Osteosarcoma

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Osteosarcoma_table_infobox_0

OsteosarcomaOsteosarcoma_header_cell_0_0_0
SpecialtyOsteosarcoma_header_cell_0_1_0 OncologyOsteosarcoma_cell_0_1_1

An osteosarcoma (OS) or osteogenic sarcoma (OGS) (or simply bone cancer) is a cancerous tumor in a bone. Osteosarcoma_sentence_0

Specifically, it is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchymal origin (and thus a sarcoma) and that exhibits osteoblastic differentiation and produces malignant osteoid. Osteosarcoma_sentence_1

Osteosarcoma is the most common histological form of primary bone sarcoma. Osteosarcoma_sentence_2

It is most prevalent in teenagers and young adults. Osteosarcoma_sentence_3

Signs and symptoms Osteosarcoma_section_0

Many patients first complain of pain that may be worse at night, may be intermittent and of varying intensity and may have been occurring for some time. Osteosarcoma_sentence_4

Teenagers who are active in sports often complain of pain in the lower femur, or immediately below the knee. Osteosarcoma_sentence_5

If the tumor is large, it can present as overt localised swelling. Osteosarcoma_sentence_6

Sometimes a sudden fracture is the first symptom, because the affected bone is not as strong as normal bone and may fracture abnormally with minor trauma. Osteosarcoma_sentence_7

In cases of more deep-seated tumors that are not as close to the skin, such as those originating in the pelvis, localised swelling may not be apparent. Osteosarcoma_sentence_8

Causes Osteosarcoma_section_1

Several research groups are investigating cancer stem cells and their potential to cause tumors along with genes and proteins causative in different phenotypes. Osteosarcoma_sentence_9

Radiotherapy for unrelated conditions may be a rare cause. Osteosarcoma_sentence_10

Osteosarcoma_unordered_list_0

There is no clear association between water fluoridation and cancer or deaths due to cancer, both for cancer in general and also specifically for bone cancer and osteosarcoma. Osteosarcoma_sentence_11

Series of research concluded that concentration of fluoride in water doesn't associate with osteosarcoma. Osteosarcoma_sentence_12

The beliefs regarding association of fluoride exposure and osteosarcoma stem from a study of US National Toxicology program in 1990, which showed uncertain evidence of association of fluoride and osteosarcoma in male rats. Osteosarcoma_sentence_13

But there is still no solid evidence of cancer-causing tendency of fluoride in mice. Osteosarcoma_sentence_14

Fluoridation of water has been practiced around the world to improve citizens' dental health. Osteosarcoma_sentence_15

It is also deemed as major health success. Osteosarcoma_sentence_16

Fluoride concentration levels in water supplies are regulated, such as United States Environmental Protection Agency regulates fluoride levels to not be greater than 4 milligrams per liter. Osteosarcoma_sentence_17

Actually, water supplies already have natural occurring fluoride, but many communities chose to add more fluoride to the point that it can reduce tooth decay. Osteosarcoma_sentence_18

Fluoride is also known for its ability to cause new bone formation. Osteosarcoma_sentence_19

Yet, further research shows no osteosarcoma risks from fluoridated water in humans. Osteosarcoma_sentence_20

Most of the research involved counting number of osteosarcoma patients cases in particular areas which has difference concentrations of fluoride in drinking water. Osteosarcoma_sentence_21

The statistic analysis of the data shows no significant difference in occurrences of osteosarcoma cases in different fluoridated regions. Osteosarcoma_sentence_22

Another important research involved collecting bone samples from osteosarcoma patients to measure fluoride concentration and compare them to bone samples of newly diagnosed malignant bone tumors. Osteosarcoma_sentence_23

The result is that the median fluoride concentrations in bone samples of osteosarcoma patients and tumor controls are not significantly different. Osteosarcoma_sentence_24

Not only fluoride concentration in bones, Fluoride exposures of osteosarcoma patients are also proven to be not significantly different from healthy people. Osteosarcoma_sentence_25

Mechanism Osteosarcoma_section_2

Osteosarcomas tend to occur at the sites of bone growth, presumably because proliferation makes osteoblastic cells in this region prone to acquire mutations that could lead to transformation of cells (the RB gene and p53 gene are commonly involved). Osteosarcoma_sentence_26

Due to this tendency, high incidence of osteosarcoma is seen in some large dog breeds (St. Bernards and Great Danes). Osteosarcoma_sentence_27

