Osteosarcoma overview: Difference between revisions

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{{Osteosarcoma}}
{{Osteosarcoma}}
==Overview==
==Overview==
Bone cancer is a malignant (cancerous) tumor of the bone that destroys normal bone tissue. Osteosarcoma is the most common type of malignant bone cancer, accounting for 35% of primary bone malignancies. It is a malignant tumor that is characterized by the direct formation of bone or osteoid tissue by the tumor cells. Malignant tumors that begin in bone tissue are called primary bone cancer. Osteosarcoma may be classified according to the [[World Health Organization]]’s histologic classification of bone tumors into three groups. The osteosarcomas may be localized at the end of the long bones (commonly in the [[metaphysis]]). Most often it affects the upper end of the [[tibia]], [[humerus]], or lower end of the [[femur]]. On [[gross pathology]], areas of bone formation, [[hemorrhage]], [[fibrosis]], and cystic degeneration on cut surface are characteristic findings of osteosarcoma. On microscopic [[histopathological]] analysis, presence of [[osteoid]] within the tumor, [[pleomorphic]] cells, [[anaplastic]] cells, and atypical [[mitoses]] are characteristic findings of osteosarcoma. There are no established causes for osteosarcoma. The common risk factors in the development of osteosarcoma are [[radiation]] to bones, [[alkylating antineoplastic agents]], [[Paget disease]], multiple hereditary [[osteochondromas]], [[fibrous dysplasia]], [[Bloom syndrome]], [[Rothmund-Thomson syndrome]], and [[Li-Fraumeni syndrome]]. Common complications of osteosarcoma include pathologic fracture and [[metastasis]]. The most common symptoms of osteosarcoma include [[bone pain]] that may be worse at night, [[swelling]], and redness at the site of the tumor. On x-ray, osteosarcoma is characterized by [[medullary]] and [[Cortical bone|cortical]] bone destruction, [[periosteal reaction]], tumor matrix [[calcification]], and soft tissue mass. On MRI, osteosarcoma is characterized by intermediate intensity of soft tissue and low signal intensity of [[ossified]] components on T1. High signal intensity of soft tissue and low signal intensity of ossified components on [[Magnetic resonance imaging|T2]]. The predominant therapy for osteosarcoma is [[neoadjuvant]] [[chemotherapy]] ([[chemotherapy]] given before surgery) followed by surgical resection.  The most common drugs used to treat osteosarcoma are [[cisplatin]], [[doxorubicin]] and high-dose [[methotrexate]].
[[Bone cancer]] is a [[malignant]] ([[cancerous]]) [[tumor]] of the [[bone]] that destroys normal [[bone]] tissue. [[Osteosarcoma]] is the most common type of [[malignant]] [[bone cancer]], accounting for 35% of primary bone [[malignancies]]. It is a [[Malignant tumors|malignant tumor]] that is characterized by the direct formation of bone or [[osteoid]] tissue by the [[Tumor cell|tumor]] cells. [[Malignant tumors]] that begin in bone [[tissue]] are called primary bone cancer. [[Osteosarcoma]] may be classified according to the [[World Health Organization]]’s histologic classification of [[bone tumors]] into three groups. The [[Osteosarcoma|osteosarcomas]] may be localized at the end of the [[long bones]] (commonly in the [[metaphysis]]). Most often it affects the upper end of the [[tibia]], [[humerus]], or lower end of the [[femur]]. On [[gross pathology]], areas of bone formation, [[hemorrhage]], [[fibrosis]], and [[cystic]] degeneration on cut surface are characteristic findings of [[osteosarcoma]]. On microscopic [[histopathological]] analysis, presence of [[osteoid]] within the tumor, [[pleomorphic]] cells, [[anaplastic]] cells, and atypical [[mitoses]] are characteristic findings of [[osteosarcoma]]. There are no established causes for [[osteosarcoma]]. The common risk factors in the development of [[osteosarcoma]] are [[radiation]] to bones, [[alkylating antineoplastic agents]], [[Paget disease]], multiple hereditary [[osteochondromas]], [[fibrous dysplasia]], [[Bloom syndrome]], [[Rothmund-Thomson syndrome]], and [[Li-Fraumeni syndrome]]. Common complications of osteosarcoma include pathologic [[fracture]] and [[metastasis]]. The most common symptoms of [[osteosarcoma]] include [[bone pain]] that may be worse at night, [[swelling]], and redness at the site of the [[tumor]]. On [[X-rays|x-ray]], [[osteosarcoma]] is characterized by [[medullary]] and [[Cortical bone|cortical]] bone destruction, [[periosteal reaction]], tumor [[matrix]] [[calcification]], and soft tissue [[mass]]. On [[Magnetic resonance imaging|MRI]], [[osteosarcoma]] is characterized by intermediate intensity of soft tissue and low signal intensity of [[ossified]] components on [[T1]]. High signal intensity of soft tissue and low signal intensity of ossified components on [[Magnetic resonance imaging|T2]]. The predominant therapy for [[osteosarcoma]] is [[neoadjuvant]] [[chemotherapy]] ([[chemotherapy]] given before [[surgery]]) followed by surgical [[resection]].  The most common drugs used to treat osteosarcoma are [[cisplatin]], [[doxorubicin]] and high-dose [[methotrexate]].


== Historical perspective <ref name="pmid27990273">{{cite journal |vauthors=Bielack SS, Hecker-Nolting S, Blattmann C, Kager L |title=Advances in the management of osteosarcoma |journal=F1000Res |volume=5 |issue= |pages=2767 |date=2016 |pmid=27990273 |pmc=5130082 |doi=10.12688/f1000research.9465.1 |url=}}</ref><ref name="pmid27990273">{{cite journal |vauthors=Bielack SS, Hecker-Nolting S, Blattmann C, Kager L |title=Advances in the management of osteosarcoma |journal=F1000Res |volume=5 |issue= |pages=2767 |date=2016 |pmid=27990273 |pmc=5130082 |doi=10.12688/f1000research.9465.1 |url=}}</ref> <ref name="pmid20213394">{{cite journal |vauthors=Jaffe N |title=Osteosarcoma: review of the past, impact on the future. The American experience |journal=Cancer Treat. Res. |volume=152 |issue= |pages=239–62 |date=2009 |pmid=20213394 |doi=10.1007/978-1-4419-0284-9_12 |url=}}</ref><ref name="pmid25070231">{{cite journal |vauthors=Moore DD, Luu HH |title=Osteosarcoma |journal=Cancer Treat. Res. |volume=162 |issue= |pages=65–92 |date=2014 |pmid=25070231 |doi=10.1007/978-3-319-07323-1_4 |url=}}</ref><ref name="pmid23781130">{{cite journal |vauthors=Jaffe N, Puri A, Gelderblom H |title=Osteosarcoma: evolution of treatment paradigms |journal=Sarcoma |volume=2013 |issue= |pages=203531 |date=2013 |pmid=23781130 |pmc=3678494 |doi=10.1155/2013/203531 |url=}}</ref><ref name="pmid19197972">{{cite journal |vauthors=Mirabello L, Troisi RJ, Savage SA |title=Osteosarcoma incidence and survival rates from 1973 to 2004: data from the Surveillance, Epidemiology, and End Results Program |journal=Cancer |volume=115 |issue=7 |pages=1531–43 |date=April 2009 |pmid=19197972 |pmc=2813207 |doi=10.1002/cncr.24121 |url=}}</ref>==
== Historical perspective ==
[[Osteosarcoma]] is known as the most common bone malignant tumor. [[Osteosarcoma]] is an ancient disease and is not completely understood, yet. Nobody knows when and who discovered Osteosarcoma, but recent Paleontology discoveries revealed that [[Osteosarcoma]] has a long story in planet earth. Resent discoverers in Germany revealed a 240 million-year-old highly malignant tumor in the fossilized leg bone of a stem turtle<ref name="pmid30730547">{{cite journal |vauthors=Haridy Y, Witzmann F, Asbach P, Schoch RR, Fröbisch N, Rothschild BM |title=Triassic Cancer-Osteosarcoma in a 240-Million-Year-Old Stem-Turtle |journal=JAMA Oncol |volume= |issue= |pages= |date=February 2019 |pmid=30730547 |doi=10.1001/jamaoncol.2018.6766 |url=}}</ref>. Its been found that osteosarcoma is the earliest case of human cancer which was found on the 1.7 million-year-old fossil of an early ancestor of mankind in Swartkrans cave in South Africa. In 1990, a thousand-year-old mummy of a woman in her mid-30s of age had with a malignant tumor in her upper-left arm which that mass had grown so large that it might burst through her skin while she was still alive.
[[Osteosarcoma]] is known as the most common bone [[malignant]] [[tumor]]. [[Osteosarcoma]] is an ancient disease and is not completely understood, yet. Nobody knows when and who discovered [[osteosarcoma]], but recent [[Paleontology]] discoveries revealed that [[osteosarcoma]] has a long story on planet earth. Recent discoverers in Germany revealed a 240 million-year-old highly [[malignant]] tumor in the fossilized leg bone of a stem turtle. It is been found that [[osteosarcoma]] is the earliest case of human cancer which was found on the 1.7 million-year-old fossil of an early ancestor of mankind in Swartkrans cave in South Africa. In 1990, a thousand-year-old mummy of a woman in her mid-30s of age had with a malignant [[tumor]] in her upper-left arm which that [[mass]] had grown so large that it might burst through her [[skin]] while she was still alive.


