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{{Use dmy dates|date=December 2017}}
{{Use American English|date=December 2017}}
{{Infobox medical condition (new)
| name = Sarcoma
| pronounce =
| synonyms = Sarcomas, sarcomata
| image = Nibib 030207 105309 sarcoma.jpg
| caption = [[Optical coherence tomography]] (OCT) image of a sarcoma
| field = [[Oncology]]
| symptoms =
| complications =
| onset =
| duration =
| types =
| causes =
| risks =
| diagnosis =
| differential =
| prevention =
| treatment =
| medication =
| prognosis =
| frequency =
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}}
A '''sarcoma''' is a [[malignant tumor]], a type of [[cancer]] that arises from transformed [[Cell (biology)|cells]] of [[mesenchyme|mesenchymal]] ([[connective tissue]]) origin.<ref>{{cite journal | vauthors = Yang J, Ren Z, Du X, Hao M, Zhou W | title = The role of mesenchymal stem/progenitor cells in sarcoma: update and dispute | journal = Stem Cell Investigation | volume = 1 | pages = 18 | date = 2014-10-27 | pmid = 27358864 | pmc = 4923508 | doi = 10.3978/j.issn.2306-9759.2014.10.01 }}</ref><ref name=":1" /> Connective tissue is a broad term that includes [[cancellous bone|bone]], [[cartilage]], [[Body fat|fat]], [[vascular]], or [[Haematopoiesis|hematopoietic]] tissues, and sarcomas can arise in any of these types of tissues.<ref name=":1" /><ref name=":2" /> 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.<ref name=":0" /> Sarcomas are ''primary'' connective tissue tumors, meaning that they arise in connective tissues.<ref name=":1" /> This is in contrast to ''secondary'' (or "metastatic") connective tissue tumors, which occur when a cancer from elsewhere in the body (such as the lungs, breast tissue or prostate) spreads to the connective tissue.<ref>{{Cite web|url=https://www.cancer.gov/types/metastatic-cancer|title=Metastatic Cancer|date=2015-05-12|website=National Cancer Institute|language=en|access-date=2019-03-22}}</ref> Sarcomas are one of five different [[List of cancer types|types of cancer]], classified by the [[list of distinct cell types in the adult human body|cell type]] from which they originate.<ref name=def>{{cite web|title=Defining Cancer| url=http://www.cancer.gov/cancertopics/cancerlibrary/what-is-cancer|website=National Cancer Institute|date=17 September 2007|access-date=10 June 2014}}</ref> The word ''sarcoma'' is derived from the [[Ancient Greek|Greek]] {{Lang|grc|σάρκωμα}} {{Lang|grc-latn|sarkōma}} 'fleshy excrescence or substance', itself from [[wikt:σάρξ|σάρξ]] {{Lang|grc-latn|sarx}} meaning 'flesh'.<ref>{{LSJ|sa/rkwma|σάρκωμα}}, {{LSJ|sa/rc|σάρξ|ref}}.</ref><ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/sarcoma|title=Definition of SARCOMA|website=www.merriam-webster.com|language=en|access-date=2019-03-22}}</ref><ref>{{OEtymD|sarcoma}}</ref>
== Classification ==
Sarcomas are typically divided into two major groups: [[bone sarcoma]]s and [[soft-tissue sarcoma]]s,<ref name=":1">{{Cite book|title=Cancer and its Management | edition = Seventh | vauthors = Tobias J |publisher=John Wiley & Sons, Ltd.|year=2015|isbn=978-1-118-46875-3|location=Chichester, West Sussex, PO198SQ, UK|pages=446}}</ref> each of which has multiple subtypes. In the United States, the American Joint Committee on Cancer (AJCC) publishes guidelines that classify the subtypes of sarcoma.<ref name=":0">{{Cite book|title=AJCC Cancer Staging Manual, Eight Edition| vauthors = Amin MB |publisher=Springer International Publishing AG Switzerland|year=2017|isbn=978-3-319-40617-6|location=Chicago, IL|pages=471–548}}</ref> These subtypes are as follows:
===Subtypes of bone sarcoma===
* [[Osteosarcoma]]
* [[Chondrosarcoma]]
* Poorly differentiated round/spindle cell tumors (includes [[Ewing sarcoma]])
* [[Hemangioendothelioma]]
* [[Angiosarcoma]]
* [[Fibrosarcoma]]/myofibrosarcoma
* [[Chordoma]]
* [[Adamantinoma]]
* Other:
** [[Liposarcoma]]
** [[Leiomyosarcoma]]
** [[Malignant peripheral nerve sheath tumor]]
** [[Rhabdomyosarcoma]]
** [[Synovial sarcoma]]
** Malignant solitary fibrous tumor.<ref name=":0" />
===Subtypes of soft-tissue sarcoma===
* [[Liposarcoma]] (includes the following varieties: [[Liposarcoma#Atypical lipomatous tumor/well-differentiated liposarcoma|atypical lipomatous tumor/well-differentiated liposarcoma]], [[Liposarcoma#Dedifferentiated liposarcoma|dedifferentiated liposarcoma]], [[Liposarcoma#Myxoid liposarcoma|myxoid sarcoma]], [[Liposarcoma#Pleomorphic liposarcoma|pleomorphic liposarcoma]], and [[Liposarcoma#Myxoid pleomorphic liposarcoma|myxoid pleomorphic liposarcoma]]
* Atypical lipomatous tumor
* [[Dermatofibrosarcoma protuberans]] (includes pigmented varieties)
* [[Dermatofibrosarcoma protuberans, fibrosarcomatous]]
* [[Giant cell fibroblastoma]]
* Malignant [[solitary fibrous tumor]]
* [[Inflammatory myofibroblastic tumour|Inflammatory myofibroblastic tumor]]
* [[Low-grade myofibroblastic sarcoma]]
* [[Fibrosarcoma]] (includes adult and sclerosing epithelioid varieties)
* Myxofibrosarcoma (formerly myxoid malignant fibrous histiocytoma)
* [[Low-grade fibromyxoid sarcoma]]
* Giant cell tumor of soft tissues
* [[Leiomyosarcoma]]
* Malignant [[glomus tumor]]
* [[Rhabdomyosarcoma]] (includes the following varieties: embryonal, alveolar, pleomorphic, and spindle cell/sclerosing)
* [[Hemangioendothelioma]] (includes the following varieties: retiform, pseudomyogenic, and epithelioid)
* [[Angiosarcoma]] of soft tissue
* Extraskeletal osteosarcoma
* [[Gastrointestinal stromal tumor]], malignant (GIST)
* [[Malignant peripheral nerve sheath tumor]] (includes epithelioid variety)
* Malignant Triton tumor
* Malignant [[granular cell tumor]]
* Malignant ossifying fibromyxoid tumor
* Stromal sarcoma not otherwise specified
* Myoepithelial carcinoma
* Malignant phosphaturic mesenchymal tumor
* [[Synovial sarcoma]] (includes the following varieties: spindle cell, biphasic, and not otherwise specified)
* [[Epithelioid sarcoma]]
* [[Alveolar soft part sarcoma]]
* Clear cell sarcoma of soft tissue
* Extraskeletal myxoid chondrosarcoma
* Extraskeletal Ewing sarcoma
* [[Interdigitating dendritic cell sarcoma]]
* [[Desmoplastic small-round-cell tumor|Desmoplastic small round cell tumor]]
* Extrarenal rhabdoid tumor
* [[Perivascular epithelioid cell tumour|Perivascular epithelioid cell tumor]], not otherwise specified
* Intimal sarcoma
* Undifferentiated [[spindle cell sarcoma]]
* Undifferentiated pleomorphic sarcoma
* Undifferentiated round cell sarcoma
* Undifferentiated epithelioid sarcoma
* Undifferentiated sarcoma, not otherwise specified.<ref name=":0" />
== Signs and symptoms ==
Symptoms of bone sarcomas typically include bone pain, especially at night, and swelling around the site of the tumor.<ref name=":1" />
Symptoms of [[soft-tissue sarcoma]]s vary, but they often present as firm, painless lumps or nodules.<ref name=":1" /> Gastrointestinal stromal tumors (a subtype of soft-tissue sarcoma) often are asymptomatic, but can be associated with vague complaints of abdominal pain, a feeling of fullness, or other signs of intestinal obstruction.<ref name=":1" />
==Cause==
=== Causes and risk factors ===
The cause of most '''bone sarcomas''' is not known,<ref name=":2">{{Cite book|title=DeVita, Hellman and Rosenberg's Cancer: Principles & Practice of Oncology | edition = 10th| vauthors = DeVita Jr V |publisher=Wolters Kluwer Health|year=2015|isbn=978-1-4511-9294-0|location=Philadelphia, PA|pages=1241–1313}}</ref> but several factors are associated with an increased risk of developing bone sarcoma. Previous exposure to ionizing radiation (such as prior radiation therapy) is one such risk factor.<ref name=":1" /> Therapeutic radiation is associated with sarcoma after 10 to 20 years.<ref>{{Cite web |title=UpToDate |url=https://www.uptodate.com/contents/radiation-associated-sarcomas#! |access-date=2023-03-19 |website=www.uptodate.com}}</ref> Mole removal in irradiated tissue may stimulate a sarcoma secondary to healing. Exposure to alkylating agents, such as those found in [[Alkylating antineoplastic agent|certain cancer chemotherapeutic medicines]], also increases the risk of bone sarcoma.<ref name=":2" /> Certain inherited genetic syndromes, including [[Li–Fraumeni syndrome|Li-Fraumeni syndrome]], heritable RB1 gene mutations, and [[Paget's disease of bone]], are associated with an increased risk of developing bone sarcomas.<ref name=":1" />
Most '''soft-tissue sarcomas''' arise from what doctors call "sporadic" (or random) genetic mutations within an affected person's cells.<ref name=":2" /> Nevertheless, there are certain risk factors associated with an increased risk of developing soft-tissue sarcoma. Previous exposure to [[ionizing radiation]] is one such risk factor.<ref name=":1" /> Exposure to vinyl chloride (e.g., such as the fumes encountered in the production of [[polyvinyl chloride]] (PVC)), [[arsenic]] and [[Thorotrast]] all are associated with an increased risk of angiosarcoma.<ref name=":1" /><ref name=":2" /> Lymphedema, such as that resulting from certain types of breast cancer treatment, also is a risk factor for development of angiosarcoma.<ref name=":2" /> As with bone sarcomas, certain inherited genetic syndromes also are associated with an increased risk of developing soft-tissue sarcoma, including [[Li–Fraumeni syndrome|Li-Fraumeni syndrome]], [[familial adenomatous polyposis]], [[Neurofibromatosis type I|neurofibromatosis type 1]], and heritable RB1 gene mutations.<ref name=":2" /> [[Kaposi's sarcoma]] is caused by [[Kaposi's sarcoma-associated herpesvirus]] (HHV-8).
== Mechanisms ==
The mechanisms by which healthy cells transform into cancer cells are described in detail elsewhere (see [[Cancer]] main page; [[Carcinogenesis]] main page). The precise molecular changes that result in sarcoma are not always known, but certain types of sarcomas are associated with particular genetic mutations.<ref name=":1" /><ref name=":2" /> Examples include:
* Most cases of Ewing sarcoma are associated with a [[chromosomal translocation]] in which part of [[chromosome 11]] fuses with part of [[chromosome 22]].<ref name=":1" /> This results in the [[Ewing sarcoma breakpoint region 1|EWS gene]] becoming fused to other genes, including the [[FLI1|FLI1 gene]] in 90% of Ewing cases and [[ERG (gene)|ERG gene]] in 5-10% of cases.<ref name=":1" /> These fusions result in the production of abnormal proteins, although how these abnormal proteins result in cancer is not fully known.<ref name=":1" />
* Dermatofibrosarcoma protuberans often is associated with a chromosomal translocation in which the [[Collagen, type I, alpha 1|COL1A1 gene]] becomes fused to the [[PDGFRB|PDGFRB gene]].<ref name=":2" /> This results in over-active [[Platelet-derived growth factor|PDGF]] signaling, which is thought to promote cell division and ultimately lead to tumor development.<ref name=":2" />
* Inflammatory myofibroblastic tumor often is associated with rearrangements of the [[Anaplastic lymphoma kinase|ALK gene]], and occasionally with rearrangements of the [[HMGA2|HMGA2 gene]].<ref name=":2" />
* Giant cell tumor of soft tissue frequently is associated with a chromosomal translocation between [[chromosome 1]] and [[chromosome 2]], in which the [[Macrophage colony-stimulating factor|CSF1 gene]] becomes fused with the [[Collagen, type VI, alpha 3|COL6A3 gene]].<ref name=":2" /> This results in increased CSF1 protein production, which is thought to play a role in cancer development.<ref name=":2" />
* Many liposarcomas are associated with duplication of part of chromosome 12, which results in extra copies of known cancer-promoting genes ("[[oncogene]]s") such as the [[Cyclin-dependent kinase 4|CDK4 gene]], the [[Mdm2|MDM2 gene]] and the [[HMGA2|HMGA2 gene]].<ref name=":2" />
==Diagnosis==
===Bone sarcomas===
{{Main|Bone sarcoma}}
Diagnosis of [[bone sarcoma]]s begins with a thorough history and physical examination which may reveal characteristic signs and symptoms (see Signs and Symptoms above).<ref name=":2" /> Laboratory studies are not particularly useful in diagnosis, although some bone sarcomas (such as osteosarcoma) may be associated with elevated [[alkaline phosphatase]] levels, while others (such as Ewing Sarcoma) can be associated with elevated [[erythrocyte sedimentation rate]].<ref name=":3">{{Cite book|title=Dahlin's Bone Tumors| vauthors = Unni K |publisher=Lippincott Williams & Wilkins|year=2010|isbn=978-0-7817-6242-7|location=Philadelphia, PA|pages=1–8}}</ref> Importantly, however, none of these laboratory findings are specific to bone sarcomas, meaning that elevations in these lab values are associated with many other conditions as well as sarcoma, and thus cannot be relied upon to conclusively diagnose sarcoma.<ref name=":2" /> Imaging studies are critically important in diagnosis, and most clinicians will order a plain [[Radiography|radiograph]] (X-ray) initially.<ref name=":2" /> Other imaging studies commonly used in diagnosis include [[magnetic resonance imaging]] (MRI) studies and [[Bone scintigraphy|radioisotope bone scans]].<ref name=":3" /><ref name=":2" /> A [[CT scan]] is typically not used in diagnosis of most types of bone sarcoma, although it is an important tool for staging (see below).<ref name=":2" /> Definitive diagnosis requires biopsy of the tumor and careful review of the biopsy specimen by an experienced pathologist.<ref name=":2" />
===Soft-tissue sarcomas===
{{Main|Soft-tissue sarcoma}}
Diagnosis of [[soft-tissue sarcoma]]s also begins with a thorough history and physical examination.<ref name=":2" /> Imaging studies can include either CT or MRI, although CT tends to be preferred for soft-tissue sarcomas located in the [[thorax]], [[abdomen]], or [[Retroperitoneal space|retroperitoneum]].<ref name=":2" /> [[Positron emission tomography]] (PET) also may be useful in diagnosis, although its most common use is for staging (see below).<ref name=":2" /> As with bone sarcomas, definitive diagnosis requires biopsy of the tumor with evaluation of histology by a trained pathologist.<ref name=":2" /><ref>{{Cite journal| vauthors = Rastogi S, Aggarwal A, Shishak S, Barwad A, Dhamija E, Pandey R, Mridha AR, Khan SA, Deo SS, Sharma MC | display-authors = 6 |date=2019-08-09|title=Discordance of Histo-pathological Diagnosis of Patients with Soft Tissue Sarcoma Referred to Tertiary Care Center |url= http://waocp.com/journal/index.php/apjcc/article/view/274 |journal= Asian Pacific Journal of Cancer Care|volume=4 |issue=4 |pages=119–123 |doi=10.31557/apjcc.2019.4.4.119-123 |doi-access=free }}</ref>
=== Staging ===
In general, [[cancer staging]] refers to how advanced a cancer is, and usually it is based upon factors such as tumor size and whether it has spread to other parts of the body.<ref name=":2" /><ref>{{Cite web|url=https://www.cancer.gov/about-cancer/diagnosis-staging/staging|title=Staging|date=2015-03-09|website=National Cancer Institute|language=en|access-date=2019-03-21}}</ref> Staging is important because the stage affects the [[prognosis]] (likely outcome), as well as the types of treatments that are likely to be effective against the cancer.<ref name=":1" /><ref name=":0" /> With sarcomas, staging requires a determination of whether the tumor has grown into surrounding tissues ("local invasion"), as well as imaging to determine whether it has spread (a process known as "[[metastasis]]") to lymph nodes (forming "nodal metastases") or to other tissues or organs in the body (forming "distant metastases").<ref name=":0" />
The most common imaging tools used for staging '''bone sarcomas''' are MRI or CT to evaluate the primary tumor, contrast-enhanced CT of the chest to evaluate whether the cancer has spread (i.e., metastasized) to the lungs, and radioisotope bone scan to evaluate whether the cancer has spread to other bones.<ref name=":0" /> Staging for '''soft-tissue sarcomas''' typically includes imaging of the primary tumor by MRI or CT to determine tumor size, as well as contrast-enhanced CT of the chest to evaluate for metastatic tumors in the lungs.<ref name=":0" />
===Grade===
Like some other cancers, sarcomas are assigned a [[Grading (tumors)|grade]] (low, intermediate, or high) based on the appearance of the tumor cells under a microscope.<ref name=":6">{{Cite web|url=https://www.cancer.gov/about-cancer/diagnosis-staging/prognosis/tumor-grade-fact-sheet|title=Tumor Grade|date=2013-05-09|website=National Cancer Institute|language=en|access-date=2019-03-21}}</ref> In general, grade refers to how aggressive the cancer is and how likely it is to spread to other parts of the body ("metastasize").<ref name=":6" /> Low-grade sarcomas have a better prognosis than higher-grade sarcomas, and are usually treated surgically, although sometimes radiation therapy or chemotherapy are used.<ref name=":2" /><ref name=":0" /> Intermediate- and high-grade sarcomas are more frequently treated with a combination of surgery, chemotherapy, or radiation therapy.<ref name=Buecker05>{{cite journal | vauthors = Buecker P |title=Sarcoma: A Diagnosis of Patience |journal=ESUN |volume=2 |issue=5 |year=2005 |url=http://sarcomahelp.org/articles/patience.html | access-date=2009-04-15}}</ref> Since high-grade tumors are more likely to undergo metastasis (invasion and spread to locoregional and distant sites), they are treated more aggressively. The recognition that many sarcomas are sensitive to chemotherapy has dramatically improved the survival of patients. For example, in the era before chemotherapy, long-term survival for pediatric patients with localized osteosarcoma was only about 20%, but now has risen to 60–70%.<ref>{{cite journal | vauthors = Longhi A, Errani C, De Paolis M, Mercuri M, Bacci G | title = Primary bone osteosarcoma in the pediatric age: state of the art | journal = Cancer Treatment Reviews | volume = 32 | issue = 6 | pages = 423–436 | date = October 2006 | pmid = 16860938 | doi = 10.1016/j.ctrv.2006.05.005 }}</ref>
== Screening ==
In the US, the US Preventive Services Task Force (USPSTF) publishes guidelines recommending [[Cancer screening|preventive screening]] for certain types of common cancers and other diseases.<ref name=":4">{{Cite web|url=https://www.uspreventiveservicestaskforce.org/BrowseRec/Index|title=Published Recommendations - US Preventive Services Task Force|website=www.uspreventiveservicestaskforce.org|access-date=2019-03-20}}</ref> {{As of|2019|March}}, the USPSTF does not recommend screening for sarcoma,<ref name=":4" /> possibly because it is a very rare type of cancer (see Epidemiology below).
The American Cancer Society (ACS) also publishes guidelines recommending preventive screening for certain types of common cancers.<ref name=":5">{{Cite web|url=https://www.cancer.org/healthy/find-cancer-early/cancer-screening-guidelines/american-cancer-society-guidelines-for-the-early-detection-of-cancer.html|title=Cancer Screening Guidelines {{!}} Detecting Cancer Early|website=www.cancer.org|language=en|access-date=2019-03-20}}</ref> Like the USPSTF, {{As of|2019|March|lc=y}} ACS does not recommend preventive screening for sarcoma.<ref name=":5" />
The [[Sarcoma Foundation of America]] (SFA) is a cancer research organisation. It was founded in 2000 with the main intent of researching possible cures to sarcoma-type cancers.
== Treatment ==
{{multiple image
| width=150
| image1=Osteochondromyxosarcoma 1.jpg
| alt1=Before
| image2=Osteochondromyxosarcoma 5.jpg
| alt2=After
| footer=Surgical removal of [[Osteosarcoma|osteo]][[Chondrosarcoma|chondro]][[Myxosarcoma|myxo]]sarcoma
}}
[[Surgery]] is the most common form of the treatment for most sarcomas that have not spread to other parts of the body.<ref name=":2" /><ref name="Morris05">{{cite journal| vauthors = Morris C |year=2005|title=Malignant Fibrous Histiocytoma (MFH)|url=http://sarcomahelp.org/mfh.html|journal=ESUN|volume=2|issue=2|access-date=2011-10-19}}</ref> [[Limb-sparing techniques|Limb-sparing surgery]], as opposed to amputation, can now be used to save the limbs of patients in at least 90% of extremity (arm or leg) sarcoma cases.<ref name="Morris05" /> Additional treatments, including [[chemotherapy]], [[radiation therapy]] (also called "radiotherapy") and [[proton therapy]], may be administered ''before surgery'' (called "[[Neoadjuvant therapy|neoadjuvant]]" chemotherapy or radiotherapy) or ''after surgery'' (called "[[Adjuvant therapy|adjuvant]]" chemotherapy or radiotherapy).<ref name=":2" /><ref name="Buecker05" /> The use of neoadjuvant or adjuvant chemotherapy and radiotherapy significantly improves the prognosis for many sarcoma patients.<ref name=":2" /><ref>{{cite journal| vauthors = Baker L |year=2006|title=A Rose is a Rose or a Thorn is a Thorn|url=http://sarcomahelp.org/articles/chemotherapy-rose.html|journal=ESUN|volume=3|issue=5|access-date=2011-10-19}}</ref> Treatment can be a long and arduous process, lasting about a year for many patients.<ref name="Buecker05" />
* [[Liposarcoma]] treatment consists of surgical resection, with chemotherapy not being used outside of the investigative setting. Adjuvant radiotherapy may also be used after surgical excision for liposarcoma.<ref>{{EMedicine|article|1102007|Liposarcoma Treatment & Management|treatment}}</ref>
* Rhabdomyosarcoma is treated with surgery, radiotherapy, or chemotherapy.<ref>{{cite web|url=http://www.childrenshospital.org/az/Site1068/mainpageS1068P0.html|title=Rhabdomyosarcoma|publisher=Boston Children's Hospital}}</ref> The majority of rhabdomyosarcoma patients have a 50–85% survival rate.<ref>{{cite journal| vauthors = Wexler L |year=2004|title=Rhabdomyosarcoma|url=http://sarcomahelp.org/rhabdomyosarcoma.html|journal=ESUN|volume=1|issue=4|access-date=2011-10-19}}</ref>
* Osteosarcoma is a tumor of the bone that is treated with surgical resection of as much of the cancer as possible, often along with [[neoadjuvant chemotherapy]].<ref>{{EMedicine|article|1256857|Osteosarcoma Treatment & Management|treatment}}</ref> Radiotherapy is a second alternative although not as successful.
Expression of receptor [[B7-H3]] provides a promising target for new immunotherapeutic strategies.
In childhood sarcomas, the cytotoxic agent [[cyclophosphamide]] is widely used and has shown good anti-tumour efficacy.<ref>{{cite journal | vauthors = Mulder RL, Paulides M, Langer T, Kremer LC, van Dalen EC | title = Cyclophosphamide versus ifosfamide for paediatric and young adult bone and soft tissue sarcoma patients | journal = The Cochrane Database of Systematic Reviews | issue = 9 | pages = CD006300 | date = September 2015 | volume = 2015 | pmid = 26421585 | pmc = 7389335 | doi = 10.1002/14651858.cd006300.pub4 }}</ref>
It is believed that higher doses of chemotherapy might improve survival. However, high doses of chemotherapy stop the production of blood cells in the bone marrow and can be harmful. Stem cells collected from people before high‐dose chemotherapy can be transplanted back to the person if the blood cell count gets too low; this is called autologous hematopoietic stem cell transplantation. Research to investigate if using high‐dose chemotherapy followed by autologous hematopoietic stem cell transplantation was more favourable than standard‐dose chemotherapy <ref>{{cite journal | vauthors = Peinemann F, Enk H, Smith LA | title = Autologous hematopoietic stem cell transplantation following high-dose chemotherapy for nonrhabdomyosarcoma soft tissue sarcomas | journal = The Cochrane Database of Systematic Reviews | volume = 4 | pages = CD008216 | date = April 2017 | issue = 7 | pmid = 28407197 | pmc = 6478255 | doi = 10.1002/14651858.cd008216.pub5 }}</ref> found only one RCT and this did not favour either of the two treatment arms with respect to overall survival. Further evidence is needed through well‐designed clinical trials.
== Prognosis ==
=== Factors that affect prognosis ===
The AJCC has identified several factors that affect prognosis of '''bone sarcomas''':<ref name=":0" />
* '''Size of the tumor''': larger tumors tend to have a worse prognosis compared to smaller tumors.
* '''Spread of tumor to surrounding tissues''': tumors that have spread locally to surrounding tissues tend to have a worse prognosis compared to tumors that have not spread beyond their place of origin.
* '''Stage and presence of metastases''': tumors that have spread ("metastasized") to the lymph nodes (which is rare for bone sarcomas) or other organs or tissues (for example, to the lungs) have a worse prognosis compared to tumors that have not metastasized.
* '''Tumor grade''': higher grade tumors (grades 2 and 3) tend to have a worse prognosis compared to low grade (grade 1) tumors.
* '''Skeletal location''': tumors originating in the spine or pelvic bones tend to have a worse prognosis compared to tumors originating in arm or leg bones.
For '''soft-tissue sarcomas other than GISTs,''' factors that affect prognosis include:<ref name=":0" />
* '''Stage''': as with bone sarcomas, tumors that have metastasized have a worse prognosis compared to tumors that have not metastasized.
* '''Grade''': the AJCC recommends using a grading system called the French Federation of Cancer Centers Sarcoma Group (FNCLCC) Grade for soft-tissue sarcomas, with high-grade tumors having a worse prognosis compared to low-grade tumors.
For '''GISTs''', the key factor that affects prognosis is:<ref name=":0" />
* '''Mitotic rate''': [[Mitosis|mitotic]] rate refers to the fraction of [[Cell (biology)|cells]] that are actively [[Cell division|dividing]] within the tumor; GISTs that have a high mitotic rate have a worse prognosis compared to GISTs that have a low mitotic rate.
=== Outcome data ===
According to data published by the US National Cancer Institute (NCI), the overall 5-year survival for '''bone sarcomas''' is 66.9%.<ref name=":8">{{Cite web|url=https://seer.cancer.gov/statfacts/html/bones.html|title=Bone and Joint Cancer - Cancer Stat Facts|website=SEER|language=en|access-date=2019-03-27}}</ref> The American Cancer Society (ACS) estimates that 1,660 people in the US will die in 2019 from bone sarcomas, accounting for 0.3% of all cancer deaths.<ref name=":7" /> The [[median]] age at death is 61 years old, although death can occur in any age group.<ref name=":8" /> Thus, 12.3% of bone sarcoma deaths occur in people under 20 years old, 13.8% occur in people 20–34 years old, 5.5% occur in people 35–44 years old, 9.3% occur in people 45–54 years old, 13.5% occur in people 55–64 years old, 16.2% occur in people 65–74 years old, 16.4% occur in people 75–84 years old, and 13.1% occur in people 85 years or older.<ref name=":8" />
For '''soft-tissue sarcomas''', the overall 5-year survival (irrespective of stage) is 64.5%, but survival is affected by many factors, including stage.<ref name=":9">{{Cite web|url=https://seer.cancer.gov/statfacts/html/soft.html|title=Soft Tissue Cancer - Cancer Stat Facts|website=SEER|language=en|access-date=2019-03-27}}</ref> Thus, the 5-year survival is 80.8% for soft-tissue sarcomas that have not spread beyond the primary tumor ("localized" tumors), 58.0% for soft-tissue sarcomas that have spread only to nearby lymph nodes, and 16.4% for soft-tissue sarcomas that have spread to distant organs.<ref name=":9" /> The ACS estimates that 5,270 people will die from soft-tissue sarcoma in 2019, accounting for 0.9% of all cancer deaths.<ref name=":7" />
==Epidemiology==
Sarcomas are quite rare.<ref name=":1" /> The risk of a previously healthy person receiving a new diagnosis of bone cancer is less than 0.001%, while the risk of receiving a new diagnosis of soft-tissue sarcoma is between 0.0014 and 0.005%.<ref name=":2" /> The American Cancer Society estimates that in the United States there will be 3,500 new cases of bone sarcoma in 2019, and 12,750 new cases of soft-tissue sarcoma.<ref name=":7">{{cite journal | vauthors = Siegel RL, Miller KD, Jemal A | title = Cancer statistics, 2019 | journal = CA: A Cancer Journal for Clinicians | volume = 69 | issue = 1 | pages = 7–34 | date = January 2019 | pmid = 30620402 | doi = 10.3322/caac.21551 | doi-access = free }}</ref> Considering that the total estimated number of new cancer diagnoses (all types of cancer) is 1,762,450, this means bone sarcomas represent only 0.2% of all new cancer diagnoses (making them the 30th most common type of cancer<ref name=":8" />) and soft-tissue sarcomas represent only 0.7% (making them the 22nd most common type of cancer<ref name=":9" />) of all new cancer diagnoses in the US in 2019.<ref name=":7" /> These estimates are similar to previously reported data.<ref name=":2" />
Sarcomas affect people of all ages. Around 50% of bone sarcomas and 20% of soft-tissue sarcomas are diagnosed in people under the age of 35.<ref>{{cite journal | vauthors = Darling J |title=A Different View of Sarcoma Statistics |journal=ESUN |volume=4 |issue=6 |year=2007 |url=http://sarcomahelp.org/articles/sarcoma-statistics.html | access-date=2012-10-06}}</ref> Some sarcomas, such as [[leiomyosarcoma]], [[chondrosarcoma]], and [[gastrointestinal stromal tumor]] (GIST), are more common in adults than in children.<ref name=":1" /> Most high-grade bone sarcomas, including [[Ewing's sarcoma]] and [[osteosarcoma]], are much more common in children and young adults.<ref name=":1" />
== In fossils ==
In 2016, scientists reported the discovery of an [[osteosarcoma]] tumor in a 1.6–1.8 million-year-old fossil from the skeleton of the now-extinct [[hominin]] species ''[[Australopithecus sediba]]'', making it the earliest-known case of human cancer.<ref>{{Cite web|url=https://www.cnn.com/2016/07/28/health/oldest-human-cancer-found/index.html|title=Scientists find cancer in million-year-old fossil| vauthors = Willingham AJ |website=CNN|date=28 July 2016|access-date=2019-03-27}}</ref><ref>{{cite journal | vauthors = Randolph-Quinney PS, Williams SA, Steyn M, Meyer MR, Smilg JS, Churchill SE, Odes EJ, Augustine T, Tafforeau P, Berger LR | display-authors = 6 |title=Osteogenic tumour in Australopithecus sediba: Earliest hominin evidence for neoplastic disease |journal=South African Journal of Science |date=2016 |volume=112 |issue=7/8 | doi = 10.17159/sajs.2016/20150470 |url=https://sajs.co.za/article/view/3562|doi-access=free }}</ref>
== Research ==
Treatment of sarcoma, especially when the sarcoma has spread, or "metastasized", often requires chemotherapy but existing chemotherapeutic medicines are associated with significant toxicities and are not highly effective in killing cancer cells.<ref name=":2" /> Therefore, research to identify new medications to treat sarcoma is being conducted {{as of|2019|alt=as of 2019}}.<ref name=":2" /> One possibility is the use of [[cancer immunotherapy]] (e.g., immune checkpoint inhibitors like anti-PD1, anti-PDL1, and anti-CTLA4 agents) to treat sarcomas.<ref name=":10">{{cite journal | vauthors = Thanindratarn P, Dean DC, Nelson SD, Hornicek FJ, Duan Z | title = Advances in immune checkpoint inhibitors for bone sarcoma therapy | journal = Journal of Bone Oncology | volume = 15 | pages = 100221 | date = April 2019 | pmid = 30775238 | pmc = 6365405 | doi = 10.1016/j.jbo.2019.100221 | doi-access = free }}</ref> This is not yet an established treatment tool.<ref name=":10" /> Other strategies, such as small-molecule [[targeted therapy]], biologic agents (e.g., [[small interfering RNA]] molecules), and [[nanoparticle]]-directed therapy, also are being investigated.<ref name=":2" />
Sameer Rastogi et al. has shown long lasting responses in few sarcomas (UPS & ASPS) on immunotherapy.<ref name=":33">Indian experience with immunotherapy in sarcoma and gastrointestinal stromal tumors: a retrospective study
Rohit Reddy, Raja Mounika Velagapudi,Sameer Rastogi
Future Science OA 0 0:0 https://www.future-science.com/doi/full/10.2144/fsoa-2021-0117</ref>
Research to understand the specific genetic and molecular factors that cause sarcoma to develop is underway.<ref name=":2" /> This could allow for the design of new targeted therapies and allow physicians to more accurately predict a patient's prognosis.<ref name=":2" />
Presence of the [[H3-B3 immunoregulatory checkpoint receptor]] in the tumor cells provides the opportunity for clinical trial testing of new drugs and targeted agents and immunotherapies in development.