The tumor may be localized at the end of the long bone (commonly in the metaphysis). Osteosarcoma_sentence_28

Most often it affects the proximal end of tibia or humerus, or distal end of femur. Osteosarcoma_sentence_29

Osteosarcoma tends to affect regions around the knee in 60% of cases, 15% around the hip, 10% at the shoulder, and 8% in the jaw. Osteosarcoma_sentence_30

The tumor is solid, hard, irregular ("fir-tree," "moth-eaten", or "sun-burst" appearance on X-ray examination) due to the tumor spicules of calcified bone radiating in right angles. Osteosarcoma_sentence_31

These right angles form what is known as a Codman triangle, which is characteristic but not diagnostic of osteosarcoma. Osteosarcoma_sentence_32

Surrounding tissues are infiltrated. Osteosarcoma_sentence_33

Microscopically: The characteristic feature of osteosarcoma is presence of osteoid (bone formation) within the tumor. Osteosarcoma_sentence_34

Tumor cells are very pleomorphic (anaplastic), some are giant, numerous atypical mitoses. Osteosarcoma_sentence_35

These cells produce osteoid describing irregular trabeculae (amorphous, eosinophilic/pink) with or without central calcification (hematoxylinophilic/blue, granular)—tumor bone. Osteosarcoma_sentence_36

Tumor cells are included in the osteoid matrix. Osteosarcoma_sentence_37

Depending on the features of the tumor cells present (whether they resemble bone cells, cartilage cells, or fibroblast cells), the tumor can be subclassified. Osteosarcoma_sentence_38

Osteosarcomas may exhibit multinucleated osteoclast-like giant cells. Osteosarcoma_sentence_39

Diagnosis Osteosarcoma_section_3

Family physicians and orthopedists rarely see a malignant bone tumor (most bone tumors are benign). Osteosarcoma_sentence_40

The route to osteosarcoma diagnosis usually begins with an X-ray, continues with a combination of scans (CT scan, PET scan, bone scan, MRI) and ends with a surgical biopsy. Osteosarcoma_sentence_41

A characteristic often seen in an X-ray is Codman's triangle, which is basically a subperiosteal lesion formed when the periosteum is raised due to the tumor. Osteosarcoma_sentence_42

Films are suggestive, but bone biopsy is the only definitive method to determine whether a tumor is malignant or benign. Osteosarcoma_sentence_43

Most times, the early signs of osteosarcoma are caught on X-rays taken during routine dental check-ups. Osteosarcoma_sentence_44

Osteosarcoma frequently develops in the mandible (lower jaw); accordingly, dentists are trained to look for signs that may suggest osteosarcoma. Osteosarcoma_sentence_45

Even though radiographic findings for this cancer vary greatly, one usually sees a symmetrical widening of the periodontal ligament space. Osteosarcoma_sentence_46

If the dentist has reason to suspects osteosarcoma or another underlying disorder, he or she would refer the patient to an Oral & Maxillofacial surgeon for biopsy. Osteosarcoma_sentence_47

A biopsy of suspected osteosarcoma outside of the facial region should be performed by a qualified orthopedic oncologist. Osteosarcoma_sentence_48

The American Cancer Society states: "Probably in no other cancer is it as important to perform this procedure properly. Osteosarcoma_sentence_49

An improperly performed biopsy may make it difficult to save the affected limb from amputation." Osteosarcoma_sentence_50

It may also metastasise to the lungs, mainly appearing on the chest X-ray as solitary or multiple round nodules most common at the lower regions. Osteosarcoma_sentence_51

Variants Osteosarcoma_section_4

Osteosarcoma_unordered_list_1

  • Conventional: osteoblastic, chondroblastic, fibroblastic OSOsteosarcoma_item_1_5
  • Telangiectatic OSOsteosarcoma_item_1_6
  • Small cell OSOsteosarcoma_item_1_7
  • Low-grade central OSOsteosarcoma_item_1_8
  • Periosteal OSOsteosarcoma_item_1_9
  • Paraosteal OSOsteosarcoma_item_1_10
  • Secondary OSOsteosarcoma_item_1_11
  • High-grade surface OSOsteosarcoma_item_1_12
  • Extraskeletal OSOsteosarcoma_item_1_13

Treatment Osteosarcoma_section_5

A complete radical, surgical, en bloc resection of the cancer, is the treatment of choice in osteosarcoma. Osteosarcoma_sentence_52