==Classification<ref name="pmid24002129">{{cite journal |vauthors=Duong LM, Richardson LC |title=Descriptive epidemiology of malignant primary osteosarcoma using population-based registries, United States, 1999-2008 |journal=J Registry Manag |volume=40 |issue=2 |pages=59–64 |date=2013 |pmid=24002129 |pmc=4476493 |doi= |url=}}</ref>==
==Classification==
[[Osteosarcoma]] (OS) is a rare bone cancer which affects both adolescents and young adults. Osteosarcoma was classified as primary and secondary. Later the the [[World Health Organization]] sub-typed as intramedullry/central and surface osteosarcoma with a number of sub-types under each group.
[[Osteosarcoma]] (OS) is a rare [[bone cancer]] that affects both adolescents and young adults. [[Osteosarcoma]] was classified as primary and secondary. Later the [[World Health Organization]] sub-typed as [[intramedullary]]/central and surface [[osteosarcoma]] with a number of sub-types under each group.


==Pathophysiology<ref name="pmid19915470">{{cite journal |vauthors=Kim HJ, Chalmers PN, Morris CD |title=Pediatric osteogenic sarcoma |journal=Curr. Opin. Pediatr. |volume=22 |issue=1 |pages=61–6 |date=February 2010 |pmid=19915470 |doi=10.1097/MOP.0b013e328334581f |url=}}</ref><ref name="pmid25070231">{{cite journal |vauthors=Moore DD, Luu HH |title=Osteosarcoma |journal=Cancer Treat. Res. |volume=162 |issue= |pages=65–92 |date=2014 |pmid=25070231 |doi=10.1007/978-3-319-07323-1_4 |url=}}</ref><ref name="pmid20179183">{{cite journal |vauthors=Ilaslan H, Schils J, Nageotte W, Lietman SA, Sundaram M |title=Clinical presentation and imaging of bone and soft-tissue sarcomas |journal=Cleve Clin J Med |volume=77 Suppl 1 |issue= |pages=S2–7 |date=March 2010 |pmid=20179183 |doi=10.3949/ccjm.77.s1.01 |url=}}</ref><ref name="pmid21037356">{{cite journal |vauthors=Wu PK, Chen WM, Lee OK, Chen CF, Huang CK, Chen TH |title=The prognosis for patients with osteosarcoma who have received prior manipulative therapy |journal=J Bone Joint Surg Br |volume=92 |issue=11 |pages=1580–5 |date=November 2010 |pmid=21037356 |doi=10.1302/0301-620X.92B11.24706 |url=}}</ref><ref name="pmid29980176">{{cite journal |vauthors=Obiedat H, Alrabadi N, Sultan E, Al Shatti M, Zihlif M |title=The effect of ERCC1 and ERCC2 gene polymorphysims on response to cisplatin based therapy in osteosarcoma patients |journal=BMC Med. Genet. |volume=19 |issue=1 |pages=112 |date=July 2018 |pmid=29980176 |pmc=6035436 |doi=10.1186/s12881-018-0627-4 |url=}}</ref>==
==Pathophysiology==
Traditionally, our knowledge about osteosarcoma has been mostly anatomical but it should be noted that [[Osteosarcoma|it]] arises most commonly in the metaphyseal region of long bones, within the medullary cavity, then [[Osteosarcoma|it]] involves the bone cortex; consequently a pseudocapsule forms around the penetrating tumor. Osteosarcoma is characterised as a highly cellular tumor consisted of: pleomorphic spindle-shaped cells responsible for the producing an osteoid matrix. However, recent developments in the field of medical sciences and the molecular biology have provided huge insights regarding the molecular pathogenesis of [[osteosarcoma]].
Traditionally, our knowledge about [[osteosarcoma]] has been mostly [[anatomical]] but it should be noted that [[Osteosarcoma|it]] arises most commonly in the [[metaphyseal]] region of long bones, within the medullary cavity, then [[Osteosarcoma|it]] involves the bone [[cortex]]; consequently a pseudocapsule forms around the penetrating [[Tumor cell|tumor]]. [[Osteosarcoma]] is characterized as a highly cellular tumor consisted of [[Pleomorphism|pleomorphic]] spindle-shaped cells responsible for producing an [[osteoid]] [[matrix]]. However, recent developments in the field of medical sciences and [[Molecular Biology|molecular]] biology have provided huge insights regarding the molecular pathogenesis of [[osteosarcoma]].


==Causes<ref name="pmid21037356">{{cite journal |vauthors=Wu PK, Chen WM, Lee OK, Chen CF, Huang CK, Chen TH |title=The prognosis for patients with osteosarcoma who have received prior manipulative therapy |journal=J Bone Joint Surg Br |volume=92 |issue=11 |pages=1580–5 |date=November 2010 |pmid=21037356 |doi=10.1302/0301-620X.92B11.24706 |url=}}</ref><ref name="pmid28810933">{{cite journal |vauthors=Ma C, Han J, Dong D, Wang N |title=MicroRNA-152 Suppresses Human Osteosarcoma Cell Proliferation and Invasion by Targeting E2F Transcription Factor 3 |journal=Oncol. Res. |volume=26 |issue=5 |pages=765–773 |date=June 2018 |pmid=28810933 |doi=10.3727/096504017X15021536183535 |url=}}</ref><ref name="pmid29980176">{{cite journal |vauthors=Obiedat H, Alrabadi N, Sultan E, Al Shatti M, Zihlif M |title=The effect of ERCC1 and ERCC2 gene polymorphysims on response to cisplatin based therapy in osteosarcoma patients |journal=BMC Med. Genet. |volume=19 |issue=1 |pages=112 |date=July 2018 |pmid=29980176 |pmc=6035436 |doi=10.1186/s12881-018-0627-4 |url=}}</ref>==
==Causes==
There are no established causes for osteosarcoma. However, some studies show that an increased level of [[C-Fos|c-fos]] [[proto-oncogene]] expression can lead to osteosarcoma.
There are no established causes for [[osteosarcoma]]. However, some studies show that an increased level of [[C-Fos|c-fos]] [[proto-oncogene]] expression can lead to [[osteosarcoma]].