==Awareness==
In the US, July is widely recognized as Sarcoma Awareness Month.<ref>{{cite web |title=Cancer Awareness Dates |publisher=American Society of Clinical Oncology |url=http://www.cancer.net/research-and-advocacy/cancer-awareness-dates|date=19 December 2013 }}</ref> The UK has a Sarcoma Awareness Week in July led by [[Sarcoma UK]], the bone and soft-tissue cancer charity.<ref>{{cite web |title=Sarcoma Awareness Week 2018 |publisher=Sarcoma UK |url=https://sarcoma.org.uk/get-involved/SAW|access-date=13 April 2018|date=25 January 2016 }}</ref>
American YouTuber [[Technoblade]] was diagnosed with sarcoma in August 2021, and died from his illness in June 2022 after the cancer metastasized. He had raised over $500,000 in a charity stream. Many YouTubers have raised awareness and donated to charities such as the Sarcoma Foundation of America after Technoblade's diagnosis and passing. To date, Technoblade's fans have raised over $1,000,000 for sarcoma research.<ref>{{Cite web |last=Saunders |first=Cindy |date=2022-07-01 |title=Technoblade Tribute |url=https://www.curesarcoma.org/technoblade-tribute/ |access-date=2022-11-10 |website=Sarcoma Foundation of America |language=en-US}}</ref>
== References ==
{{Reflist}}
== External links ==
* [http://www.cancer.gov/types/bone/hp Bone sarcoma] at the National Cancer Institute
* [https://www.reininsarcoma.org/what-is-sarcoma-2/ What is Sarcoma?]
* [https://sarcomahelp.org/ Sarcoma Help from the Liddy Shriver Sarcoma Initiative]
{{Medical resources
| DiseasesDB =
| ICD10 =
| ICD9 =
| ICDO = {{ICDO|8800|3}}
| OMIM =
| MedlinePlus =
| eMedicineSubj =
| eMedicineTopic =
| MeshID = D012509
| SNOMED CT = 424413001
}}
{{Soft tissue tumors and sarcomas |state=collapsed}}
{{Osseous and chondromatous tumors |state=collapsed}}
{{Vascular tumors |state=collapsed}}
{{Authority control}}
[[Category:Sarcoma| ]]
[[Category:Anatomical pathology]]
[[Category:Soft tissue disorders]]' |
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{{Infobox medical condition (new)
| name = Sarcoma
| pronounce =
| synonyms = Sarcomas, sarcomata
| image = Nibib 030207 105309 sarcoma.jpg
| caption = [[Optical coherence tomography]] (OCT) image of a sarcoma
| field = [[Oncology]]
| symptoms =
| complications =
| onset =
| duration =
| types =
| causes =
| risks =
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}}
A '''sarcoma''' is a [[malignant tumor]], a type of [[cancer]] that arises from [[Cell (biology)|cells]] of [[mesenchyme|mesenchymal]] ([[connective tissue]]) origin.<ref>{{cite journal | vauthors = Yang J, Ren Z, Du X, Hao M, Zhou W | title = The role of mesenchymal stem/progenitor cells in sarcoma: update and dispute | journal = Stem Cell Investigation | volume = 1 | pages = 18 | date = 2014-10-27 | pmid = 27358864 | pmc = 4923508 | doi = 10.3978/j.issn.2306-9759.2014.10.01 }}</ref><ref name=":1" /> Connective tissue is a broad term that includes [[cancellous bone|bone]], [[cartilage]], [[Body fat|fat]], [[vascular]], or [[Haematopoiesis|other structural]] tissues, and sarcomas can arise in any of these types of tissues.<ref name=":1" /><ref name=":2" /> 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.<ref name=":0" /> Sarcomas are ''primary'' connective tissue tumors, meaning that they arise in connective tissues.<ref name=":1" /> This is in contrast to ''secondary'' (or "metastatic") connective tissue tumors, which occur when a cancer from elsewhere in the body (such as the lungs, breast tissue or prostate) spreads to the connective tissue.<ref>{{Cite web|url=https://www.cancer.gov/types/metastatic-cancer|title=Metastatic Cancer|date=2015-05-12|website=National Cancer Institute|language=en|access-date=2019-03-22}}</ref> Sarcomas are one of five different [[List of cancer types|types of cancer]], classified by the [[list of distinct cell types in the adult human body|cell type]] from which they originate.<ref name=def>{{cite web|title=Defining Cancer| url=http://www.cancer.gov/cancertopics/cancerlibrary/what-is-cancer|website=National Cancer Institute|date=17 September 2007|access-date=10 June 2014}}</ref> The word ''sarcoma'' is derived from the [[Ancient Greek|Greek]] {{Lang|grc|σάρκωμα}} {{Lang|grc-latn|sarkōma}} 'fleshy excrescence or substance', itself from [[wikt:σάρξ|σάρξ]] {{Lang|grc-latn|sarx}} meaning 'flesh'.<ref>{{LSJ|sa/rkwma|σάρκωμα}}, {{LSJ|sa/rc|σάρξ|ref}}.</ref><ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/sarcoma|title=Definition of SARCOMA|website=www.merriam-webster.com|language=en|access-date=2019-03-22}}</ref><ref>{{OEtymD|sarcoma}}</ref>
== Classification ==
Sarcomas are typically divided into two major groups: [[bone sarcoma]]s and [[soft-tissue sarcoma]]s,<ref name=":1">{{Cite book|title=Cancer and its Management | edition = Seventh | vauthors = Tobias J |publisher=John Wiley & Sons, Ltd.|year=2015|isbn=978-1-118-46875-3|location=Chichester, West Sussex, PO198SQ, UK|pages=446}}</ref> each of which has multiple subtypes. In the United States, the American Joint Committee on Cancer (AJCC) publishes guidelines that classify the subtypes of sarcoma.<ref name=":0">{{Cite book|title=AJCC Cancer Staging Manual, Eight Edition| vauthors = Amin MB |publisher=Springer International Publishing AG Switzerland|year=2017|isbn=978-3-319-40617-6|location=Chicago, IL|pages=471–548}}</ref> These subtypes are as follows:
===Subtypes of bone sarcoma===
* [[Osteosarcoma]]
* [[Chondrosarcoma]]
* Poorly differentiated round/spindle cell tumors (includes [[Ewing sarcoma]])
* [[Hemangioendothelioma]]
* [[Angiosarcoma]]
* [[Fibrosarcoma]]/myofibrosarcoma
* [[Chordoma]]
* [[Adamantinoma]]
* Other:
** [[Liposarcoma]]
** [[Leiomyosarcoma]]
** [[Malignant peripheral nerve sheath tumor]]
** [[Rhabdomyosarcoma]]
** [[Synovial sarcoma]]
** Malignant solitary fibrous tumor.<ref name=":0" />
===Subtypes of soft-tissue sarcoma===
* [[Liposarcoma]] (includes the following varieties: [[Liposarcoma#Atypical lipomatous tumor/well-differentiated liposarcoma|atypical lipomatous tumor/well-differentiated liposarcoma]], [[Liposarcoma#Dedifferentiated liposarcoma|dedifferentiated liposarcoma]], [[Liposarcoma#Myxoid liposarcoma|myxoid sarcoma]], [[Liposarcoma#Pleomorphic liposarcoma|pleomorphic liposarcoma]], and [[Liposarcoma#Myxoid pleomorphic liposarcoma|myxoid pleomorphic liposarcoma]]
* Atypical lipomatous tumor
* [[Dermatofibrosarcoma protuberans]] (includes pigmented varieties)
* [[Dermatofibrosarcoma protuberans, fibrosarcomatous]]
* [[Giant cell fibroblastoma]]
* Malignant [[solitary fibrous tumor]]
* [[Inflammatory myofibroblastic tumour|Inflammatory myofibroblastic tumor]]
* [[Low-grade myofibroblastic sarcoma]]
* [[Fibrosarcoma]] (includes adult and sclerosing epithelioid varieties)
* Myxofibrosarcoma (formerly myxoid malignant fibrous histiocytoma)
* [[Low-grade fibromyxoid sarcoma]]
* Giant cell tumor of soft tissues
* [[Leiomyosarcoma]]
* Malignant [[glomus tumor]]
* [[Rhabdomyosarcoma]] (includes the following varieties: embryonal, alveolar, pleomorphic, and spindle cell/sclerosing)
* [[Hemangioendothelioma]] (includes the following varieties: retiform, pseudomyogenic, and epithelioid)
* [[Angiosarcoma]] of soft tissue
* Extraskeletal osteosarcoma
* [[Gastrointestinal stromal tumor]], malignant (GIST)
* [[Malignant peripheral nerve sheath tumor]] (includes epithelioid variety)
* Malignant Triton tumor
* Malignant [[granular cell tumor]]
* Malignant ossifying fibromyxoid tumor
* Stromal sarcoma not otherwise specified
* Myoepithelial carcinoma
* Malignant phosphaturic mesenchymal tumor
* [[Synovial sarcoma]] (includes the following varieties: spindle cell, biphasic, and not otherwise specified)
* [[Epithelioid sarcoma]]
* [[Alveolar soft part sarcoma]]
* Clear cell sarcoma of soft tissue
* Extraskeletal myxoid chondrosarcoma
* Extraskeletal Ewing sarcoma
* [[Interdigitating dendritic cell sarcoma]]
* [[Desmoplastic small-round-cell tumor|Desmoplastic small round cell tumor]]
* Extrarenal rhabdoid tumor
* [[Perivascular epithelioid cell tumour|Perivascular epithelioid cell tumor]], not otherwise specified
* Intimal sarcoma
* Undifferentiated [[spindle cell sarcoma]]
* Undifferentiated pleomorphic sarcoma
* Undifferentiated round cell sarcoma
* Undifferentiated epithelioid sarcoma
* Undifferentiated sarcoma, not otherwise specified.<ref name=":0" />
== Signs and symptoms ==
Symptoms of bone sarcomas typically include bone pain, especially at night, and swelling around the site of the tumor.<ref name=":1" />
Symptoms of [[soft-tissue sarcoma]]s vary, but they often present as firm, often times painless lumps or nodules.<ref name=":1" /> Gastrointestinal stromal tumors (GIST, a subtype of soft-tissue sarcoma) often are asymptomatic, but can be associated with vague complaints of abdominal pain, bleeding into the intestines, a feeling of fullness, or other signs of intestinal obstruction.<ref name=":1" />
==Cause==
=== Causes and risk factors ===
The cause of most '''bone sarcomas''' is not known,<ref name=":2">{{Cite book|title=DeVita, Hellman and Rosenberg's Cancer: Principles & Practice of Oncology | edition = 10th| vauthors = DeVita Jr V |publisher=Wolters Kluwer Health|year=2015|isbn=978-1-4511-9294-0|location=Philadelphia, PA|pages=1241–1313}}</ref> but several factors are associated with an increased risk of developing bone sarcoma. Previous exposure to ionizing radiation (such as prior radiation therapy) is one such risk factor.<ref name=":1" /> Therapeutic radiation is associated with sarcoma after 10 to 20 years.<ref>{{Cite web |title=UpToDate |url=https://www.uptodate.com/contents/radiation-associated-sarcomas#! |access-date=2023-03-19 |website=www.uptodate.com}}</ref> Exposure to alkylating agents, such as those found in [[Alkylating antineoplastic agent|certain cancer chemotherapeutic medicines]], also increases the risk of bone sarcoma.<ref name=":2" /> Certain inherited genetic syndromes, including [[Li–Fraumeni syndrome|Li-Fraumeni syndrome]], inherited ''RB1'' gene mutations, and [[Paget's disease of bone]] are associated with an increased risk of developing bone sarcomas.<ref name=":1" />
Most '''soft-tissue sarcomas''' arise from what doctors call "sporadic" (or random) genetic mutations within an affected person's cells.<ref name=":2" /> Nevertheless, there are certain risk factors associated with an increased risk of developing soft-tissue sarcoma. Previous exposure to [[ionizing radiation]] is one such risk factor.<ref name=":1" /> Exposure to vinyl chloride (e.g., such as the fumes encountered in the production of [[polyvinyl chloride]] (PVC)), [[arsenic]] and [[Thorotrast]] all are associated with an increased risk of angiosarcoma.<ref name=":1" /><ref name=":2" /> Lymphedema, such as that resulting from certain types of breast cancer treatment, also is a risk factor for development of angiosarcoma.<ref name=":2" /> As with bone sarcomas, certain inherited genetic syndromes also are associated with an increased risk of developing soft-tissue sarcoma, including [[Li–Fraumeni syndrome|Li-Fraumeni syndrome]], [[familial adenomatous polyposis]], [[Neurofibromatosis type I|neurofibromatosis type 1]], and heritable ''RB1'' gene mutations.<ref name=":2" /> [[Kaposi's sarcoma|Kaposi sarcoma]] is caused by [[Kaposi's sarcoma-associated herpesvirus|Kaposi sarcoma-associated herpesvirus]] (HHV-8).
== Mechanisms ==
The mechanisms by which healthy cells transform into cancer cells are described in detail elsewhere (see [[Cancer]] main page; [[Carcinogenesis]] main page). The precise molecular changes that result in sarcoma are not always known, but certain types of sarcomas are associated with particular genetic mutations.<ref name=":1" /><ref name=":2" /> Examples include:
* Most cases of Ewing sarcoma are associated with a [[chromosomal translocation]] in which part of [[chromosome 11]] fuses with part of [[chromosome 22]].<ref name=":1" /> This results in the [[Ewing sarcoma breakpoint region 1|''EWSR1'' gene]] becoming fused to other genes, including the [[FLI1|''FLI1'' gene]] in 90% of Ewing cases and [[ERG (gene)|''ERG'' gene]] in 5-10% of cases.<ref name=":1" /> These fusions result in the production of abnormal proteins, although how these abnormal proteins result in cancer is not fully known.<ref name=":1" />
* Dermatofibrosarcoma protuberans often is associated with a chromosomal translocation in which the [[Collagen, type I, alpha 1|''COL1A1'' gene]] becomes fused to the [[PDGFRB|''PDGFRB'' gene]].<ref name=":2" /> This results in over-active [[Platelet-derived growth factor|PDGF]] signaling, which is thought to promote cell division and ultimately lead to tumor development.<ref name=":2" />
* Inflammatory myofibroblastic tumor often is associated with rearrangements of the [[Anaplastic lymphoma kinase|''ALK'' gene]], and occasionally with rearrangements of the [[HMGA2|''HMGA2'' gene]].<ref name=":2" />
* Tenosynovial giant cell tumor (not a sarcoma, but a non-metastasizing and locally aggressive soft tissue tumor) frequently is associated with a chromosomal translocation between [[chromosome 1]] and [[chromosome 2]], in which the [[Macrophage colony-stimulating factor|''CSF1'' gene]] becomes fused with the [[Collagen, type VI, alpha 3|''COL6A3'' gene]].<ref name=":2" /> This results in increased CSF1 protein production, which is thought to play a role in cancer development.<ref name=":2" />
* Many liposarcomas are associated with amplification of part of chromosome 12, which results in extra copies of known cancer-promoting genes ("[[oncogene]]s") such as the [[Cyclin-dependent kinase 4|''CDK4'' gene]], the [[Mdm2|''MDM2'' gene]] and the [[HMGA2|''HMGA2'' gene]].<ref name=":2" />
==Diagnosis==
===Bone sarcomas===
{{Main|Bone sarcoma}}
Diagnosis of [[bone sarcoma]]s begins with a thorough history and physical examination which may reveal characteristic signs and symptoms (see Signs and Symptoms above).<ref name=":2" /> Laboratory studies are not particularly useful in diagnosis, although some bone sarcomas (such as osteosarcoma) may be associated with elevated [[alkaline phosphatase]] levels, while others (such as Ewing sarcoma) can be associated with elevated [[erythrocyte sedimentation rate]].<ref name=":3">{{Cite book|title=Dahlin's Bone Tumors| vauthors = Unni K |publisher=Lippincott Williams & Wilkins|year=2010|isbn=978-0-7817-6242-7|location=Philadelphia, PA|pages=1–8}}</ref> Importantly, however, none of these laboratory findings are specific to bone sarcomas, meaning that elevations in these lab values are associated with many other conditions as well as sarcoma, and thus cannot be relied upon to conclusively diagnose sarcoma.<ref name=":2" /> Imaging studies are critically important in diagnosis, and most clinicians will order a plain [[Radiography|radiograph]] (X-ray) initially.<ref name=":2" /> Other imaging studies commonly used in diagnosis include [[magnetic resonance imaging]] (MRI) studies and [[Bone scintigraphy|radioisotope bone scans]].<ref name=":3" /><ref name=":2" /> A [[CT scan]] is typically not used in diagnosis of most types of bone sarcoma, although it is an important tool for staging (see below).<ref name=":2" /> Definitive diagnosis requires biopsy of the tumor and careful review of the biopsy specimen by an experienced pathologist.<ref name=":2" />
===Soft-tissue sarcomas===
{{Main|Soft-tissue sarcoma}}
Diagnosis of [[soft-tissue sarcoma]]s also begins with a thorough history and physical examination.<ref name=":2" /> Imaging studies can include either CT or MRI, although CT tends to be preferred for soft-tissue sarcomas located in the [[thorax]], [[abdomen]], or [[Retroperitoneal space|retroperitoneum]].<ref name=":2" /> [[Positron emission tomography]] (PET) also may be useful in diagnosis, although its most common use is for staging (see below).<ref name=":2" /> As with bone sarcomas, definitive diagnosis requires biopsy of the tumor with evaluation of histology by a trained pathologist.<ref name=":2" /><ref>{{Cite journal| vauthors = Rastogi S, Aggarwal A, Shishak S, Barwad A, Dhamija E, Pandey R, Mridha AR, Khan SA, Deo SS, Sharma MC | display-authors = 6 |date=2019-08-09|title=Discordance of Histo-pathological Diagnosis of Patients with Soft Tissue Sarcoma Referred to Tertiary Care Center |url= http://waocp.com/journal/index.php/apjcc/article/view/274 |journal= Asian Pacific Journal of Cancer Care|volume=4 |issue=4 |pages=119–123 |doi=10.31557/apjcc.2019.4.4.119-123 |doi-access=free }}</ref>
=== Staging ===
In general, [[cancer staging]] refers to how advanced a cancer is, and usually it is based upon factors such as tumor size and whether it has spread to other parts of the body.<ref name=":2" /><ref>{{Cite web|url=https://www.cancer.gov/about-cancer/diagnosis-staging/staging|title=Staging|date=2015-03-09|website=National Cancer Institute|language=en|access-date=2019-03-21}}</ref> Staging is important because the stage affects the [[prognosis]] (likely outcome), as well as the types of treatments that are likely to be effective against the cancer.<ref name=":1" /><ref name=":0" /> With sarcomas, staging requires a determination of whether the tumor has grown into surrounding tissues ("local invasion"), as well as imaging to determine whether it has spread (a process known as "[[metastasis]]") to lymph nodes (forming "nodal metastases") or to other tissues or organs in the body (forming "distant metastases").<ref name=":0" />
The most common imaging tools used for staging '''bone sarcomas''' are MRI or CT to evaluate the primary tumor, contrast-enhanced CT of the chest to evaluate whether the cancer has spread (i.e., metastasized) to the lungs, and radioisotope bone scan to evaluate whether the cancer has spread to other bones.<ref name=":0" /> Staging for '''soft-tissue sarcomas''' typically includes imaging of the primary tumor by MRI or CT to determine tumor size, as well as contrast-enhanced CT of the chest to evaluate for metastatic tumors in the lungs.<ref name=":0" />
===Grade===
Like some other cancers, sarcomas are assigned a [[Grading (tumors)|grade]] (low, intermediate, or high) based on the appearance of the tumor cells under a microscope.<ref name=":6">{{Cite web|url=https://www.cancer.gov/about-cancer/diagnosis-staging/prognosis/tumor-grade-fact-sheet|title=Tumor Grade|date=2013-05-09|website=National Cancer Institute|language=en|access-date=2019-03-21}}</ref> In general, grade refers to how aggressive the cancer is and how likely it is to spread to other parts of the body ("metastasize").<ref name=":6" /> Low-grade sarcomas have a better prognosis than higher-grade sarcomas, and are usually treated surgically, although sometimes radiation therapy or chemotherapy are used.<ref name=":2" /><ref name=":0" /> Intermediate- and high-grade sarcomas are more frequently treated with a combination of surgery, chemotherapy, or radiation therapy.<ref name=Buecker05>{{cite journal | vauthors = Buecker P |title=Sarcoma: A Diagnosis of Patience |journal=ESUN |volume=2 |issue=5 |year=2005 |url=http://sarcomahelp.org/articles/patience.html | access-date=2009-04-15}}</ref> Since high-grade tumors are more likely to undergo metastasis (invasion and spread to locoregional and distant sites), they are treated more aggressively. The recognition that many sarcomas are sensitive to chemotherapy has dramatically improved the survival of patients. For example, in the era before chemotherapy, long-term survival for pediatric patients with localized osteosarcoma was only about 20%, but now has risen to 60–70%.<ref>{{cite journal | vauthors = Longhi A, Errani C, De Paolis M, Mercuri M, Bacci G | title = Primary bone osteosarcoma in the pediatric age: state of the art | journal = Cancer Treatment Reviews | volume = 32 | issue = 6 | pages = 423–436 | date = October 2006 | pmid = 16860938 | doi = 10.1016/j.ctrv.2006.05.005 }}</ref>
== Screening ==
In the US, the US Preventive Services Task Force (USPSTF) publishes guidelines recommending [[Cancer screening|preventive screening]] for certain types of common cancers and other diseases.<ref name=":4">{{Cite web|url=https://www.uspreventiveservicestaskforce.org/BrowseRec/Index|title=Published Recommendations - US Preventive Services Task Force|website=www.uspreventiveservicestaskforce.org|access-date=2019-03-20}}</ref> {{As of|2019|March}}, the USPSTF does not recommend screening for sarcoma,<ref name=":4" /> possibly because it is a very rare type of cancer (see Epidemiology below).
The American Cancer Society (ACS) also publishes guidelines recommending preventive screening for certain types of common cancers.<ref name=":5">{{Cite web|url=https://www.cancer.org/healthy/find-cancer-early/cancer-screening-guidelines/american-cancer-society-guidelines-for-the-early-detection-of-cancer.html|title=Cancer Screening Guidelines {{!}} Detecting Cancer Early|website=www.cancer.org|language=en|access-date=2019-03-20}}</ref> Like the USPSTF, {{As of|2019|March|lc=y}} ACS does not recommend preventive screening for sarcoma.<ref name=":5" />
However, patients with some inherited conditions, such as [[Neurofibromatosis type I|neurofibromatosis]], may benefit from screening for development of cancers from pre-existing benign tumors called neurofibromas.
== Treatment ==
[[Surgery]] is the most common form of the treatment for most sarcomas that have not spread to other parts of the body, and for most sarcomas, surgery is the only curative treatment.<ref name=":2" /><ref name="Morris05">{{cite journal| vauthors = Morris C |year=2005|title=Malignant Fibrous Histiocytoma (MFH)|url=http://sarcomahelp.org/mfh.html|journal=ESUN|volume=2|issue=2|access-date=2011-10-19}}</ref> [[Limb-sparing techniques|Limb-sparing surgery]], as opposed to amputation, can now be used to save the limbs of patients in at least 90% of extremity (arm or leg) sarcoma cases.<ref name="Morris05" /> Additional treatments, including [[chemotherapy]], [[radiation therapy]] (also called "radiotherapy"), which includes [[proton therapy]], may be administered ''before surgery'' (called "[[Neoadjuvant therapy|neoadjuvant]]" chemotherapy or radiotherapy) or ''after surgery'' (called "[[Adjuvant therapy|adjuvant]]" chemotherapy or radiotherapy).<ref name=":2" /><ref name="Buecker05" /> The use of neoadjuvant or adjuvant chemotherapy and radiotherapy significantly improves the prognosis for many sarcoma patients.<ref name=":2" /><ref>{{cite journal| vauthors = Baker L |year=2006|title=A Rose is a Rose or a Thorn is a Thorn|url=http://sarcomahelp.org/articles/chemotherapy-rose.html|journal=ESUN|volume=3|issue=5|access-date=2011-10-19}}</ref> Treatment can be a long and arduous process, lasting about a year for many patients.<ref name="Buecker05" />
* [[Liposarcoma]] treatment usually consists of surgical resection, with chemotherapy considered depending on the aggressiveness of the sarcoma. Radiotherapy may also be used before or after surgical excision for liposarcoma.<ref>{{EMedicine|article|1102007|Liposarcoma Treatment & Management|treatment}}</ref>
* Pediatric rhabdomyosarcoma is usually treated with chemotherapy, surgery, and sometimes radiotherapy.<ref>{{cite web|url=http://www.childrenshospital.org/az/Site1068/mainpageS1068P0.html|title=Rhabdomyosarcoma|publisher=Boston Children's Hospital}}</ref> Pediatric rhabdomyosarcoma patients have a 50–85% long term survival rate.<ref>{{cite journal| vauthors = Wexler L |year=2004|title=Rhabdomyosarcoma|url=http://sarcomahelp.org/rhabdomyosarcoma.html|journal=ESUN|volume=1|issue=4|access-date=2011-10-19}}</ref>
* Osteosarcoma is a cancer of the bone that is treated with surgical resection of as much of the cancer as possible, often along with [[neoadjuvant chemotherapy|chemotherapy]].<ref>{{EMedicine|article|1256857|Osteosarcoma Treatment & Management|treatment}}</ref> Radiotherapy is a second alternative to surgery, although not as successful.
It was believed that higher doses of chemotherapy might improve survival. However, high doses of chemotherapy stop the production of blood cells in the bone marrow and can be harmful. Stem cells collected from people before high‐dose chemotherapy can be transplanted back to the person if the blood cell count gets too low; this is called autologous hematopoietic stem cell transplantation, or high dose therapy with stem cell rescue. Research to investigate if using high‐dose chemotherapy followed by autologous hematopoietic stem cell transplantation was more favourable than standard‐dose chemotherapy <ref>{{cite journal | vauthors = Peinemann F, Enk H, Smith LA | title = Autologous hematopoietic stem cell transplantation following high-dose chemotherapy for nonrhabdomyosarcoma soft tissue sarcomas | journal = The Cochrane Database of Systematic Reviews | volume = 4 | pages = CD008216 | date = April 2017 | issue = 7 | pmid = 28407197 | pmc = 6478255 | doi = 10.1002/14651858.cd008216.pub5 }}</ref> found only one RCT and this did not favour either of the two treatment arms with respect to overall survival. As a result, high dose chemotherapy with stem cell rescue is generally considered appropriate only in the research setting.
== Prognosis ==
=== Factors that affect prognosis ===
The AJCC has identified several factors that affect prognosis of '''bone sarcomas''':<ref name=":0" />
* '''Size of the tumor''': larger tumors tend to have a worse prognosis compared to smaller tumors.
* '''Spread of tumor to surrounding tissues''': tumors that have spread locally to surrounding tissues tend to have a worse prognosis compared to tumors that have not spread beyond their place of origin.
* '''Stage and presence of metastases''': tumors that have spread ("metastasized") to the lymph nodes (which is rare for bone sarcomas) or other organs or tissues (for example, to the lungs) have a worse prognosis compared to tumors that have not metastasized.
* '''Tumor grade''': higher grade tumors (grades 2 and 3) tend to have a worse prognosis compared to low grade (grade 1) tumors.
* '''Skeletal location''': tumors originating in the spine or pelvic bones tend to have a worse prognosis compared to tumors originating in arm or leg bones.
For '''soft-tissue sarcomas other than GISTs,''' factors that affect prognosis include:<ref name=":0" />
* '''Stage''': as with bone sarcomas, tumors that have metastasized have a worse prognosis compared to tumors that have not metastasized.
* '''Grade''': the AJCC recommends using a grading system called the French Federation of Cancer Centers Sarcoma Group (FNCLCC) Grade for soft-tissue sarcomas, with high-grade tumors having a worse prognosis compared to low-grade tumors.
For '''GISTs''', the key factor that affects prognosis is:<ref name=":0" />
* '''Mitotic rate''': [[Mitosis|mitotic]] rate refers to the fraction of [[Cell (biology)|cells]] that are actively [[Cell division|dividing]] within the tumor; GISTs that have a high mitotic rate have a worse prognosis compared to GISTs that have a low mitotic rate.
=== Outcome data ===
According to data published by the US National Cancer Institute (NCI), the overall 5-year survival for '''bone sarcomas''' is 66.9%.<ref name=":8">{{Cite web|url=https://seer.cancer.gov/statfacts/html/bones.html|title=Bone and Joint Cancer - Cancer Stat Facts|website=SEER|language=en|access-date=2019-03-27}}</ref> The American Cancer Society (ACS) estimates that 2,140 people in the US will die in 2023 from bone sarcomas, accounting for 0.3% of all cancer deaths.<ref name=":7">{{Cite journal |last=Siegel |first=Rebecca L. |last2=Miller |first2=Kimberly D. |last3=Wagle |first3=Nikita Sandeep |last4=Jemal |first4=Ahmedin |date=2023 |title=Cancer statistics, 2023 |url=https://pubmed.ncbi.nlm.nih.gov/36633525 |journal=CA: a cancer journal for clinicians |volume=73 |issue=1 |pages=17–48 |doi=10.3322/caac.21763 |issn=1542-4863 |pmid=36633525}}</ref> The [[median]] age at death is 61 years old, although death can occur in any age group.<ref name=":8" /> Thus, 12.3% of bone sarcoma deaths occur in people under 20 years old, 13.8% occur in people 20–34 years old, 5.5% occur in people 35–44 years old, 9.3% occur in people 45–54 years old, 13.5% occur in people 55–64 years old, 16.2% occur in people 65–74 years old, 16.4% occur in people 75–84 years old, and 13.1% occur in people 85 years or older.<ref name=":8" />
For '''soft-tissue sarcomas''', the overall 5-year survival (irrespective of stage) is 64.5%, but survival is affected by many factors, including stage.<ref name=":9">{{Cite web|url=https://seer.cancer.gov/statfacts/html/soft.html|title=Soft Tissue Cancer - Cancer Stat Facts|website=SEER|language=en|access-date=2019-03-27}}</ref> Thus, the 5-year survival is 80.8% for soft-tissue sarcomas that have not spread beyond the primary tumor ("localized" tumors), 58.0% for soft-tissue sarcomas that have spread only to nearby lymph nodes, and 16.4% for soft-tissue sarcomas that have spread to distant organs.<ref name=":9" /> The ACS estimates that 5,140 people will die from soft-tissue sarcoma in 2023, accounting for 0.9% of all cancer deaths.<ref name=":7" />
==Epidemiology==
Sarcomas are rare cancers.<ref name=":1" /> The risk of a previously healthy person receiving a new diagnosis of bone cancer is less than 0.001%, while the risk of receiving a new diagnosis of soft-tissue sarcoma is between 0.0014 and 0.005%.<ref name=":2" /> The American Cancer Society estimates that in the United States there will be 3,970 new cases of bone sarcoma in 2023, and 13,400 new cases of soft-tissue sarcoma.<ref name=":7" /> Considering that the total estimated number of new cancer diagnoses (all types of cancer) is 1,958,310, this means bone sarcomas represent only 0.2% of all new cancer diagnoses (making them the 30th most common type of cancer<ref name=":8" />) and soft-tissue sarcomas represent only 0.7% (making them the 22nd most common type of cancer<ref name=":9" />) of all new cancer diagnoses in the US in 2023.<ref name=":7" /> These estimates are similar to previously reported data.<ref name=":2" />
Sarcomas affect people of all ages. Around 50% of bone sarcomas and 20% of soft-tissue sarcomas are diagnosed in people under the age of 35.<ref>{{cite journal | vauthors = Darling J |title=A Different View of Sarcoma Statistics |journal=ESUN |volume=4 |issue=6 |year=2007 |url=http://sarcomahelp.org/articles/sarcoma-statistics.html | access-date=2012-10-06}}</ref> Some sarcomas, such as [[leiomyosarcoma]], [[chondrosarcoma]], and [[gastrointestinal stromal tumor]] (GIST), are more common in adults than in children.<ref name=":1" /> Most high-grade bone sarcomas, including [[Ewing's sarcoma|Ewing sarcoma]] and [[osteosarcoma]], are much more common in children and young adults.<ref name=":1" />
== In fossils ==
In 2016, scientists reported the discovery of an [[osteosarcoma]] tumor in a 1.6–1.8 million-year-old fossil from the skeleton of the now-extinct [[hominin]] species ''[[Australopithecus sediba]]'', making it the earliest-known case of human cancer.<ref>{{Cite web|url=https://www.cnn.com/2016/07/28/health/oldest-human-cancer-found/index.html|title=Scientists find cancer in million-year-old fossil| vauthors = Willingham AJ |website=CNN|date=28 July 2016|access-date=2019-03-27}}</ref><ref>{{cite journal | vauthors = Randolph-Quinney PS, Williams SA, Steyn M, Meyer MR, Smilg JS, Churchill SE, Odes EJ, Augustine T, Tafforeau P, Berger LR | display-authors = 6 |title=Osteogenic tumour in Australopithecus sediba: Earliest hominin evidence for neoplastic disease |journal=South African Journal of Science |date=2016 |volume=112 |issue=7/8 | doi = 10.17159/sajs.2016/20150470 |url=https://sajs.co.za/article/view/3562|doi-access=free }}</ref>
== Research ==
Treatment of sarcoma, especially when the sarcoma has spread, or "metastasized", often requires chemotherapy but existing chemotherapeutic medicines are associated with significant toxicities and are not highly effective in killing cancer cells.<ref name=":2" /> Therefore, research to identify new medications to treat sarcoma is being conducted {{as of|2023|alt=as of 2019}}.<ref name=":2" /> One new type of therapy still under investigation is the use of [[cancer immunotherapy]] (e.g., immune checkpoint inhibitors like anti-PD1, anti-PDL1, and anti-CTLA4 agents) to treat sarcomas.<ref name=":10">{{cite journal | vauthors = Thanindratarn P, Dean DC, Nelson SD, Hornicek FJ, Duan Z | title = Advances in immune checkpoint inhibitors for bone sarcoma therapy | journal = Journal of Bone Oncology | volume = 15 | pages = 100221 | date = April 2019 | pmid = 30775238 | pmc = 6365405 | doi = 10.1016/j.jbo.2019.100221 | doi-access = free }}</ref> These drugs are not yet FDA- or other regulator-approved treatment.<ref name=":10" /> Other strategies, such as small-molecule [[targeted therapy]], biologic agents (e.g., [[small interfering RNA]] molecules), and [[nanoparticle]]-directed therapy, also are under active investigated.<ref name=":2" />
Research to understand the specific genetic and molecular factors that cause sarcoma to develop is underway.<ref name=":2" /> This could allow for the design of new targeted therapies and allow physicians to more accurately predict a patient's prognosis.<ref name=":2" />
==Awareness==
In the US, July is widely recognized as Sarcoma Awareness Month.<ref>{{cite web |title=Cancer Awareness Dates |publisher=American Society of Clinical Oncology |url=http://www.cancer.net/research-and-advocacy/cancer-awareness-dates|date=19 December 2013 }}</ref> The UK has a Sarcoma Awareness Week in July led by [[Sarcoma UK]], the bone and soft-tissue cancer charity.<ref>{{cite web |title=Sarcoma Awareness Week 2018 |publisher=Sarcoma UK |url=https://sarcoma.org.uk/get-involved/SAW|access-date=13 April 2018|date=25 January 2016 }}</ref>
American YouTuber [[Technoblade]] was diagnosed with sarcoma in August 2021, and died from his illness in June 2022 after the cancer metastasized. He had raised over $500,000 in a charity stream. Many YouTubers have raised awareness and donated to charities such as the [[Sarcoma Foundation of America]] after Technoblade's diagnosis and passing. To date, Technoblade's fans have raised over $1,000,000 for sarcoma research.<ref>{{Cite web |last=Saunders |first=Cindy |date=2022-07-01 |title=Technoblade Tribute |url=https://www.curesarcoma.org/technoblade-tribute/ |access-date=2022-11-10 |website=Sarcoma Foundation of America |language=en-US}}</ref>
== References ==
{{Reflist}}
== External links ==
* [http://www.cancer.gov/types/bone/hp Bone sarcoma] at the National Cancer Institute
* [https://www.reininsarcoma.org/what-is-sarcoma-2/ What is Sarcoma?]
