Osteosarcoma overview

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

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

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

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

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

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

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

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

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

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

# Diagnosis

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

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

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

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

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

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

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

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

## Other Imaging Findings
Bone scan in osteosarcoma is used to observe abnormal areas of bone and metastasis.

## Other Diagnostic Studies
A bone scan in osteosarcomais used to observe abnormal areas of bone and metastasis.

# Treatment

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

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