==Differential Diagnosis<ref name="pmid19915470">{{cite journal |vauthors=Kim HJ, Chalmers PN, Morris CD |title=Pediatric osteogenic sarcoma |journal=Curr. Opin. Pediatr. |volume=22 |issue=1 |pages=61–6 |date=February 2010 |pmid=19915470 |doi=10.1097/MOP.0b013e328334581f |url=}}</ref><ref name="pmid25070231">{{cite journal |vauthors=Moore DD, Luu HH |title=Osteosarcoma |journal=Cancer Treat. Res. |volume=162 |issue= |pages=65–92 |date=2014 |pmid=25070231 |doi=10.1007/978-3-319-07323-1_4 |url=}}</ref><ref name="pmid20179183">{{cite journal |vauthors=Ilaslan H, Schils J, Nageotte W, Lietman SA, Sundaram M |title=Clinical presentation and imaging of bone and soft-tissue sarcomas |journal=Cleve Clin J Med |volume=77 Suppl 1 |issue= |pages=S2–7 |date=March 2010 |pmid=20179183 |doi=10.3949/ccjm.77.s1.01 |url=}}</ref><ref name="pmid21037356">{{cite journal |vauthors=Wu PK, Chen WM, Lee OK, Chen CF, Huang CK, Chen TH |title=The prognosis for patients with osteosarcoma who have received prior manipulative therapy |journal=J Bone Joint Surg Br |volume=92 |issue=11 |pages=1580–5 |date=November 2010 |pmid=21037356 |doi=10.1302/0301-620X.92B11.24706 |url=}}</ref><ref name="pmid29980176">{{cite journal |vauthors=Obiedat H, Alrabadi N, Sultan E, Al Shatti M, Zihlif M |title=The effect of ERCC1 and ERCC2 gene polymorphysims on response to cisplatin based therapy in osteosarcoma patients |journal=BMC Med. Genet. |volume=19 |issue=1 |pages=112 |date=July 2018 |pmid=29980176 |pmc=6035436 |doi=10.1186/s12881-018-0627-4 |url=}}</ref>==
==Differential Diagnosis==
Osteosarcoma must be differentiated from other diseases such as: any type of bone lesions caused by infection and/or tumors. Features such as the eccentric location of the tumor in the metaphyseal portion of the bone and the skeletal location help to distinguish osteosarcoma from Ewing sarcoma. Bone metastases from other primary tumours, less frequent in the young than in adult patients, should also be considered.
[[Osteosarcoma]] must be differentiated from other diseases such as any type of bone lesions caused by infection and/or tumors. Features such as the eccentric location of the tumor in the [[metaphyseal]] portion of the bone and the [[skeletal]] location help to distinguish [[osteosarcoma]] from [[Ewing sarcoma]]. Bone [[metastases]] from other primary tumors, less frequent in the young than in adult patients, should also be considered.


==Epidemiology and Demographics<ref name="pmid25889105">{{cite journal |vauthors=Foley JM, Scholten DJ, Monks NR, Cherba D, Monsma DJ, Davidson P, Dylewski D, Dykema K, Winn ME, Steensma MR |title=Anoikis-resistant subpopulations of human osteosarcoma display significant chemoresistance and are sensitive to targeted epigenetic therapies predicted by expression profiling |journal=J Transl Med |volume=13 |issue= |pages=110 |date=April 2015 |pmid=25889105 |pmc=4419490 |doi=10.1186/s12967-015-0466-4 |url=}}</ref><ref name="pmid30923668">{{cite journal |vauthors=Huang X, Zhao J, Bai J, Shen H, Zhang B, Deng L, Sun C, Liu Y, Zhang J, Zheng J |title=Risk and clinicopathological features of osteosarcoma metastasis to the lung: A population-based study |journal=J Bone Oncol |volume=16 |issue= |pages=100230 |date=June 2019 |pmid=30923668 |pmc=6423404 |doi=10.1016/j.jbo.2019.100230 |url=}}</ref><ref name="pmid29065898">{{cite journal |vauthors=Simpson S, Dunning MD, de Brot S, Grau-Roma L, Mongan NP, Rutland CS |title=Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics |journal=Acta Vet. Scand. |volume=59 |issue=1 |pages=71 |date=October 2017 |pmid=29065898 |pmc=5655853 |doi=10.1186/s13028-017-0341-9 |url=}}</ref><ref name="pmid25070231">{{cite journal |vauthors=Moore DD, Luu HH |title=Osteosarcoma |journal=Cancer Treat. Res. |volume=162 |issue= |pages=65–92 |date=2014 |pmid=25070231 |doi=10.1007/978-3-319-07323-1_4 |url=}}</ref>==
==Epidemiology and Demographics==
Osteosarcoma is the most common nonhematologic primary malignant bone neoplasm causing 35% of primary bone malignancies and occurs at any age, it usually affects patients in the second and third decade of life with a peak incidence between 13 and 16 years of age. It is the 8th leading cancer in children under age 15, comprising 2.4% of all malignancies in pediatric patients and about 20% of all primary bone cancers. The overall incidence of osteosarcoma in U.S. population under 24 years of age are estimated at 0.44 cases for 100,000 individuals. Osteosarcoma is slightly more common in males than in females. Primary osteosarcoma typically occurs in young patients (10-20 years) with 75% occurring before the age of 20. Secondary osteosarcoma occurs in elderly patients.
[[Osteosarcoma]] is the most common nonhematologic primary malignant bone [[neoplasm]] causing 35% of primary bone [[malignancies]] and occurs at any age, it usually affects patients in the second and third decade of life with a peak incidence between 13 and 16 years of age. It is the 8th leading cancer in children under age 15, comprising 2.4% of all malignancies in [[Pediatrics|pediatric]] patients and about 20% of all primary bone cancers. The overall incidence of [[osteosarcoma]] in the U.S. population under 24 years of age is estimated at 0.44 cases for 100,000 individuals. [[Osteosarcoma]] is slightly more common in males than in females. Primary [[osteosarcoma]] typically occurs in young patients (10-20 years) with 75% occurring before the age of 20. Secondary [[osteosarcoma]] occurs in elderly patients.
==Risk Factors<ref name="pmid27986268">{{cite journal |vauthors=Stern N, Sakji I, Defachelles AS, Lervat C, Ryckewaert T, Marliot G, Peugniez C, Deplanque D, Penel N |title=[Incidence and risk factors for ifosfamide-related encephalopathy in sarcoma patients] |language=French |journal=Bull Cancer |volume=104 |issue=3 |pages=208–212 |date=March 2017 |pmid=27986268 |doi=10.1016/j.bulcan.2016.11.007 |url=}}</ref><ref name="pmid27860191">{{cite journal |vauthors=Endicott AA, Morimoto LM, Kline CN, Wiemels JL, Metayer C, Walsh KM |title=Perinatal factors associated with clinical presentation of osteosarcoma in children and adolescents |journal=Pediatr Blood Cancer |volume=64 |issue=6 |pages= |date=June 2017 |pmid=27860191 |doi=10.1002/pbc.26349 |url=}}</ref><ref name="pmid23824394">{{cite journal |vauthors=Miller BJ, Cram P, Lynch CF, Buckwalter JA |title=Risk factors for metastatic disease at presentation with osteosarcoma: an analysis of the SEER database |journal=J Bone Joint Surg Am |volume=95 |issue=13 |pages=e89 |date=July 2013 |pmid=23824394 |pmc=3689260 |doi=10.2106/JBJS.L.01189 |url=}}</ref><ref name="pmid26400284">{{cite journal |vauthors=Zhang HF, Yan JP, Zhuang YS, Han GQ |title=Association between angiogenic growth factor genetic polymorphisms and the risk of osteosarcoma |journal=Genet. Mol. Res. |volume=14 |issue=3 |pages=10524–9 |date=September 2015 |pmid=26400284 |doi=10.4238/2015.September.8.14 |url=}}</ref>==
==Risk Factors==
Common risk factors in the development of osteosarcoma are radiation to bones, alkylating antineoplastic agents, Paget disease, multiple hereditary osteochondromas, fibrous dysplasia, Bloom syndrome,Rothmund-Thomson syndrome, and Li-Fraumeni syndrome.
Common [[Risk factor|risk factors]] in the development of [[osteosarcoma]] are radiation to bones, alkylating [[Antineoplastic agents|antineoplastic]] agents, [[Paget disease]], multiple hereditary [[osteochondromas]], fibrous dysplasia, [[Bloom syndrome]], [[Rothmund-Thomson syndrome]], and [[Li-Fraumeni syndrome]].