* [https://sarcomahelp.org/ Sarcoma Help from the Liddy Shriver Sarcoma Initiative]
{{Medical resources
| DiseasesDB =
| ICD10 =
| ICD9 =
| ICDO = {{ICDO|8800|3}}
| OMIM =
| MedlinePlus =
| eMedicineSubj =
| eMedicineTopic =
| MeshID = D012509
| SNOMED CT = 424413001
}}
{{Soft tissue tumors and sarcomas |state=collapsed}}
{{Osseous and chondromatous tumors |state=collapsed}}
{{Vascular tumors |state=collapsed}}
{{Authority control}}
[[Category:Sarcoma| ]]
[[Category:Anatomical pathology]]
[[Category:Soft tissue disorders]]' |
Unified diff of changes made by edit (edit_diff) | '@@ -25,5 +25,5 @@
| deaths =
}}
-A '''sarcoma''' is a [[malignant tumor]], a type of [[cancer]] that arises from transformed [[Cell (biology)|cells]] of [[mesenchyme|mesenchymal]] ([[connective tissue]]) origin.<ref>{{cite journal | vauthors = Yang J, Ren Z, Du X, Hao M, Zhou W | title = The role of mesenchymal stem/progenitor cells in sarcoma: update and dispute | journal = Stem Cell Investigation | volume = 1 | pages = 18 | date = 2014-10-27 | pmid = 27358864 | pmc = 4923508 | doi = 10.3978/j.issn.2306-9759.2014.10.01 }}</ref><ref name=":1" /> Connective tissue is a broad term that includes [[cancellous bone|bone]], [[cartilage]], [[Body fat|fat]], [[vascular]], or [[Haematopoiesis|hematopoietic]] tissues, and sarcomas can arise in any of these types of tissues.<ref name=":1" /><ref name=":2" /> 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.<ref name=":0" /> Sarcomas are ''primary'' connective tissue tumors, meaning that they arise in connective tissues.<ref name=":1" /> This is in contrast to ''secondary'' (or "metastatic") connective tissue tumors, which occur when a cancer from elsewhere in the body (such as the lungs, breast tissue or prostate) spreads to the connective tissue.<ref>{{Cite web|url=https://www.cancer.gov/types/metastatic-cancer|title=Metastatic Cancer|date=2015-05-12|website=National Cancer Institute|language=en|access-date=2019-03-22}}</ref> Sarcomas are one of five different [[List of cancer types|types of cancer]], classified by the [[list of distinct cell types in the adult human body|cell type]] from which they originate.<ref name=def>{{cite web|title=Defining Cancer| url=http://www.cancer.gov/cancertopics/cancerlibrary/what-is-cancer|website=National Cancer Institute|date=17 September 2007|access-date=10 June 2014}}</ref> The word ''sarcoma'' is derived from the [[Ancient Greek|Greek]] {{Lang|grc|σάρκωμα}} {{Lang|grc-latn|sarkōma}} 'fleshy excrescence or substance', itself from [[wikt:σάρξ|σάρξ]] {{Lang|grc-latn|sarx}} meaning 'flesh'.<ref>{{LSJ|sa/rkwma|σάρκωμα}}, {{LSJ|sa/rc|σάρξ|ref}}.</ref><ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/sarcoma|title=Definition of SARCOMA|website=www.merriam-webster.com|language=en|access-date=2019-03-22}}</ref><ref>{{OEtymD|sarcoma}}</ref>
+A '''sarcoma''' is a [[malignant tumor]], a type of [[cancer]] that arises from [[Cell (biology)|cells]] of [[mesenchyme|mesenchymal]] ([[connective tissue]]) origin.<ref>{{cite journal | vauthors = Yang J, Ren Z, Du X, Hao M, Zhou W | title = The role of mesenchymal stem/progenitor cells in sarcoma: update and dispute | journal = Stem Cell Investigation | volume = 1 | pages = 18 | date = 2014-10-27 | pmid = 27358864 | pmc = 4923508 | doi = 10.3978/j.issn.2306-9759.2014.10.01 }}</ref><ref name=":1" /> Connective tissue is a broad term that includes [[cancellous bone|bone]], [[cartilage]], [[Body fat|fat]], [[vascular]], or [[Haematopoiesis|other structural]] tissues, and sarcomas can arise in any of these types of tissues.<ref name=":1" /><ref name=":2" /> 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.<ref name=":0" /> Sarcomas are ''primary'' connective tissue tumors, meaning that they arise in connective tissues.<ref name=":1" /> This is in contrast to ''secondary'' (or "metastatic") connective tissue tumors, which occur when a cancer from elsewhere in the body (such as the lungs, breast tissue or prostate) spreads to the connective tissue.<ref>{{Cite web|url=https://www.cancer.gov/types/metastatic-cancer|title=Metastatic Cancer|date=2015-05-12|website=National Cancer Institute|language=en|access-date=2019-03-22}}</ref> Sarcomas are one of five different [[List of cancer types|types of cancer]], classified by the [[list of distinct cell types in the adult human body|cell type]] from which they originate.<ref name=def>{{cite web|title=Defining Cancer| url=http://www.cancer.gov/cancertopics/cancerlibrary/what-is-cancer|website=National Cancer Institute|date=17 September 2007|access-date=10 June 2014}}</ref> The word ''sarcoma'' is derived from the [[Ancient Greek|Greek]] {{Lang|grc|σάρκωμα}} {{Lang|grc-latn|sarkōma}} 'fleshy excrescence or substance', itself from [[wikt:σάρξ|σάρξ]] {{Lang|grc-latn|sarx}} meaning 'flesh'.<ref>{{LSJ|sa/rkwma|σάρκωμα}}, {{LSJ|sa/rc|σάρξ|ref}}.</ref><ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/sarcoma|title=Definition of SARCOMA|website=www.merriam-webster.com|language=en|access-date=2019-03-22}}</ref><ref>{{OEtymD|sarcoma}}</ref>
== Classification ==
@@ -94,24 +94,24 @@
Symptoms of bone sarcomas typically include bone pain, especially at night, and swelling around the site of the tumor.<ref name=":1" />
-Symptoms of [[soft-tissue sarcoma]]s vary, but they often present as firm, painless lumps or nodules.<ref name=":1" /> Gastrointestinal stromal tumors (a subtype of soft-tissue sarcoma) often are asymptomatic, but can be associated with vague complaints of abdominal pain, a feeling of fullness, or other signs of intestinal obstruction.<ref name=":1" />
+Symptoms of [[soft-tissue sarcoma]]s vary, but they often present as firm, often times painless lumps or nodules.<ref name=":1" /> Gastrointestinal stromal tumors (GIST, a subtype of soft-tissue sarcoma) often are asymptomatic, but can be associated with vague complaints of abdominal pain, bleeding into the intestines, a feeling of fullness, or other signs of intestinal obstruction.<ref name=":1" />
==Cause==
=== Causes and risk factors ===
-The cause of most '''bone sarcomas''' is not known,<ref name=":2">{{Cite book|title=DeVita, Hellman and Rosenberg's Cancer: Principles & Practice of Oncology | edition = 10th| vauthors = DeVita Jr V |publisher=Wolters Kluwer Health|year=2015|isbn=978-1-4511-9294-0|location=Philadelphia, PA|pages=1241–1313}}</ref> but several factors are associated with an increased risk of developing bone sarcoma. Previous exposure to ionizing radiation (such as prior radiation therapy) is one such risk factor.<ref name=":1" /> Therapeutic radiation is associated with sarcoma after 10 to 20 years.<ref>{{Cite web |title=UpToDate |url=https://www.uptodate.com/contents/radiation-associated-sarcomas#! |access-date=2023-03-19 |website=www.uptodate.com}}</ref> Mole removal in irradiated tissue may stimulate a sarcoma secondary to healing. Exposure to alkylating agents, such as those found in [[Alkylating antineoplastic agent|certain cancer chemotherapeutic medicines]], also increases the risk of bone sarcoma.<ref name=":2" /> Certain inherited genetic syndromes, including [[Li–Fraumeni syndrome|Li-Fraumeni syndrome]], heritable RB1 gene mutations, and [[Paget's disease of bone]], are associated with an increased risk of developing bone sarcomas.<ref name=":1" />
+The cause of most '''bone sarcomas''' is not known,<ref name=":2">{{Cite book|title=DeVita, Hellman and Rosenberg's Cancer: Principles & Practice of Oncology | edition = 10th| vauthors = DeVita Jr V |publisher=Wolters Kluwer Health|year=2015|isbn=978-1-4511-9294-0|location=Philadelphia, PA|pages=1241–1313}}</ref> but several factors are associated with an increased risk of developing bone sarcoma. Previous exposure to ionizing radiation (such as prior radiation therapy) is one such risk factor.<ref name=":1" /> Therapeutic radiation is associated with sarcoma after 10 to 20 years.<ref>{{Cite web |title=UpToDate |url=https://www.uptodate.com/contents/radiation-associated-sarcomas#! |access-date=2023-03-19 |website=www.uptodate.com}}</ref> Exposure to alkylating agents, such as those found in [[Alkylating antineoplastic agent|certain cancer chemotherapeutic medicines]], also increases the risk of bone sarcoma.<ref name=":2" /> Certain inherited genetic syndromes, including [[Li–Fraumeni syndrome|Li-Fraumeni syndrome]], inherited ''RB1'' gene mutations, and [[Paget's disease of bone]] are associated with an increased risk of developing bone sarcomas.<ref name=":1" />
-Most '''soft-tissue sarcomas''' arise from what doctors call "sporadic" (or random) genetic mutations within an affected person's cells.<ref name=":2" /> Nevertheless, there are certain risk factors associated with an increased risk of developing soft-tissue sarcoma. Previous exposure to [[ionizing radiation]] is one such risk factor.<ref name=":1" /> Exposure to vinyl chloride (e.g., such as the fumes encountered in the production of [[polyvinyl chloride]] (PVC)), [[arsenic]] and [[Thorotrast]] all are associated with an increased risk of angiosarcoma.<ref name=":1" /><ref name=":2" /> Lymphedema, such as that resulting from certain types of breast cancer treatment, also is a risk factor for development of angiosarcoma.<ref name=":2" /> As with bone sarcomas, certain inherited genetic syndromes also are associated with an increased risk of developing soft-tissue sarcoma, including [[Li–Fraumeni syndrome|Li-Fraumeni syndrome]], [[familial adenomatous polyposis]], [[Neurofibromatosis type I|neurofibromatosis type 1]], and heritable RB1 gene mutations.<ref name=":2" /> [[Kaposi's sarcoma]] is caused by [[Kaposi's sarcoma-associated herpesvirus]] (HHV-8).
+Most '''soft-tissue sarcomas''' arise from what doctors call "sporadic" (or random) genetic mutations within an affected person's cells.<ref name=":2" /> Nevertheless, there are certain risk factors associated with an increased risk of developing soft-tissue sarcoma. Previous exposure to [[ionizing radiation]] is one such risk factor.<ref name=":1" /> Exposure to vinyl chloride (e.g., such as the fumes encountered in the production of [[polyvinyl chloride]] (PVC)), [[arsenic]] and [[Thorotrast]] all are associated with an increased risk of angiosarcoma.<ref name=":1" /><ref name=":2" /> Lymphedema, such as that resulting from certain types of breast cancer treatment, also is a risk factor for development of angiosarcoma.<ref name=":2" /> As with bone sarcomas, certain inherited genetic syndromes also are associated with an increased risk of developing soft-tissue sarcoma, including [[Li–Fraumeni syndrome|Li-Fraumeni syndrome]], [[familial adenomatous polyposis]], [[Neurofibromatosis type I|neurofibromatosis type 1]], and heritable ''RB1'' gene mutations.<ref name=":2" /> [[Kaposi's sarcoma|Kaposi sarcoma]] is caused by [[Kaposi's sarcoma-associated herpesvirus|Kaposi sarcoma-associated herpesvirus]] (HHV-8).
== Mechanisms ==
The mechanisms by which healthy cells transform into cancer cells are described in detail elsewhere (see [[Cancer]] main page; [[Carcinogenesis]] main page). The precise molecular changes that result in sarcoma are not always known, but certain types of sarcomas are associated with particular genetic mutations.<ref name=":1" /><ref name=":2" /> Examples include:
-* Most cases of Ewing sarcoma are associated with a [[chromosomal translocation]] in which part of [[chromosome 11]] fuses with part of [[chromosome 22]].<ref name=":1" /> This results in the [[Ewing sarcoma breakpoint region 1|EWS gene]] becoming fused to other genes, including the [[FLI1|FLI1 gene]] in 90% of Ewing cases and [[ERG (gene)|ERG gene]] in 5-10% of cases.<ref name=":1" /> These fusions result in the production of abnormal proteins, although how these abnormal proteins result in cancer is not fully known.<ref name=":1" />
-* Dermatofibrosarcoma protuberans often is associated with a chromosomal translocation in which the [[Collagen, type I, alpha 1|COL1A1 gene]] becomes fused to the [[PDGFRB|PDGFRB gene]].<ref name=":2" /> This results in over-active [[Platelet-derived growth factor|PDGF]] signaling, which is thought to promote cell division and ultimately lead to tumor development.<ref name=":2" />
-* Inflammatory myofibroblastic tumor often is associated with rearrangements of the [[Anaplastic lymphoma kinase|ALK gene]], and occasionally with rearrangements of the [[HMGA2|HMGA2 gene]].<ref name=":2" />
-* Giant cell tumor of soft tissue frequently is associated with a chromosomal translocation between [[chromosome 1]] and [[chromosome 2]], in which the [[Macrophage colony-stimulating factor|CSF1 gene]] becomes fused with the [[Collagen, type VI, alpha 3|COL6A3 gene]].<ref name=":2" /> This results in increased CSF1 protein production, which is thought to play a role in cancer development.<ref name=":2" />
-* Many liposarcomas are associated with duplication of part of chromosome 12, which results in extra copies of known cancer-promoting genes ("[[oncogene]]s") such as the [[Cyclin-dependent kinase 4|CDK4 gene]], the [[Mdm2|MDM2 gene]] and the [[HMGA2|HMGA2 gene]].<ref name=":2" />
+* Most cases of Ewing sarcoma are associated with a [[chromosomal translocation]] in which part of [[chromosome 11]] fuses with part of [[chromosome 22]].<ref name=":1" /> This results in the [[Ewing sarcoma breakpoint region 1|''EWSR1'' gene]] becoming fused to other genes, including the [[FLI1|''FLI1'' gene]] in 90% of Ewing cases and [[ERG (gene)|''ERG'' gene]] in 5-10% of cases.<ref name=":1" /> These fusions result in the production of abnormal proteins, although how these abnormal proteins result in cancer is not fully known.<ref name=":1" />
+* Dermatofibrosarcoma protuberans often is associated with a chromosomal translocation in which the [[Collagen, type I, alpha 1|''COL1A1'' gene]] becomes fused to the [[PDGFRB|''PDGFRB'' gene]].<ref name=":2" /> This results in over-active [[Platelet-derived growth factor|PDGF]] signaling, which is thought to promote cell division and ultimately lead to tumor development.<ref name=":2" />
+* Inflammatory myofibroblastic tumor often is associated with rearrangements of the [[Anaplastic lymphoma kinase|''ALK'' gene]], and occasionally with rearrangements of the [[HMGA2|''HMGA2'' gene]].<ref name=":2" />
+* Tenosynovial giant cell tumor (not a sarcoma, but a non-metastasizing and locally aggressive soft tissue tumor) frequently is associated with a chromosomal translocation between [[chromosome 1]] and [[chromosome 2]], in which the [[Macrophage colony-stimulating factor|''CSF1'' gene]] becomes fused with the [[Collagen, type VI, alpha 3|''COL6A3'' gene]].<ref name=":2" /> This results in increased CSF1 protein production, which is thought to play a role in cancer development.<ref name=":2" />
+* Many liposarcomas are associated with amplification of part of chromosome 12, which results in extra copies of known cancer-promoting genes ("[[oncogene]]s") such as the [[Cyclin-dependent kinase 4|''CDK4'' gene]], the [[Mdm2|''MDM2'' gene]] and the [[HMGA2|''HMGA2'' gene]].<ref name=":2" />
==Diagnosis==
===Bone sarcomas===
{{Main|Bone sarcoma}}
-Diagnosis of [[bone sarcoma]]s begins with a thorough history and physical examination which may reveal characteristic signs and symptoms (see Signs and Symptoms above).<ref name=":2" /> Laboratory studies are not particularly useful in diagnosis, although some bone sarcomas (such as osteosarcoma) may be associated with elevated [[alkaline phosphatase]] levels, while others (such as Ewing Sarcoma) can be associated with elevated [[erythrocyte sedimentation rate]].<ref name=":3">{{Cite book|title=Dahlin's Bone Tumors| vauthors = Unni K |publisher=Lippincott Williams & Wilkins|year=2010|isbn=978-0-7817-6242-7|location=Philadelphia, PA|pages=1–8}}</ref> Importantly, however, none of these laboratory findings are specific to bone sarcomas, meaning that elevations in these lab values are associated with many other conditions as well as sarcoma, and thus cannot be relied upon to conclusively diagnose sarcoma.<ref name=":2" /> Imaging studies are critically important in diagnosis, and most clinicians will order a plain [[Radiography|radiograph]] (X-ray) initially.<ref name=":2" /> Other imaging studies commonly used in diagnosis include [[magnetic resonance imaging]] (MRI) studies and [[Bone scintigraphy|radioisotope bone scans]].<ref name=":3" /><ref name=":2" /> A [[CT scan]] is typically not used in diagnosis of most types of bone sarcoma, although it is an important tool for staging (see below).<ref name=":2" /> Definitive diagnosis requires biopsy of the tumor and careful review of the biopsy specimen by an experienced pathologist.<ref name=":2" />
+Diagnosis of [[bone sarcoma]]s begins with a thorough history and physical examination which may reveal characteristic signs and symptoms (see Signs and Symptoms above).<ref name=":2" /> Laboratory studies are not particularly useful in diagnosis, although some bone sarcomas (such as osteosarcoma) may be associated with elevated [[alkaline phosphatase]] levels, while others (such as Ewing sarcoma) can be associated with elevated [[erythrocyte sedimentation rate]].<ref name=":3">{{Cite book|title=Dahlin's Bone Tumors| vauthors = Unni K |publisher=Lippincott Williams & Wilkins|year=2010|isbn=978-0-7817-6242-7|location=Philadelphia, PA|pages=1–8}}</ref> Importantly, however, none of these laboratory findings are specific to bone sarcomas, meaning that elevations in these lab values are associated with many other conditions as well as sarcoma, and thus cannot be relied upon to conclusively diagnose sarcoma.<ref name=":2" /> Imaging studies are critically important in diagnosis, and most clinicians will order a plain [[Radiography|radiograph]] (X-ray) initially.<ref name=":2" /> Other imaging studies commonly used in diagnosis include [[magnetic resonance imaging]] (MRI) studies and [[Bone scintigraphy|radioisotope bone scans]].<ref name=":3" /><ref name=":2" /> A [[CT scan]] is typically not used in diagnosis of most types of bone sarcoma, although it is an important tool for staging (see below).<ref name=":2" /> Definitive diagnosis requires biopsy of the tumor and careful review of the biopsy specimen by an experienced pathologist.<ref name=":2" />
===Soft-tissue sarcomas===
@@ -132,25 +132,13 @@
The American Cancer Society (ACS) also publishes guidelines recommending preventive screening for certain types of common cancers.<ref name=":5">{{Cite web|url=https://www.cancer.org/healthy/find-cancer-early/cancer-screening-guidelines/american-cancer-society-guidelines-for-the-early-detection-of-cancer.html|title=Cancer Screening Guidelines {{!}} Detecting Cancer Early|website=www.cancer.org|language=en|access-date=2019-03-20}}</ref> Like the USPSTF, {{As of|2019|March|lc=y}} ACS does not recommend preventive screening for sarcoma.<ref name=":5" />
-The [[Sarcoma Foundation of America]] (SFA) is a cancer research organisation. It was founded in 2000 with the main intent of researching possible cures to sarcoma-type cancers.
+However, patients with some inherited conditions, such as [[Neurofibromatosis type I|neurofibromatosis]], may benefit from screening for development of cancers from pre-existing benign tumors called neurofibromas.
== Treatment ==
-{{multiple image
-| width=150
-| image1=Osteochondromyxosarcoma 1.jpg
-| alt1=Before
-| image2=Osteochondromyxosarcoma 5.jpg
-| alt2=After
-| footer=Surgical removal of [[Osteosarcoma|osteo]][[Chondrosarcoma|chondro]][[Myxosarcoma|myxo]]sarcoma
-}}
-[[Surgery]] is the most common form of the treatment for most sarcomas that have not spread to other parts of the body.<ref name=":2" /><ref name="Morris05">{{cite journal| vauthors = Morris C |year=2005|title=Malignant Fibrous Histiocytoma (MFH)|url=http://sarcomahelp.org/mfh.html|journal=ESUN|volume=2|issue=2|access-date=2011-10-19}}</ref> [[Limb-sparing techniques|Limb-sparing surgery]], as opposed to amputation, can now be used to save the limbs of patients in at least 90% of extremity (arm or leg) sarcoma cases.<ref name="Morris05" /> Additional treatments, including [[chemotherapy]], [[radiation therapy]] (also called "radiotherapy") and [[proton therapy]], may be administered ''before surgery'' (called "[[Neoadjuvant therapy|neoadjuvant]]" chemotherapy or radiotherapy) or ''after surgery'' (called "[[Adjuvant therapy|adjuvant]]" chemotherapy or radiotherapy).<ref name=":2" /><ref name="Buecker05" /> The use of neoadjuvant or adjuvant chemotherapy and radiotherapy significantly improves the prognosis for many sarcoma patients.<ref name=":2" /><ref>{{cite journal| vauthors = Baker L |year=2006|title=A Rose is a Rose or a Thorn is a Thorn|url=http://sarcomahelp.org/articles/chemotherapy-rose.html|journal=ESUN|volume=3|issue=5|access-date=2011-10-19}}</ref> Treatment can be a long and arduous process, lasting about a year for many patients.<ref name="Buecker05" />
-* [[Liposarcoma]] treatment consists of surgical resection, with chemotherapy not being used outside of the investigative setting. Adjuvant radiotherapy may also be used after surgical excision for liposarcoma.<ref>{{EMedicine|article|1102007|Liposarcoma Treatment & Management|treatment}}</ref>
-* Rhabdomyosarcoma is treated with surgery, radiotherapy, or chemotherapy.<ref>{{cite web|url=http://www.childrenshospital.org/az/Site1068/mainpageS1068P0.html|title=Rhabdomyosarcoma|publisher=Boston Children's Hospital}}</ref> The majority of rhabdomyosarcoma patients have a 50–85% survival rate.<ref>{{cite journal| vauthors = Wexler L |year=2004|title=Rhabdomyosarcoma|url=http://sarcomahelp.org/rhabdomyosarcoma.html|journal=ESUN|volume=1|issue=4|access-date=2011-10-19}}</ref>
-* Osteosarcoma is a tumor of the bone that is treated with surgical resection of as much of the cancer as possible, often along with [[neoadjuvant chemotherapy]].<ref>{{EMedicine|article|1256857|Osteosarcoma Treatment & Management|treatment}}</ref> Radiotherapy is a second alternative although not as successful.
+[[Surgery]] is the most common form of the treatment for most sarcomas that have not spread to other parts of the body, and for most sarcomas, surgery is the only curative treatment.<ref name=":2" /><ref name="Morris05">{{cite journal| vauthors = Morris C |year=2005|title=Malignant Fibrous Histiocytoma (MFH)|url=http://sarcomahelp.org/mfh.html|journal=ESUN|volume=2|issue=2|access-date=2011-10-19}}</ref> [[Limb-sparing techniques|Limb-sparing surgery]], as opposed to amputation, can now be used to save the limbs of patients in at least 90% of extremity (arm or leg) sarcoma cases.<ref name="Morris05" /> Additional treatments, including [[chemotherapy]], [[radiation therapy]] (also called "radiotherapy"), which includes [[proton therapy]], may be administered ''before surgery'' (called "[[Neoadjuvant therapy|neoadjuvant]]" chemotherapy or radiotherapy) or ''after surgery'' (called "[[Adjuvant therapy|adjuvant]]" chemotherapy or radiotherapy).<ref name=":2" /><ref name="Buecker05" /> The use of neoadjuvant or adjuvant chemotherapy and radiotherapy significantly improves the prognosis for many sarcoma patients.<ref name=":2" /><ref>{{cite journal| vauthors = Baker L |year=2006|title=A Rose is a Rose or a Thorn is a Thorn|url=http://sarcomahelp.org/articles/chemotherapy-rose.html|journal=ESUN|volume=3|issue=5|access-date=2011-10-19}}</ref> Treatment can be a long and arduous process, lasting about a year for many patients.<ref name="Buecker05" />
+* [[Liposarcoma]] treatment usually consists of surgical resection, with chemotherapy considered depending on the aggressiveness of the sarcoma. Radiotherapy may also be used before or after surgical excision for liposarcoma.<ref>{{EMedicine|article|1102007|Liposarcoma Treatment & Management|treatment}}</ref>
+* Pediatric rhabdomyosarcoma is usually treated with chemotherapy, surgery, and sometimes radiotherapy.<ref>{{cite web|url=http://www.childrenshospital.org/az/Site1068/mainpageS1068P0.html|title=Rhabdomyosarcoma|publisher=Boston Children's Hospital}}</ref> Pediatric rhabdomyosarcoma patients have a 50–85% long term survival rate.<ref>{{cite journal| vauthors = Wexler L |year=2004|title=Rhabdomyosarcoma|url=http://sarcomahelp.org/rhabdomyosarcoma.html|journal=ESUN|volume=1|issue=4|access-date=2011-10-19}}</ref>
+* Osteosarcoma is a cancer of the bone that is treated with surgical resection of as much of the cancer as possible, often along with [[neoadjuvant chemotherapy|chemotherapy]].<ref>{{EMedicine|article|1256857|Osteosarcoma Treatment & Management|treatment}}</ref> Radiotherapy is a second alternative to surgery, although not as successful.
-Expression of receptor [[B7-H3]] provides a promising target for new immunotherapeutic strategies.
-
-In childhood sarcomas, the cytotoxic agent [[cyclophosphamide]] is widely used and has shown good anti-tumour efficacy.<ref>{{cite journal | vauthors = Mulder RL, Paulides M, Langer T, Kremer LC, van Dalen EC | title = Cyclophosphamide versus ifosfamide for paediatric and young adult bone and soft tissue sarcoma patients | journal = The Cochrane Database of Systematic Reviews | issue = 9 | pages = CD006300 | date = September 2015 | volume = 2015 | pmid = 26421585 | pmc = 7389335 | doi = 10.1002/14651858.cd006300.pub4 }}</ref>
-
-It is believed that higher doses of chemotherapy might improve survival. However, high doses of chemotherapy stop the production of blood cells in the bone marrow and can be harmful. Stem cells collected from people before high‐dose chemotherapy can be transplanted back to the person if the blood cell count gets too low; this is called autologous hematopoietic stem cell transplantation. Research to investigate if using high‐dose chemotherapy followed by autologous hematopoietic stem cell transplantation was more favourable than standard‐dose chemotherapy <ref>{{cite journal | vauthors = Peinemann F, Enk H, Smith LA | title = Autologous hematopoietic stem cell transplantation following high-dose chemotherapy for nonrhabdomyosarcoma soft tissue sarcomas | journal = The Cochrane Database of Systematic Reviews | volume = 4 | pages = CD008216 | date = April 2017 | issue = 7 | pmid = 28407197 | pmc = 6478255 | doi = 10.1002/14651858.cd008216.pub5 }}</ref> found only one RCT and this did not favour either of the two treatment arms with respect to overall survival. Further evidence is needed through well‐designed clinical trials.
+It was believed that higher doses of chemotherapy might improve survival. However, high doses of chemotherapy stop the production of blood cells in the bone marrow and can be harmful. Stem cells collected from people before high‐dose chemotherapy can be transplanted back to the person if the blood cell count gets too low; this is called autologous hematopoietic stem cell transplantation, or high dose therapy with stem cell rescue. Research to investigate if using high‐dose chemotherapy followed by autologous hematopoietic stem cell transplantation was more favourable than standard‐dose chemotherapy <ref>{{cite journal | vauthors = Peinemann F, Enk H, Smith LA | title = Autologous hematopoietic stem cell transplantation following high-dose chemotherapy for nonrhabdomyosarcoma soft tissue sarcomas | journal = The Cochrane Database of Systematic Reviews | volume = 4 | pages = CD008216 | date = April 2017 | issue = 7 | pmid = 28407197 | pmc = 6478255 | doi = 10.1002/14651858.cd008216.pub5 }}</ref> found only one RCT and this did not favour either of the two treatment arms with respect to overall survival. As a result, high dose chemotherapy with stem cell rescue is generally considered appropriate only in the research setting.