Although about 90% of patients are able to have limb-salvage surgery, complications, particularly infection, prosthetic loosening and non-union, or local tumor recurrence may cause the need for further surgery or amputation. Osteosarcoma_sentence_53

Mifamurtide is used after a patient has had surgery to remove the tumor and together with chemotherapy to kill remaining cancer cells to reduce the risk of cancer recurrence. Osteosarcoma_sentence_54

Also, the option to have rotationplasty after the tumor is taken out exists. Osteosarcoma_sentence_55

Patients with osteosarcoma are best managed by a medical oncologist and an orthopedic oncologist experienced in managing sarcomas. Osteosarcoma_sentence_56

Current standard treatment is to use neoadjuvant chemotherapy (chemotherapy given before surgery) followed by surgical resection. Osteosarcoma_sentence_57

The percentage of tumor cell necrosis (cell death) seen in the tumor after surgery gives an idea of the prognosis and also lets the oncologist know if the chemotherapy regimen should be altered after surgery. Osteosarcoma_sentence_58

Standard therapy is a combination of limb-salvage orthopedic surgery when possible (or amputation in some cases) and a combination of high-dose methotrexate with leucovorin rescue, intra-arterial cisplatin, adriamycin, ifosfamide with mesna, BCD (bleomycin, cyclophosphamide, dactinomycin), etoposide, and muramyl tripeptide. Osteosarcoma_sentence_59

Rotationplasty may be used. Osteosarcoma_sentence_60

Ifosfamide can be used as an adjuvant treatment if the necrosis rate is low. Osteosarcoma_sentence_61

Despite the success of chemotherapy for osteosarcoma, it has one of the lowest survival rates for pediatric cancer. Osteosarcoma_sentence_62

The best reported 10-year survival rate is 92%; the protocol used is an aggressive intra-arterial regimen that individualizes therapy based on arteriographic response. Osteosarcoma_sentence_63

Three-year event-free survival ranges from 50% to 75%, and five-year survival ranges from 60% to 85+% in some studies. Osteosarcoma_sentence_64

Overall, 65–70% patients treated five years ago will be alive today. Osteosarcoma_sentence_65

These survival rates are overall averages and vary greatly depending on the individual necrosis rate. Osteosarcoma_sentence_66

Filgrastim or pegfilgrastim help with white blood cell counts and neutrophil counts. Osteosarcoma_sentence_67

Blood transfusions and epoetin alfa help with anemia. Osteosarcoma_sentence_68

Computational analysis on a panel of osteosarcoma cell lines identified new shared and specific therapeutic targets (proteomic and genetic) in osteosarcoma, while phenotypes showed an increased role of tumor microenvironments. Osteosarcoma_sentence_69

Prognosis Osteosarcoma_section_6

Prognosis is separated into three groups. Osteosarcoma_sentence_70

Osteosarcoma_unordered_list_2

  • Stage I osteosarcoma is rare and includes parosteal osteosarcoma or low-grade central osteosarcoma. It has an excellent prognosis (>90%) with wide resection.Osteosarcoma_item_2_14
  • Stage II prognosis depends on the site of the tumor (proximal tibia, femur, pelvis, etc.), size of the tumor mass, and the degree of necrosis from neoadjuvant chemotherapy. Other pathological factors such as the degree of p-glycoprotein, whether the tumor is cxcr4-positive, or Her2-positive are also important, as these are associated with distant metastases to the lung. The prognosis for patients with metastatic osteosarcoma improves with longer times to metastases (more than 12 months to 4 months), a smaller number of metastases, and their resectability. It is better to have fewer metastases than longer time to metastases. Those with a longer length of time (more than 24 months) and few nodules (two or fewer) have the best prognosis, with a two-year survival after the metastases of 50%, five-year of 40%, and 10-year of 20%. If metastases are both local and regional, the prognosis is worse.Osteosarcoma_item_2_15
  • Initial presentation of stage III osteosarcoma with lung metastases depends on the resectability of the primary tumor and lung nodules, degree of necrosis of the primary tumor, and maybe the number of metastases. Overall survival prognosis is about 30%.Osteosarcoma_item_2_16

Deaths due to malignant neoplasms of the bones and joints account for an unknown number of childhood cancer deaths. Osteosarcoma_sentence_71

Mortality rates due to osteosarcoma have been declining at about 1.3% per year. Osteosarcoma_sentence_72

Long-term survival probabilities for osteosarcoma have improved dramatically during the late 20th century and approximated 68% in 2009. Osteosarcoma_sentence_73