== Screening ==
According to the U.S. Preventive Service Task Force ([[United states preventive services task force recommendations scheme|USPSTF]]), there is insufficient evidence to recommend routine [[screening]] for [[osteosarcoma]].


==Screening<ref>Osteosarcoma. U.S. Preventive Services Task Force.http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=osteosarcoma</ref>==
==Natural History, Complications and Prognosis==
According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for osteosarcoma.
Common [[Complication (medicine)|complications]] of osteosarcoma include [[Bone fracture|pathologic fracture]] and [[metastasis]]. Pre-treatment factors that influence the outcome of the osteosarcoma are primary tumor site, size of the primary tumor, and site of [[metastasis]]. After the administration of preoperative [[chemotherapy]], factors that influence the outcome of the osteosarcoma are the adequacy of tumor resection and [[necrosis]] following induction or [[neoadjuvant chemotherapy]]. The 5-year survival rate of osteosarcoma after adequate therapy is approximately 60-80%.


==Natural History, Complications and Prognosis<ref name="pmid29115164">{{cite journal |vauthors=Liu W, Zhao X, Zhang YJ, Fang GW, Xue Y |title=MicroRNA-375 as a potential serum biomarker for the diagnosis, prognosis, and chemosensitivity prediction of osteosarcoma |journal=J. Int. Med. Res. |volume=46 |issue=3 |pages=975–983 |date=March 2018 |pmid=29115164 |pmc=5972241 |doi=10.1177/0300060517734114 |url=}}</ref><ref name="pmid26665241">{{cite journal |vauthors=Friebele JC, Peck J, Pan X, Abdel-Rasoul M, Mayerson JL |title=Osteosarcoma: A Meta-Analysis and Review of the Literature |journal=Am J. Orthop. |volume=44 |issue=12 |pages=547–53 |date=December 2015 |pmid=26665241 |doi= |url=}}</ref><ref name="pmid24345772">{{cite journal |vauthors=Luetke A, Meyers PA, Lewis I, Juergens H |title=Osteosarcoma treatment - where do we stand? A state of the art review |journal=Cancer Treat. Rev. |volume=40 |issue=4 |pages=523–32 |date=May 2014 |pmid=24345772 |doi=10.1016/j.ctrv.2013.11.006 |url=}}</ref><ref name="pmid27037440">{{cite journal |vauthors=Parry MC, Laitinen M, Albergo J, Jeys L, Carter S, Gaston CL, Sumathi V, Grimer RJ |title=Osteosarcoma of the pelvis |journal=Bone Joint J |volume=98-B |issue=4 |pages=555–63 |date=April 2016 |pmid=27037440 |doi=10.1302/0301-620X.98B4.36583 |url=}}</ref><ref name="pmid25022788">{{cite journal |vauthors=Yonemoto T, Hosono A, Iwata S, Kamoda H, Hagiwara Y, Fujiwara T, Kawai A, Ishii T |title=The prognosis of osteosarcoma occurring as second malignancy of childhood cancers may be favorable: experience of two cancer centers in Japan |journal=Int. J. Clin. Oncol. |volume=20 |issue=3 |pages=613–6 |date=June 2015 |pmid=25022788 |doi=10.1007/s10147-014-0729-8 |url=}}</ref><ref name="pmid27651036">{{cite journal |vauthors=Kager L, Tamamyan G, Bielack S |title=Novel insights and therapeutic interventions for pediatric osteosarcoma |journal=Future Oncol |volume=13 |issue=4 |pages=357–368 |date=February 2017 |pmid=27651036 |doi=10.2217/fon-2016-0261 |url=}}</ref>==
== Diagnosis ==
Common [[Complication (medicine)|complications]] of osteosarcoma include [[Bone fracture|pathologic fracture]] and [[metastasis]]. Pre-treatment factors that influence outcome of the osteosarcoma are primary tumor site, size of the primary tumor, and site of [[metastasis]]. After administration of preoperative [[chemotherapy]], factors that influence outcome of the osteosarcoma are adequacy of tumor resection and [[necrosis]] following induction or [[neoadjuvant chemotherapy]]. The 5 year survival rate of osteosarcoma after adequate therapy is approximately 60-80%.


===Staging===
According to the [[American Joint Committee on Cancer]] ([[American Joint Committee on Cancer|AJCC]]), there are four stages of [[osteosarcoma]] based on the size of the primary tumor, [[metastasis]], the involvement of [[lymph nodes]], and grade of the [[tumor]]. For the purpose of treatment, there are only two stages of [[High-grade osteosarcoma|high-grade]] [[osteosarcoma]]: [[Localized disease|localized]] [[osteosarcoma]] and [[metastatic]] [[osteosarcoma]]


===History and Symptoms===
The most common symptoms of [[osteosarcoma]] include [[bone pain]] that may worsen at night, [[swelling]], and [[redness]] at the site of the [[tumor]]. The affected bone is not as strong as normal bones and may [[fracture]] with minor trauma (a pathological fracture).


==Diagnosis==
== Physical Examination ==
===Staging<ref name="pmid25070231">{{cite journal |vauthors=Moore DD, Luu HH |title=Osteosarcoma |journal=Cancer Treat. Res. |volume=162 |issue= |pages=65–92 |date=2014 |pmid=25070231 |doi=10.1007/978-3-319-07323-1_4 |url=}}</ref><ref name="pmid28195881">{{cite journal |vauthors=Cates JM |title=Comparison of the AJCC, MSTS, and Modified Spanier Systems for Clinical and Pathologic Staging of Osteosarcoma |journal=Am. J. Surg. Pathol. |volume=41 |issue=3 |pages=405–413 |date=March 2017 |pmid=28195881 |doi=10.1097/PAS.0000000000000774 |url=}}</ref><ref name="pmid29182106">{{cite journal |vauthors=Biazzo A, De Paolis M |title=Multidisciplinary approach to osteosarcoma |journal=Acta Orthop Belg |volume=82 |issue=4 |pages=690–698 |date=December 2016 |pmid=29182106 |doi= |url=}}</ref><ref name="pmid29200101">{{cite journal |vauthors=Cates JMM |title=Modeling Continuous Prognostic Factors in Survival Analysis: Implications for Tumor Staging and Assessing Chemotherapy Effect in Osteosarcoma |journal=Am. J. Surg. Pathol. |volume=42 |issue=4 |pages=485–491 |date=April 2018 |pmid=29200101 |doi=10.1097/PAS.0000000000000995 |url=}}</ref><ref name="pmid27138473">{{cite journal |vauthors=Jeys LM, Thorne CJ, Parry M, Gaston CL, Sumathi VP, Grimer JR |title=A Novel System for the Surgical Staging of Primary High-grade Osteosarcoma: The Birmingham Classification |journal=Clin. Orthop. Relat. Res. |volume=475 |issue=3 |pages=842–850 |date=March 2017 |pmid=27138473 |pmc=5289182 |doi=10.1007/s11999-016-4851-y |url=}}</ref>===
[[Physical examination]] findings will depend on the location of the [[osteosarcoma]]. Common physical examination findings of [[osteosarcoma]] are localized [[swelling]] and [[tenderness]] at the site of the tumor.
According to the American Joint Committee on Cancer (AJCC), there are four stages of osteosarcoma based on the size of primary tumor, [[metastasis]], involvement of [[lymph nodes]], and grade of the tumor. For the purpose of treatment, there are only two stages of high-grade osteosarcoma: [[Localized disease|localized]] osteosarcoma and [[metastatic]] osteosarcoma.