== Prognosis ==
@@ -172,12 +160,12 @@
=== Outcome data ===
-According to data published by the US National Cancer Institute (NCI), the overall 5-year survival for '''bone sarcomas''' is 66.9%.<ref name=":8">{{Cite web|url=https://seer.cancer.gov/statfacts/html/bones.html|title=Bone and Joint Cancer - Cancer Stat Facts|website=SEER|language=en|access-date=2019-03-27}}</ref> The American Cancer Society (ACS) estimates that 1,660 people in the US will die in 2019 from bone sarcomas, accounting for 0.3% of all cancer deaths.<ref name=":7" /> The [[median]] age at death is 61 years old, although death can occur in any age group.<ref name=":8" /> Thus, 12.3% of bone sarcoma deaths occur in people under 20 years old, 13.8% occur in people 20–34 years old, 5.5% occur in people 35–44 years old, 9.3% occur in people 45–54 years old, 13.5% occur in people 55–64 years old, 16.2% occur in people 65–74 years old, 16.4% occur in people 75–84 years old, and 13.1% occur in people 85 years or older.<ref name=":8" />
+According to data published by the US National Cancer Institute (NCI), the overall 5-year survival for '''bone sarcomas''' is 66.9%.<ref name=":8">{{Cite web|url=https://seer.cancer.gov/statfacts/html/bones.html|title=Bone and Joint Cancer - Cancer Stat Facts|website=SEER|language=en|access-date=2019-03-27}}</ref> The American Cancer Society (ACS) estimates that 2,140 people in the US will die in 2023 from bone sarcomas, accounting for 0.3% of all cancer deaths.<ref name=":7">{{Cite journal |last=Siegel |first=Rebecca L. |last2=Miller |first2=Kimberly D. |last3=Wagle |first3=Nikita Sandeep |last4=Jemal |first4=Ahmedin |date=2023 |title=Cancer statistics, 2023 |url=https://pubmed.ncbi.nlm.nih.gov/36633525 |journal=CA: a cancer journal for clinicians |volume=73 |issue=1 |pages=17–48 |doi=10.3322/caac.21763 |issn=1542-4863 |pmid=36633525}}</ref> The [[median]] age at death is 61 years old, although death can occur in any age group.<ref name=":8" /> Thus, 12.3% of bone sarcoma deaths occur in people under 20 years old, 13.8% occur in people 20–34 years old, 5.5% occur in people 35–44 years old, 9.3% occur in people 45–54 years old, 13.5% occur in people 55–64 years old, 16.2% occur in people 65–74 years old, 16.4% occur in people 75–84 years old, and 13.1% occur in people 85 years or older.<ref name=":8" />
-For '''soft-tissue sarcomas''', the overall 5-year survival (irrespective of stage) is 64.5%, but survival is affected by many factors, including stage.<ref name=":9">{{Cite web|url=https://seer.cancer.gov/statfacts/html/soft.html|title=Soft Tissue Cancer - Cancer Stat Facts|website=SEER|language=en|access-date=2019-03-27}}</ref> Thus, the 5-year survival is 80.8% for soft-tissue sarcomas that have not spread beyond the primary tumor ("localized" tumors), 58.0% for soft-tissue sarcomas that have spread only to nearby lymph nodes, and 16.4% for soft-tissue sarcomas that have spread to distant organs.<ref name=":9" /> The ACS estimates that 5,270 people will die from soft-tissue sarcoma in 2019, accounting for 0.9% of all cancer deaths.<ref name=":7" />
+For '''soft-tissue sarcomas''', the overall 5-year survival (irrespective of stage) is 64.5%, but survival is affected by many factors, including stage.<ref name=":9">{{Cite web|url=https://seer.cancer.gov/statfacts/html/soft.html|title=Soft Tissue Cancer - Cancer Stat Facts|website=SEER|language=en|access-date=2019-03-27}}</ref> Thus, the 5-year survival is 80.8% for soft-tissue sarcomas that have not spread beyond the primary tumor ("localized" tumors), 58.0% for soft-tissue sarcomas that have spread only to nearby lymph nodes, and 16.4% for soft-tissue sarcomas that have spread to distant organs.<ref name=":9" /> The ACS estimates that 5,140 people will die from soft-tissue sarcoma in 2023, accounting for 0.9% of all cancer deaths.<ref name=":7" />
==Epidemiology==
-Sarcomas are quite rare.<ref name=":1" /> The risk of a previously healthy person receiving a new diagnosis of bone cancer is less than 0.001%, while the risk of receiving a new diagnosis of soft-tissue sarcoma is between 0.0014 and 0.005%.<ref name=":2" /> The American Cancer Society estimates that in the United States there will be 3,500 new cases of bone sarcoma in 2019, and 12,750 new cases of soft-tissue sarcoma.<ref name=":7">{{cite journal | vauthors = Siegel RL, Miller KD, Jemal A | title = Cancer statistics, 2019 | journal = CA: A Cancer Journal for Clinicians | volume = 69 | issue = 1 | pages = 7–34 | date = January 2019 | pmid = 30620402 | doi = 10.3322/caac.21551 | doi-access = free }}</ref> Considering that the total estimated number of new cancer diagnoses (all types of cancer) is 1,762,450, this means bone sarcomas represent only 0.2% of all new cancer diagnoses (making them the 30th most common type of cancer<ref name=":8" />) and soft-tissue sarcomas represent only 0.7% (making them the 22nd most common type of cancer<ref name=":9" />) of all new cancer diagnoses in the US in 2019.<ref name=":7" /> These estimates are similar to previously reported data.<ref name=":2" />
+Sarcomas are rare cancers.<ref name=":1" /> The risk of a previously healthy person receiving a new diagnosis of bone cancer is less than 0.001%, while the risk of receiving a new diagnosis of soft-tissue sarcoma is between 0.0014 and 0.005%.<ref name=":2" /> The American Cancer Society estimates that in the United States there will be 3,970 new cases of bone sarcoma in 2023, and 13,400 new cases of soft-tissue sarcoma.<ref name=":7" /> Considering that the total estimated number of new cancer diagnoses (all types of cancer) is 1,958,310, this means bone sarcomas represent only 0.2% of all new cancer diagnoses (making them the 30th most common type of cancer<ref name=":8" />) and soft-tissue sarcomas represent only 0.7% (making them the 22nd most common type of cancer<ref name=":9" />) of all new cancer diagnoses in the US in 2023.<ref name=":7" /> These estimates are similar to previously reported data.<ref name=":2" />
-Sarcomas affect people of all ages. Around 50% of bone sarcomas and 20% of soft-tissue sarcomas are diagnosed in people under the age of 35.<ref>{{cite journal | vauthors = Darling J |title=A Different View of Sarcoma Statistics |journal=ESUN |volume=4 |issue=6 |year=2007 |url=http://sarcomahelp.org/articles/sarcoma-statistics.html | access-date=2012-10-06}}</ref> Some sarcomas, such as [[leiomyosarcoma]], [[chondrosarcoma]], and [[gastrointestinal stromal tumor]] (GIST), are more common in adults than in children.<ref name=":1" /> Most high-grade bone sarcomas, including [[Ewing's sarcoma]] and [[osteosarcoma]], are much more common in children and young adults.<ref name=":1" />
+Sarcomas affect people of all ages. Around 50% of bone sarcomas and 20% of soft-tissue sarcomas are diagnosed in people under the age of 35.<ref>{{cite journal | vauthors = Darling J |title=A Different View of Sarcoma Statistics |journal=ESUN |volume=4 |issue=6 |year=2007 |url=http://sarcomahelp.org/articles/sarcoma-statistics.html | access-date=2012-10-06}}</ref> Some sarcomas, such as [[leiomyosarcoma]], [[chondrosarcoma]], and [[gastrointestinal stromal tumor]] (GIST), are more common in adults than in children.<ref name=":1" /> Most high-grade bone sarcomas, including [[Ewing's sarcoma|Ewing sarcoma]] and [[osteosarcoma]], are much more common in children and young adults.<ref name=":1" />
== In fossils ==
@@ -185,18 +173,12 @@
== Research ==
-Treatment of sarcoma, especially when the sarcoma has spread, or "metastasized", often requires chemotherapy but existing chemotherapeutic medicines are associated with significant toxicities and are not highly effective in killing cancer cells.<ref name=":2" /> Therefore, research to identify new medications to treat sarcoma is being conducted {{as of|2019|alt=as of 2019}}.<ref name=":2" /> One possibility is the use of [[cancer immunotherapy]] (e.g., immune checkpoint inhibitors like anti-PD1, anti-PDL1, and anti-CTLA4 agents) to treat sarcomas.<ref name=":10">{{cite journal | vauthors = Thanindratarn P, Dean DC, Nelson SD, Hornicek FJ, Duan Z | title = Advances in immune checkpoint inhibitors for bone sarcoma therapy | journal = Journal of Bone Oncology | volume = 15 | pages = 100221 | date = April 2019 | pmid = 30775238 | pmc = 6365405 | doi = 10.1016/j.jbo.2019.100221 | doi-access = free }}</ref> This is not yet an established treatment tool.<ref name=":10" /> Other strategies, such as small-molecule [[targeted therapy]], biologic agents (e.g., [[small interfering RNA]] molecules), and [[nanoparticle]]-directed therapy, also are being investigated.<ref name=":2" />
-
-Sameer Rastogi et al. has shown long lasting responses in few sarcomas (UPS & ASPS) on immunotherapy.<ref name=":33">Indian experience with immunotherapy in sarcoma and gastrointestinal stromal tumors: a retrospective study
-Rohit Reddy, Raja Mounika Velagapudi,Sameer Rastogi
-Future Science OA 0 0:0 https://www.future-science.com/doi/full/10.2144/fsoa-2021-0117</ref>
+Treatment of sarcoma, especially when the sarcoma has spread, or "metastasized", often requires chemotherapy but existing chemotherapeutic medicines are associated with significant toxicities and are not highly effective in killing cancer cells.<ref name=":2" /> Therefore, research to identify new medications to treat sarcoma is being conducted {{as of|2023|alt=as of 2019}}.<ref name=":2" /> One new type of therapy still under investigation is the use of [[cancer immunotherapy]] (e.g., immune checkpoint inhibitors like anti-PD1, anti-PDL1, and anti-CTLA4 agents) to treat sarcomas.<ref name=":10">{{cite journal | vauthors = Thanindratarn P, Dean DC, Nelson SD, Hornicek FJ, Duan Z | title = Advances in immune checkpoint inhibitors for bone sarcoma therapy | journal = Journal of Bone Oncology | volume = 15 | pages = 100221 | date = April 2019 | pmid = 30775238 | pmc = 6365405 | doi = 10.1016/j.jbo.2019.100221 | doi-access = free }}</ref> These drugs are not yet FDA- or other regulator-approved treatment.<ref name=":10" /> Other strategies, such as small-molecule [[targeted therapy]], biologic agents (e.g., [[small interfering RNA]] molecules), and [[nanoparticle]]-directed therapy, also are under active investigated.<ref name=":2" />
Research to understand the specific genetic and molecular factors that cause sarcoma to develop is underway.<ref name=":2" /> This could allow for the design of new targeted therapies and allow physicians to more accurately predict a patient's prognosis.<ref name=":2" />
-
-Presence of the [[H3-B3 immunoregulatory checkpoint receptor]] in the tumor cells provides the opportunity for clinical trial testing of new drugs and targeted agents and immunotherapies in development.
==Awareness==
In the US, July is widely recognized as Sarcoma Awareness Month.<ref>{{cite web |title=Cancer Awareness Dates |publisher=American Society of Clinical Oncology |url=http://www.cancer.net/research-and-advocacy/cancer-awareness-dates|date=19 December 2013 }}</ref> The UK has a Sarcoma Awareness Week in July led by [[Sarcoma UK]], the bone and soft-tissue cancer charity.<ref>{{cite web |title=Sarcoma Awareness Week 2018 |publisher=Sarcoma UK |url=https://sarcoma.org.uk/get-involved/SAW|access-date=13 April 2018|date=25 January 2016 }}</ref>
-American YouTuber [[Technoblade]] was diagnosed with sarcoma in August 2021, and died from his illness in June 2022 after the cancer metastasized. He had raised over $500,000 in a charity stream. Many YouTubers have raised awareness and donated to charities such as the Sarcoma Foundation of America after Technoblade's diagnosis and passing. To date, Technoblade's fans have raised over $1,000,000 for sarcoma research.<ref>{{Cite web |last=Saunders |first=Cindy |date=2022-07-01 |title=Technoblade Tribute |url=https://www.curesarcoma.org/technoblade-tribute/ |access-date=2022-11-10 |website=Sarcoma Foundation of America |language=en-US}}</ref>
+American YouTuber [[Technoblade]] was diagnosed with sarcoma in August 2021, and died from his illness in June 2022 after the cancer metastasized. He had raised over $500,000 in a charity stream. Many YouTubers have raised awareness and donated to charities such as the [[Sarcoma Foundation of America]] after Technoblade's diagnosis and passing. To date, Technoblade's fans have raised over $1,000,000 for sarcoma research.<ref>{{Cite web |last=Saunders |first=Cindy |date=2022-07-01 |title=Technoblade Tribute |url=https://www.curesarcoma.org/technoblade-tribute/ |access-date=2022-11-10 |website=Sarcoma Foundation of America |language=en-US}}</ref>
== References ==
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0 => 'A '''sarcoma''' is a [[malignant tumor]], a type of [[cancer]] that arises from [[Cell (biology)|cells]] of [[mesenchyme|mesenchymal]] ([[connective tissue]]) origin.<ref>{{cite journal | vauthors = Yang J, Ren Z, Du X, Hao M, Zhou W | title = The role of mesenchymal stem/progenitor cells in sarcoma: update and dispute | journal = Stem Cell Investigation | volume = 1 | pages = 18 | date = 2014-10-27 | pmid = 27358864 | pmc = 4923508 | doi = 10.3978/j.issn.2306-9759.2014.10.01 }}</ref><ref name=":1" /> Connective tissue is a broad term that includes [[cancellous bone|bone]], [[cartilage]], [[Body fat|fat]], [[vascular]], or [[Haematopoiesis|other structural]] tissues, and sarcomas can arise in any of these types of tissues.<ref name=":1" /><ref name=":2" /> 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.<ref name=":0" /> Sarcomas are ''primary'' connective tissue tumors, meaning that they arise in connective tissues.<ref name=":1" /> This is in contrast to ''secondary'' (or "metastatic") connective tissue tumors, which occur when a cancer from elsewhere in the body (such as the lungs, breast tissue or prostate) spreads to the connective tissue.<ref>{{Cite web|url=https://www.cancer.gov/types/metastatic-cancer|title=Metastatic Cancer|date=2015-05-12|website=National Cancer Institute|language=en|access-date=2019-03-22}}</ref> Sarcomas are one of five different [[List of cancer types|types of cancer]], classified by the [[list of distinct cell types in the adult human body|cell type]] from which they originate.<ref name=def>{{cite web|title=Defining Cancer| url=http://www.cancer.gov/cancertopics/cancerlibrary/what-is-cancer|website=National Cancer Institute|date=17 September 2007|access-date=10 June 2014}}</ref> The word ''sarcoma'' is derived from the [[Ancient Greek|Greek]] {{Lang|grc|σάρκωμα}} {{Lang|grc-latn|sarkōma}} 'fleshy excrescence or substance', itself from [[wikt:σάρξ|σάρξ]] {{Lang|grc-latn|sarx}} meaning 'flesh'.<ref>{{LSJ|sa/rkwma|σάρκωμα}}, {{LSJ|sa/rc|σάρξ|ref}}.</ref><ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/sarcoma|title=Definition of SARCOMA|website=www.merriam-webster.com|language=en|access-date=2019-03-22}}</ref><ref>{{OEtymD|sarcoma}}</ref>',
1 => 'Symptoms of [[soft-tissue sarcoma]]s vary, but they often present as firm, often times painless lumps or nodules.<ref name=":1" /> Gastrointestinal stromal tumors (GIST, a subtype of soft-tissue sarcoma) often are asymptomatic, but can be associated with vague complaints of abdominal pain, bleeding into the intestines, a feeling of fullness, or other signs of intestinal obstruction.<ref name=":1" />',
2 => 'The cause of most '''bone sarcomas''' is not known,<ref name=":2">{{Cite book|title=DeVita, Hellman and Rosenberg's Cancer: Principles & Practice of Oncology | edition = 10th| vauthors = DeVita Jr V |publisher=Wolters Kluwer Health|year=2015|isbn=978-1-4511-9294-0|location=Philadelphia, PA|pages=1241–1313}}</ref> but several factors are associated with an increased risk of developing bone sarcoma. Previous exposure to ionizing radiation (such as prior radiation therapy) is one such risk factor.<ref name=":1" /> Therapeutic radiation is associated with sarcoma after 10 to 20 years.<ref>{{Cite web |title=UpToDate |url=https://www.uptodate.com/contents/radiation-associated-sarcomas#! |access-date=2023-03-19 |website=www.uptodate.com}}</ref> Exposure to alkylating agents, such as those found in [[Alkylating antineoplastic agent|certain cancer chemotherapeutic medicines]], also increases the risk of bone sarcoma.<ref name=":2" /> Certain inherited genetic syndromes, including [[Li–Fraumeni syndrome|Li-Fraumeni syndrome]], inherited ''RB1'' gene mutations, and [[Paget's disease of bone]] are associated with an increased risk of developing bone sarcomas.<ref name=":1" />',
3 => 'Most '''soft-tissue sarcomas''' arise from what doctors call "sporadic" (or random) genetic mutations within an affected person's cells.<ref name=":2" /> Nevertheless, there are certain risk factors associated with an increased risk of developing soft-tissue sarcoma. Previous exposure to [[ionizing radiation]] is one such risk factor.<ref name=":1" /> Exposure to vinyl chloride (e.g., such as the fumes encountered in the production of [[polyvinyl chloride]] (PVC)), [[arsenic]] and [[Thorotrast]] all are associated with an increased risk of angiosarcoma.<ref name=":1" /><ref name=":2" /> Lymphedema, such as that resulting from certain types of breast cancer treatment, also is a risk factor for development of angiosarcoma.<ref name=":2" /> As with bone sarcomas, certain inherited genetic syndromes also are associated with an increased risk of developing soft-tissue sarcoma, including [[Li–Fraumeni syndrome|Li-Fraumeni syndrome]], [[familial adenomatous polyposis]], [[Neurofibromatosis type I|neurofibromatosis type 1]], and heritable ''RB1'' gene mutations.<ref name=":2" /> [[Kaposi's sarcoma|Kaposi sarcoma]] is caused by [[Kaposi's sarcoma-associated herpesvirus|Kaposi sarcoma-associated herpesvirus]] (HHV-8).',
4 => '* Most cases of Ewing sarcoma are associated with a [[chromosomal translocation]] in which part of [[chromosome 11]] fuses with part of [[chromosome 22]].<ref name=":1" /> This results in the [[Ewing sarcoma breakpoint region 1|''EWSR1'' gene]] becoming fused to other genes, including the [[FLI1|''FLI1'' gene]] in 90% of Ewing cases and [[ERG (gene)|''ERG'' gene]] in 5-10% of cases.<ref name=":1" /> These fusions result in the production of abnormal proteins, although how these abnormal proteins result in cancer is not fully known.<ref name=":1" />',
5 => '* Dermatofibrosarcoma protuberans often is associated with a chromosomal translocation in which the [[Collagen, type I, alpha 1|''COL1A1'' gene]] becomes fused to the [[PDGFRB|''PDGFRB'' gene]].<ref name=":2" /> This results in over-active [[Platelet-derived growth factor|PDGF]] signaling, which is thought to promote cell division and ultimately lead to tumor development.<ref name=":2" />',
6 => '* Inflammatory myofibroblastic tumor often is associated with rearrangements of the [[Anaplastic lymphoma kinase|''ALK'' gene]], and occasionally with rearrangements of the [[HMGA2|''HMGA2'' gene]].<ref name=":2" />',
7 => '* Tenosynovial giant cell tumor (not a sarcoma, but a non-metastasizing and locally aggressive soft tissue tumor) frequently is associated with a chromosomal translocation between [[chromosome 1]] and [[chromosome 2]], in which the [[Macrophage colony-stimulating factor|''CSF1'' gene]] becomes fused with the [[Collagen, type VI, alpha 3|''COL6A3'' gene]].<ref name=":2" /> This results in increased CSF1 protein production, which is thought to play a role in cancer development.<ref name=":2" />',
8 => '* Many liposarcomas are associated with amplification of part of chromosome 12, which results in extra copies of known cancer-promoting genes ("[[oncogene]]s") such as the [[Cyclin-dependent kinase 4|''CDK4'' gene]], the [[Mdm2|''MDM2'' gene]] and the [[HMGA2|''HMGA2'' gene]].<ref name=":2" />',
9 => 'Diagnosis of [[bone sarcoma]]s begins with a thorough history and physical examination which may reveal characteristic signs and symptoms (see Signs and Symptoms above).<ref name=":2" /> Laboratory studies are not particularly useful in diagnosis, although some bone sarcomas (such as osteosarcoma) may be associated with elevated [[alkaline phosphatase]] levels, while others (such as Ewing sarcoma) can be associated with elevated [[erythrocyte sedimentation rate]].<ref name=":3">{{Cite book|title=Dahlin's Bone Tumors| vauthors = Unni K |publisher=Lippincott Williams & Wilkins|year=2010|isbn=978-0-7817-6242-7|location=Philadelphia, PA|pages=1–8}}</ref> Importantly, however, none of these laboratory findings are specific to bone sarcomas, meaning that elevations in these lab values are associated with many other conditions as well as sarcoma, and thus cannot be relied upon to conclusively diagnose sarcoma.<ref name=":2" /> Imaging studies are critically important in diagnosis, and most clinicians will order a plain [[Radiography|radiograph]] (X-ray) initially.<ref name=":2" /> Other imaging studies commonly used in diagnosis include [[magnetic resonance imaging]] (MRI) studies and [[Bone scintigraphy|radioisotope bone scans]].<ref name=":3" /><ref name=":2" /> A [[CT scan]] is typically not used in diagnosis of most types of bone sarcoma, although it is an important tool for staging (see below).<ref name=":2" /> Definitive diagnosis requires biopsy of the tumor and careful review of the biopsy specimen by an experienced pathologist.<ref name=":2" />',
10 => 'However, patients with some inherited conditions, such as [[Neurofibromatosis type I|neurofibromatosis]], may benefit from screening for development of cancers from pre-existing benign tumors called neurofibromas. ',
11 => '[[Surgery]] is the most common form of the treatment for most sarcomas that have not spread to other parts of the body, and for most sarcomas, surgery is the only curative treatment.<ref name=":2" /><ref name="Morris05">{{cite journal| vauthors = Morris C |year=2005|title=Malignant Fibrous Histiocytoma (MFH)|url=http://sarcomahelp.org/mfh.html|journal=ESUN|volume=2|issue=2|access-date=2011-10-19}}</ref> [[Limb-sparing techniques|Limb-sparing surgery]], as opposed to amputation, can now be used to save the limbs of patients in at least 90% of extremity (arm or leg) sarcoma cases.<ref name="Morris05" /> Additional treatments, including [[chemotherapy]], [[radiation therapy]] (also called "radiotherapy"), which includes [[proton therapy]], may be administered ''before surgery'' (called "[[Neoadjuvant therapy|neoadjuvant]]" chemotherapy or radiotherapy) or ''after surgery'' (called "[[Adjuvant therapy|adjuvant]]" chemotherapy or radiotherapy).<ref name=":2" /><ref name="Buecker05" /> The use of neoadjuvant or adjuvant chemotherapy and radiotherapy significantly improves the prognosis for many sarcoma patients.<ref name=":2" /><ref>{{cite journal| vauthors = Baker L |year=2006|title=A Rose is a Rose or a Thorn is a Thorn|url=http://sarcomahelp.org/articles/chemotherapy-rose.html|journal=ESUN|volume=3|issue=5|access-date=2011-10-19}}</ref> Treatment can be a long and arduous process, lasting about a year for many patients.<ref name="Buecker05" />',
12 => '* [[Liposarcoma]] treatment usually consists of surgical resection, with chemotherapy considered depending on the aggressiveness of the sarcoma. Radiotherapy may also be used before or after surgical excision for liposarcoma.<ref>{{EMedicine|article|1102007|Liposarcoma Treatment & Management|treatment}}</ref>',
13 => '* Pediatric rhabdomyosarcoma is usually treated with chemotherapy, surgery, and sometimes radiotherapy.<ref>{{cite web|url=http://www.childrenshospital.org/az/Site1068/mainpageS1068P0.html|title=Rhabdomyosarcoma|publisher=Boston Children's Hospital}}</ref> Pediatric rhabdomyosarcoma patients have a 50–85% long term survival rate.<ref>{{cite journal| vauthors = Wexler L |year=2004|title=Rhabdomyosarcoma|url=http://sarcomahelp.org/rhabdomyosarcoma.html|journal=ESUN|volume=1|issue=4|access-date=2011-10-19}}</ref>',
14 => '* Osteosarcoma is a cancer of the bone that is treated with surgical resection of as much of the cancer as possible, often along with [[neoadjuvant chemotherapy|chemotherapy]].<ref>{{EMedicine|article|1256857|Osteosarcoma Treatment & Management|treatment}}</ref> Radiotherapy is a second alternative to surgery, although not as successful.',
15 => 'It was believed that higher doses of chemotherapy might improve survival. However, high doses of chemotherapy stop the production of blood cells in the bone marrow and can be harmful. Stem cells collected from people before high‐dose chemotherapy can be transplanted back to the person if the blood cell count gets too low; this is called autologous hematopoietic stem cell transplantation, or high dose therapy with stem cell rescue. Research to investigate if using high‐dose chemotherapy followed by autologous hematopoietic stem cell transplantation was more favourable than standard‐dose chemotherapy <ref>{{cite journal | vauthors = Peinemann F, Enk H, Smith LA | title = Autologous hematopoietic stem cell transplantation following high-dose chemotherapy for nonrhabdomyosarcoma soft tissue sarcomas | journal = The Cochrane Database of Systematic Reviews | volume = 4 | pages = CD008216 | date = April 2017 | issue = 7 | pmid = 28407197 | pmc = 6478255 | doi = 10.1002/14651858.cd008216.pub5 }}</ref> found only one RCT and this did not favour either of the two treatment arms with respect to overall survival. As a result, high dose chemotherapy with stem cell rescue is generally considered appropriate only in the research setting. ',
16 => 'According to data published by the US National Cancer Institute (NCI), the overall 5-year survival for '''bone sarcomas''' is 66.9%.<ref name=":8">{{Cite web|url=https://seer.cancer.gov/statfacts/html/bones.html|title=Bone and Joint Cancer - Cancer Stat Facts|website=SEER|language=en|access-date=2019-03-27}}</ref> The American Cancer Society (ACS) estimates that 2,140 people in the US will die in 2023 from bone sarcomas, accounting for 0.3% of all cancer deaths.<ref name=":7">{{Cite journal |last=Siegel |first=Rebecca L. |last2=Miller |first2=Kimberly D. |last3=Wagle |first3=Nikita Sandeep |last4=Jemal |first4=Ahmedin |date=2023 |title=Cancer statistics, 2023 |url=https://pubmed.ncbi.nlm.nih.gov/36633525 |journal=CA: a cancer journal for clinicians |volume=73 |issue=1 |pages=17–48 |doi=10.3322/caac.21763 |issn=1542-4863 |pmid=36633525}}</ref> The [[median]] age at death is 61 years old, although death can occur in any age group.<ref name=":8" /> Thus, 12.3% of bone sarcoma deaths occur in people under 20 years old, 13.8% occur in people 20–34 years old, 5.5% occur in people 35–44 years old, 9.3% occur in people 45–54 years old, 13.5% occur in people 55–64 years old, 16.2% occur in people 65–74 years old, 16.4% occur in people 75–84 years old, and 13.1% occur in people 85 years or older.<ref name=":8" />',
17 => 'For '''soft-tissue sarcomas''', the overall 5-year survival (irrespective of stage) is 64.5%, but survival is affected by many factors, including stage.<ref name=":9">{{Cite web|url=https://seer.cancer.gov/statfacts/html/soft.html|title=Soft Tissue Cancer - Cancer Stat Facts|website=SEER|language=en|access-date=2019-03-27}}</ref> Thus, the 5-year survival is 80.8% for soft-tissue sarcomas that have not spread beyond the primary tumor ("localized" tumors), 58.0% for soft-tissue sarcomas that have spread only to nearby lymph nodes, and 16.4% for soft-tissue sarcomas that have spread to distant organs.<ref name=":9" /> The ACS estimates that 5,140 people will die from soft-tissue sarcoma in 2023, accounting for 0.9% of all cancer deaths.<ref name=":7" />',
18 => 'Sarcomas are rare cancers.<ref name=":1" /> The risk of a previously healthy person receiving a new diagnosis of bone cancer is less than 0.001%, while the risk of receiving a new diagnosis of soft-tissue sarcoma is between 0.0014 and 0.005%.<ref name=":2" /> The American Cancer Society estimates that in the United States there will be 3,970 new cases of bone sarcoma in 2023, and 13,400 new cases of soft-tissue sarcoma.<ref name=":7" /> Considering that the total estimated number of new cancer diagnoses (all types of cancer) is 1,958,310, this means bone sarcomas represent only 0.2% of all new cancer diagnoses (making them the 30th most common type of cancer<ref name=":8" />) and soft-tissue sarcomas represent only 0.7% (making them the 22nd most common type of cancer<ref name=":9" />) of all new cancer diagnoses in the US in 2023.<ref name=":7" /> These estimates are similar to previously reported data.<ref name=":2" />',
19 => 'Sarcomas affect people of all ages. Around 50% of bone sarcomas and 20% of soft-tissue sarcomas are diagnosed in people under the age of 35.<ref>{{cite journal | vauthors = Darling J |title=A Different View of Sarcoma Statistics |journal=ESUN |volume=4 |issue=6 |year=2007 |url=http://sarcomahelp.org/articles/sarcoma-statistics.html | access-date=2012-10-06}}</ref> Some sarcomas, such as [[leiomyosarcoma]], [[chondrosarcoma]], and [[gastrointestinal stromal tumor]] (GIST), are more common in adults than in children.<ref name=":1" /> Most high-grade bone sarcomas, including [[Ewing's sarcoma|Ewing sarcoma]] and [[osteosarcoma]], are much more common in children and young adults.<ref name=":1" />',
20 => 'Treatment of sarcoma, especially when the sarcoma has spread, or "metastasized", often requires chemotherapy but existing chemotherapeutic medicines are associated with significant toxicities and are not highly effective in killing cancer cells.<ref name=":2" /> Therefore, research to identify new medications to treat sarcoma is being conducted {{as of|2023|alt=as of 2019}}.<ref name=":2" /> One new type of therapy still under investigation is the use of [[cancer immunotherapy]] (e.g., immune checkpoint inhibitors like anti-PD1, anti-PDL1, and anti-CTLA4 agents) to treat sarcomas.<ref name=":10">{{cite journal | vauthors = Thanindratarn P, Dean DC, Nelson SD, Hornicek FJ, Duan Z | title = Advances in immune checkpoint inhibitors for bone sarcoma therapy | journal = Journal of Bone Oncology | volume = 15 | pages = 100221 | date = April 2019 | pmid = 30775238 | pmc = 6365405 | doi = 10.1016/j.jbo.2019.100221 | doi-access = free }}</ref> These drugs are not yet FDA- or other regulator-approved treatment.<ref name=":10" /> Other strategies, such as small-molecule [[targeted therapy]], biologic agents (e.g., [[small interfering RNA]] molecules), and [[nanoparticle]]-directed therapy, also are under active investigated.<ref name=":2" />',
21 => 'American YouTuber [[Technoblade]] was diagnosed with sarcoma in August 2021, and died from his illness in June 2022 after the cancer metastasized. He had raised over $500,000 in a charity stream. Many YouTubers have raised awareness and donated to charities such as the [[Sarcoma Foundation of America]] after Technoblade's diagnosis and passing. To date, Technoblade's fans have raised over $1,000,000 for sarcoma research.<ref>{{Cite web |last=Saunders |first=Cindy |date=2022-07-01 |title=Technoblade Tribute |url=https://www.curesarcoma.org/technoblade-tribute/ |access-date=2022-11-10 |website=Sarcoma Foundation of America |language=en-US}}</ref>'