Epidemiology Osteosarcoma_section_7

Osteosarcoma is the eighth-most common form of childhood cancer, comprising 2.4% of all malignancies in pediatric patients, and about 20% of all primary bone cancers. Osteosarcoma_sentence_74

Incidence rates for osteosarcoma in U.S. patients under 20 years of age are estimated at 5.0 per million per year in the general population, with a slight variation between individuals of black, Hispanic, and white ethnicities (6.8, 6.5, and 4.6 per million per year, respectively). Osteosarcoma_sentence_75

It is slightly more common in males (5.4 per million per year) than in females (4.0 per million per year). Osteosarcoma_sentence_76

It originates more frequently in the metaphyseal region of tubular long bones, with 42% occurring in the femur, 19% in the tibia, and 10% in the humerus. Osteosarcoma_sentence_77

About 8% of all cases occur in the skull and jaw, and another 8% in the pelvis. Osteosarcoma_sentence_78

Around 300 of the 900 people diagnosed in the United States will die each year. Osteosarcoma_sentence_79

A second peak in incidence occurs in the elderly, usually associated with an underlying bone pathology such as Paget's disease of bone. Osteosarcoma_sentence_80

Other animals Osteosarcoma_section_8

Risk factors Osteosarcoma_section_9

Osteosarcoma is the most common bone tumor in dogs and typically afflicts middle-aged large and giant breed dogs such as Irish Wolfhounds, Greyhounds, German Shepherds, Rottweilers, mountain breeds (Great Pyrenees, St. Bernard, Leonberger, Newfoundland), Doberman Pinschers and Great Danes. Osteosarcoma_sentence_81

It has a 10-fold greater incidence in dogs than humans. Osteosarcoma_sentence_82

A hereditary base has been shown in St. Bernard dogs. Osteosarcoma_sentence_83

Spayed/neutered dogs have twice the risk of intact ones to develop osteosarcoma. Osteosarcoma_sentence_84

Infestation with the parasite Spirocerca lupi can cause osteosarcoma of the esophagus. Osteosarcoma_sentence_85

Clinical presentation Osteosarcoma_section_10

The most commonly affected bones are the proximal humerus, the distal radius, the distal femur, and the tibia, following the basic premise "far from the elbow, close to the knee". Osteosarcoma_sentence_86

Other sites include the ribs, the mandible, the spine, and the pelvis. Osteosarcoma_sentence_87

Rarely, osteosarcoma may arise from soft tissues (extraskeletal osteosarcoma). Osteosarcoma_sentence_88

Metastasis of tumors involving the limb bones is very common, usually to the lungs. Osteosarcoma_sentence_89

The tumor causes a great deal of pain, and can even lead to fracture of the affected bone. Osteosarcoma_sentence_90

As with human osteosarcoma, bone biopsy is the definitive method to reach a final diagnosis. Osteosarcoma_sentence_91

Osteosarcoma should be differentiated from other bone tumours and a range of other lesions, such as osteomyelitis. Osteosarcoma_sentence_92

Differential diagnosis of the osteosarcoma of the skull in particular includes, among others, chondrosarcoma and the multilobular tumour of bone. Osteosarcoma_sentence_93

Treatment and prognosis Osteosarcoma_section_11

Amputation is the initial treatment, although this alone will not prevent metastasis. Osteosarcoma_sentence_94

Chemotherapy combined with amputation improves the survival time, but most dogs still die within a year. Osteosarcoma_sentence_95

Surgical techniques designed to save the leg (limb-sparing procedures) do not improve the prognosis. Osteosarcoma_sentence_96

Some current studies indicate osteoclast inhibitors such as alendronate and pamidronate may have beneficial effects on the quality of life by reducing osteolysis, thus reducing the degree of pain, as well as the risk of pathological fractures. Osteosarcoma_sentence_97

Cats Osteosarcoma_section_12

Osteosarcoma is also the most common bone tumor in cats, although not as frequently encountered, and most typically affects the rear legs. Osteosarcoma_sentence_98

The cancer is generally less aggressive in cats than in dogs, so amputation alone can lead to a significant survival time in many affected cats, though post-amputation chemotherapy is recommended when a high grade is confirmed on histopathology. Osteosarcoma_sentence_99


Credits to the contents of this page go to the authors of the corresponding Wikipedia page: en.wikipedia.org/wiki/Osteosarcoma.