===History and Symptoms<ref name="pmid25070231">{{cite journal |vauthors=Moore DD, Luu HH |title=Osteosarcoma |journal=Cancer Treat. Res. |volume=162 |issue= |pages=65–92 |date=2014 |pmid=25070231 |doi=10.1007/978-3-319-07323-1_4 |url=}}</ref><ref name="pmid29182106">{{cite journal |vauthors=Biazzo A, De Paolis M |title=Multidisciplinary approach to osteosarcoma |journal=Acta Orthop Belg |volume=82 |issue=4 |pages=690–698 |date=December 2016 |pmid=29182106 |doi= |url=}}</ref><ref name="pmid29492676">{{cite journal |vauthors=Kumar R, Kumar M, Malhotra K, Patel S |title=Primary Osteosarcoma in the Elderly Revisited: Current Concepts in Diagnosis and Treatment |journal=Curr Oncol Rep |volume=20 |issue=2 |pages=13 |date=February 2018 |pmid=29492676 |doi=10.1007/s11912-018-0658-1 |url=}}</ref>===
==Laboratory Findings==
The most common symptoms of osteosarcoma include [[bone pain]] that may worse at night, [[swelling]], and [[redness]] at the site of the tumor. The affected bone is not as strong as normal bones and may fracture with minor trauma (a pathological fracture).
Laboratory tests for [[osteosarcoma]] include [[complete blood count]] (CBC), serum [[alkaline phosphatase]] and [[lactate dehydrogenase]].


==Biopsy==
[[Biopsy]] of [[osteosarcoma]] is important for confirming the [[Diagnosis-related group|diagnosis]] and for determining the [[Histology|histologic]] subtype. [[Biopsy]] may be performed [[percutaneously]] with either a [[Fine-needle aspiration|fine-needle]], or a wide-bore needle, or through a formal [[incision]].


===Physical Examination<ref name="pmid19915470">{{cite journal |vauthors=Kim HJ, Chalmers PN, Morris CD |title=Pediatric osteogenic sarcoma |journal=Curr. Opin. Pediatr. |volume=22 |issue=1 |pages=61–6 |date=February 2010 |pmid=19915470 |doi=10.1097/MOP.0b013e328334581f |url=}}</ref><ref name="pmid25070231">{{cite journal |vauthors=Moore DD, Luu HH |title=Osteosarcoma |journal=Cancer Treat. Res. |volume=162 |issue= |pages=65–92 |date=2014 |pmid=25070231 |doi=10.1007/978-3-319-07323-1_4 |url=}}</ref><ref name="pmid20179183">{{cite journal |vauthors=Ilaslan H, Schils J, Nageotte W, Lietman SA, Sundaram M |title=Clinical presentation and imaging of bone and soft-tissue sarcomas |journal=Cleve Clin J Med |volume=77 Suppl 1 |issue= |pages=S2–7 |date=March 2010 |pmid=20179183 |doi=10.3949/ccjm.77.s1.01 |url=}}</ref><ref name="pmid21037356">{{cite journal |vauthors=Wu PK, Chen WM, Lee OK, Chen CF, Huang CK, Chen TH |title=The prognosis for patients with osteosarcoma who have received prior manipulative therapy |journal=J Bone Joint Surg Br |volume=92 |issue=11 |pages=1580–5 |date=November 2010 |pmid=21037356 |doi=10.1302/0301-620X.92B11.24706 |url=}}</ref><ref name="pmid29980176">{{cite journal |vauthors=Obiedat H, Alrabadi N, Sultan E, Al Shatti M, Zihlif M |title=The effect of ERCC1 and ERCC2 gene polymorphysims on response to cisplatin based therapy in osteosarcoma patients |journal=BMC Med. Genet. |volume=19 |issue=1 |pages=112 |date=July 2018 |pmid=29980176 |pmc=6035436 |doi=10.1186/s12881-018-0627-4 |url=}}</ref>===
==X Ray ==
Physical examination findings will depend on the location of the osteosarcoma. Common physical examination findings of osteosarcoma are localized [[swelling]] and [[tenderness]] at the site of the tumor.
On [[x-ray]], [[osteosarcoma]]<nowiki/>is characterized by [[medullary]] and [[cortical bone]] destruction, [[periosteal reaction]], tumor matrix [[calcification]], and soft tissue mass.


===Laboratory Findings<ref name="pmid19915470">{{cite journal |vauthors=Kim HJ, Chalmers PN, Morris CD |title=Pediatric osteogenic sarcoma |journal=Curr. Opin. Pediatr. |volume=22 |issue=1 |pages=61–6 |date=February 2010 |pmid=19915470 |doi=10.1097/MOP.0b013e328334581f |url=}}</ref><ref name="pmid25070231">{{cite journal |vauthors=Moore DD, Luu HH |title=Osteosarcoma |journal=Cancer Treat. Res. |volume=162 |issue= |pages=65–92 |date=2014 |pmid=25070231 |doi=10.1007/978-3-319-07323-1_4 |url=}}</ref><ref name="pmid20179183">{{cite journal |vauthors=Ilaslan H, Schils J, Nageotte W, Lietman SA, Sundaram M |title=Clinical presentation and imaging of bone and soft-tissue sarcomas |journal=Cleve Clin J Med |volume=77 Suppl 1 |issue= |pages=S2–7 |date=March 2010 |pmid=20179183 |doi=10.3949/ccjm.77.s1.01 |url=}}</ref><ref name="pmid21037356">{{cite journal |vauthors=Wu PK, Chen WM, Lee OK, Chen CF, Huang CK, Chen TH |title=The prognosis for patients with osteosarcoma who have received prior manipulative therapy |journal=J Bone Joint Surg Br |volume=92 |issue=11 |pages=1580–5 |date=November 2010 |pmid=21037356 |doi=10.1302/0301-620X.92B11.24706 |url=}}</ref><ref name="pmid29980176">{{cite journal |vauthors=Obiedat H, Alrabadi N, Sultan E, Al Shatti M, Zihlif M |title=The effect of ERCC1 and ERCC2 gene polymorphysims on response to cisplatin based therapy in osteosarcoma patients |journal=BMC Med. Genet. |volume=19 |issue=1 |pages=112 |date=July 2018 |pmid=29980176 |pmc=6035436 |doi=10.1186/s12881-018-0627-4 |url=}}</ref>===
==CT ==
Laboratory tests for osteosarcoma include [[complete blood count]] (CBC), serum [[alkaline phosphatase]] and [[lactate dehydrogenase]].
[[Computed tomography|CT scan]] in [[osteosarcoma]] may be helpful in [[biopsy]] and [[Cancer staging|staging]]. [[Computed tomography|CT]] scan adds little to plain [[radiography]] and [[Magnetic resonance imaging|MRI]] in direct assessment of the tumor.