] |
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0 => 'A '''sarcoma''' is a [[malignant tumor]], a type of [[cancer]] that arises from transformed [[Cell (biology)|cells]] of [[mesenchyme|mesenchymal]] ([[connective tissue]]) origin.<ref>{{cite journal | vauthors = Yang J, Ren Z, Du X, Hao M, Zhou W | title = The role of mesenchymal stem/progenitor cells in sarcoma: update and dispute | journal = Stem Cell Investigation | volume = 1 | pages = 18 | date = 2014-10-27 | pmid = 27358864 | pmc = 4923508 | doi = 10.3978/j.issn.2306-9759.2014.10.01 }}</ref><ref name=":1" /> Connective tissue is a broad term that includes [[cancellous bone|bone]], [[cartilage]], [[Body fat|fat]], [[vascular]], or [[Haematopoiesis|hematopoietic]] tissues, and sarcomas can arise in any of these types of tissues.<ref name=":1" /><ref name=":2" /> 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.<ref name=":0" /> Sarcomas are ''primary'' connective tissue tumors, meaning that they arise in connective tissues.<ref name=":1" /> This is in contrast to ''secondary'' (or "metastatic") connective tissue tumors, which occur when a cancer from elsewhere in the body (such as the lungs, breast tissue or prostate) spreads to the connective tissue.<ref>{{Cite web|url=https://www.cancer.gov/types/metastatic-cancer|title=Metastatic Cancer|date=2015-05-12|website=National Cancer Institute|language=en|access-date=2019-03-22}}</ref> Sarcomas are one of five different [[List of cancer types|types of cancer]], classified by the [[list of distinct cell types in the adult human body|cell type]] from which they originate.<ref name=def>{{cite web|title=Defining Cancer| url=http://www.cancer.gov/cancertopics/cancerlibrary/what-is-cancer|website=National Cancer Institute|date=17 September 2007|access-date=10 June 2014}}</ref> The word ''sarcoma'' is derived from the [[Ancient Greek|Greek]] {{Lang|grc|σάρκωμα}} {{Lang|grc-latn|sarkōma}} 'fleshy excrescence or substance', itself from [[wikt:σάρξ|σάρξ]] {{Lang|grc-latn|sarx}} meaning 'flesh'.<ref>{{LSJ|sa/rkwma|σάρκωμα}}, {{LSJ|sa/rc|σάρξ|ref}}.</ref><ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/sarcoma|title=Definition of SARCOMA|website=www.merriam-webster.com|language=en|access-date=2019-03-22}}</ref><ref>{{OEtymD|sarcoma}}</ref>',
1 => 'Symptoms of [[soft-tissue sarcoma]]s vary, but they often present as firm, painless lumps or nodules.<ref name=":1" /> Gastrointestinal stromal tumors (a subtype of soft-tissue sarcoma) often are asymptomatic, but can be associated with vague complaints of abdominal pain, a feeling of fullness, or other signs of intestinal obstruction.<ref name=":1" />',
2 => 'The cause of most '''bone sarcomas''' is not known,<ref name=":2">{{Cite book|title=DeVita, Hellman and Rosenberg's Cancer: Principles & Practice of Oncology | edition = 10th| vauthors = DeVita Jr V |publisher=Wolters Kluwer Health|year=2015|isbn=978-1-4511-9294-0|location=Philadelphia, PA|pages=1241–1313}}</ref> but several factors are associated with an increased risk of developing bone sarcoma. Previous exposure to ionizing radiation (such as prior radiation therapy) is one such risk factor.<ref name=":1" /> Therapeutic radiation is associated with sarcoma after 10 to 20 years.<ref>{{Cite web |title=UpToDate |url=https://www.uptodate.com/contents/radiation-associated-sarcomas#! |access-date=2023-03-19 |website=www.uptodate.com}}</ref> Mole removal in irradiated tissue may stimulate a sarcoma secondary to healing. Exposure to alkylating agents, such as those found in [[Alkylating antineoplastic agent|certain cancer chemotherapeutic medicines]], also increases the risk of bone sarcoma.<ref name=":2" /> Certain inherited genetic syndromes, including [[Li–Fraumeni syndrome|Li-Fraumeni syndrome]], heritable RB1 gene mutations, and [[Paget's disease of bone]], are associated with an increased risk of developing bone sarcomas.<ref name=":1" />',
3 => 'Most '''soft-tissue sarcomas''' arise from what doctors call "sporadic" (or random) genetic mutations within an affected person's cells.<ref name=":2" /> Nevertheless, there are certain risk factors associated with an increased risk of developing soft-tissue sarcoma. Previous exposure to [[ionizing radiation]] is one such risk factor.<ref name=":1" /> Exposure to vinyl chloride (e.g., such as the fumes encountered in the production of [[polyvinyl chloride]] (PVC)), [[arsenic]] and [[Thorotrast]] all are associated with an increased risk of angiosarcoma.<ref name=":1" /><ref name=":2" /> Lymphedema, such as that resulting from certain types of breast cancer treatment, also is a risk factor for development of angiosarcoma.<ref name=":2" /> As with bone sarcomas, certain inherited genetic syndromes also are associated with an increased risk of developing soft-tissue sarcoma, including [[Li–Fraumeni syndrome|Li-Fraumeni syndrome]], [[familial adenomatous polyposis]], [[Neurofibromatosis type I|neurofibromatosis type 1]], and heritable RB1 gene mutations.<ref name=":2" /> [[Kaposi's sarcoma]] is caused by [[Kaposi's sarcoma-associated herpesvirus]] (HHV-8).',
4 => '* Most cases of Ewing sarcoma are associated with a [[chromosomal translocation]] in which part of [[chromosome 11]] fuses with part of [[chromosome 22]].<ref name=":1" /> This results in the [[Ewing sarcoma breakpoint region 1|EWS gene]] becoming fused to other genes, including the [[FLI1|FLI1 gene]] in 90% of Ewing cases and [[ERG (gene)|ERG gene]] in 5-10% of cases.<ref name=":1" /> These fusions result in the production of abnormal proteins, although how these abnormal proteins result in cancer is not fully known.<ref name=":1" />',
5 => '* Dermatofibrosarcoma protuberans often is associated with a chromosomal translocation in which the [[Collagen, type I, alpha 1|COL1A1 gene]] becomes fused to the [[PDGFRB|PDGFRB gene]].<ref name=":2" /> This results in over-active [[Platelet-derived growth factor|PDGF]] signaling, which is thought to promote cell division and ultimately lead to tumor development.<ref name=":2" />',
6 => '* Inflammatory myofibroblastic tumor often is associated with rearrangements of the [[Anaplastic lymphoma kinase|ALK gene]], and occasionally with rearrangements of the [[HMGA2|HMGA2 gene]].<ref name=":2" />',
7 => '* Giant cell tumor of soft tissue frequently is associated with a chromosomal translocation between [[chromosome 1]] and [[chromosome 2]], in which the [[Macrophage colony-stimulating factor|CSF1 gene]] becomes fused with the [[Collagen, type VI, alpha 3|COL6A3 gene]].<ref name=":2" /> This results in increased CSF1 protein production, which is thought to play a role in cancer development.<ref name=":2" />',
8 => '* Many liposarcomas are associated with duplication of part of chromosome 12, which results in extra copies of known cancer-promoting genes ("[[oncogene]]s") such as the [[Cyclin-dependent kinase 4|CDK4 gene]], the [[Mdm2|MDM2 gene]] and the [[HMGA2|HMGA2 gene]].<ref name=":2" />',
9 => 'Diagnosis of [[bone sarcoma]]s begins with a thorough history and physical examination which may reveal characteristic signs and symptoms (see Signs and Symptoms above).<ref name=":2" /> Laboratory studies are not particularly useful in diagnosis, although some bone sarcomas (such as osteosarcoma) may be associated with elevated [[alkaline phosphatase]] levels, while others (such as Ewing Sarcoma) can be associated with elevated [[erythrocyte sedimentation rate]].<ref name=":3">{{Cite book|title=Dahlin's Bone Tumors| vauthors = Unni K |publisher=Lippincott Williams & Wilkins|year=2010|isbn=978-0-7817-6242-7|location=Philadelphia, PA|pages=1–8}}</ref> Importantly, however, none of these laboratory findings are specific to bone sarcomas, meaning that elevations in these lab values are associated with many other conditions as well as sarcoma, and thus cannot be relied upon to conclusively diagnose sarcoma.<ref name=":2" /> Imaging studies are critically important in diagnosis, and most clinicians will order a plain [[Radiography|radiograph]] (X-ray) initially.<ref name=":2" /> Other imaging studies commonly used in diagnosis include [[magnetic resonance imaging]] (MRI) studies and [[Bone scintigraphy|radioisotope bone scans]].<ref name=":3" /><ref name=":2" /> A [[CT scan]] is typically not used in diagnosis of most types of bone sarcoma, although it is an important tool for staging (see below).<ref name=":2" /> Definitive diagnosis requires biopsy of the tumor and careful review of the biopsy specimen by an experienced pathologist.<ref name=":2" />',
10 => 'The [[Sarcoma Foundation of America]] (SFA) is a cancer research organisation. It was founded in 2000 with the main intent of researching possible cures to sarcoma-type cancers.',
11 => '{{multiple image',
12 => '| width=150',
13 => '| image1=Osteochondromyxosarcoma 1.jpg',
14 => '| alt1=Before',
15 => '| image2=Osteochondromyxosarcoma 5.jpg',
16 => '| alt2=After',
17 => '| footer=Surgical removal of [[Osteosarcoma|osteo]][[Chondrosarcoma|chondro]][[Myxosarcoma|myxo]]sarcoma',
18 => '}}',
19 => '[[Surgery]] is the most common form of the treatment for most sarcomas that have not spread to other parts of the body.<ref name=":2" /><ref name="Morris05">{{cite journal| vauthors = Morris C |year=2005|title=Malignant Fibrous Histiocytoma (MFH)|url=http://sarcomahelp.org/mfh.html|journal=ESUN|volume=2|issue=2|access-date=2011-10-19}}</ref> [[Limb-sparing techniques|Limb-sparing surgery]], as opposed to amputation, can now be used to save the limbs of patients in at least 90% of extremity (arm or leg) sarcoma cases.<ref name="Morris05" /> Additional treatments, including [[chemotherapy]], [[radiation therapy]] (also called "radiotherapy") and [[proton therapy]], may be administered ''before surgery'' (called "[[Neoadjuvant therapy|neoadjuvant]]" chemotherapy or radiotherapy) or ''after surgery'' (called "[[Adjuvant therapy|adjuvant]]" chemotherapy or radiotherapy).<ref name=":2" /><ref name="Buecker05" /> The use of neoadjuvant or adjuvant chemotherapy and radiotherapy significantly improves the prognosis for many sarcoma patients.<ref name=":2" /><ref>{{cite journal| vauthors = Baker L |year=2006|title=A Rose is a Rose or a Thorn is a Thorn|url=http://sarcomahelp.org/articles/chemotherapy-rose.html|journal=ESUN|volume=3|issue=5|access-date=2011-10-19}}</ref> Treatment can be a long and arduous process, lasting about a year for many patients.<ref name="Buecker05" />',
20 => '* [[Liposarcoma]] treatment consists of surgical resection, with chemotherapy not being used outside of the investigative setting. Adjuvant radiotherapy may also be used after surgical excision for liposarcoma.<ref>{{EMedicine|article|1102007|Liposarcoma Treatment & Management|treatment}}</ref>',
21 => '* Rhabdomyosarcoma is treated with surgery, radiotherapy, or chemotherapy.<ref>{{cite web|url=http://www.childrenshospital.org/az/Site1068/mainpageS1068P0.html|title=Rhabdomyosarcoma|publisher=Boston Children's Hospital}}</ref> The majority of rhabdomyosarcoma patients have a 50–85% survival rate.<ref>{{cite journal| vauthors = Wexler L |year=2004|title=Rhabdomyosarcoma|url=http://sarcomahelp.org/rhabdomyosarcoma.html|journal=ESUN|volume=1|issue=4|access-date=2011-10-19}}</ref>',
22 => '* Osteosarcoma is a tumor of the bone that is treated with surgical resection of as much of the cancer as possible, often along with [[neoadjuvant chemotherapy]].<ref>{{EMedicine|article|1256857|Osteosarcoma Treatment & Management|treatment}}</ref> Radiotherapy is a second alternative although not as successful.',
23 => 'Expression of receptor [[B7-H3]] provides a promising target for new immunotherapeutic strategies.',
24 => '',
25 => 'In childhood sarcomas, the cytotoxic agent [[cyclophosphamide]] is widely used and has shown good anti-tumour efficacy.<ref>{{cite journal | vauthors = Mulder RL, Paulides M, Langer T, Kremer LC, van Dalen EC | title = Cyclophosphamide versus ifosfamide for paediatric and young adult bone and soft tissue sarcoma patients | journal = The Cochrane Database of Systematic Reviews | issue = 9 | pages = CD006300 | date = September 2015 | volume = 2015 | pmid = 26421585 | pmc = 7389335 | doi = 10.1002/14651858.cd006300.pub4 }}</ref>',
26 => '',
27 => 'It is believed that higher doses of chemotherapy might improve survival. However, high doses of chemotherapy stop the production of blood cells in the bone marrow and can be harmful. Stem cells collected from people before high‐dose chemotherapy can be transplanted back to the person if the blood cell count gets too low; this is called autologous hematopoietic stem cell transplantation. Research to investigate if using high‐dose chemotherapy followed by autologous hematopoietic stem cell transplantation was more favourable than standard‐dose chemotherapy <ref>{{cite journal | vauthors = Peinemann F, Enk H, Smith LA | title = Autologous hematopoietic stem cell transplantation following high-dose chemotherapy for nonrhabdomyosarcoma soft tissue sarcomas | journal = The Cochrane Database of Systematic Reviews | volume = 4 | pages = CD008216 | date = April 2017 | issue = 7 | pmid = 28407197 | pmc = 6478255 | doi = 10.1002/14651858.cd008216.pub5 }}</ref> found only one RCT and this did not favour either of the two treatment arms with respect to overall survival. Further evidence is needed through well‐designed clinical trials.',
28 => 'According to data published by the US National Cancer Institute (NCI), the overall 5-year survival for '''bone sarcomas''' is 66.9%.<ref name=":8">{{Cite web|url=https://seer.cancer.gov/statfacts/html/bones.html|title=Bone and Joint Cancer - Cancer Stat Facts|website=SEER|language=en|access-date=2019-03-27}}</ref> The American Cancer Society (ACS) estimates that 1,660 people in the US will die in 2019 from bone sarcomas, accounting for 0.3% of all cancer deaths.<ref name=":7" /> The [[median]] age at death is 61 years old, although death can occur in any age group.<ref name=":8" /> Thus, 12.3% of bone sarcoma deaths occur in people under 20 years old, 13.8% occur in people 20–34 years old, 5.5% occur in people 35–44 years old, 9.3% occur in people 45–54 years old, 13.5% occur in people 55–64 years old, 16.2% occur in people 65–74 years old, 16.4% occur in people 75–84 years old, and 13.1% occur in people 85 years or older.<ref name=":8" />',
29 => 'For '''soft-tissue sarcomas''', the overall 5-year survival (irrespective of stage) is 64.5%, but survival is affected by many factors, including stage.<ref name=":9">{{Cite web|url=https://seer.cancer.gov/statfacts/html/soft.html|title=Soft Tissue Cancer - Cancer Stat Facts|website=SEER|language=en|access-date=2019-03-27}}</ref> Thus, the 5-year survival is 80.8% for soft-tissue sarcomas that have not spread beyond the primary tumor ("localized" tumors), 58.0% for soft-tissue sarcomas that have spread only to nearby lymph nodes, and 16.4% for soft-tissue sarcomas that have spread to distant organs.<ref name=":9" /> The ACS estimates that 5,270 people will die from soft-tissue sarcoma in 2019, accounting for 0.9% of all cancer deaths.<ref name=":7" />',
30 => 'Sarcomas are quite rare.<ref name=":1" /> The risk of a previously healthy person receiving a new diagnosis of bone cancer is less than 0.001%, while the risk of receiving a new diagnosis of soft-tissue sarcoma is between 0.0014 and 0.005%.<ref name=":2" /> The American Cancer Society estimates that in the United States there will be 3,500 new cases of bone sarcoma in 2019, and 12,750 new cases of soft-tissue sarcoma.<ref name=":7">{{cite journal | vauthors = Siegel RL, Miller KD, Jemal A | title = Cancer statistics, 2019 | journal = CA: A Cancer Journal for Clinicians | volume = 69 | issue = 1 | pages = 7–34 | date = January 2019 | pmid = 30620402 | doi = 10.3322/caac.21551 | doi-access = free }}</ref> Considering that the total estimated number of new cancer diagnoses (all types of cancer) is 1,762,450, this means bone sarcomas represent only 0.2% of all new cancer diagnoses (making them the 30th most common type of cancer<ref name=":8" />) and soft-tissue sarcomas represent only 0.7% (making them the 22nd most common type of cancer<ref name=":9" />) of all new cancer diagnoses in the US in 2019.<ref name=":7" /> These estimates are similar to previously reported data.<ref name=":2" />',
31 => 'Sarcomas affect people of all ages. Around 50% of bone sarcomas and 20% of soft-tissue sarcomas are diagnosed in people under the age of 35.<ref>{{cite journal | vauthors = Darling J |title=A Different View of Sarcoma Statistics |journal=ESUN |volume=4 |issue=6 |year=2007 |url=http://sarcomahelp.org/articles/sarcoma-statistics.html | access-date=2012-10-06}}</ref> Some sarcomas, such as [[leiomyosarcoma]], [[chondrosarcoma]], and [[gastrointestinal stromal tumor]] (GIST), are more common in adults than in children.<ref name=":1" /> Most high-grade bone sarcomas, including [[Ewing's sarcoma]] and [[osteosarcoma]], are much more common in children and young adults.<ref name=":1" />',
32 => 'Treatment of sarcoma, especially when the sarcoma has spread, or "metastasized", often requires chemotherapy but existing chemotherapeutic medicines are associated with significant toxicities and are not highly effective in killing cancer cells.<ref name=":2" /> Therefore, research to identify new medications to treat sarcoma is being conducted {{as of|2019|alt=as of 2019}}.<ref name=":2" /> One possibility is the use of [[cancer immunotherapy]] (e.g., immune checkpoint inhibitors like anti-PD1, anti-PDL1, and anti-CTLA4 agents) to treat sarcomas.<ref name=":10">{{cite journal | vauthors = Thanindratarn P, Dean DC, Nelson SD, Hornicek FJ, Duan Z | title = Advances in immune checkpoint inhibitors for bone sarcoma therapy | journal = Journal of Bone Oncology | volume = 15 | pages = 100221 | date = April 2019 | pmid = 30775238 | pmc = 6365405 | doi = 10.1016/j.jbo.2019.100221 | doi-access = free }}</ref> This is not yet an established treatment tool.<ref name=":10" /> Other strategies, such as small-molecule [[targeted therapy]], biologic agents (e.g., [[small interfering RNA]] molecules), and [[nanoparticle]]-directed therapy, also are being investigated.<ref name=":2" />',
33 => '',
34 => 'Sameer Rastogi et al. has shown long lasting responses in few sarcomas (UPS & ASPS) on immunotherapy.<ref name=":33">Indian experience with immunotherapy in sarcoma and gastrointestinal stromal tumors: a retrospective study',
35 => 'Rohit Reddy, Raja Mounika Velagapudi,Sameer Rastogi',
36 => 'Future Science OA 0 0:0 https://www.future-science.com/doi/full/10.2144/fsoa-2021-0117</ref>',
37 => '',
38 => 'Presence of the [[H3-B3 immunoregulatory checkpoint receptor]] in the tumor cells provides the opportunity for clinical trial testing of new drugs and targeted agents and immunotherapies in development.',
39 => 'American YouTuber [[Technoblade]] was diagnosed with sarcoma in August 2021, and died from his illness in June 2022 after the cancer metastasized. He had raised over $500,000 in a charity stream. Many YouTubers have raised awareness and donated to charities such as the Sarcoma Foundation of America after Technoblade's diagnosis and passing. To date, Technoblade's fans have raised over $1,000,000 for sarcoma research.<ref>{{Cite web |last=Saunders |first=Cindy |date=2022-07-01 |title=Technoblade Tribute |url=https://www.curesarcoma.org/technoblade-tribute/ |access-date=2022-11-10 |website=Sarcoma Foundation of America |language=en-US}}</ref>'
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Parsed HTML source of the new revision (new_html) | '<div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><style data-mw-deduplicate="TemplateStyles:r1033289096">.mw-parser-output .hatnote{font-style:italic}.mw-parser-output div.hatnote{padding-left:1.6em;margin-bottom:0.5em}.mw-parser-output .hatnote i{font-style:normal}.mw-parser-output .hatnote+link+.hatnote{margin-top:-0.5em}</style><div role="note" class="hatnote navigation-not-searchable">For the journal, see <a href="/enwiki/wiki/Sarcoma_(journal)" class="mw-redirect" title="Sarcoma (journal)">Sarcoma (journal)</a>.</div>
<p class="mw-empty-elt">
</p>
<div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Medical condition</div><style data-mw-deduplicate="TemplateStyles:r1066479718">.mw-parser-output .infobox-subbox{padding:0;border:none;margin:-3px;width:auto;min-width:100%;font-size:100%;clear:none;float:none;background-color:transparent}.mw-parser-output .infobox-3cols-child{margin:auto}.mw-parser-output .infobox .navbar{font-size:100%}body.skin-minerva .mw-parser-output .infobox-header,body.skin-minerva .mw-parser-output .infobox-subheader,body.skin-minerva .mw-parser-output .infobox-above,body.skin-minerva .mw-parser-output .infobox-title,body.skin-minerva .mw-parser-output .infobox-image,body.skin-minerva .mw-parser-output .infobox-full-data,body.skin-minerva .mw-parser-output .infobox-below{text-align:center}</style><table class="infobox"><tbody><tr><th colspan="2" class="infobox-above" style="background:#ccc">Sarcoma</th></tr><tr><th scope="row" class="infobox-label">Other names</th><td class="infobox-data">Sarcomas, sarcomata</td></tr><tr><td colspan="2" class="infobox-full-data"><span class="mw-default-size" typeof="mw:File/Frameless"><a href="/enwiki/wiki/File:Nibib_030207_105309_sarcoma.jpg" class="mw-file-description"><img src="/upwiki/wikipedia/commons/thumb/3/38/Nibib_030207_105309_sarcoma.jpg/300px-Nibib_030207_105309_sarcoma.jpg" decoding="async" width="300" height="226" class="mw-file-element" srcset="/upwiki/wikipedia/commons/thumb/3/38/Nibib_030207_105309_sarcoma.jpg/450px-Nibib_030207_105309_sarcoma.jpg 1.5x, /upwiki/wikipedia/commons/3/38/Nibib_030207_105309_sarcoma.jpg 2x" data-file-width="530" data-file-height="400" /></a></span></td></tr><tr><td colspan="2" class="infobox-full-data"><a href="/enwiki/wiki/Optical_coherence_tomography" title="Optical coherence tomography">Optical coherence tomography</a> (OCT) image of a sarcoma</td></tr><tr><th scope="row" class="infobox-label"><a href="/enwiki/wiki/Medical_specialty" title="Medical specialty">Specialty</a></th><td class="infobox-data"><a href="/enwiki/wiki/Oncology" title="Oncology">Oncology</a></td></tr></tbody></table>
<p>A <b>sarcoma</b> is a <a href="/enwiki/wiki/Malignant_tumor" class="mw-redirect" title="Malignant tumor">malignant tumor</a>, a type of <a href="/enwiki/wiki/Cancer" title="Cancer">cancer</a> that arises from <a href="/enwiki/wiki/Cell_(biology)" title="Cell (biology)">cells</a> of <a href="/enwiki/wiki/Mesenchyme" title="Mesenchyme">mesenchymal</a> (<a href="/enwiki/wiki/Connective_tissue" title="Connective tissue">connective tissue</a>) origin.<sup id="cite_ref-1" class="reference"><a href="#cite_note-1">[1]</a></sup><sup id="cite_ref-:1_2-0" class="reference"><a href="#cite_note-:1-2">[2]</a></sup> Connective tissue is a broad term that includes <a href="/enwiki/wiki/Cancellous_bone" class="mw-redirect" title="Cancellous bone">bone</a>, <a href="/enwiki/wiki/Cartilage" title="Cartilage">cartilage</a>, <a href="/enwiki/wiki/Body_fat" class="mw-redirect" title="Body fat">fat</a>, <a href="/enwiki/wiki/Vascular" class="mw-redirect" title="Vascular">vascular</a>, or <a href="/enwiki/wiki/Haematopoiesis" title="Haematopoiesis">other structural</a> tissues, and sarcomas can arise in any of these types of tissues.<sup id="cite_ref-:1_2-1" class="reference"><a href="#cite_note-:1-2">[2]</a></sup><sup id="cite_ref-:2_3-0" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> 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.<sup id="cite_ref-:0_4-0" class="reference"><a href="#cite_note-:0-4">[4]</a></sup> Sarcomas are <i>primary</i> connective tissue tumors, meaning that they arise in connective tissues.<sup id="cite_ref-:1_2-2" class="reference"><a href="#cite_note-:1-2">[2]</a></sup> This is in contrast to <i>secondary</i> (or "metastatic") connective tissue tumors, which occur when a cancer from elsewhere in the body (such as the lungs, breast tissue or prostate) spreads to the connective tissue.<sup id="cite_ref-5" class="reference"><a href="#cite_note-5">[5]</a></sup> Sarcomas are one of five different <a href="/enwiki/wiki/List_of_cancer_types" title="List of cancer types">types of cancer</a>, classified by the <a href="/enwiki/wiki/List_of_distinct_cell_types_in_the_adult_human_body" title="List of distinct cell types in the adult human body">cell type</a> from which they originate.<sup id="cite_ref-def_6-0" class="reference"><a href="#cite_note-def-6">[6]</a></sup> The word <i>sarcoma</i> is derived from the <a href="/enwiki/wiki/Ancient_Greek" title="Ancient Greek">Greek</a> <span title="Ancient Greek (to 1453)-language text"><span lang="grc">σάρκωμα</span></span> <span title="Ancient Greek (to 1453)-language text"><i lang="grc-Latn">sarkōma</i></span> 'fleshy excrescence or substance', itself from <a href="https://en.wiktionary.org/wiki/%CF%83%CE%AC%CF%81%CE%BE" class="extiw" title="wikt:σάρξ">σάρξ</a> <span title="Ancient Greek (to 1453)-language text"><i lang="grc-Latn">sarx</i></span> meaning 'flesh'.<sup id="cite_ref-7" class="reference"><a href="#cite_note-7">[7]</a></sup><sup id="cite_ref-8" class="reference"><a href="#cite_note-8">[8]</a></sup><sup id="cite_ref-9" class="reference"><a href="#cite_note-9">[9]</a></sup>
</p>
<div id="toc" class="toc" role="navigation" aria-labelledby="mw-toc-heading"><input type="checkbox" role="button" id="toctogglecheckbox" class="toctogglecheckbox" style="display:none" /><div class="toctitle" lang="en" dir="ltr"><h2 id="mw-toc-heading">Contents</h2><span class="toctogglespan"><label class="toctogglelabel" for="toctogglecheckbox"></label></span></div>
<ul>
<li class="toclevel-1 tocsection-1"><a href="#Classification"><span class="tocnumber">1</span> <span class="toctext">Classification</span></a>
<ul>
<li class="toclevel-2 tocsection-2"><a href="#Subtypes_of_bone_sarcoma"><span class="tocnumber">1.1</span> <span class="toctext">Subtypes of bone sarcoma</span></a></li>
<li class="toclevel-2 tocsection-3"><a href="#Subtypes_of_soft-tissue_sarcoma"><span class="tocnumber">1.2</span> <span class="toctext">Subtypes of soft-tissue sarcoma</span></a></li>
</ul>
</li>
<li class="toclevel-1 tocsection-4"><a href="#Signs_and_symptoms"><span class="tocnumber">2</span> <span class="toctext">Signs and symptoms</span></a></li>
<li class="toclevel-1 tocsection-5"><a href="#Cause"><span class="tocnumber">3</span> <span class="toctext">Cause</span></a>
<ul>
<li class="toclevel-2 tocsection-6"><a href="#Causes_and_risk_factors"><span class="tocnumber">3.1</span> <span class="toctext">Causes and risk factors</span></a></li>
</ul>
</li>
<li class="toclevel-1 tocsection-7"><a href="#Mechanisms"><span class="tocnumber">4</span> <span class="toctext">Mechanisms</span></a></li>
<li class="toclevel-1 tocsection-8"><a href="#Diagnosis"><span class="tocnumber">5</span> <span class="toctext">Diagnosis</span></a>
<ul>
<li class="toclevel-2 tocsection-9"><a href="#Bone_sarcomas"><span class="tocnumber">5.1</span> <span class="toctext">Bone sarcomas</span></a></li>
<li class="toclevel-2 tocsection-10"><a href="#Soft-tissue_sarcomas"><span class="tocnumber">5.2</span> <span class="toctext">Soft-tissue sarcomas</span></a></li>
<li class="toclevel-2 tocsection-11"><a href="#Staging"><span class="tocnumber">5.3</span> <span class="toctext">Staging</span></a></li>
<li class="toclevel-2 tocsection-12"><a href="#Grade"><span class="tocnumber">5.4</span> <span class="toctext">Grade</span></a></li>
</ul>
</li>
<li class="toclevel-1 tocsection-13"><a href="#Screening"><span class="tocnumber">6</span> <span class="toctext">Screening</span></a></li>
<li class="toclevel-1 tocsection-14"><a href="#Treatment"><span class="tocnumber">7</span> <span class="toctext">Treatment</span></a></li>
<li class="toclevel-1 tocsection-15"><a href="#Prognosis"><span class="tocnumber">8</span> <span class="toctext">Prognosis</span></a>
<ul>
<li class="toclevel-2 tocsection-16"><a href="#Factors_that_affect_prognosis"><span class="tocnumber">8.1</span> <span class="toctext">Factors that affect prognosis</span></a></li>
<li class="toclevel-2 tocsection-17"><a href="#Outcome_data"><span class="tocnumber">8.2</span> <span class="toctext">Outcome data</span></a></li>
</ul>
</li>
<li class="toclevel-1 tocsection-18"><a href="#Epidemiology"><span class="tocnumber">9</span> <span class="toctext">Epidemiology</span></a></li>
<li class="toclevel-1 tocsection-19"><a href="#In_fossils"><span class="tocnumber">10</span> <span class="toctext">In fossils</span></a></li>
<li class="toclevel-1 tocsection-20"><a href="#Research"><span class="tocnumber">11</span> <span class="toctext">Research</span></a></li>
<li class="toclevel-1 tocsection-21"><a href="#Awareness"><span class="tocnumber">12</span> <span class="toctext">Awareness</span></a></li>
<li class="toclevel-1 tocsection-22"><a href="#References"><span class="tocnumber">13</span> <span class="toctext">References</span></a></li>
<li class="toclevel-1 tocsection-23"><a href="#External_links"><span class="tocnumber">14</span> <span class="toctext">External links</span></a></li>
</ul>
</div>
<h2><span class="mw-headline" id="Classification">Classification</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=1" title="Edit section: Classification"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h2>
<p>Sarcomas are typically divided into two major groups: <a href="/enwiki/wiki/Bone_sarcoma" title="Bone sarcoma">bone sarcomas</a> and <a href="/enwiki/wiki/Soft-tissue_sarcoma" title="Soft-tissue sarcoma">soft-tissue sarcomas</a>,<sup id="cite_ref-:1_2-3" class="reference"><a href="#cite_note-:1-2">[2]</a></sup> each of which has multiple subtypes. In the United States, the American Joint Committee on Cancer (AJCC) publishes guidelines that classify the subtypes of sarcoma.<sup id="cite_ref-:0_4-1" class="reference"><a href="#cite_note-:0-4">[4]</a></sup> These subtypes are as follows:
</p>
<h3><span class="mw-headline" id="Subtypes_of_bone_sarcoma">Subtypes of bone sarcoma</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=2" title="Edit section: Subtypes of bone sarcoma"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h3>
<ul><li><a href="/enwiki/wiki/Osteosarcoma" title="Osteosarcoma">Osteosarcoma</a></li>
<li><a href="/enwiki/wiki/Chondrosarcoma" title="Chondrosarcoma">Chondrosarcoma</a></li>
<li>Poorly differentiated round/spindle cell tumors (includes <a href="/enwiki/wiki/Ewing_sarcoma" title="Ewing sarcoma">Ewing sarcoma</a>)</li>
