene)</span> Protein-coding gene in the species Homo sapiens

Exostosin glycosyltransferase-2 is a protein that in humans is encoded by the EXT2 gene.

References

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  2. ↑ Sekharappa, V; Amritanand R; Krishnan V; David KS (February 2014). "Symptomatic solitary osteochondroma of the subaxial cervical spine in a 52-year-old patient". Asian Spine J. 8 (1): 84–88. doi:10.4184/asj.2014.8.1.84. PMC   3939376 . PMID   24596611.
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  9. 1 2 Wiweger, Malgorzata; De Andrea CE; Scheepstra KW; Zhao Z; Hogendoorn PC (March 2014). "Possible effects of EXT2 on mesenchymal differentiation– lessons from the zebrafish". Orphanet Journal of Rare Diseases. 9 (35): 35. doi: 10.1186/1750-1172-9-35 . PMC   4004154 . PMID   24628984.
  10. ↑ Zuntini, M; Salvatore M; Pedrini E; Parra A; Sgariglia F; Magrelli A; Taruscio D; Sangiorgi L (December 2010). "MicroRNA profiling of multiple osteochondromas: identification of disease-specific and normal cartilage signatures". Clin. Genet. 78 (6): 507–516. doi:10.1111/j.1399-0004.2010.01490.x. PMID   20662852. S2CID   21999710.
  11. 1 2 3 4 5 6 7 8 "Osteochondroma". American Academy of Orthopedic Surgeons. Retrieved 15 March 2014.
  12. ↑ Wuyts, Wim (21 November 2013). GeneReviews. Seattle, WA: University of Washington, Seattle.
  13. 1 2 3 Bovée, Judith VMG (13 February 2008). "Multiple Osteochondromas". Orphanet Journal of Rare Diseases. 3 (1): 3. doi: 10.1186/1750-1172-3-3 . PMC   2276198 . PMID   18271966.
  14. ↑ MORRIS, CHRISTOPHER W.; Morris, Christopher G.; Press, Academic (1992). Academic Press Dictionary of Science and Technology. Gulf Professional Publishing. p. 1539. ISBN   9780122004001.
  15. ↑ "Osteochondroma". Bone Tumor.org. Retrieved 25 March 2014.
  16. ↑ "Osteochondroma". PhysioPedia. Retrieved 25 March 2014.
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