===Biopsy<ref name="pmid25070231">{{cite journal |vauthors=Moore DD, Luu HH |title=Osteosarcoma |journal=Cancer Treat. Res. |volume=162 |issue= |pages=65–92 |date=2014 |pmid=25070231 |doi=10.1007/978-3-319-07323-1_4 |url=}}</ref><ref name="pmid20179183">{{cite journal |vauthors=Ilaslan H, Schils J, Nageotte W, Lietman SA, Sundaram M |title=Clinical presentation and imaging of bone and soft-tissue sarcomas |journal=Cleve Clin J Med |volume=77 Suppl 1 |issue= |pages=S2–7 |date=March 2010 |pmid=20179183 |doi=10.3949/ccjm.77.s1.01 |url=}}</ref><ref name="pmid21037356">{{cite journal |vauthors=Wu PK, Chen WM, Lee OK, Chen CF, Huang CK, Chen TH |title=The prognosis for patients with osteosarcoma who have received prior manipulative therapy |journal=J Bone Joint Surg Br |volume=92 |issue=11 |pages=1580–5 |date=November 2010 |pmid=21037356 |doi=10.1302/0301-620X.92B11.24706 |url=}}</ref><ref name="pmid29980176">{{cite journal |vauthors=Obiedat H, Alrabadi N, Sultan E, Al Shatti M, Zihlif M |title=The effect of ERCC1 and ERCC2 gene polymorphysims on response to cisplatin based therapy in osteosarcoma patients |journal=BMC Med. Genet. |volume=19 |issue=1 |pages=112 |date=July 2018 |pmid=29980176 |pmc=6035436 |doi=10.1186/s12881-018-0627-4 |url=}}</ref>===
==MRI==
[[Biopsy]] of osteosarcoma is important for confirming the diagnosis and for determining the histologic subtype.<ref>Osteosarcoma. surgwiki. http://www.surgwiki.com/wiki/Diseases_of_bone_and_joints#SURGERY_4 </ref> Biopsy may be performed [[percutaneously]] with either a fine-needle, or a wide-bore needle, or through a formal incision.
On [[Magnetic resonance imaging|MRI]], [[osteosarcoma]] is characterized by an intermediate intensity of soft tissue and low signal intensity of ossified components on [[T1]]. The high signal intensity of soft tissue and low signal intensity of [[Ossification|ossified]] components on T2. Considerable contrast enhancement of solid components on [[T1]] contrast.


===X Ray <ref name="pmid6425164">{{cite journal |vauthors=Gürtler KF, Riebel T, Beron G, Heller M, Euler A |title=[Comparison of x-ray plain films, x-ray tomograms and computed tomograms in lung nodules in children and adolescents] |language=German |journal=Rofo |volume=140 |issue=4 |pages=416–20 |date=April 1984 |pmid=6425164 |doi=10.1055/s-2008-1052998 |url=}}</ref><ref name="pmid3022331">{{cite journal |vauthors=Riebel T, Knop J, Winkler K, Delling G |title=[Comparative x-ray and nuclear medical studies of osteosarcomas to evaluate the effectiveness of preoperative chemotherapy] |language=German |journal=Rofo |volume=145 |issue=4 |pages=365–72 |date=October 1986 |pmid=3022331 |doi=10.1055/s-2008-1048952 |url=}}</ref><ref name="pmid3889998">{{cite journal |vauthors=Dinkel E, Uhl H, Roeren T |title=[Lung metastases--limitations and possibilities of radiologic diagnosis] |language=German |journal=Radiologe |volume=25 |issue=4 |pages=158–65 |date=April 1985 |pmid=3889998 |doi= |url=}}</ref><ref name="pmid7042255">{{cite journal |vauthors=Kesselring FO, Penn W |title=Radiological aspects of 'classic' primary osteosarcoma: value of some radiological investigations: A review |journal=Diagn Imaging |volume=51 |issue=2 |pages=78–92 |date=1982 |pmid=7042255 |doi= |url=}}</ref>===
===Other Imaging Findings===
On x-ray, osteosarcoma is characterized by [[medullary]] and [[cortical bone]] destruction, [[periosteal reaction]], tumor matrix [[calcification]], and soft tissue mass.
[[Bone scan]] in [[osteosarcoma]] is used to observe abnormal areas of bone and [[metastasis]].
 
===CT <ref name="pmid26304877">{{cite journal |vauthors=Isakoff MS, Bielack SS, Meltzer P, Gorlick R |title=Osteosarcoma: Current Treatment and a Collaborative Pathway to Success |journal=J. Clin. Oncol. |volume=33 |issue=27 |pages=3029–35 |date=September 2015 |pmid=26304877 |pmc=4979196 |doi=10.1200/JCO.2014.59.4895 |url=}}</ref><ref name="pmid28808701">{{cite journal |vauthors=Sue M, Oda T, Sasaki Y, Kameta A, Okada Y, Ogura I |title=Osteosarcoma of the Mandible: a Case Report with CT, MRI and Scintigraphy |journal=Chin J Dent Res |volume=20 |issue=3 |pages=169–172 |date=2017 |pmid=28808701 |doi=10.3290/j.cjdr.a38772 |url=}}</ref><ref name="pmid27836366">{{cite journal |vauthors=Heaton TE, Hammond WJ, Farber BA, Pallos V, Meyers PA, Chou AJ, Price AP, LaQuaglia MP |title=A 20-year retrospective analysis of CT-based pre-operative identification of pulmonary metastases in patients with osteosarcoma: A single-center review |journal=J. Pediatr. Surg. |volume=52 |issue=1 |pages=115–119 |date=January 2017 |pmid=27836366 |pmc=5384104 |doi=10.1016/j.jpedsurg.2016.10.034 |url=}}</ref><ref name="pmid28391820">{{cite journal |vauthors=Huang L, Xia W, Zhang B, Qiu B, Gao X |title=MSFCN-multiple supervised fully convolutional networks for the osteosarcoma segmentation of CT images |journal=Comput Methods Programs Biomed |volume=143 |issue= |pages=67–74 |date=May 2017 |pmid=28391820 |doi=10.1016/j.cmpb.2017.02.013 |url=}}</ref><ref name="pmid25058144">{{cite journal |vauthors=Xia T, Guan Y, Chen Y, Li J |title=Askin tumor: CT and FDG-PET/CT imaging findings and follow-up |journal=Medicine (Baltimore) |volume=93 |issue=6 |pages=e42 |date=July 2014 |pmid=25058144 |pmc=4602428 |doi=10.1097/MD.0000000000000042 |url=}}</ref>===
CT scan in osteosarcoma may be helpful in [[biopsy]] and [[Cancer staging|staging]]. CT scan adds little to plain [[radiography]] and MRI in direct assessment of the tumor.
 
===MRI<ref name="pmid28806574">{{cite journal |vauthors=Degnan AJ, Chung CY, Shah AJ |title=Quantitative diffusion-weighted magnetic resonance imaging assessment of chemotherapy treatment response of pediatric osteosarcoma and Ewing sarcoma malignant bone tumors |journal=Clin Imaging |volume=47 |issue= |pages=9–13 |date=2018 |pmid=28806574 |doi=10.1016/j.clinimag.2017.08.003 |url=}}</ref><ref name="pmid24247589">{{cite journal |vauthors=Uchiyama Y, Matsumoto K, Murakami S, Kanesaki T, Matsumoto A, Kishino M, Furukawa S |title=MRI in a case of osteosarcoma in the temporomandibular joint |journal=Dentomaxillofac Radiol |volume=43 |issue=2 |pages=20130280 |date=2014 |pmid=24247589 |pmc=4064616 |doi=10.1259/dmfr.20130280 |url=}}</ref><ref name="pmid26385785">{{cite journal |vauthors=Wakabayashi H, Saito J, Taki J, Hashimoto N, Tsuchiya H, Gabata T, Kinuya S |title=Triple-phase contrast-enhanced MRI for the prediction of preoperative chemotherapeutic effect in patients with osteosarcoma: comparison with (99m)Tc-MIBI scintigraphy |journal=Skeletal Radiol. |volume=45 |issue=1 |pages=87–95 |date=January 2016 |pmid=26385785 |doi=10.1007/s00256-015-2250-1 |url=}}</ref>===
On MRI, osteosarcoma is characterized by intermediate intensity of soft tissue and low signal intensity of ossified components on T1. High signal intensity of soft tissue and low signal intensity of ossified components on T2. Considerable contrast enhancement of solid components on T1 contrast.
 