<li><a href="/enwiki/wiki/Hemangioendothelioma" title="Hemangioendothelioma">Hemangioendothelioma</a></li>
<li><a href="/enwiki/wiki/Angiosarcoma" title="Angiosarcoma">Angiosarcoma</a></li>
<li><a href="/enwiki/wiki/Fibrosarcoma" title="Fibrosarcoma">Fibrosarcoma</a>/myofibrosarcoma</li>
<li><a href="/enwiki/wiki/Chordoma" title="Chordoma">Chordoma</a></li>
<li><a href="/enwiki/wiki/Adamantinoma" title="Adamantinoma">Adamantinoma</a></li>
<li>Other:
<ul><li><a href="/enwiki/wiki/Liposarcoma" title="Liposarcoma">Liposarcoma</a></li>
<li><a href="/enwiki/wiki/Leiomyosarcoma" title="Leiomyosarcoma">Leiomyosarcoma</a></li>
<li><a href="/enwiki/wiki/Malignant_peripheral_nerve_sheath_tumor" title="Malignant peripheral nerve sheath tumor">Malignant peripheral nerve sheath tumor</a></li>
<li><a href="/enwiki/wiki/Rhabdomyosarcoma" title="Rhabdomyosarcoma">Rhabdomyosarcoma</a></li>
<li><a href="/enwiki/wiki/Synovial_sarcoma" title="Synovial sarcoma">Synovial sarcoma</a></li>
<li>Malignant solitary fibrous tumor.<sup id="cite_ref-:0_4-2" class="reference"><a href="#cite_note-:0-4">[4]</a></sup></li></ul></li></ul>
<h3><span class="mw-headline" id="Subtypes_of_soft-tissue_sarcoma">Subtypes of soft-tissue sarcoma</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=3" title="Edit section: Subtypes of soft-tissue sarcoma"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h3>
<ul><li><a href="/enwiki/wiki/Liposarcoma" title="Liposarcoma">Liposarcoma</a> (includes the following varieties: <a href="/enwiki/wiki/Liposarcoma#Atypical_lipomatous_tumor/well-differentiated_liposarcoma" title="Liposarcoma">atypical lipomatous tumor/well-differentiated liposarcoma</a>, <a href="/enwiki/wiki/Liposarcoma#Dedifferentiated_liposarcoma" title="Liposarcoma">dedifferentiated liposarcoma</a>, <a href="/enwiki/wiki/Liposarcoma#Myxoid_liposarcoma" title="Liposarcoma">myxoid sarcoma</a>, <a href="/enwiki/wiki/Liposarcoma#Pleomorphic_liposarcoma" title="Liposarcoma">pleomorphic liposarcoma</a>, and <a href="/enwiki/wiki/Liposarcoma#Myxoid_pleomorphic_liposarcoma" title="Liposarcoma">myxoid pleomorphic liposarcoma</a></li>
<li>Atypical lipomatous tumor</li>
<li><a href="/enwiki/wiki/Dermatofibrosarcoma_protuberans" title="Dermatofibrosarcoma protuberans">Dermatofibrosarcoma protuberans</a> (includes pigmented varieties)</li>
<li><a href="/enwiki/wiki/Dermatofibrosarcoma_protuberans,_fibrosarcomatous" title="Dermatofibrosarcoma protuberans, fibrosarcomatous">Dermatofibrosarcoma protuberans, fibrosarcomatous</a></li>
<li><a href="/enwiki/wiki/Giant_cell_fibroblastoma" class="mw-redirect" title="Giant cell fibroblastoma">Giant cell fibroblastoma</a></li>
<li>Malignant <a href="/enwiki/wiki/Solitary_fibrous_tumor" title="Solitary fibrous tumor">solitary fibrous tumor</a></li>
<li><a href="/enwiki/wiki/Inflammatory_myofibroblastic_tumour" title="Inflammatory myofibroblastic tumour">Inflammatory myofibroblastic tumor</a></li>
<li><a href="/enwiki/wiki/Low-grade_myofibroblastic_sarcoma" title="Low-grade myofibroblastic sarcoma">Low-grade myofibroblastic sarcoma</a></li>
<li><a href="/enwiki/wiki/Fibrosarcoma" title="Fibrosarcoma">Fibrosarcoma</a> (includes adult and sclerosing epithelioid varieties)</li>
<li>Myxofibrosarcoma (formerly myxoid malignant fibrous histiocytoma)</li>
<li><a href="/enwiki/wiki/Low-grade_fibromyxoid_sarcoma" title="Low-grade fibromyxoid sarcoma">Low-grade fibromyxoid sarcoma</a></li>
<li>Giant cell tumor of soft tissues</li>
<li><a href="/enwiki/wiki/Leiomyosarcoma" title="Leiomyosarcoma">Leiomyosarcoma</a></li>
<li>Malignant <a href="/enwiki/wiki/Glomus_tumor" title="Glomus tumor">glomus tumor</a></li>
<li><a href="/enwiki/wiki/Rhabdomyosarcoma" title="Rhabdomyosarcoma">Rhabdomyosarcoma</a> (includes the following varieties: embryonal, alveolar, pleomorphic, and spindle cell/sclerosing)</li>
<li><a href="/enwiki/wiki/Hemangioendothelioma" title="Hemangioendothelioma">Hemangioendothelioma</a> (includes the following varieties: retiform, pseudomyogenic, and epithelioid)</li>
<li><a href="/enwiki/wiki/Angiosarcoma" title="Angiosarcoma">Angiosarcoma</a> of soft tissue</li>
<li>Extraskeletal osteosarcoma</li>
<li><a href="/enwiki/wiki/Gastrointestinal_stromal_tumor" title="Gastrointestinal stromal tumor">Gastrointestinal stromal tumor</a>, malignant (GIST)</li>
<li><a href="/enwiki/wiki/Malignant_peripheral_nerve_sheath_tumor" title="Malignant peripheral nerve sheath tumor">Malignant peripheral nerve sheath tumor</a> (includes epithelioid variety)</li>
<li>Malignant Triton tumor</li>
<li>Malignant <a href="/enwiki/wiki/Granular_cell_tumor" title="Granular cell tumor">granular cell tumor</a></li>
<li>Malignant ossifying fibromyxoid tumor</li>
<li>Stromal sarcoma not otherwise specified</li>
<li>Myoepithelial carcinoma</li>
<li>Malignant phosphaturic mesenchymal tumor</li>
<li><a href="/enwiki/wiki/Synovial_sarcoma" title="Synovial sarcoma">Synovial sarcoma</a> (includes the following varieties: spindle cell, biphasic, and not otherwise specified)</li>
<li><a href="/enwiki/wiki/Epithelioid_sarcoma" title="Epithelioid sarcoma">Epithelioid sarcoma</a></li>
<li><a href="/enwiki/wiki/Alveolar_soft_part_sarcoma" title="Alveolar soft part sarcoma">Alveolar soft part sarcoma</a></li>
<li>Clear cell sarcoma of soft tissue</li>
<li>Extraskeletal myxoid chondrosarcoma</li>
<li>Extraskeletal Ewing sarcoma</li>
<li><a href="/enwiki/wiki/Interdigitating_dendritic_cell_sarcoma" title="Interdigitating dendritic cell sarcoma">Interdigitating dendritic cell sarcoma</a></li>
<li><a href="/enwiki/wiki/Desmoplastic_small-round-cell_tumor" title="Desmoplastic small-round-cell tumor">Desmoplastic small round cell tumor</a></li>
<li>Extrarenal rhabdoid tumor</li>
<li><a href="/enwiki/wiki/Perivascular_epithelioid_cell_tumour" title="Perivascular epithelioid cell tumour">Perivascular epithelioid cell tumor</a>, not otherwise specified</li>
<li>Intimal sarcoma</li>
<li>Undifferentiated <a href="/enwiki/wiki/Spindle_cell_sarcoma" title="Spindle cell sarcoma">spindle cell sarcoma</a></li>
<li>Undifferentiated pleomorphic sarcoma</li>
<li>Undifferentiated round cell sarcoma</li>
<li>Undifferentiated epithelioid sarcoma</li>
<li>Undifferentiated sarcoma, not otherwise specified.<sup id="cite_ref-:0_4-3" class="reference"><a href="#cite_note-:0-4">[4]</a></sup></li></ul>
<h2><span class="mw-headline" id="Signs_and_symptoms">Signs and symptoms</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=4" title="Edit section: Signs and symptoms"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h2>
<p>Symptoms of bone sarcomas typically include bone pain, especially at night, and swelling around the site of the tumor.<sup id="cite_ref-:1_2-4" class="reference"><a href="#cite_note-:1-2">[2]</a></sup>
</p><p>Symptoms of <a href="/enwiki/wiki/Soft-tissue_sarcoma" title="Soft-tissue sarcoma">soft-tissue sarcomas</a> vary, but they often present as firm, often times painless lumps or nodules.<sup id="cite_ref-:1_2-5" class="reference"><a href="#cite_note-:1-2">[2]</a></sup> Gastrointestinal stromal tumors (GIST, a subtype of soft-tissue sarcoma) often are asymptomatic, but can be associated with vague complaints of abdominal pain, bleeding into the intestines, a feeling of fullness, or other signs of intestinal obstruction.<sup id="cite_ref-:1_2-6" class="reference"><a href="#cite_note-:1-2">[2]</a></sup>
</p>
<h2><span class="mw-headline" id="Cause">Cause</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=5" title="Edit section: Cause"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h2>
<h3><span class="mw-headline" id="Causes_and_risk_factors">Causes and risk factors</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=6" title="Edit section: Causes and risk factors"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h3>
<p>The cause of most <b>bone sarcomas</b> is not known,<sup id="cite_ref-:2_3-1" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> but several factors are associated with an increased risk of developing bone sarcoma. Previous exposure to ionizing radiation (such as prior radiation therapy) is one such risk factor.<sup id="cite_ref-:1_2-7" class="reference"><a href="#cite_note-:1-2">[2]</a></sup> Therapeutic radiation is associated with sarcoma after 10 to 20 years.<sup id="cite_ref-10" class="reference"><a href="#cite_note-10">[10]</a></sup> Exposure to alkylating agents, such as those found in <a href="/enwiki/wiki/Alkylating_antineoplastic_agent" title="Alkylating antineoplastic agent">certain cancer chemotherapeutic medicines</a>, also increases the risk of bone sarcoma.<sup id="cite_ref-:2_3-2" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> Certain inherited genetic syndromes, including <a href="/enwiki/wiki/Li%E2%80%93Fraumeni_syndrome" title="Li–Fraumeni syndrome">Li-Fraumeni syndrome</a>, inherited <i>RB1</i> gene mutations, and <a href="/enwiki/wiki/Paget%27s_disease_of_bone" title="Paget's disease of bone">Paget's disease of bone</a> are associated with an increased risk of developing bone sarcomas.<sup id="cite_ref-:1_2-8" class="reference"><a href="#cite_note-:1-2">[2]</a></sup>
</p><p>Most <b>soft-tissue sarcomas</b> arise from what doctors call "sporadic" (or random) genetic mutations within an affected person's cells.<sup id="cite_ref-:2_3-3" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> Nevertheless, there are certain risk factors associated with an increased risk of developing soft-tissue sarcoma. Previous exposure to <a href="/enwiki/wiki/Ionizing_radiation" title="Ionizing radiation">ionizing radiation</a> is one such risk factor.<sup id="cite_ref-:1_2-9" class="reference"><a href="#cite_note-:1-2">[2]</a></sup> Exposure to vinyl chloride (e.g., such as the fumes encountered in the production of <a href="/enwiki/wiki/Polyvinyl_chloride" title="Polyvinyl chloride">polyvinyl chloride</a> (PVC)), <a href="/enwiki/wiki/Arsenic" title="Arsenic">arsenic</a> and <a href="/enwiki/wiki/Thorotrast" title="Thorotrast">Thorotrast</a> all are associated with an increased risk of angiosarcoma.<sup id="cite_ref-:1_2-10" class="reference"><a href="#cite_note-:1-2">[2]</a></sup><sup id="cite_ref-:2_3-4" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> Lymphedema, such as that resulting from certain types of breast cancer treatment, also is a risk factor for development of angiosarcoma.<sup id="cite_ref-:2_3-5" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> As with bone sarcomas, certain inherited genetic syndromes also are associated with an increased risk of developing soft-tissue sarcoma, including <a href="/enwiki/wiki/Li%E2%80%93Fraumeni_syndrome" title="Li–Fraumeni syndrome">Li-Fraumeni syndrome</a>, <a href="/enwiki/wiki/Familial_adenomatous_polyposis" title="Familial adenomatous polyposis">familial adenomatous polyposis</a>, <a href="/enwiki/wiki/Neurofibromatosis_type_I" title="Neurofibromatosis type I">neurofibromatosis type 1</a>, and heritable <i>RB1</i> gene mutations.<sup id="cite_ref-:2_3-6" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> <a href="/enwiki/wiki/Kaposi%27s_sarcoma" title="Kaposi's sarcoma">Kaposi sarcoma</a> is caused by <a href="/enwiki/wiki/Kaposi%27s_sarcoma-associated_herpesvirus" title="Kaposi's sarcoma-associated herpesvirus">Kaposi sarcoma-associated herpesvirus</a> (HHV-8).
</p>
<h2><span class="mw-headline" id="Mechanisms">Mechanisms</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=7" title="Edit section: Mechanisms"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h2>
<p>The mechanisms by which healthy cells transform into cancer cells are described in detail elsewhere (see <a href="/enwiki/wiki/Cancer" title="Cancer">Cancer</a> main page; <a href="/enwiki/wiki/Carcinogenesis" title="Carcinogenesis">Carcinogenesis</a> main page). The precise molecular changes that result in sarcoma are not always known, but certain types of sarcomas are associated with particular genetic mutations.<sup id="cite_ref-:1_2-11" class="reference"><a href="#cite_note-:1-2">[2]</a></sup><sup id="cite_ref-:2_3-7" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> Examples include:
</p>
<ul><li>Most cases of Ewing sarcoma are associated with a <a href="/enwiki/wiki/Chromosomal_translocation" title="Chromosomal translocation">chromosomal translocation</a> in which part of <a href="/enwiki/wiki/Chromosome_11" title="Chromosome 11">chromosome 11</a> fuses with part of <a href="/enwiki/wiki/Chromosome_22" title="Chromosome 22">chromosome 22</a>.<sup id="cite_ref-:1_2-12" class="reference"><a href="#cite_note-:1-2">[2]</a></sup> This results in the <a href="/enwiki/wiki/Ewing_sarcoma_breakpoint_region_1" class="mw-redirect" title="Ewing sarcoma breakpoint region 1"><i>EWSR1</i> gene</a> becoming fused to other genes, including the <a href="/enwiki/wiki/FLI1" title="FLI1"><i>FLI1</i> gene</a> in 90% of Ewing cases and <a href="/enwiki/wiki/ERG_(gene)" title="ERG (gene)"><i>ERG</i> gene</a> in 5-10% of cases.<sup id="cite_ref-:1_2-13" class="reference"><a href="#cite_note-:1-2">[2]</a></sup> These fusions result in the production of abnormal proteins, although how these abnormal proteins result in cancer is not fully known.<sup id="cite_ref-:1_2-14" class="reference"><a href="#cite_note-:1-2">[2]</a></sup></li>
<li>Dermatofibrosarcoma protuberans often is associated with a chromosomal translocation in which the <a href="/enwiki/wiki/Collagen,_type_I,_alpha_1" title="Collagen, type I, alpha 1"><i>COL1A1</i> gene</a> becomes fused to the <a href="/enwiki/wiki/PDGFRB" title="PDGFRB"><i>PDGFRB</i> gene</a>.<sup id="cite_ref-:2_3-8" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> This results in over-active <a href="/enwiki/wiki/Platelet-derived_growth_factor" title="Platelet-derived growth factor">PDGF</a> signaling, which is thought to promote cell division and ultimately lead to tumor development.<sup id="cite_ref-:2_3-9" class="reference"><a href="#cite_note-:2-3">[3]</a></sup></li>
<li>Inflammatory myofibroblastic tumor often is associated with rearrangements of the <a href="/enwiki/wiki/Anaplastic_lymphoma_kinase" title="Anaplastic lymphoma kinase"><i>ALK</i> gene</a>, and occasionally with rearrangements of the <a href="/enwiki/wiki/HMGA2" title="HMGA2"><i>HMGA2</i> gene</a>.<sup id="cite_ref-:2_3-10" class="reference"><a href="#cite_note-:2-3">[3]</a></sup></li>
<li>Tenosynovial giant cell tumor (not a sarcoma, but a non-metastasizing and locally aggressive soft tissue tumor) frequently is associated with a chromosomal translocation between <a href="/enwiki/wiki/Chromosome_1" title="Chromosome 1">chromosome 1</a> and <a href="/enwiki/wiki/Chromosome_2" title="Chromosome 2">chromosome 2</a>, in which the <a href="/enwiki/wiki/Macrophage_colony-stimulating_factor" title="Macrophage colony-stimulating factor"><i>CSF1</i> gene</a> becomes fused with the <a href="/enwiki/wiki/Collagen,_type_VI,_alpha_3" title="Collagen, type VI, alpha 3"><i>COL6A3</i> gene</a>.<sup id="cite_ref-:2_3-11" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> This results in increased CSF1 protein production, which is thought to play a role in cancer development.<sup id="cite_ref-:2_3-12" class="reference"><a href="#cite_note-:2-3">[3]</a></sup></li>
<li>Many liposarcomas are associated with amplification of part of chromosome 12, which results in extra copies of known cancer-promoting genes ("<a href="/enwiki/wiki/Oncogene" title="Oncogene">oncogenes</a>") such as the <a href="/enwiki/wiki/Cyclin-dependent_kinase_4" title="Cyclin-dependent kinase 4"><i>CDK4</i> gene</a>, the <a href="/enwiki/wiki/Mdm2" title="Mdm2"><i>MDM2</i> gene</a> and the <a href="/enwiki/wiki/HMGA2" title="HMGA2"><i>HMGA2</i> gene</a>.<sup id="cite_ref-:2_3-13" class="reference"><a href="#cite_note-:2-3">[3]</a></sup></li></ul>
<h2><span class="mw-headline" id="Diagnosis">Diagnosis</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=8" title="Edit section: Diagnosis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h2>
<h3><span class="mw-headline" id="Bone_sarcomas">Bone sarcomas</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=9" title="Edit section: Bone sarcomas"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h3>
<link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1033289096"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/enwiki/wiki/Bone_sarcoma" title="Bone sarcoma">Bone sarcoma</a></div>
<p>Diagnosis of <a href="/enwiki/wiki/Bone_sarcoma" title="Bone sarcoma">bone sarcomas</a> begins with a thorough history and physical examination which may reveal characteristic signs and symptoms (see Signs and Symptoms above).<sup id="cite_ref-:2_3-14" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> Laboratory studies are not particularly useful in diagnosis, although some bone sarcomas (such as osteosarcoma) may be associated with elevated <a href="/enwiki/wiki/Alkaline_phosphatase" title="Alkaline phosphatase">alkaline phosphatase</a> levels, while others (such as Ewing sarcoma) can be associated with elevated <a href="/enwiki/wiki/Erythrocyte_sedimentation_rate" title="Erythrocyte sedimentation rate">erythrocyte sedimentation rate</a>.<sup id="cite_ref-:3_11-0" class="reference"><a href="#cite_note-:3-11">[11]</a></sup> Importantly, however, none of these laboratory findings are specific to bone sarcomas, meaning that elevations in these lab values are associated with many other conditions as well as sarcoma, and thus cannot be relied upon to conclusively diagnose sarcoma.<sup id="cite_ref-:2_3-15" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> Imaging studies are critically important in diagnosis, and most clinicians will order a plain <a href="/enwiki/wiki/Radiography" title="Radiography">radiograph</a> (X-ray) initially.<sup id="cite_ref-:2_3-16" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> Other imaging studies commonly used in diagnosis include <a href="/enwiki/wiki/Magnetic_resonance_imaging" title="Magnetic resonance imaging">magnetic resonance imaging</a> (MRI) studies and <a href="/enwiki/wiki/Bone_scintigraphy" title="Bone scintigraphy">radioisotope bone scans</a>.<sup id="cite_ref-:3_11-1" class="reference"><a href="#cite_note-:3-11">[11]</a></sup><sup id="cite_ref-:2_3-17" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> A <a href="/enwiki/wiki/CT_scan" title="CT scan">CT scan</a> is typically not used in diagnosis of most types of bone sarcoma, although it is an important tool for staging (see below).<sup id="cite_ref-:2_3-18" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> Definitive diagnosis requires biopsy of the tumor and careful review of the biopsy specimen by an experienced pathologist.<sup id="cite_ref-:2_3-19" class="reference"><a href="#cite_note-:2-3">[3]</a></sup>
</p>
<h3><span class="mw-headline" id="Soft-tissue_sarcomas">Soft-tissue sarcomas</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=10" title="Edit section: Soft-tissue sarcomas"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h3>
<link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1033289096"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/enwiki/wiki/Soft-tissue_sarcoma" title="Soft-tissue sarcoma">Soft-tissue sarcoma</a></div>
<p>Diagnosis of <a href="/enwiki/wiki/Soft-tissue_sarcoma" title="Soft-tissue sarcoma">soft-tissue sarcomas</a> also begins with a thorough history and physical examination.<sup id="cite_ref-:2_3-20" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> Imaging studies can include either CT or MRI, although CT tends to be preferred for soft-tissue sarcomas located in the <a href="/enwiki/wiki/Thorax" title="Thorax">thorax</a>, <a href="/enwiki/wiki/Abdomen" title="Abdomen">abdomen</a>, or <a href="/enwiki/wiki/Retroperitoneal_space" title="Retroperitoneal space">retroperitoneum</a>.<sup id="cite_ref-:2_3-21" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> <a href="/enwiki/wiki/Positron_emission_tomography" title="Positron emission tomography">Positron emission tomography</a> (PET) also may be useful in diagnosis, although its most common use is for staging (see below).<sup id="cite_ref-:2_3-22" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> As with bone sarcomas, definitive diagnosis requires biopsy of the tumor with evaluation of histology by a trained pathologist.<sup id="cite_ref-:2_3-23" class="reference"><a href="#cite_note-:2-3">[3]</a></sup><sup id="cite_ref-12" class="reference"><a href="#cite_note-12">[12]</a></sup>
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<h3><span class="mw-headline" id="Staging">Staging</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=11" title="Edit section: Staging"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h3>
<p>In general, <a href="/enwiki/wiki/Cancer_staging" title="Cancer staging">cancer staging</a> refers to how advanced a cancer is, and usually it is based upon factors such as tumor size and whether it has spread to other parts of the body.<sup id="cite_ref-:2_3-24" class="reference"><a href="#cite_note-:2-3">[3]</a></sup><sup id="cite_ref-13" class="reference"><a href="#cite_note-13">[13]</a></sup> Staging is important because the stage affects the <a href="/enwiki/wiki/Prognosis" title="Prognosis">prognosis</a> (likely outcome), as well as the types of treatments that are likely to be effective against the cancer.<sup id="cite_ref-:1_2-15" class="reference"><a href="#cite_note-:1-2">[2]</a></sup><sup id="cite_ref-:0_4-4" class="reference"><a href="#cite_note-:0-4">[4]</a></sup> With sarcomas, staging requires a determination of whether the tumor has grown into surrounding tissues ("local invasion"), as well as imaging to determine whether it has spread (a process known as "<a href="/enwiki/wiki/Metastasis" title="Metastasis">metastasis</a>") to lymph nodes (forming "nodal metastases") or to other tissues or organs in the body (forming "distant metastases").<sup id="cite_ref-:0_4-5" class="reference"><a href="#cite_note-:0-4">[4]</a></sup>
</p><p>The most common imaging tools used for staging <b>bone sarcomas</b> are MRI or CT to evaluate the primary tumor, contrast-enhanced CT of the chest to evaluate whether the cancer has spread (i.e., metastasized) to the lungs, and radioisotope bone scan to evaluate whether the cancer has spread to other bones.<sup id="cite_ref-:0_4-6" class="reference"><a href="#cite_note-:0-4">[4]</a></sup> Staging for <b>soft-tissue sarcomas</b> typically includes imaging of the primary tumor by MRI or CT to determine tumor size, as well as contrast-enhanced CT of the chest to evaluate for metastatic tumors in the lungs.<sup id="cite_ref-:0_4-7" class="reference"><a href="#cite_note-:0-4">[4]</a></sup>
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<h3><span class="mw-headline" id="Grade">Grade</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=12" title="Edit section: Grade"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h3>
<p>Like some other cancers, sarcomas are assigned a <a href="/enwiki/wiki/Grading_(tumors)" title="Grading (tumors)">grade</a> (low, intermediate, or high) based on the appearance of the tumor cells under a microscope.<sup id="cite_ref-:6_14-0" class="reference"><a href="#cite_note-:6-14">[14]</a></sup> In general, grade refers to how aggressive the cancer is and how likely it is to spread to other parts of the body ("metastasize").<sup id="cite_ref-:6_14-1" class="reference"><a href="#cite_note-:6-14">[14]</a></sup> Low-grade sarcomas have a better prognosis than higher-grade sarcomas, and are usually treated surgically, although sometimes radiation therapy or chemotherapy are used.<sup id="cite_ref-:2_3-25" class="reference"><a href="#cite_note-:2-3">[3]</a></sup><sup id="cite_ref-:0_4-8" class="reference"><a href="#cite_note-:0-4">[4]</a></sup> Intermediate- and high-grade sarcomas are more frequently treated with a combination of surgery, chemotherapy, or radiation therapy.<sup id="cite_ref-Buecker05_15-0" class="reference"><a href="#cite_note-Buecker05-15">[15]</a></sup> Since high-grade tumors are more likely to undergo metastasis (invasion and spread to locoregional and distant sites), they are treated more aggressively. The recognition that many sarcomas are sensitive to chemotherapy has dramatically improved the survival of patients. For example, in the era before chemotherapy, long-term survival for pediatric patients with localized osteosarcoma was only about 20%, but now has risen to 60–70%.<sup id="cite_ref-16" class="reference"><a href="#cite_note-16">[16]</a></sup>
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<h2><span class="mw-headline" id="Screening">Screening</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=13" title="Edit section: Screening"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h2>
<p>In the US, the US Preventive Services Task Force (USPSTF) publishes guidelines recommending <a href="/enwiki/wiki/Cancer_screening" title="Cancer screening">preventive screening</a> for certain types of common cancers and other diseases.<sup id="cite_ref-:4_17-0" class="reference"><a href="#cite_note-:4-17">[17]</a></sup> As of March 2019<sup class="plainlinks noexcerpt noprint asof-tag update" style="display:none;"><a class="external text" href="https://en.wikipedia.org/enwiki/w/index.php?title=Sarcoma&action=edit">[update]</a></sup>, the USPSTF does not recommend screening for sarcoma,<sup id="cite_ref-:4_17-1" class="reference"><a href="#cite_note-:4-17">[17]</a></sup> possibly because it is a very rare type of cancer (see Epidemiology below).
</p><p>The American Cancer Society (ACS) also publishes guidelines recommending preventive screening for certain types of common cancers.<sup id="cite_ref-:5_18-0" class="reference"><a href="#cite_note-:5-18">[18]</a></sup> Like the USPSTF, as of March 2019<sup class="plainlinks noexcerpt noprint asof-tag update" style="display:none;"><a class="external text" href="https://en.wikipedia.org/enwiki/w/index.php?title=Sarcoma&action=edit">[update]</a></sup> ACS does not recommend preventive screening for sarcoma.<sup id="cite_ref-:5_18-1" class="reference"><a href="#cite_note-:5-18">[18]</a></sup>
</p><p>However, patients with some inherited conditions, such as <a href="/enwiki/wiki/Neurofibromatosis_type_I" title="Neurofibromatosis type I">neurofibromatosis</a>, may benefit from screening for development of cancers from pre-existing benign tumors called neurofibromas.
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<h2><span class="mw-headline" id="Treatment">Treatment</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=14" title="Edit section: Treatment"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h2>
<p><a href="/enwiki/wiki/Surgery" title="Surgery">Surgery</a> is the most common form of the treatment for most sarcomas that have not spread to other parts of the body, and for most sarcomas, surgery is the only curative treatment.<sup id="cite_ref-:2_3-26" class="reference"><a href="#cite_note-:2-3">[3]</a></sup><sup id="cite_ref-Morris05_19-0" class="reference"><a href="#cite_note-Morris05-19">[19]</a></sup> <a href="/enwiki/wiki/Limb-sparing_techniques" title="Limb-sparing techniques">Limb-sparing surgery</a>, as opposed to amputation, can now be used to save the limbs of patients in at least 90% of extremity (arm or leg) sarcoma cases.<sup id="cite_ref-Morris05_19-1" class="reference"><a href="#cite_note-Morris05-19">[19]</a></sup> Additional treatments, including <a href="/enwiki/wiki/Chemotherapy" title="Chemotherapy">chemotherapy</a>, <a href="/enwiki/wiki/Radiation_therapy" title="Radiation therapy">radiation therapy</a> (also called "radiotherapy"), which includes <a href="/enwiki/wiki/Proton_therapy" title="Proton therapy">proton therapy</a>, may be administered <i>before surgery</i> (called "<a href="/enwiki/wiki/Neoadjuvant_therapy" title="Neoadjuvant therapy">neoadjuvant</a>" chemotherapy or radiotherapy) or <i>after surgery</i> (called "<a href="/enwiki/wiki/Adjuvant_therapy" title="Adjuvant therapy">adjuvant</a>" chemotherapy or radiotherapy).<sup id="cite_ref-:2_3-27" class="reference"><a href="#cite_note-:2-3">[3]</a></sup><sup id="cite_ref-Buecker05_15-1" class="reference"><a href="#cite_note-Buecker05-15">[15]</a></sup> The use of neoadjuvant or adjuvant chemotherapy and radiotherapy significantly improves the prognosis for many sarcoma patients.<sup id="cite_ref-:2_3-28" class="reference"><a href="#cite_note-:2-3">[3]</a></sup><sup id="cite_ref-20" class="reference"><a href="#cite_note-20">[20]</a></sup> Treatment can be a long and arduous process, lasting about a year for many patients.<sup id="cite_ref-Buecker05_15-2" class="reference"><a href="#cite_note-Buecker05-15">[15]</a></sup>
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<ul><li><a href="/enwiki/wiki/Liposarcoma" title="Liposarcoma">Liposarcoma</a> treatment usually consists of surgical resection, with chemotherapy considered depending on the aggressiveness of the sarcoma. Radiotherapy may also be used before or after surgical excision for liposarcoma.<sup id="cite_ref-21" class="reference"><a href="#cite_note-21">[21]</a></sup></li>
<li>Pediatric rhabdomyosarcoma is usually treated with chemotherapy, surgery, and sometimes radiotherapy.<sup id="cite_ref-22" class="reference"><a href="#cite_note-22">[22]</a></sup> Pediatric rhabdomyosarcoma patients have a 50–85% long term survival rate.<sup id="cite_ref-23" class="reference"><a href="#cite_note-23">[23]</a></sup></li>
<li>Osteosarcoma is a cancer of the bone that is treated with surgical resection of as much of the cancer as possible, often along with <a href="/enwiki/wiki/Neoadjuvant_chemotherapy" class="mw-redirect" title="Neoadjuvant chemotherapy">chemotherapy</a>.<sup id="cite_ref-24" class="reference"><a href="#cite_note-24">[24]</a></sup> Radiotherapy is a second alternative to surgery, although not as successful.</li></ul>
<p>It was believed that higher doses of chemotherapy might improve survival. However, high doses of chemotherapy stop the production of blood cells in the bone marrow and can be harmful. Stem cells collected from people before high‐dose chemotherapy can be transplanted back to the person if the blood cell count gets too low; this is called autologous hematopoietic stem cell transplantation, or high dose therapy with stem cell rescue. Research to investigate if using high‐dose chemotherapy followed by autologous hematopoietic stem cell transplantation was more favourable than standard‐dose chemotherapy <sup id="cite_ref-25" class="reference"><a href="#cite_note-25">[25]</a></sup> found only one RCT and this did not favour either of the two treatment arms with respect to overall survival. As a result, high dose chemotherapy with stem cell rescue is generally considered appropriate only in the research setting.