===Other Imaging Findings<ref name="pmid25070231">{{cite journal |vauthors=Moore DD, Luu HH |title=Osteosarcoma |journal=Cancer Treat. Res. |volume=162 |issue= |pages=65–92 |date=2014 |pmid=25070231 |doi=10.1007/978-3-319-07323-1_4 |url=}}</ref><ref name="pmid29772552">{{cite journal |vauthors=Zhang X, Guan Z |title=PET/CT in the diagnosis and prognosis of osteosarcoma |journal=Front Biosci (Landmark Ed) |volume=23 |issue= |pages=2157–2165 |date=June 2018 |pmid=29772552 |doi= |url=}}</ref><ref name="pmid28965545">{{cite journal |vauthors=Costelloe CM, Chuang HH, Daw NC |title=PET/CT of Osteosarcoma and Ewing Sarcoma |journal=Semin Roentgenol |volume=52 |issue=4 |pages=255–268 |date=October 2017 |pmid=28965545 |doi=10.1053/j.ro.2017.04.007 |url=}}</ref><ref name="pmid27841678">{{cite journal |vauthors=Selmic LE, Griffin LR, Nolan MW, Custis J, Randall E, Withrow SJ |title=Use of PET/CT and Stereotactic Radiation Therapy for the Diagnosis and Treatment of Osteosarcoma Metastases |journal=J Am Anim Hosp Assoc |volume=53 |issue=1 |pages=52–58 |date=2017 |pmid=27841678 |doi=10.5326/JAAHA-MS-6359 |url=}}</ref>===
Bone scan in osteosarcoma is used to observe abnormal areas of bone and [[metastasis]].<ref>Osteosarcoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/bone/diagnosis/?region=bc</ref>


===Other Diagnostic Studies===
===Other Diagnostic Studies===
Bone scan in osteosarcoma is used to observe abnormal areas of bone and metastasis<ref name="pmid25070231">{{cite journal |vauthors=Moore DD, Luu HH |title=Osteosarcoma |journal=Cancer Treat. Res. |volume=162 |issue= |pages=65–92 |date=2014 |pmid=25070231 |doi=10.1007/978-3-319-07323-1_4 |url=}}</ref><ref name="pmid29772552">{{cite journal |vauthors=Zhang X, Guan Z |title=PET/CT in the diagnosis and prognosis of osteosarcoma |journal=Front Biosci (Landmark Ed) |volume=23 |issue= |pages=2157–2165 |date=June 2018 |pmid=29772552 |doi= |url=}}</ref><ref name="pmid28965545">{{cite journal |vauthors=Costelloe CM, Chuang HH, Daw NC |title=PET/CT of Osteosarcoma and Ewing Sarcoma |journal=Semin Roentgenol |volume=52 |issue=4 |pages=255–268 |date=October 2017 |pmid=28965545 |doi=10.1053/j.ro.2017.04.007 |url=}}</ref><ref name="pmid27841678">{{cite journal |vauthors=Selmic LE, Griffin LR, Nolan MW, Custis J, Randall E, Withrow SJ |title=Use of PET/CT and Stereotactic Radiation Therapy for the Diagnosis and Treatment of Osteosarcoma Metastases |journal=J Am Anim Hosp Assoc |volume=53 |issue=1 |pages=52–58 |date=2017 |pmid=27841678 |doi=10.5326/JAAHA-MS-6359 |url=}}</ref>.
A [[bone scan]] in [[osteosarcoma]]<nowiki/>is used to observe abnormal areas of bone and [[metastasis]].


==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
The predominant therapy for osteosarcoma is [[neoadjuvant]] [[chemotherapy]] ([[chemotherapy]] given before surgery) followed by [[surgical resection]]. The most common drugs used to treat osteosarcoma are [[cisplatin]], [[doxorubicin]] and high-dose [[methotrexate]]. [[Ifosfamide]] can be used as an [[adjuvant treatment]] if the [[necrosis]] rate is low. [[Samarium]] is a radioactive drug that targets areas where bone cells are growing, such as tumor cells in the bone. It helps relieve bone pain.
The predominant therapy for [[osteosarcoma]] is [[neoadjuvant]] [[chemotherapy]] ([[chemotherapy]] given before [[surgery]]) followed by [[surgical resection]]. The most common drugs used to treat [[osteosarcoma]] are [[cisplatin]], [[doxorubicin]] and high-dose [[methotrexate]]. [[Ifosfamide]] can be used as an [[adjuvant treatment]] if the [[necrosis]] rate is low. [[Samarium]] is a radioactive drug that targets areas where bone cells are growing, such as tumor cells in the bone. It helps relieve bone pain.


===Surgery<ref name="pmid27116252">{{cite journal |vauthors=Han G, Bi WZ, Xu M, Jia JP, Wang Y |title=Amputation Versus Limb-Salvage Surgery in Patients with Osteosarcoma: A Meta-analysis |journal=World J Surg |volume=40 |issue=8 |pages=2016–27 |date=August 2016 |pmid=27116252 |doi=10.1007/s00268-016-3500-7 |url=}}</ref><ref name="pmid26614941">{{cite journa<ref name="pmid26660089">{{cite journal |vauthors=Anderson ME, Wu JS, Vargas SO |title=CORR (®) Tumor Board: Does Microwave Ablation of the Tumor Edge Allow for Joint-sparing Surgery in Patients with Osteosarcoma of the Proximal Tibia? |journal=Clin. Orthop. Relat. Res. |volume=474 |issue=5 |pages=1110–2 |date=May 2016 |pmid=26660089 |doi=10.1007/s11999-015-4660-8 |url=}}</ref><ref name="pmid26997197">{{cite journal |vauthors=Ma L, Zhou Y, Zhu Y, Lin Z, Wang Y, Zhang Y, Xia H, Mao C |title=3D-printed guiding templates for improved osteosarcoma resection |journal=Sci Rep |volume=6 |issue= |pages=23335 |date=March 2016 |pmid=26997197 |pmc=4800413 |doi=10.1038/srep23335 |url=}}</ref><ref name="pmid27840351">{{cite journal |vauthors=Kamal AF, Widyawarman H, Husodo K, Hutagalung EU, Rajabto W |title=Clinical Outcome and Survival of Osteosarcoma Patients in Cipto Mangunkusumo Hospital: Limb Salvage Surgery versus Amputation |journal=Acta Med Indones |volume=48 |issue=3 |pages=175–183 |date=July 2016 |pmid=27840351 |doi= |url=}}</ref>===
===Surgery===
The mainstay of therapy for osteosarcoma is [[surgical resection]]. Rather than using the standard staging system, a simpler system is often used when planning treatment for osteosarcoma. This system divides osteosarcomas into 2 groups: [[Localized disease|localized]] osteosarcoma and [[metastatic]] osteosarcoma.
The mainstay of therapy for [[osteosarcoma]] is [[surgical resection]]. Rather than using the standard staging system, a simpler system is often used when planning treatment for [[osteosarcoma]]. This system divides osteosarcomas into 2 groups: [[Localized disease|localized]] [[osteosarcoma]] and [[metastatic]] [[osteosarcoma]].


==References==
==References==

Latest revision as of 15:47, 19 October 2019


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammadmain Rezazadehsaatlou[2].