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<h2><span class="mw-headline" id="Prognosis">Prognosis</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=15" title="Edit section: Prognosis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h2>
<h3><span class="mw-headline" id="Factors_that_affect_prognosis">Factors that affect prognosis</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=16" title="Edit section: Factors that affect prognosis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h3>
<p>The AJCC has identified several factors that affect prognosis of <b>bone sarcomas</b>:<sup id="cite_ref-:0_4-9" class="reference"><a href="#cite_note-:0-4">[4]</a></sup>
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<ul><li><b>Size of the tumor</b>: larger tumors tend to have a worse prognosis compared to smaller tumors.</li>
<li><b>Spread of tumor to surrounding tissues</b>: tumors that have spread locally to surrounding tissues tend to have a worse prognosis compared to tumors that have not spread beyond their place of origin.</li>
<li><b>Stage and presence of metastases</b>: tumors that have spread ("metastasized") to the lymph nodes (which is rare for bone sarcomas) or other organs or tissues (for example, to the lungs) have a worse prognosis compared to tumors that have not metastasized.</li>
<li><b>Tumor grade</b>: higher grade tumors (grades 2 and 3) tend to have a worse prognosis compared to low grade (grade 1) tumors.</li>
<li><b>Skeletal location</b>: tumors originating in the spine or pelvic bones tend to have a worse prognosis compared to tumors originating in arm or leg bones.</li></ul>
<p>For <b>soft-tissue sarcomas other than GISTs,</b> factors that affect prognosis include:<sup id="cite_ref-:0_4-10" class="reference"><a href="#cite_note-:0-4">[4]</a></sup>
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<ul><li><b>Stage</b>: as with bone sarcomas, tumors that have metastasized have a worse prognosis compared to tumors that have not metastasized.</li>
<li><b>Grade</b>: the AJCC recommends using a grading system called the French Federation of Cancer Centers Sarcoma Group (FNCLCC) Grade for soft-tissue sarcomas, with high-grade tumors having a worse prognosis compared to low-grade tumors.</li></ul>
<p>For <b>GISTs</b>, the key factor that affects prognosis is:<sup id="cite_ref-:0_4-11" class="reference"><a href="#cite_note-:0-4">[4]</a></sup>
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<ul><li><b>Mitotic rate</b>: <a href="/enwiki/wiki/Mitosis" title="Mitosis">mitotic</a> rate refers to the fraction of <a href="/enwiki/wiki/Cell_(biology)" title="Cell (biology)">cells</a> that are actively <a href="/enwiki/wiki/Cell_division" title="Cell division">dividing</a> within the tumor; GISTs that have a high mitotic rate have a worse prognosis compared to GISTs that have a low mitotic rate.</li></ul>
<h3><span class="mw-headline" id="Outcome_data">Outcome data</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=17" title="Edit section: Outcome data"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h3>
<p>According to data published by the US National Cancer Institute (NCI), the overall 5-year survival for <b>bone sarcomas</b> is 66.9%.<sup id="cite_ref-:8_26-0" class="reference"><a href="#cite_note-:8-26">[26]</a></sup> The American Cancer Society (ACS) estimates that 2,140 people in the US will die in 2023 from bone sarcomas, accounting for 0.3% of all cancer deaths.<sup id="cite_ref-:7_27-0" class="reference"><a href="#cite_note-:7-27">[27]</a></sup> The <a href="/enwiki/wiki/Median" title="Median">median</a> age at death is 61 years old, although death can occur in any age group.<sup id="cite_ref-:8_26-1" class="reference"><a href="#cite_note-:8-26">[26]</a></sup> Thus, 12.3% of bone sarcoma deaths occur in people under 20 years old, 13.8% occur in people 20–34 years old, 5.5% occur in people 35–44 years old, 9.3% occur in people 45–54 years old, 13.5% occur in people 55–64 years old, 16.2% occur in people 65–74 years old, 16.4% occur in people 75–84 years old, and 13.1% occur in people 85 years or older.<sup id="cite_ref-:8_26-2" class="reference"><a href="#cite_note-:8-26">[26]</a></sup>
</p><p>For <b>soft-tissue sarcomas</b>, the overall 5-year survival (irrespective of stage) is 64.5%, but survival is affected by many factors, including stage.<sup id="cite_ref-:9_28-0" class="reference"><a href="#cite_note-:9-28">[28]</a></sup> Thus, the 5-year survival is 80.8% for soft-tissue sarcomas that have not spread beyond the primary tumor ("localized" tumors), 58.0% for soft-tissue sarcomas that have spread only to nearby lymph nodes, and 16.4% for soft-tissue sarcomas that have spread to distant organs.<sup id="cite_ref-:9_28-1" class="reference"><a href="#cite_note-:9-28">[28]</a></sup> The ACS estimates that 5,140 people will die from soft-tissue sarcoma in 2023, accounting for 0.9% of all cancer deaths.<sup id="cite_ref-:7_27-1" class="reference"><a href="#cite_note-:7-27">[27]</a></sup>
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<h2><span class="mw-headline" id="Epidemiology">Epidemiology</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=18" title="Edit section: Epidemiology"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h2>
<p>Sarcomas are rare cancers.<sup id="cite_ref-:1_2-16" class="reference"><a href="#cite_note-:1-2">[2]</a></sup> The risk of a previously healthy person receiving a new diagnosis of bone cancer is less than 0.001%, while the risk of receiving a new diagnosis of soft-tissue sarcoma is between 0.0014 and 0.005%.<sup id="cite_ref-:2_3-29" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> The American Cancer Society estimates that in the United States there will be 3,970 new cases of bone sarcoma in 2023, and 13,400 new cases of soft-tissue sarcoma.<sup id="cite_ref-:7_27-2" class="reference"><a href="#cite_note-:7-27">[27]</a></sup> Considering that the total estimated number of new cancer diagnoses (all types of cancer) is 1,958,310, this means bone sarcomas represent only 0.2% of all new cancer diagnoses (making them the 30th most common type of cancer<sup id="cite_ref-:8_26-3" class="reference"><a href="#cite_note-:8-26">[26]</a></sup>) and soft-tissue sarcomas represent only 0.7% (making them the 22nd most common type of cancer<sup id="cite_ref-:9_28-2" class="reference"><a href="#cite_note-:9-28">[28]</a></sup>) of all new cancer diagnoses in the US in 2023.<sup id="cite_ref-:7_27-3" class="reference"><a href="#cite_note-:7-27">[27]</a></sup> These estimates are similar to previously reported data.<sup id="cite_ref-:2_3-30" class="reference"><a href="#cite_note-:2-3">[3]</a></sup>
</p><p>Sarcomas affect people of all ages. Around 50% of bone sarcomas and 20% of soft-tissue sarcomas are diagnosed in people under the age of 35.<sup id="cite_ref-29" class="reference"><a href="#cite_note-29">[29]</a></sup> Some sarcomas, such as <a href="/enwiki/wiki/Leiomyosarcoma" title="Leiomyosarcoma">leiomyosarcoma</a>, <a href="/enwiki/wiki/Chondrosarcoma" title="Chondrosarcoma">chondrosarcoma</a>, and <a href="/enwiki/wiki/Gastrointestinal_stromal_tumor" title="Gastrointestinal stromal tumor">gastrointestinal stromal tumor</a> (GIST), are more common in adults than in children.<sup id="cite_ref-:1_2-17" class="reference"><a href="#cite_note-:1-2">[2]</a></sup> Most high-grade bone sarcomas, including <a href="/enwiki/wiki/Ewing%27s_sarcoma" class="mw-redirect" title="Ewing's sarcoma">Ewing sarcoma</a> and <a href="/enwiki/wiki/Osteosarcoma" title="Osteosarcoma">osteosarcoma</a>, are much more common in children and young adults.<sup id="cite_ref-:1_2-18" class="reference"><a href="#cite_note-:1-2">[2]</a></sup>
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<h2><span class="mw-headline" id="In_fossils">In fossils</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=19" title="Edit section: In fossils"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h2>
<p>In 2016, scientists reported the discovery of an <a href="/enwiki/wiki/Osteosarcoma" title="Osteosarcoma">osteosarcoma</a> tumor in a 1.6–1.8 million-year-old fossil from the skeleton of the now-extinct <a href="/enwiki/wiki/Hominin" class="mw-redirect" title="Hominin">hominin</a> species <i><a href="/enwiki/wiki/Australopithecus_sediba" title="Australopithecus sediba">Australopithecus sediba</a></i>, making it the earliest-known case of human cancer.<sup id="cite_ref-30" class="reference"><a href="#cite_note-30">[30]</a></sup><sup id="cite_ref-31" class="reference"><a href="#cite_note-31">[31]</a></sup>
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<h2><span class="mw-headline" id="Research">Research</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=20" title="Edit section: Research"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h2>
<p>Treatment of sarcoma, especially when the sarcoma has spread, or "metastasized", often requires chemotherapy but existing chemotherapeutic medicines are associated with significant toxicities and are not highly effective in killing cancer cells.<sup id="cite_ref-:2_3-31" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> Therefore, research to identify new medications to treat sarcoma is being conducted as of 2019<sup class="plainlinks noexcerpt noprint asof-tag update" style="display:none;"><a class="external text" href="https://en.wikipedia.org/enwiki/w/index.php?title=Sarcoma&action=edit">[update]</a></sup>.<sup id="cite_ref-:2_3-32" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> One new type of therapy still under investigation is the use of <a href="/enwiki/wiki/Cancer_immunotherapy" title="Cancer immunotherapy">cancer immunotherapy</a> (e.g., immune checkpoint inhibitors like anti-PD1, anti-PDL1, and anti-CTLA4 agents) to treat sarcomas.<sup id="cite_ref-:10_32-0" class="reference"><a href="#cite_note-:10-32">[32]</a></sup> These drugs are not yet FDA- or other regulator-approved treatment.<sup id="cite_ref-:10_32-1" class="reference"><a href="#cite_note-:10-32">[32]</a></sup> Other strategies, such as small-molecule <a href="/enwiki/wiki/Targeted_therapy" title="Targeted therapy">targeted therapy</a>, biologic agents (e.g., <a href="/enwiki/wiki/Small_interfering_RNA" title="Small interfering RNA">small interfering RNA</a> molecules), and <a href="/enwiki/wiki/Nanoparticle" title="Nanoparticle">nanoparticle</a>-directed therapy, also are under active investigated.<sup id="cite_ref-:2_3-33" class="reference"><a href="#cite_note-:2-3">[3]</a></sup>
</p><p>Research to understand the specific genetic and molecular factors that cause sarcoma to develop is underway.<sup id="cite_ref-:2_3-34" class="reference"><a href="#cite_note-:2-3">[3]</a></sup> This could allow for the design of new targeted therapies and allow physicians to more accurately predict a patient's prognosis.<sup id="cite_ref-:2_3-35" class="reference"><a href="#cite_note-:2-3">[3]</a></sup>
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<h2><span class="mw-headline" id="Awareness">Awareness</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=21" title="Edit section: Awareness"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h2>
<p>In the US, July is widely recognized as Sarcoma Awareness Month.<sup id="cite_ref-33" class="reference"><a href="#cite_note-33">[33]</a></sup> The UK has a Sarcoma Awareness Week in July led by <a href="/enwiki/w/index.php?title=Sarcoma_UK&action=edit&redlink=1" class="new" title="Sarcoma UK (page does not exist)">Sarcoma UK</a>, the bone and soft-tissue cancer charity.<sup id="cite_ref-34" class="reference"><a href="#cite_note-34">[34]</a></sup>
</p><p>American YouTuber <a href="/enwiki/wiki/Technoblade" title="Technoblade">Technoblade</a> was diagnosed with sarcoma in August 2021, and died from his illness in June 2022 after the cancer metastasized. He had raised over $500,000 in a charity stream. Many YouTubers have raised awareness and donated to charities such as the <a href="/enwiki/wiki/Sarcoma_Foundation_of_America" title="Sarcoma Foundation of America">Sarcoma Foundation of America</a> after Technoblade's diagnosis and passing. To date, Technoblade's fans have raised over $1,000,000 for sarcoma research.<sup id="cite_ref-35" class="reference"><a href="#cite_note-35">[35]</a></sup>
</p>
<h2><span class="mw-headline" id="References">References</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=22" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h2>
<style data-mw-deduplicate="TemplateStyles:r1011085734">.mw-parser-output .reflist{font-size:90%;margin-bottom:0.5em;list-style-type:decimal}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist">
<div class="mw-references-wrap mw-references-columns"><ol class="references">
<li id="cite_note-1"><span class="mw-cite-backlink"><b><a href="#cite_ref-1">^</a></b></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1133582631">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free a,.mw-parser-output .citation .cs1-lock-free a{background:url("/upwiki/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited a,.mw-parser-output .id-lock-registration a,.mw-parser-output .citation .cs1-lock-limited a,.mw-parser-output .citation .cs1-lock-registration a{background:url("/upwiki/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription a,.mw-parser-output .citation .cs1-lock-subscription a{background:url("/upwiki/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("/upwiki/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:#d33}.mw-parser-output .cs1-visible-error{color:#d33}.mw-parser-output .cs1-maint{display:none;color:#3a3;margin-left:0.3em}.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}</style><cite id="CITEREFYangRenDuHao2014" class="citation journal cs1">Yang J, Ren Z, Du X, Hao M, Zhou W (27 October 2014). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923508">"The role of mesenchymal stem/progenitor cells in sarcoma: update and dispute"</a>. <i>Stem Cell Investigation</i>. <b>1</b>: 18. <a href="/enwiki/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.3978%2Fj.issn.2306-9759.2014.10.01">10.3978/j.issn.2306-9759.2014.10.01</a>. <a href="/enwiki/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="cs1-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923508">4923508</a></span>. <a href="/enwiki/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/27358864">27358864</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Stem+Cell+Investigation&rft.atitle=The+role+of+mesenchymal+stem%2Fprogenitor+cells+in+sarcoma%3A+update+and+dispute&rft.volume=1&rft.pages=18&rft.date=2014-10-27&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC4923508%23id-name%3DPMC&rft_id=info%3Apmid%2F27358864&rft_id=info%3Adoi%2F10.3978%2Fj.issn.2306-9759.2014.10.01&rft.aulast=Yang&rft.aufirst=J&rft.au=Ren%2C+Z&rft.au=Du%2C+X&rft.au=Hao%2C+M&rft.au=Zhou%2C+W&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC4923508&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
</li>
<li id="cite_note-:1-2"><span class="mw-cite-backlink">^ <a href="#cite_ref-:1_2-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-:1_2-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-:1_2-2"><sup><i><b>c</b></i></sup></a> <a href="#cite_ref-:1_2-3"><sup><i><b>d</b></i></sup></a> <a href="#cite_ref-:1_2-4"><sup><i><b>e</b></i></sup></a> <a href="#cite_ref-:1_2-5"><sup><i><b>f</b></i></sup></a> <a href="#cite_ref-:1_2-6"><sup><i><b>g</b></i></sup></a> <a href="#cite_ref-:1_2-7"><sup><i><b>h</b></i></sup></a> <a href="#cite_ref-:1_2-8"><sup><i><b>i</b></i></sup></a> <a href="#cite_ref-:1_2-9"><sup><i><b>j</b></i></sup></a> <a href="#cite_ref-:1_2-10"><sup><i><b>k</b></i></sup></a> <a href="#cite_ref-:1_2-11"><sup><i><b>l</b></i></sup></a> <a href="#cite_ref-:1_2-12"><sup><i><b>m</b></i></sup></a> <a href="#cite_ref-:1_2-13"><sup><i><b>n</b></i></sup></a> <a href="#cite_ref-:1_2-14"><sup><i><b>o</b></i></sup></a> <a href="#cite_ref-:1_2-15"><sup><i><b>p</b></i></sup></a> <a href="#cite_ref-:1_2-16"><sup><i><b>q</b></i></sup></a> <a href="#cite_ref-:1_2-17"><sup><i><b>r</b></i></sup></a> <a href="#cite_ref-:1_2-18"><sup><i><b>s</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite id="CITEREFTobias2015" class="citation book cs1">Tobias J (2015). <i>Cancer and its Management</i> (Seventh ed.). Chichester, West Sussex, PO198SQ, UK: John Wiley & Sons, Ltd. p. 446. <a href="/enwiki/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/enwiki/wiki/Special:BookSources/978-1-118-46875-3" title="Special:BookSources/978-1-118-46875-3"><bdi>978-1-118-46875-3</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Cancer+and+its+Management&rft.place=Chichester%2C+West+Sussex%2C+PO198SQ%2C+UK&rft.pages=446&rft.edition=Seventh&rft.pub=John+Wiley+%26+Sons%2C+Ltd.&rft.date=2015&rft.isbn=978-1-118-46875-3&rft.aulast=Tobias&rft.aufirst=J&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span><span class="cs1-maint citation-comment"><code class="cs1-code">{{<a href="/enwiki/wiki/Template:Cite_book" title="Template:Cite book">cite book</a>}}</code>: CS1 maint: location (<a href="/enwiki/wiki/Category:CS1_maint:_location" title="Category:CS1 maint: location">link</a>)</span></span>
</li>
<li id="cite_note-:2-3"><span class="mw-cite-backlink">^ <a href="#cite_ref-:2_3-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-:2_3-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-:2_3-2"><sup><i><b>c</b></i></sup></a> <a href="#cite_ref-:2_3-3"><sup><i><b>d</b></i></sup></a> <a href="#cite_ref-:2_3-4"><sup><i><b>e</b></i></sup></a> <a href="#cite_ref-:2_3-5"><sup><i><b>f</b></i></sup></a> <a href="#cite_ref-:2_3-6"><sup><i><b>g</b></i></sup></a> <a href="#cite_ref-:2_3-7"><sup><i><b>h</b></i></sup></a> <a href="#cite_ref-:2_3-8"><sup><i><b>i</b></i></sup></a> <a href="#cite_ref-:2_3-9"><sup><i><b>j</b></i></sup></a> <a href="#cite_ref-:2_3-10"><sup><i><b>k</b></i></sup></a> <a href="#cite_ref-:2_3-11"><sup><i><b>l</b></i></sup></a> <a href="#cite_ref-:2_3-12"><sup><i><b>m</b></i></sup></a> <a href="#cite_ref-:2_3-13"><sup><i><b>n</b></i></sup></a> <a href="#cite_ref-:2_3-14"><sup><i><b>o</b></i></sup></a> <a href="#cite_ref-:2_3-15"><sup><i><b>p</b></i></sup></a> <a href="#cite_ref-:2_3-16"><sup><i><b>q</b></i></sup></a> <a href="#cite_ref-:2_3-17"><sup><i><b>r</b></i></sup></a> <a href="#cite_ref-:2_3-18"><sup><i><b>s</b></i></sup></a> <a href="#cite_ref-:2_3-19"><sup><i><b>t</b></i></sup></a> <a href="#cite_ref-:2_3-20"><sup><i><b>u</b></i></sup></a> <a href="#cite_ref-:2_3-21"><sup><i><b>v</b></i></sup></a> <a href="#cite_ref-:2_3-22"><sup><i><b>w</b></i></sup></a> <a href="#cite_ref-:2_3-23"><sup><i><b>x</b></i></sup></a> <a href="#cite_ref-:2_3-24"><sup><i><b>y</b></i></sup></a> <a href="#cite_ref-:2_3-25"><sup><i><b>z</b></i></sup></a> <a href="#cite_ref-:2_3-26"><sup><i><b>aa</b></i></sup></a> <a href="#cite_ref-:2_3-27"><sup><i><b>ab</b></i></sup></a> <a href="#cite_ref-:2_3-28"><sup><i><b>ac</b></i></sup></a> <a href="#cite_ref-:2_3-29"><sup><i><b>ad</b></i></sup></a> <a href="#cite_ref-:2_3-30"><sup><i><b>ae</b></i></sup></a> <a href="#cite_ref-:2_3-31"><sup><i><b>af</b></i></sup></a> <a href="#cite_ref-:2_3-32"><sup><i><b>ag</b></i></sup></a> <a href="#cite_ref-:2_3-33"><sup><i><b>ah</b></i></sup></a> <a href="#cite_ref-:2_3-34"><sup><i><b>ai</b></i></sup></a> <a href="#cite_ref-:2_3-35"><sup><i><b>aj</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite id="CITEREFDeVita_Jr2015" class="citation book cs1">DeVita Jr V (2015). <i>DeVita, Hellman and Rosenberg's Cancer: Principles & Practice of Oncology</i> (10th ed.). Philadelphia, PA: Wolters Kluwer Health. pp. 1241–1313. <a href="/enwiki/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/enwiki/wiki/Special:BookSources/978-1-4511-9294-0" title="Special:BookSources/978-1-4511-9294-0"><bdi>978-1-4511-9294-0</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=DeVita%2C+Hellman+and+Rosenberg%27s+Cancer%3A+Principles+%26+Practice+of+Oncology&rft.place=Philadelphia%2C+PA&rft.pages=1241-1313&rft.edition=10th&rft.pub=Wolters+Kluwer+Health&rft.date=2015&rft.isbn=978-1-4511-9294-0&rft.aulast=DeVita+Jr&rft.aufirst=V&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
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<li id="cite_note-:0-4"><span class="mw-cite-backlink">^ <a href="#cite_ref-:0_4-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-:0_4-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-:0_4-2"><sup><i><b>c</b></i></sup></a> <a href="#cite_ref-:0_4-3"><sup><i><b>d</b></i></sup></a> <a href="#cite_ref-:0_4-4"><sup><i><b>e</b></i></sup></a> <a href="#cite_ref-:0_4-5"><sup><i><b>f</b></i></sup></a> <a href="#cite_ref-:0_4-6"><sup><i><b>g</b></i></sup></a> <a href="#cite_ref-:0_4-7"><sup><i><b>h</b></i></sup></a> <a href="#cite_ref-:0_4-8"><sup><i><b>i</b></i></sup></a> <a href="#cite_ref-:0_4-9"><sup><i><b>j</b></i></sup></a> <a href="#cite_ref-:0_4-10"><sup><i><b>k</b></i></sup></a> <a href="#cite_ref-:0_4-11"><sup><i><b>l</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite id="CITEREFAmin2017" class="citation book cs1">Amin MB (2017). <i>AJCC Cancer Staging Manual, Eight Edition</i>. Chicago, IL: Springer International Publishing AG Switzerland. pp. 471–548. <a href="/enwiki/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/enwiki/wiki/Special:BookSources/978-3-319-40617-6" title="Special:BookSources/978-3-319-40617-6"><bdi>978-3-319-40617-6</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=AJCC+Cancer+Staging+Manual%2C+Eight+Edition&rft.place=Chicago%2C+IL&rft.pages=471-548&rft.pub=Springer+International+Publishing+AG+Switzerland&rft.date=2017&rft.isbn=978-3-319-40617-6&rft.aulast=Amin&rft.aufirst=MB&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
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<li id="cite_note-5"><span class="mw-cite-backlink"><b><a href="#cite_ref-5">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://www.cancer.gov/types/metastatic-cancer">"Metastatic Cancer"</a>. <i>National Cancer Institute</i>. 12 May 2015<span class="reference-accessdate">. Retrieved <span class="nowrap">22 March</span> 2019</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=National+Cancer+Institute&rft.atitle=Metastatic+Cancer&rft.date=2015-05-12&rft_id=https%3A%2F%2Fwww.cancer.gov%2Ftypes%2Fmetastatic-cancer&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
</li>
<li id="cite_note-def-6"><span class="mw-cite-backlink"><b><a href="#cite_ref-def_6-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://www.cancer.gov/cancertopics/cancerlibrary/what-is-cancer">"Defining Cancer"</a>. <i>National Cancer Institute</i>. 17 September 2007<span class="reference-accessdate">. Retrieved <span class="nowrap">10 June</span> 2014</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=National+Cancer+Institute&rft.atitle=Defining+Cancer&rft.date=2007-09-17&rft_id=http%3A%2F%2Fwww.cancer.gov%2Fcancertopics%2Fcancerlibrary%2Fwhat-is-cancer&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
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<li id="cite_note-7"><span class="mw-cite-backlink"><b><a href="#cite_ref-7">^</a></b></span> <span class="reference-text"><a rel="nofollow" class="external text" href="https://www.perseus.tufts.edu/hopper/text?doc=Perseus:text:1999.04.0057:entry=sa/rkwma"><span title="Ancient Greek (to 1453)-language text"><span lang="grc">σάρκωμα</span></span></a>, <a rel="nofollow" class="external text" href="https://www.perseus.tufts.edu/hopper/text?doc=Perseus:text:1999.04.0057:entry=sa/rc"><span title="Ancient Greek (to 1453)-language text"><span lang="grc">σάρξ</span></span></a>. <a href="/enwiki/wiki/Henry_Liddell" title="Henry Liddell">Liddell, Henry George</a>; <a href="/enwiki/wiki/Robert_Scott_(philologist)" title="Robert Scott (philologist)">Scott, Robert</a>; <i><a href="/enwiki/wiki/A_Greek%E2%80%93English_Lexicon" title="A Greek–English Lexicon">A Greek–English Lexicon</a></i> at the <a href="/enwiki/wiki/Perseus_Project" class="mw-redirect" title="Perseus Project">Perseus Project</a>.</span>
</li>
<li id="cite_note-8"><span class="mw-cite-backlink"><b><a href="#cite_ref-8">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://www.merriam-webster.com/dictionary/sarcoma">"Definition of SARCOMA"</a>. <i>www.merriam-webster.com</i><span class="reference-accessdate">. Retrieved <span class="nowrap">22 March</span> 2019</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=www.merriam-webster.com&rft.atitle=Definition+of+SARCOMA&rft_id=https%3A%2F%2Fwww.merriam-webster.com%2Fdictionary%2Fsarcoma&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
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<li id="cite_note-9"><span class="mw-cite-backlink"><b><a href="#cite_ref-9">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite id="CITEREFHarper" class="citation web cs1">Harper, Douglas. <a rel="nofollow" class="external text" href="https://www.etymonline.com/?term=sarcoma">"sarcoma"</a>. <i><a href="/enwiki/wiki/Online_Etymology_Dictionary" title="Online Etymology Dictionary">Online Etymology Dictionary</a></i>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=Online+Etymology+Dictionary&rft.atitle=sarcoma&rft.aulast=Harper&rft.aufirst=Douglas&rft_id=https%3A%2F%2Fwww.etymonline.com%2F%3Fterm%3Dsarcoma&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
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<li id="cite_note-10"><span class="mw-cite-backlink"><b><a href="#cite_ref-10">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://www.uptodate.com/contents/radiation-associated-sarcomas#!">"UpToDate"</a>. <i>www.uptodate.com</i><span class="reference-accessdate">. Retrieved <span class="nowrap">19 March</span> 2023</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=www.uptodate.com&rft.atitle=UpToDate&rft_id=https%3A%2F%2Fwww.uptodate.com%2Fcontents%2Fradiation-associated-sarcomas%23%21&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
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<li id="cite_note-:3-11"><span class="mw-cite-backlink">^ <a href="#cite_ref-:3_11-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-:3_11-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite id="CITEREFUnni2010" class="citation book cs1">Unni K (2010). <i>Dahlin's Bone Tumors</i>. Philadelphia, PA: Lippincott Williams & Wilkins. pp. 1–8. <a href="/enwiki/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/enwiki/wiki/Special:BookSources/978-0-7817-6242-7" title="Special:BookSources/978-0-7817-6242-7"><bdi>978-0-7817-6242-7</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Dahlin%27s+Bone+Tumors&rft.place=Philadelphia%2C+PA&rft.pages=1-8&rft.pub=Lippincott+Williams+%26+Wilkins&rft.date=2010&rft.isbn=978-0-7817-6242-7&rft.aulast=Unni&rft.aufirst=K&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
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<li id="cite_note-:9-28"><span class="mw-cite-backlink">^ <a href="#cite_ref-:9_28-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-:9_28-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-:9_28-2"><sup><i><b>c</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://seer.cancer.gov/statfacts/html/soft.html">"Soft Tissue Cancer - Cancer Stat Facts"</a>. <i>SEER</i><span class="reference-accessdate">. Retrieved <span class="nowrap">27 March</span> 2019</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=SEER&rft.atitle=Soft+Tissue+Cancer+-+Cancer+Stat+Facts&rft_id=https%3A%2F%2Fseer.cancer.gov%2Fstatfacts%2Fhtml%2Fsoft.html&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
</li>
<li id="cite_note-29"><span class="mw-cite-backlink"><b><a href="#cite_ref-29">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite id="CITEREFDarling2007" class="citation journal cs1">Darling J (2007). <a rel="nofollow" class="external text" href="http://sarcomahelp.org/articles/sarcoma-statistics.html">"A Different View of Sarcoma Statistics"</a>. <i>ESUN</i>. <b>4</b> (6)<span class="reference-accessdate">. Retrieved <span class="nowrap">6 October</span> 2012</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=ESUN&rft.atitle=A+Different+View+of+Sarcoma+Statistics&rft.volume=4&rft.issue=6&rft.date=2007&rft.aulast=Darling&rft.aufirst=J&rft_id=http%3A%2F%2Fsarcomahelp.org%2Farticles%2Fsarcoma-statistics.html&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
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<li id="cite_note-30"><span class="mw-cite-backlink"><b><a href="#cite_ref-30">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite id="CITEREFWillingham2016" class="citation web cs1">Willingham AJ (28 July 2016). <a rel="nofollow" class="external text" href="https://www.cnn.com/2016/07/28/health/oldest-human-cancer-found/index.html">"Scientists find cancer in million-year-old fossil"</a>. <i>CNN</i><span class="reference-accessdate">. Retrieved <span class="nowrap">27 March</span> 2019</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=CNN&rft.atitle=Scientists+find+cancer+in+million-year-old+fossil&rft.date=2016-07-28&rft.aulast=Willingham&rft.aufirst=AJ&rft_id=https%3A%2F%2Fwww.cnn.com%2F2016%2F07%2F28%2Fhealth%2Foldest-human-cancer-found%2Findex.html&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
</li>
<li id="cite_note-31"><span class="mw-cite-backlink"><b><a href="#cite_ref-31">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite id="CITEREFRandolph-QuinneyWilliamsSteynMeyer2016" class="citation journal cs1">Randolph-Quinney PS, Williams SA, Steyn M, Meyer MR, Smilg JS, Churchill SE, et al. (2016). <a rel="nofollow" class="external text" href="https://sajs.co.za/article/view/3562">"Osteogenic tumour in Australopithecus sediba: Earliest hominin evidence for neoplastic disease"</a>. <i>South African Journal of Science</i>. <b>112</b> (7/8). <a href="/enwiki/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="cs1-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.17159%2Fsajs.2016%2F20150470">10.17159/sajs.2016/20150470</a></span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=South+African+Journal+of+Science&rft.atitle=Osteogenic+tumour+in+Australopithecus+sediba%3A+Earliest+hominin+evidence+for+neoplastic+disease&rft.volume=112&rft.issue=7%2F8&rft.date=2016&rft_id=info%3Adoi%2F10.17159%2Fsajs.2016%2F20150470&rft.aulast=Randolph-Quinney&rft.aufirst=PS&rft.au=Williams%2C+SA&rft.au=Steyn%2C+M&rft.au=Meyer%2C+MR&rft.au=Smilg%2C+JS&rft.au=Churchill%2C+SE&rft.au=Odes%2C+EJ&rft.au=Augustine%2C+T&rft.au=Tafforeau%2C+P&rft.au=Berger%2C+LR&rft_id=https%3A%2F%2Fsajs.co.za%2Farticle%2Fview%2F3562&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
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<li id="cite_note-:10-32"><span class="mw-cite-backlink">^ <a href="#cite_ref-:10_32-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-:10_32-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite id="CITEREFThanindratarnDeanNelsonHornicek2019" class="citation journal cs1">Thanindratarn P, Dean DC, Nelson SD, Hornicek FJ, Duan Z (April 2019). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365405">"Advances in immune checkpoint inhibitors for bone sarcoma therapy"</a>. <i>Journal of Bone Oncology</i>. <b>15</b>: 100221. <a href="/enwiki/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="cs1-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.jbo.2019.100221">10.1016/j.jbo.2019.100221</a></span>. <a href="/enwiki/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="cs1-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365405">6365405</a></span>. <a href="/enwiki/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/30775238">30775238</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Journal+of+Bone+Oncology&rft.atitle=Advances+in+immune+checkpoint+inhibitors+for+bone+sarcoma+therapy&rft.volume=15&rft.pages=100221&rft.date=2019-04&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC6365405%23id-name%3DPMC&rft_id=info%3Apmid%2F30775238&rft_id=info%3Adoi%2F10.1016%2Fj.jbo.2019.100221&rft.aulast=Thanindratarn&rft.aufirst=P&rft.au=Dean%2C+DC&rft.au=Nelson%2C+SD&rft.au=Hornicek%2C+FJ&rft.au=Duan%2C+Z&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC6365405&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
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<li id="cite_note-33"><span class="mw-cite-backlink"><b><a href="#cite_ref-33">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="http://www.cancer.net/research-and-advocacy/cancer-awareness-dates">"Cancer Awareness Dates"</a>. American Society of Clinical Oncology. 19 December 2013.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=unknown&rft.btitle=Cancer+Awareness+Dates&rft.pub=American+Society+of+Clinical+Oncology&rft.date=2013-12-19&rft_id=http%3A%2F%2Fwww.cancer.net%2Fresearch-and-advocacy%2Fcancer-awareness-dates&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
</li>
<li id="cite_note-34"><span class="mw-cite-backlink"><b><a href="#cite_ref-34">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://sarcoma.org.uk/get-involved/SAW">"Sarcoma Awareness Week 2018"</a>. Sarcoma UK. 25 January 2016<span class="reference-accessdate">. Retrieved <span class="nowrap">13 April</span> 2018</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=unknown&rft.btitle=Sarcoma+Awareness+Week+2018&rft.pub=Sarcoma+UK&rft.date=2016-01-25&rft_id=https%3A%2F%2Fsarcoma.org.uk%2Fget-involved%2FSAW&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
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<li id="cite_note-35"><span class="mw-cite-backlink"><b><a href="#cite_ref-35">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1133582631"><cite id="CITEREFSaunders2022" class="citation web cs1">Saunders, Cindy (1 July 2022). <a rel="nofollow" class="external text" href="https://www.curesarcoma.org/technoblade-tribute/">"Technoblade Tribute"</a>. <i>Sarcoma Foundation of America</i><span class="reference-accessdate">. Retrieved <span class="nowrap">10 November</span> 2022</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=Sarcoma+Foundation+of+America&rft.atitle=Technoblade+Tribute&rft.date=2022-07-01&rft.aulast=Saunders&rft.aufirst=Cindy&rft_id=https%3A%2F%2Fwww.curesarcoma.org%2Ftechnoblade-tribute%2F&rfr_id=info%3Asid%2Fen.wikipedia.org%3ASarcoma" class="Z3988"></span></span>
</li>
</ol></div></div>
<h2><span class="mw-headline" id="External_links">External links</span><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/enwiki/w/index.php?title=Sarcoma&action=edit&section=23" title="Edit section: External links"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></h2>
<ul><li><a rel="nofollow" class="external text" href="https://www.cancer.gov/types/bone/hp">Bone sarcoma</a> at the National Cancer Institute</li>
<li><a rel="nofollow" class="external text" href="https://www.reininsarcoma.org/what-is-sarcoma-2/">What is Sarcoma?</a></li>
<li><a rel="nofollow" class="external text" href="https://sarcomahelp.org/">Sarcoma Help from the Liddy Shriver Sarcoma Initiative</a></li></ul>
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margin:0.5em 0 0.5em 0;;padding:3px"><table class="nowraplinks navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="row" class="navbox-group" style="width:1%;background: #EAECF0">Classification</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"><div style="position:relative; float:right; font-size:0.8em;"><a href="https://www.wikidata.org/wiki/Q223911" class="extiw" title="d:Q223911">D</a></div><div class="hlist" style="text-align:left;"><ul><li><b><a href="/enwiki/wiki/International_Classification_of_Diseases_for_Oncology" title="International Classification of Diseases for Oncology">ICD-O</a></b>: <a rel="nofollow" class="external text" href="https://progenetix.org/subsets/?term_id=icdom:8800_3">M8800/3</a></li><li><b><a href="/enwiki/wiki/Medical_Subject_Headings" title="Medical Subject Headings">MeSH</a></b>: <a rel="nofollow" class="external text" href="https://meshb.nlm.nih.gov/record/ui?ui=D012509">D012509</a></li><li><b><a href="/enwiki/wiki/SNOMED_CT" title="SNOMED CT">SNOMED CT</a></b>: <a rel="nofollow" class="external text" href="http://snomed.info/id/424413001">424413001</a></li></ul></div></div></td></tr></tbody></table></div>
<div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1061467846"></div><div role="navigation" class="navbox" aria-labelledby="Connective/soft_tissue_tumors_and_sarcomas" style="padding:3px"><table class="nowraplinks mw-collapsible mw-collapsed navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><style data-mw-deduplicate="TemplateStyles:r1063604349">.mw-parser-output .navbar{display:inline;font-size:88%;font-weight:normal}.mw-parser-output .navbar-collapse{float:left;text-align:left}.mw-parser-output .navbar-boxtext{word-spacing:0}.mw-parser-output .navbar ul{display:inline-block;white-space:nowrap;line-height:inherit}.mw-parser-output .navbar-brackets::before{margin-right:-0.125em;content:"[ "}.mw-parser-output .navbar-brackets::after{margin-left:-0.125em;content:" ]"}.mw-parser-output .navbar li{word-spacing:-0.125em}.mw-parser-output .navbar a>span,.mw-parser-output .navbar a>abbr{text-decoration:inherit}.mw-parser-output .navbar-mini abbr{font-variant:small-caps;border-bottom:none;text-decoration:none;cursor:inherit}.mw-parser-output .navbar-ct-full{font-size:114%;margin:0 7em}.mw-parser-output .navbar-ct-mini{font-size:114%;margin:0 4em}</style><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/enwiki/wiki/Template:Soft_tissue_tumors_and_sarcomas" title="Template:Soft tissue tumors and sarcomas"><abbr title="View this template" style=";;background:none transparent;border:none;box-shadow:none;padding:0;">v</abbr></a></li><li class="nv-talk"><a href="/enwiki/wiki/Template_talk:Soft_tissue_tumors_and_sarcomas" title="Template talk:Soft tissue tumors and sarcomas"><abbr title="Discuss this template" style=";;background:none transparent;border:none;box-shadow:none;padding:0;">t</abbr></a></li><li class="nv-edit"><a href="/enwiki/wiki/Special:EditPage/Template:Soft_tissue_tumors_and_sarcomas" title="Special:EditPage/Template:Soft tissue tumors and sarcomas"><abbr title="Edit this template" style=";;background:none transparent;border:none;box-shadow:none;padding:0;">e</abbr></a></li></ul></div><div id="Connective/soft_tissue_tumors_and_sarcomas" style="font-size:114%;margin:0 4em"><a href="/enwiki/wiki/Connective_tissue" title="Connective tissue">Connective</a>/<a href="/enwiki/wiki/Soft_tissue" title="Soft tissue">soft tissue</a> <a href="/enwiki/wiki/Neoplasm" title="Neoplasm">tumors</a> and <a class="mw-selflink selflink">sarcomas</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%">Not otherwise specified</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Soft-tissue_sarcoma" title="Soft-tissue sarcoma">Soft-tissue sarcoma</a></li>
<li><a href="/enwiki/wiki/Desmoplastic_small-round-cell_tumor" title="Desmoplastic small-round-cell tumor">Desmoplastic small-round-cell tumor</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Connective_tissue_neoplasm" title="Connective tissue neoplasm">Connective tissue neoplasm</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Fibrous_tissue_neoplasm" title="Fibrous tissue neoplasm">Fibromatous</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Fibroma" title="Fibroma">Fibroma</a>/<a href="/enwiki/wiki/Fibrosarcoma" title="Fibrosarcoma">fibrosarcoma</a>:</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Dermatofibrosarcoma_protuberans" title="Dermatofibrosarcoma protuberans">Dermatofibrosarcoma protuberans</a></li>
<li><a href="/enwiki/wiki/Desmoplastic_fibroma" title="Desmoplastic fibroma">Desmoplastic fibroma</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Fibroma" title="Fibroma">Fibroma</a>/<a href="/enwiki/wiki/Fibromatosis" title="Fibromatosis">fibromatosis</a>:</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Aggressive_fibromatosis" title="Aggressive fibromatosis">Aggressive fibromatosis</a></li>
<li><a href="/enwiki/wiki/Aggressive_infantile_fibromatosis" title="Aggressive infantile fibromatosis">Aggressive infantile fibromatosis</a></li>
<li><a href="/enwiki/wiki/Aponeurotic_fibroma" title="Aponeurotic fibroma">Aponeurotic fibroma</a></li>
<li><a href="/enwiki/wiki/Collagenous_fibroma" title="Collagenous fibroma">Collagenous fibroma</a></li>
<li><a href="/enwiki/wiki/Diffuse_infantile_fibromatosis" title="Diffuse infantile fibromatosis">Diffuse infantile fibromatosis</a></li>
<li><a href="/enwiki/wiki/Familial_myxovascular_fibromas" title="Familial myxovascular fibromas">Familial myxovascular fibromas</a></li>
<li><a href="/enwiki/wiki/Fibroma_of_tendon_sheath" title="Fibroma of tendon sheath">Fibroma of tendon sheath</a></li>
<li><a href="/enwiki/wiki/Fibromatosis_colli" title="Fibromatosis colli">Fibromatosis colli</a></li>
<li><a href="/enwiki/wiki/Infantile_digital_fibromatosis" title="Infantile digital fibromatosis">Infantile digital fibromatosis</a></li>
<li><a href="/enwiki/wiki/Juvenile_hyaline_fibromatosis" title="Juvenile hyaline fibromatosis">Juvenile hyaline fibromatosis</a></li>
<li><a href="/enwiki/wiki/Plantar_fibromatosis" title="Plantar fibromatosis">Plantar fibromatosis</a></li>
<li><a href="/enwiki/wiki/Pleomorphic_fibroma" title="Pleomorphic fibroma">Pleomorphic fibroma</a></li>
<li><a href="/enwiki/wiki/Oral_submucous_fibrosis" title="Oral submucous fibrosis">Oral submucous fibrosis</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Histiocytoma" title="Histiocytoma">Histiocytoma</a>/<a href="/enwiki/wiki/Histiocytic_sarcoma" title="Histiocytic sarcoma">histiocytic sarcoma</a>:</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Benign_fibrous_histiocytoma" class="mw-redirect" title="Benign fibrous histiocytoma">Benign fibrous histiocytoma</a></li>
<li><a href="/enwiki/wiki/Pleomorphic_undifferentiated_sarcoma" class="mw-redirect" title="Pleomorphic undifferentiated sarcoma">Malignant fibrous histiocytoma</a></li>
<li><a href="/enwiki/wiki/Atypical_fibroxanthoma" title="Atypical fibroxanthoma">Atypical fibroxanthoma</a></li>
<li><a href="/enwiki/wiki/Solitary_fibrous_tumor" title="Solitary fibrous tumor">Solitary fibrous tumor</a></li></ul>
</div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Myxoma" title="Myxoma">Myxomatous</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Myxoma" title="Myxoma">Myxoma</a>/<a href="/enwiki/wiki/Myxosarcoma" title="Myxosarcoma">myxosarcoma</a>
<ul><li><a href="/enwiki/wiki/Cutaneous_myxoma" title="Cutaneous myxoma">Cutaneous myxoma</a></li>
<li><a href="/enwiki/wiki/Superficial_acral_fibromyxoma" title="Superficial acral fibromyxoma">Superficial acral fibromyxoma</a></li></ul></li>
<li><a href="/enwiki/wiki/Aggressive_angiomyxoma" title="Aggressive angiomyxoma">Angiomyxoma</a></li>
<li><a href="/enwiki/wiki/Ossifying_fibromyxoid_tumour" title="Ossifying fibromyxoid tumour">Ossifying fibromyxoid tumour</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Fibroepithelial_neoplasms" class="mw-redirect" title="Fibroepithelial neoplasms">Fibroepithelial</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Brenner_tumour" title="Brenner tumour">Brenner tumour</a></li>
<li><a href="/enwiki/wiki/Fibroadenoma" title="Fibroadenoma">Fibroadenoma</a></li>
<li><a href="/enwiki/wiki/Phyllodes_tumor" title="Phyllodes tumor">Phyllodes tumor</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Synovial_joint" title="Synovial joint">Synovial</a>-like</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Synovial_sarcoma" title="Synovial sarcoma">Synovial sarcoma</a></li>
<li><a href="/enwiki/wiki/Clear-cell_sarcoma" class="mw-redirect" title="Clear-cell sarcoma">Clear-cell sarcoma</a></li></ul>
</div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Adipose_tissue_neoplasm" title="Adipose tissue neoplasm">Lipomatous</a></th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Lipoma" title="Lipoma">Lipoma</a>/<a href="/enwiki/wiki/Liposarcoma" title="Liposarcoma">liposarcoma</a>
<ul><li><a href="/enwiki/wiki/Myelolipoma" title="Myelolipoma">Myelolipoma</a></li>
<li><a href="/enwiki/wiki/Myxoid_liposarcoma" title="Myxoid liposarcoma">Myxoid liposarcoma</a></li></ul></li>
<li><a href="/enwiki/wiki/Perivascular_epithelioid_cell_tumour" title="Perivascular epithelioid cell tumour">PEComa</a>
<ul><li><a href="/enwiki/wiki/Angiomyolipoma" title="Angiomyolipoma">Angiomyolipoma</a></li></ul></li></ul>
<ul><li><a href="/enwiki/wiki/Chondroid_lipoma" title="Chondroid lipoma">Chondroid lipoma</a></li>
<li><a href="/enwiki/wiki/Intradermal_spindle_cell_lipoma" title="Intradermal spindle cell lipoma">Intradermal spindle cell lipoma</a></li>
<li><a href="/enwiki/wiki/Pleomorphic_lipoma" title="Pleomorphic lipoma">Pleomorphic lipoma</a></li>
<li><a href="/enwiki/wiki/Lipoblastomatosis" title="Lipoblastomatosis">Lipoblastomatosis</a></li>
<li><a href="/enwiki/wiki/Spindle_cell_lipoma" title="Spindle cell lipoma">Spindle cell lipoma</a></li>
<li><a href="/enwiki/wiki/Hibernoma" title="Hibernoma">Hibernoma</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Muscle_tissue_neoplasm" class="mw-redirect" title="Muscle tissue neoplasm">Myomatous</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><span class="nobold"><i>general:</i></span></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Myoma" title="Myoma">Myoma</a>/<a href="/enwiki/wiki/Myosarcoma" title="Myosarcoma">myosarcoma</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><span class="nobold"><i><a href="/enwiki/wiki/Smooth_muscle_tissue" class="mw-redirect" title="Smooth muscle tissue">smooth muscle</a>:</i></span></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Leiomyoma" title="Leiomyoma">Leiomyoma</a>/<a href="/enwiki/wiki/Leiomyosarcoma" title="Leiomyosarcoma">leiomyosarcoma</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><span class="nobold"><i><a href="/enwiki/wiki/Skeletal_muscle" title="Skeletal muscle">skeletal muscle</a>:</i></span></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Rhabdomyoma" title="Rhabdomyoma">Rhabdomyoma</a>/<a href="/enwiki/wiki/Rhabdomyosarcoma" title="Rhabdomyosarcoma">rhabdomyosarcoma</a>: <a href="/enwiki/wiki/Embryonal_rhabdomyosarcoma" title="Embryonal rhabdomyosarcoma">Embryonal rhabdomyosarcoma</a>
<ul><li><a href="/enwiki/wiki/Sarcoma_botryoides" title="Sarcoma botryoides">Sarcoma botryoides</a></li></ul></li>
<li><a href="/enwiki/wiki/Alveolar_rhabdomyosarcoma" title="Alveolar rhabdomyosarcoma">Alveolar rhabdomyosarcoma</a></li></ul>
</div></td></tr><tr><td colspan="2" class="navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Leiomyoma" title="Leiomyoma">Leiomyoma</a></li>
<li><a href="/enwiki/wiki/Angioleiomyoma" title="Angioleiomyoma">Angioleiomyoma</a></li>
<li><a href="/enwiki/wiki/Angiolipoleiomyoma" title="Angiolipoleiomyoma">Angiolipoleiomyoma</a></li>
<li><a href="/enwiki/wiki/Genital_leiomyoma" title="Genital leiomyoma">Genital leiomyoma</a></li>
<li><a href="/enwiki/wiki/Leiomyosarcoma" title="Leiomyosarcoma">Leiomyosarcoma</a></li>
<li><a href="/enwiki/wiki/Hereditary_leiomyomatosis_and_renal_cell_cancer_syndrome" title="Hereditary leiomyomatosis and renal cell cancer syndrome">Multiple cutaneous and uterine leiomyomatosis syndrome</a></li>
<li><a href="/enwiki/wiki/Multiple_cutaneous_leiomyoma" title="Multiple cutaneous leiomyoma">Multiple cutaneous leiomyoma</a></li>
<li><a href="/enwiki/wiki/Neural_fibrolipoma" title="Neural fibrolipoma">Neural fibrolipoma</a></li>
<li><a href="/enwiki/wiki/Solitary_cutaneous_leiomyoma" title="Solitary cutaneous leiomyoma">Solitary cutaneous leiomyoma</a></li>
<li><a href="/enwiki/wiki/Smooth_muscle_tumor_of_uncertain_malignant_potential" title="Smooth muscle tumor of uncertain malignant potential">STUMP</a></li></ul>
</div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Complex_and_mixed_tumor" class="mw-redirect" title="Complex and mixed tumor">Complex mixed and stromal</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Adenomyoma" title="Adenomyoma">Adenomyoma</a></li>
<li><a href="/enwiki/wiki/Pleomorphic_adenoma" title="Pleomorphic adenoma">Pleomorphic adenoma</a></li>
<li><a href="/enwiki/wiki/Mixed_M%C3%BCllerian_tumor" title="Mixed Müllerian tumor">Mixed Müllerian tumor</a></li>
<li><a href="/enwiki/wiki/Mesoblastic_nephroma" title="Mesoblastic nephroma">Mesoblastic nephroma</a></li>
<li><a href="/enwiki/wiki/Wilms%27_tumor" title="Wilms' tumor">Wilms' tumor</a></li>
<li><a href="/enwiki/wiki/Malignant_rhabdoid_tumour" title="Malignant rhabdoid tumour">Malignant rhabdoid tumour</a></li>
<li><a href="/enwiki/wiki/Clear-cell_sarcoma_of_the_kidney" title="Clear-cell sarcoma of the kidney">Clear-cell sarcoma of the kidney</a></li>
<li><a href="/enwiki/wiki/Hepatoblastoma" title="Hepatoblastoma">Hepatoblastoma</a></li>
<li><a href="/enwiki/wiki/Pancreatoblastoma" title="Pancreatoblastoma">Pancreatoblastoma</a></li>
<li><a href="/enwiki/wiki/Carcinosarcoma" title="Carcinosarcoma">Carcinosarcoma</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Mesothelium" title="Mesothelium">Mesothelial</a></th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Mesothelioma" title="Mesothelioma">Mesothelioma</a></li>
<li><a href="/enwiki/wiki/Adenomatoid_tumor" title="Adenomatoid tumor">Adenomatoid tumor</a></li></ul>
</div></td></tr></tbody></table></div>
<div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1061467846"></div><div role="navigation" class="navbox" aria-labelledby="Tumours_of_bone_and_cartilage" style="padding:3px"><table class="nowraplinks mw-collapsible mw-collapsed navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1063604349"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/enwiki/wiki/Template:Bone_and_cartilage_tumors" title="Template:Bone and cartilage tumors"><abbr title="View this template" style=";;background:none transparent;border:none;box-shadow:none;padding:0;">v</abbr></a></li><li class="nv-talk"><a href="/enwiki/wiki/Template_talk:Bone_and_cartilage_tumors" title="Template talk:Bone and cartilage tumors"><abbr title="Discuss this template" style=";;background:none transparent;border:none;box-shadow:none;padding:0;">t</abbr></a></li><li class="nv-edit"><a href="/enwiki/wiki/Special:EditPage/Template:Bone_and_cartilage_tumors" title="Special:EditPage/Template:Bone and cartilage tumors"><abbr title="Edit this template" style=";;background:none transparent;border:none;box-shadow:none;padding:0;">e</abbr></a></li></ul></div><div id="Tumours_of_bone_and_cartilage" style="font-size:114%;margin:0 4em">Tumours of <a href="/enwiki/wiki/Bone_tumor" title="Bone tumor">bone</a> and <a href="/enwiki/wiki/Cartilage_tumor" title="Cartilage tumor">cartilage</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Diaphysis" title="Diaphysis">Diaphysis</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Multiple_myeloma" title="Multiple myeloma">Multiple myeloma</a></li>
<li><a href="/enwiki/wiki/Epithelium" title="Epithelium">Epithelia</a>
<ul><li><a href="/enwiki/wiki/Adamantinoma" title="Adamantinoma">Adamantinoma</a></li></ul></li>
<li><a href="/enwiki/wiki/Primitive_neuroectodermal_tumor" title="Primitive neuroectodermal tumor">Primitive neuroectodermal tumor</a>
<ul><li><a href="/enwiki/wiki/Ewing_family_of_tumors" title="Ewing family of tumors">Ewing family</a></li>
<li><a href="/enwiki/wiki/Ewing_sarcoma" title="Ewing sarcoma">Ewing sarcoma</a></li></ul></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Metaphysis" title="Metaphysis">Metaphysis</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Osteoblast" title="Osteoblast">Osteoblast</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Osteoid_osteoma" title="Osteoid osteoma">Osteoid osteoma</a></li>
<li><a href="/enwiki/wiki/Osteoblastoma" title="Osteoblastoma">Osteoblastoma</a></li>
<li><a href="/enwiki/wiki/Osteoma" title="Osteoma">Osteoma</a>/<a href="/enwiki/wiki/Osteosarcoma" title="Osteosarcoma">osteosarcoma</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Chondroblast" title="Chondroblast">Chondroblast</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Chondroma" title="Chondroma">Chondroma</a>/<a href="/enwiki/wiki/Ecchondroma" title="Ecchondroma">ecchondroma</a>/<a href="/enwiki/wiki/Enchondroma" title="Enchondroma">enchondroma</a>
<ul><li><a href="/enwiki/wiki/Enchondromatosis" title="Enchondromatosis">Enchondromatosis</a></li>
<li><a href="/enwiki/wiki/Extraskeletal_chondroma" title="Extraskeletal chondroma">Extraskeletal chondroma</a></li></ul></li>
<li><a href="/enwiki/wiki/Chondrosarcoma" title="Chondrosarcoma">Chondrosarcoma</a>
<ul><li><a href="/enwiki/wiki/Mesenchymal_chondrosarcoma" class="mw-redirect" title="Mesenchymal chondrosarcoma">Mesenchymal chondrosarcoma</a></li>
<li><a href="/enwiki/wiki/Myxoid_chondrosarcoma" title="Myxoid chondrosarcoma">Myxoid chondrosarcoma</a></li></ul></li>
<li><a href="/enwiki/wiki/Osteochondroma" title="Osteochondroma">Osteochondroma</a>
<ul><li><a href="/enwiki/wiki/Osteochondromatosis" title="Osteochondromatosis">Osteochondromatosis</a></li></ul></li>
<li><a href="/enwiki/wiki/Chondromyxoid_fibroma" title="Chondromyxoid fibroma">Chondromyxoid fibroma</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Connective_tissue" title="Connective tissue">Fibrous</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Osteofibrous_dysplasia" title="Osteofibrous dysplasia">Ossifying fibroma</a></li>
<li><a href="/enwiki/wiki/Fibrosarcoma" title="Fibrosarcoma">Fibrosarcoma</a></li></ul>
</div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Epiphysis" title="Epiphysis">Epiphysis</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Chondroblast" title="Chondroblast">Chondroblast</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Chondroblastoma" title="Chondroblastoma">Chondroblastoma</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Myeloid_tissue" title="Myeloid tissue">Myeloid</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Giant-cell_tumor_of_bone" title="Giant-cell tumor of bone">Giant-cell tumor of bone</a></li></ul>
</div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Notochord" scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Notochord" title="Notochord">Notochord</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Chordoma" title="Chordoma">Chordoma</a></li></ul>
</div></td></tr></tbody></table><div></div></td></tr></tbody></table></div>
<div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1061467846"></div><div role="navigation" class="navbox" aria-labelledby="Tumours_of_blood_vessels" style="padding:3px"><table class="nowraplinks mw-collapsible mw-collapsed navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1063604349"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/enwiki/wiki/Template:Vascular_tumors" title="Template:Vascular tumors"><abbr title="View this template" style=";;background:none transparent;border:none;box-shadow:none;padding:0;">v</abbr></a></li><li class="nv-talk"><a href="/enwiki/wiki/Template_talk:Vascular_tumors" title="Template talk:Vascular tumors"><abbr title="Discuss this template" style=";;background:none transparent;border:none;box-shadow:none;padding:0;">t</abbr></a></li><li class="nv-edit"><a href="/enwiki/wiki/Special:EditPage/Template:Vascular_tumors" title="Special:EditPage/Template:Vascular tumors"><abbr title="Edit this template" style=";;background:none transparent;border:none;box-shadow:none;padding:0;">e</abbr></a></li></ul></div><div id="Tumours_of_blood_vessels" style="font-size:114%;margin:0 4em"><a href="/enwiki/wiki/Vascular_tumor" title="Vascular tumor">Tumours of blood vessels</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Blood_vessel" title="Blood vessel">Blood vessel</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Hemangiosarcoma" title="Hemangiosarcoma">Hemangiosarcoma</a></li>
<li><a href="/enwiki/wiki/Blue_rubber_bleb_nevus_syndrome" title="Blue rubber bleb nevus syndrome">Blue rubber bleb nevus syndrome</a></li>
<li><a href="/enwiki/wiki/Hemangioendothelioma" title="Hemangioendothelioma">Hemangioendothelioma</a>
<ul><li><a href="/enwiki/wiki/Composite_hemangioendothelioma" class="mw-redirect" title="Composite hemangioendothelioma">Composite</a></li>
<li><a href="/enwiki/wiki/Endovascular_papillary_hemangioendothelioma" class="mw-redirect" title="Endovascular papillary hemangioendothelioma">Endovascular papillary</a></li>
<li><a href="/enwiki/wiki/Epithelioid_hemangioendothelioma" title="Epithelioid hemangioendothelioma">Epithelioid</a></li>
<li><a href="/enwiki/wiki/Kaposiform_hemangioendothelioma" class="mw-redirect" title="Kaposiform hemangioendothelioma">Kaposiform</a></li>
<li><a href="/enwiki/wiki/Infantile_hemangioendothelioma" class="mw-redirect" title="Infantile hemangioendothelioma">Infantile</a></li>
<li><a href="/enwiki/wiki/Retiform_hemangioendothelioma" class="mw-redirect" title="Retiform hemangioendothelioma">Retiform</a>)</li>
<li><a href="/enwiki/wiki/Spindle_cell_hemangioendothelioma" class="mw-redirect" title="Spindle cell hemangioendothelioma">Spindle cell</a></li></ul></li>
<li><a href="/enwiki/wiki/Proliferating_angioendotheliomatosis" title="Proliferating angioendotheliomatosis">Proliferating angioendotheliomatosis</a></li>
<li><a href="/enwiki/wiki/Hemangiopericytoma" title="Hemangiopericytoma">Hemangiopericytoma</a></li>
<li><a href="/enwiki/wiki/Venous_lake" title="Venous lake">Venous lake</a></li>
<li><a href="/enwiki/wiki/Kaposi%27s_sarcoma" title="Kaposi's sarcoma">Kaposi's sarcoma</a>
<ul><li><a href="/enwiki/wiki/African_cutaneous_Kaposi_sarcoma" class="mw-redirect" title="African cutaneous Kaposi sarcoma">African cutaneous</a></li>
<li><a href="/enwiki/wiki/African_lymphadenopathic_Kaposi_sarcoma" class="mw-redirect" title="African lymphadenopathic Kaposi sarcoma">African lymphadenopathic</a></li>
<li><a href="/enwiki/wiki/AIDS-associated_Kaposi_sarcoma" class="mw-redirect" title="AIDS-associated Kaposi sarcoma">AIDS-associated</a></li>
<li><a href="/enwiki/wiki/Classic_Kaposi_sarcoma" class="mw-redirect" title="Classic Kaposi sarcoma">Classic</a></li>
<li><a href="/enwiki/wiki/Immunosuppression-associated_Kaposi_sarcoma" class="mw-redirect" title="Immunosuppression-associated Kaposi sarcoma">Immunosuppression-associated</a></li></ul></li>
<li><a href="/enwiki/wiki/Hemangioblastoma" title="Hemangioblastoma">Hemangioblastoma</a></li>
<li><a href="/enwiki/wiki/Hemangioma" title="Hemangioma">Hemangioma</a>
<ul><li><a href="/enwiki/wiki/Capillary_hemangioma" class="mw-redirect" title="Capillary hemangioma">Capillary</a></li>
<li><a href="/enwiki/wiki/Cavernous_hemangioma" title="Cavernous hemangioma">Cavernous</a></li>
<li><a href="/enwiki/wiki/Glomeruloid_hemangioma" title="Glomeruloid hemangioma">Glomeruloid</a></li>
<li><a href="/enwiki/wiki/Microvenular_hemangioma" title="Microvenular hemangioma">Microvenular</a></li>
<li><a href="/enwiki/wiki/Targetoid_hemosiderotic_hemangioma" title="Targetoid hemosiderotic hemangioma">Targeted hemosiderotic</a></li></ul></li>
<li><a href="/enwiki/wiki/Angioma" title="Angioma">Angioma</a>
<ul><li><a href="/enwiki/wiki/Cherry_angioma" title="Cherry angioma">Cherry</a></li>
<li><a href="/enwiki/wiki/Angioma_serpiginosum" title="Angioma serpiginosum">Seriginosum</a></li>
<li><a href="/enwiki/wiki/Spider_angioma" title="Spider angioma">Spider</a></li>
<li><a href="/enwiki/wiki/Tufted_angioma" title="Tufted angioma">Tufted</a></li></ul></li>
<li><a href="/enwiki/wiki/Universal_angiomatosis" title="Universal angiomatosis">Universal angiomatosis</a></li>
<li><a href="/enwiki/wiki/Angiokeratoma" title="Angiokeratoma">Angiokeratoma</a>
<ul><li><a href="/enwiki/wiki/Angiokeratoma_of_Mibelli" class="mw-redirect" title="Angiokeratoma of Mibelli">of Mibelli</a></li>
<li><a href="/enwiki/wiki/Angiolipoma" title="Angiolipoma">Angiolipoma</a></li></ul></li>
<li><a href="/enwiki/wiki/Pyogenic_granuloma" title="Pyogenic granuloma">Pyogenic granuloma</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/enwiki/wiki/Lymphatic_vessel_tumor" class="mw-redirect" title="Lymphatic vessel tumor">Lymphatic</a></th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Lymphangioma" title="Lymphangioma">Lymphangioma</a>/<a href="/enwiki/wiki/Lymphangiosarcoma" title="Lymphangiosarcoma">lymphangiosarcoma</a>
<ul><li><a href="/enwiki/wiki/Lymphangioma_circumscriptum" title="Lymphangioma circumscriptum">Lymphangioma circumscriptum</a></li>
<li><a href="/enwiki/wiki/Acquired_progressive_lymphangioma" title="Acquired progressive lymphangioma">Acquired progressive lymphangioma</a></li></ul></li>
<li><i><a href="/enwiki/wiki/PEComa" class="mw-redirect" title="PEComa">PEComa</a></i>
<ul><li><a href="/enwiki/wiki/Lymphangioleiomyomatosis" title="Lymphangioleiomyomatosis">Lymphangioleiomyomatosis</a></li></ul></li>
<li><a href="/enwiki/wiki/Cystic_hygroma" title="Cystic hygroma">Cystic hygroma</a></li>
<li><a href="/enwiki/wiki/Multifocal_lymphangioendotheliomatosis" title="Multifocal lymphangioendotheliomatosis">Multifocal lymphangioendotheliomatosis</a></li>
<li><a href="/enwiki/wiki/Lymphangiomatosis" title="Lymphangiomatosis">Lymphangiomatosis</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Either</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/enwiki/wiki/Angioma" title="Angioma">Angioma</a>/<a href="/enwiki/wiki/Angiosarcoma" title="Angiosarcoma">angiosarcoma</a></li>
<li><a href="/enwiki/wiki/Angiofibroma" title="Angiofibroma">Angiofibroma</a></li></ul>
</div></td></tr></tbody></table></div>
<div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1061467846"><style data-mw-deduplicate="TemplateStyles:r1038841319">.mw-parser-output .tooltip-dotted{border-bottom:1px dotted;cursor:help}</style></div><div role="navigation" class="navbox authority-control" aria-labelledby="Authority_control_databases_frameless&#124;text-top&#124;10px&#124;alt=Edit_this_at_Wikidata&#124;link=https&#58;//www.wikidata.org/wiki/Q223911#identifiers&#124;class=noprint&#124;Edit_this_at_Wikidata" style="padding:3px"><table class="nowraplinks hlist mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><div id="Authority_control_databases_frameless&#124;text-top&#124;10px&#124;alt=Edit_this_at_Wikidata&#124;link=https&#58;//www.wikidata.org/wiki/Q223911#identifiers&#124;class=noprint&#124;Edit_this_at_Wikidata" style="font-size:114%;margin:0 4em"><a href="/enwiki/wiki/Help:Authority_control" title="Help:Authority control">Authority control databases</a> <span class="mw-valign-text-top noprint" typeof="mw:File/Frameless"><a href="https://www.wikidata.org/wiki/Q223911#identifiers" title="Edit this at Wikidata"><img alt="Edit this at Wikidata" src="/upwiki/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/10px-OOjs_UI_icon_edit-ltr-progressive.svg.png" decoding="async" width="10" height="10" class="mw-file-element" srcset="/upwiki/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/15px-OOjs_UI_icon_edit-ltr-progressive.svg.png 1.5x, /upwiki/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/20px-OOjs_UI_icon_edit-ltr-progressive.svg.png 2x" data-file-width="20" data-file-height="20" /></a></span></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%">International</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><span class="uid"><a rel="nofollow" class="external text" href="http://id.worldcat.org/fast/1105477/">FAST</a></span></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">National</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><span class="uid"><a rel="nofollow" class="external text" href="http://catalogo.bne.es/uhtbin/authoritybrowse.cgi?action=display&authority_id=XX526877">Spain</a></span></li>
<li><span class="uid"><a rel="nofollow" class="external text" href="https://catalogue.bnf.fr/ark:/12148/cb11982790q">France</a></span></li>
<li><span class="uid"><a rel="nofollow" class="external text" href="https://data.bnf.fr/ark:/12148/cb11982790q">BnF data</a></span></li>
<li><span class="uid"><a rel="nofollow" class="external text" href="https://d-nb.info/gnd/4179127-7">Germany</a></span></li>
<li><span class="uid"><a rel="nofollow" class="external text" href="http://uli.nli.org.il/F/?func=find-b&local_base=NLX10&find_code=UID&request=987007556069505171">Israel</a></span></li>
<li><span class="uid"><a rel="nofollow" class="external text" href="https://id.loc.gov/authorities/sh85117504">United States</a></span></li>
<li><span class="uid"><span class="rt-commentedText tooltip tooltip-dotted" title="sarkomy"><a rel="nofollow" class="external text" href="https://aleph.nkp.cz/F/?func=find-c&local_base=aut&ccl_term=ica=ph936611&CON_LNG=ENG">Czech Republic</a></span></span></li></ul>
</div></td></tr></tbody></table></div></div>' |
Whether or not the change was made through a Tor exit node (tor_exit_node) | false |
Unix timestamp of change (timestamp) | '1699755739' |