Osteosarcoma Microchapters

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Natural History, Complications and Prognosis

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Staging

History and Symptoms

Physical Examination

Laboratory Findings

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Overview

Bone cancer is a malignant (cancerous) tumor of the bone that destroys normal bone tissue. Osteosarcoma is the most common type of malignant bone cancer, accounting for 35% of primary bone malignancies. It is a malignant tumor that is characterized by the direct formation of bone or osteoid tissue by the tumor cells. Malignant tumors that begin in bone tissue are called primary bone cancer. Osteosarcoma may be classified according to the World Health Organization’s histologic classification of bone tumors into three groups. The osteosarcomas may be localized at the end of the long bones (commonly in the metaphysis). Most often it affects the upper end of the tibia, humerus, or lower end of the femur. On gross pathology, areas of bone formation, hemorrhage, fibrosis, and cystic degeneration on cut surface are characteristic findings of osteosarcoma. On microscopic histopathological analysis, presence of osteoid within the tumor, pleomorphic cells, anaplastic cells, and atypical mitoses are characteristic findings of osteosarcoma. There are no established causes for osteosarcoma. The common risk factors in the development of osteosarcoma are radiation to bones, alkylating antineoplastic agents, Paget disease, multiple hereditary osteochondromas, fibrous dysplasia, Bloom syndrome, Rothmund-Thomson syndrome, and Li-Fraumeni syndrome. Common complications of osteosarcoma include pathologic fracture and metastasis. The most common symptoms of osteosarcoma include bone pain that may be worse at night, swelling, and redness at the site of the tumor. On x-ray, osteosarcoma is characterized by medullary and cortical bone destruction, periosteal reaction, tumor matrix calcification, and soft tissue mass. On MRI, osteosarcoma is characterized by intermediate intensity of soft tissue and low signal intensity of ossified components on T1. High signal intensity of soft tissue and low signal intensity of ossified components on T2. The predominant therapy for osteosarcoma is neoadjuvant chemotherapy (chemotherapy given before surgery) followed by surgical resection. The most common drugs used to treat osteosarcoma are cisplatin, doxorubicin and high-dose methotrexate.

Historical perspective

Osteosarcoma is known as the most common bone malignant tumor. Osteosarcoma is an ancient disease and is not completely understood, yet. Nobody knows when and who discovered osteosarcoma, but recent Paleontology discoveries revealed that osteosarcoma has a long story on planet earth. Recent discoverers in Germany revealed a 240 million-year-old highly malignant tumor in the fossilized leg bone of a stem turtle. It is been found that osteosarcoma is the earliest case of human cancer which was found on the 1.7 million-year-old fossil of an early ancestor of mankind in Swartkrans cave in South Africa. In 1990, a thousand-year-old mummy of a woman in her mid-30s of age had with a malignant tumor in her upper-left arm which that mass had grown so large that it might burst through her skin while she was still alive.

Classification

Osteosarcoma (OS) is a rare bone cancer that affects both adolescents and young adults. Osteosarcoma was classified as primary and secondary. Later the World Health Organization sub-typed as intramedullary/central and surface osteosarcoma with a number of sub-types under each group.

Pathophysiology

Traditionally, our knowledge about osteosarcoma has been mostly anatomical but it should be noted that it arises most commonly in the metaphyseal region of long bones, within the medullary cavity, then it involves the bone cortex; consequently a pseudocapsule forms around the penetrating tumor. Osteosarcoma is characterized as a highly cellular tumor consisted of pleomorphic spindle-shaped cells responsible for producing an osteoid matrix. However, recent developments in the field of medical sciences and molecular biology have provided huge insights regarding the molecular pathogenesis of osteosarcoma.

Causes

There are no established causes for osteosarcoma. However, some studies show that an increased level of c-fos proto-oncogene expression can lead to osteosarcoma.

Differential Diagnosis

Osteosarcoma must be differentiated from other diseases such as any type of bone lesions caused by infection and/or tumors. Features such as the eccentric location of the tumor in the metaphyseal portion of the bone and the skeletal location help to distinguish osteosarcoma from Ewing sarcoma. Bone metastases from other primary tumors, less frequent in the young than in adult patients, should also be considered.

Epidemiology and Demographics

Osteosarcoma is the most common nonhematologic primary malignant bone neoplasm causing 35% of primary bone malignancies and occurs at any age, it usually affects patients in the second and third decade of life with a peak incidence between 13 and 16 years of age. It is the 8th leading cancer in children under age 15, comprising 2.4% of all malignancies in pediatric patients and about 20% of all primary bone cancers. The overall incidence of osteosarcoma in the U.S. population under 24 years of age is estimated at 0.44 cases for 100,000 individuals. Osteosarcoma is slightly more common in males than in females. Primary osteosarcoma typically occurs in young patients (10-20 years) with 75% occurring before the age of 20. Secondary osteosarcoma occurs in elderly patients.

Risk Factors

Common risk factors in the development of osteosarcoma are radiation to bones, alkylating antineoplastic agents, Paget disease, multiple hereditary osteochondromas, fibrous dysplasia, Bloom syndrome, Rothmund-Thomson syndrome, and Li-Fraumeni syndrome.

Screening

According to the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for osteosarcoma.

Natural History, Complications and Prognosis

Common complications of osteosarcoma include pathologic fracture and metastasis. Pre-treatment factors that influence the outcome of the osteosarcoma are primary tumor site, size of the primary tumor, and site of metastasis. After the administration of preoperative chemotherapy, factors that influence the outcome of the osteosarcoma are the adequacy of tumor resection and necrosis following induction or neoadjuvant chemotherapy. The 5-year survival rate of osteosarcoma after adequate therapy is approximately 60-80%.

Diagnosis

Staging

According to the American Joint Committee on Cancer (AJCC), there are four stages of osteosarcoma based on the size of the primary tumor, metastasis, the involvement of lymph nodes, and grade of the tumor. For the purpose of treatment, there are only two stages of high-grade osteosarcoma: localized osteosarcoma and metastatic osteosarcoma

History and Symptoms

The most common symptoms of osteosarcoma include bone pain that may worsen at night, swelling, and redness at the site of the tumor. The affected bone is not as strong as normal bones and may fracture with minor trauma (a pathological fracture).

Physical Examination

Physical examination findings will depend on the location of the osteosarcoma. Common physical examination findings of osteosarcoma are localized swelling and tenderness at the site of the tumor.

Laboratory Findings

Laboratory tests for osteosarcoma include complete blood count (CBC), serum alkaline phosphatase and lactate dehydrogenase.

Biopsy

Biopsy of osteosarcoma is important for confirming the diagnosis and for determining the histologic subtype. Biopsy may be performed percutaneously with either a fine-needle, or a wide-bore needle, or through a formal incision.

X Ray

On x-ray, osteosarcomais characterized by medullary and cortical bone destruction, periosteal reaction, tumor matrix calcification, and soft tissue mass.

CT

CT scan in osteosarcoma may be helpful in biopsy and staging. CT scan adds little to plain radiography and MRI in direct assessment of the tumor.

MRI

On MRI, osteosarcoma is characterized by an intermediate intensity of soft tissue and low signal intensity of ossified components on T1. The high signal intensity of soft tissue and low signal intensity of ossified components on T2. Considerable contrast enhancement of solid components on T1 contrast.

Other Imaging Findings

Bone scan in osteosarcoma is used to observe abnormal areas of bone and metastasis.

Other Diagnostic Studies

A bone scan in osteosarcomais used to observe abnormal areas of bone and metastasis.

Treatment

Medical Therapy

The predominant therapy for osteosarcoma is neoadjuvant chemotherapy (chemotherapy given before surgery) followed by surgical resection. The most common drugs used to treat osteosarcoma are cisplatin, doxorubicin and high-dose methotrexate. Ifosfamide can be used as an adjuvant treatment if the necrosis rate is low. Samarium is a radioactive drug that targets areas where bone cells are growing, such as tumor cells in the bone. It helps relieve bone pain.

Surgery

The mainstay of therapy for osteosarcoma is surgical resection. Rather than using the standard staging system, a simpler system is often used when planning treatment for osteosarcoma. This system divides osteosarcomas into 2 groups: localized osteosarcoma and metastatic osteosarcoma.

References

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